[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"diffuse-intrinsic-pontine-glioma\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:diffuse-intrinsic-pontine-glioma":30},{"pageToken":4,"total":5,"offset":6,"count":7,"results":8},null,28,0,25,[9,50,81,102,147,180,209,246,267,287,307,330,352,385,414,439,469,492,521,552,575,594,619,647,676],{"id":10,"slug":11,"hasResults":12,"nctId":13,"briefTitle":14,"officialTitle":15,"acronym":16,"eligibilityCriteria":17,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":20,"enrollmentInfo":21,"targetDuration":4,"studyType":24,"phases":25,"briefSummary":27,"conditions":28,"keywords":31,"overallStatus":37,"whyStopped":4,"lastUpdateSubmitDate":38,"lastUpdatePostDateStruct":39,"startDateStruct":42,"completionDateStruct":44,"leadSponsor":46,"locationsCount":49},"100588843","phase-1-il-8-receptor-modified-cd70-car-t-cell-therapy-in-cd70-newly-diagnosed-and-recurrent-pediatric-high-grade-glioma-phgg-and-newly-diagnosed-diffuse-intrinsic-pontine-glioma-nddipg-100588843",false,"NCT06946680","IL-8 Receptor-modified CD70 CAR T Cell Therapy in CD70+ Newly Diagnosed and Recurrent Pediatric High-grade Glioma (pHGG) and Newly Diagnosed Diffuse Intrinsic Pontine Glioma (ndDIPG)","Peds IMPACT: Phase I Study -To Assess Safety and Feasibility of IL-8 Receptor Modified Patient-derived Activated CD70 CAR T Cell Therapy in Newly Diagnosed and Recurrent CD70+ Pediatric High-Grade Gliomas (pHGG) and Diffuse Intrinsic Pontine Glioma (ndDIPG)","Peds IMPACT","Inclusion Criteria:\n\nAt enrollment:\n\n* Patients with a histologically confirmed diagnosis of:\n\n  * Newly diagnosed high-grade glioma (WHO Grade III or IV)\n  * Newly diagnosed DIPG (after first 2 HGG patients are treated)\n  * Recurrent or progressive high-grade glioma\n* Age 4-18 years old for ndHGG. Age 4-30 for rHGG. Age 4-30 for nd DIPG.\n* Patients with M+ disease without gliomatosis cerebri (see definition under exclusion criteria) ARE eligible.\n* Patients with primary spinal cord tumors ARE eligible.\n* CD70 positive (≥5%, 1+) The tumors from the surgical resection by immunohistochemistry will be confirmed by validated assay performed at UF Health Pathology, CLIA certified Lab.\n* CD70 tumor expression performed on paraffin-embedded tumor specimens will be evaluated. Tumor expression will be scored on a scale of 0 to 3 staining intensity:\n\n  0 = Negative\n  1. = Low level\n  2. = Moderate level\n  3. = High level The criteria for inclusion will be at least 5% of the cells scoring 1+ staining intensity (\\> 5%, 1+).\n* Karnofsky Performance Status (KPS, for patients \\>16yo) or Lansky Performance Score (LPS, for patients ≤16yo) of \\> 60% (Appendix C)\n* Patients who are unable to walk because of neurologic deficits, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score provided the neurological deficit is stable.\n\nOrgan Function:\n\n* CBC with differential with adequate bone marrow function as defined below:\n* Absolute neutrophil count (ANC) ≥ 1000 cells\u002Fmm3.\n* Platelet count ≥ 75,000 cells\u002Fmm3. (Unsupported, no transfusion within 4 days.)\n* Hemoglobin ≥ 8 g\u002Fdl. (May receive transfusions)\n* Adequate renal function as defined below:\n* Serum creatinine \\\u003C 1.5 x institutional upper limit of normal for age and gender. Patients who do not meet the criteria but have a 24-hour Creatinine Clearance or GFR (radioisotope or iothalamate) ≥ 70 mL\u002Fmin\u002F1.73 m2 are eligible.\n* Adequate hepatic function as defined below:\n* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) for age\n* ALT ≤ 3 times institutional upper limits of normal for age\n* AST ≤ 3 times institutional upper limits of normal for age\n* Patients with neurological deficits should have deficits that are stable for a minimum of 7 days prior to enrollment.\n* Signed parental permission and, as appropriate, assent from pediatric patients age ≥14. If the patient's mental status precludes their informed consent, the legally authorized representative may give informed consent. Consent or permission\u002Fassent will be obtained at screening (before PBMC collection) and before treatment with CAR T-cells.\n* For females with childbearing potential, a negative serum pregnancy test at enrollment.\n* Women of childbearing potential (WOCBP) must be willing to use an acceptable contraceptive method to avoid pregnancy throughout the study and for at least 24 weeks after the last dose of the study drug.\n* Males with female partners of childbearing potential must agree to practice adequate contraceptive methods throughout the study and should avoid conceiving children for 24 weeks following the last dose of the study drug.\n* Prior Therapy for recurrent Cohort only:\n* Patients with recurrent or progressive disease must have received prior radiotherapy +\u002F- chemotherapy.\n* Patients must have recovered from the acute treatment related toxicities (≤ Grade 1) prior to enrollment.\n* Patients must have received their last dose of known myelosuppressive anticancer therapy at least 21 days prior to enrollment. Patients must have received their last dose of non-myelosuppressive chemotherapy at least 7 days prior to enrollment.\n* Patients must have received their last dose of the investigational or biologic agent ≥ 7 days prior to study enrollment. Monoclonal antibody treatment and agents with known prolonged half-lives: Patient must have received their last dose of the agent ≥ 28 days prior to study enrollment.\n* Patients with recurrent or progressive HGG must have had their last fraction of:\n* Craniospinal irradiation, whole brain radiation, total body irradiation or radiation to spine ≥ 6 weeks (42 days) prior to enrollment.\n* Focal irradiation ≥ 14 days prior to enrollment.\n* ≥ 12 weeks (84 days) since autologous stem cell transplant prior to enrollment.\n* \\> 42 days since completion of any other type of adoptive cellular therapy prior to enrollment\n\nPrior to lymphodepletion and therapy:\n\n* Appropriate bridging therapy (radiation\u002Fre-irradiation and\u002For salvage chemotherapy, dependent on cohort) was initiated within 7 weeks of surgery RT or other protocol directed anti-cancer therapy is without significant toxicity that persisted over 4 weeks.\n* Early postoperative progression: Patients who progress during radiation treatment that are clinically stable and meet eligibility criteria prior to the start of lymphodepletion may continue on study. If these criteria are not met, these patients will be withdrawn from the study.\n* Neurologic Status\n* In patients with neurological deficits, deficits should be stable for a minimum of 7 days prior to the start of treatment. A baseline detailed neurological exam should clearly document the neurological status of the patient prior to the start of treatment.\n* In patients with seizure disorders, seizures must be well controlled prior to the start of treatment.\n* Performance Status Karnofsky Performance Scale (KPS for \\> 16 years of age) or Lansky Performance Score (LPS for ≤ 16 years of age) (Appendix C) assessed within one week prior to the start of treatment must be ≥ 60%.\n* Organ Function Patients must have adequate organ and bone marrow function as defined in Section 3.1.\n* Pregnancy Testing Female patients of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to the start of treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.\n* Corticosteroids: A maximum dose of 0.75 mg\u002Fkg\u002Fday with maximum of 4mg\u002Fday.\n* No active infection: No fever exceeding 38.5 °C and no acute antibiotics, antiviral, or antifungal PO or IV therapy.\n\nExclusion Criteria:\n\n* Prior invasive malignancy (except for non-melanomatous skin cancer) unless disease-free for ≥ 3 years. (In situ cancer is permissible)\n* Spinal metastasis or gliomatosis cerebri. Gliomatosis cerebri - clear tumor involvement of multiple areas (\\>3 lobes), OR presence of clinical and\u002For radiographic evidence of impending herniation or spinal cord compression.\n* The patient is not a candidate for cellular therapy as assessed by the study bone marrow transplant physician.\n* Known immunosuppressive disease or human immunodeficiency virus (HIV) infection.\n\nHIV-positive patients are ineligible due to the unknown safety and efficacy of infusing these patients with CAR T cells genetically modified using retroviral vectors. Additionally, the immunosuppression used for treatment in this study will pose an unacceptable risk.\n\n• Concurrent illness: Patients with active autoimmune disease, documented history of autoimmune disease\u002Fsyndrome, or any other condition that requires ongoing systemic steroids or systemic immunosuppressive agents, except\n\n* Patients with vitiligo or resolved asthma\u002Fatopy\n* Patients with hypothyroidism stable on hormone replacement or Sjogren's syndrome\n* Patients requiring physiologic doses of corticosteroids (up to 0.5 mg\u002Fm2\u002Fday dexamethasone equivalent)\n* History of or ongoing pneumonitis or significant interstitial lung disease.\n* Ongoing or active uncontrolled infection.\n* Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the opinion of the investigator, would compromise the patient's ability to tolerate protocol therapy, put them at additional risk for toxicity or would interfere with the study procedures or results.\n* Patients with any of the following cardiac diseases:\n* New York Heart Association (NYHA) functional class III or IV\n* Clinically significant cardiac arrhythmia including, but not limited to, Torsade de pointes or requiring a pacemaker\n* Left ventricular ejection fraction below 50% as determined by echocardiography (ECHO)\n* Pregnant or lactating women due to possible adverse effects on the developing fetus or infant.\n* Patients who are receiving any other anti-cancer or investigational drug therapy are ineligible.\n* Patients who have received the last vaccination of a live vaccine ≤ 30 days prior to enrollment are ineligible.\n* Patients who have received an inactivated virus, peptide, or mRNA vaccine within 14 days of the start of protocol therapy are ineligible.\n* Inability to participate: Patients who in the opinion of the investigator are unwilling or unable to return for required follow-up visits or obtain follow-up studies required to assess toxicity of therapy or to adhere to drug administration plan, other study procedures, and study restrictions.\n* Patients treated on any other therapeutic clinical protocols within 30 days prior to enrollment.\n* For females of childbearing potential, a negative serum pregnancy test at enrollment.","ALL","4 Years","30 Years",{"count":22,"type":23},24,"ESTIMATED","INTERVENTIONAL",[26],"PHASE1","This is a phase I study to assess the safety and feasibility of IL-8 receptor modified patient-derived activated CD70 CAR T cell therapy in newly diagnosed and recurrent CD70+ Pediatric High-Grade Gliomas (pHGG) and Diffuse Intrinsic Pontine Glioma (ndDIPG)",[29,30],"High-grade Glioma","Diffuse Intrinsic Pontine Glioma",[32,33,34,35,36],"CAR T Cell","Brain Tumor","Brain Cancer","Immunotherapy","Glioblastoma","NOT_YET_RECRUITING","2026-06-30",{"date":40,"type":41},"2026-07-01","ACTUAL",{"date":43,"type":23},"2026-07",{"date":45,"type":23},"2045-12",{"name":47,"class":48},"University of Florida","OTHER",1,{"id":51,"slug":52,"hasResults":12,"nctId":53,"briefTitle":54,"officialTitle":55,"acronym":4,"eligibilityCriteria":56,"healthyVolunteers":12,"sex":18,"minAge":4,"maxAge":57,"enrollmentInfo":58,"targetDuration":4,"studyType":24,"phases":60,"briefSummary":62,"conditions":63,"keywords":70,"overallStatus":72,"whyStopped":4,"lastUpdateSubmitDate":38,"lastUpdatePostDateStruct":73,"startDateStruct":74,"completionDateStruct":76,"leadSponsor":78,"locationsCount":80},"100551831","phase-1-eflornithine-dfmo-and-amxt-1501-for-neuroblastoma-cns-tumors-and-sarcomas-100551831","NCT06465199","Eflornithine (DFMO) and AMXT 1501 for Neuroblastoma, CNS Tumors, and Sarcomas","A Phase I\u002FII Study Using Eflornithine (DFMO) and AMXT 1501 for Relapsed and Refractory Neuroblastoma, CNS Tumors, and Sarcomas","Inclusion Criteria:\n\n1. Age:\n\n   All participants : Must be a maximum of 26 years of age at diagnosis\n\n   Age at enrollment by Phase:\n   1. Safety Run-in (Dose level 1)-The first three (3) participants enrolled will be ≥ 12 years of age at enrollment. Once evaluated for safety by DSMB, we will move on to the next three (3) participants enrolled who will be ≥6 years of age at enrollment. Once evaluated for safety by DSMB, we will move on to the Phase I.\n   2. Phase I and II: ≤ 26 years of age at diagnosis.\n2. Pathology\n\n   All participants must have a confirmed pathologic diagnosis of tumor type (except for DIPG):\n   * Relapsed\u002Frefractory Neuroblastoma (NB)\n   * Relapsed\u002Frefractory Embryonal tumor with multilayer rosettes (ETMR)\n   * Relapsed\u002Frefractory Atypical teratoid rhabdoid tumor (ATRT)\n   * Newly diagnosed Diffuse Intrinsic Pontine Glioma (DIPG)- radiologic diagnosis acceptable\n   * Relapsed\u002Frefractory Ewing Sarcoma (EWS)\n   * Relapsed\u002Frefractory Osteosarcoma (OST)\n3. Tumor assessment:\n\n   Disease staging must be performed at baseline during the 28 day screening period prior to first dose of study drug.\n4. Disease Status:\n\n   Relapsed or Refractory Neuroblastoma Relapsed disease defined as: High-risk neuroblastoma that was previously in remission after standard therapy (at least 4 cycles of aggressive multi-drug induction chemotherapy, with or without radiation, surgery, and immunotherapy, or according to a standard high-risk treatment\u002Fneuroblastoma protocol).\n\n   Refractory disease defined as: High-risk neuroblastoma that 1) failed to achieve CR after at least 4 cycles of aggressive multi-drug induction chemotherapy with or without radiation and surgery, followed by immunotherapy, or according to a standard high-risk treatment\u002Fneuroblastoma protocol, or 2) progression during upfront therapy or 3) with disease remaining after standard immunotherapy.\n\n   Eligible NB participants may have active disease or no active disease.\n\n   NB participants with no active disease need to meet the following criteria:\n\n   Timing from prior therapy: Enrollment (first dose of study drug) no later than 60 days from most recent therapy.\n\n   NB participants with active disease need to meet the following criteria:\n   * Received at least one recent treatment for their relapse\u002Frefractory disease and is stable (SD) or better on this treatment.\n   * Participants must not have disease in any organs (including lungs, liver, or brain).\n\n   Relapsed or refractory ETMR\u002FATRT Participants that have relapsed following standard of care therapy or having progressed during standard of care therapy and non-responsive\u002Fprogressive to accepted curative therapy, including up-front chemotherapy and radiation and\u002For high-dose chemotherapy with stem cell rescue.\n\n   ETMR\u002FATRT participants with no active disease need to meet the following criteria:\n\n   Timing from prior therapy: Enrollment (first dose of study drug) no later than 60 days from most recent therapy.\n\n   ETMR\u002FATRT participants with active disease need to meet the following criteria:\n\n   • Received at least one recent treatment for their relapse\u002Frefractory disease and is stable (SD) or better on this treatment.\n\n   Newly Diagnosed Diffuse Intrinsic Pontine Glioma (DIPG) Participants with DIPG to start greater than 30 days, and no longer than 60 days, after standard of care radiation therapy.\n\n   Participants with newly-diagnosed typical DIPG, defined as tumors with a pontine epicenter and diffuse involvement of the pons on at least 1 axial T2-weighted image, are eligible. No histologic confirmation is required. Participants with metastatic disease are not eligible. Participants with a biopsy and no evidence of H3K27m mutations are eligible as long as they meet radiographic criteria. Participants with H3K27m altered DMG outside of the brainstem are not eligible. Participants with progression or recurrence after initial standard of care radiation are ineligible.\n\n   Relapsed or refractory Ewing sarcoma and osteosarcoma Participants that have relapsed following standard of care therapy or having progressed during standard of care therapy. Standard of care therapy for Ewing sarcoma and osteosarcoma includes multi-agent chemotherapy with local control consisting of either surgery or radiation therapy.\n\n   EWS\u002FOST Participants with no active disease need to meet the following criteria:\n\n   Timing from prior therapy: Enrollment (first dose of study drug) no later than 60 days from most recent therapy.\n\n   EWS\u002FOST Participants with active disease need to meet the following criteria:\n\n   • Received at least one recent treatment for their relapse\u002Frefractory disease and is stable (SD) or better on this treatment.\n5. Participants must be able to swallow capsules.\n6. Participants with CNS disease currently taking steroids must have been on a stable dose of steroids for at least one week and must not have progressive hydrocephalus at enrollment.\n7. Participants must have fully recovered from the acute toxic effects of all prior anti- cancer chemotherapy and be within the following timelines:\n\n   1. Myelosuppressive chemotherapy: Must not have received within 2 weeks of enrollment onto this study (6 weeks if prior nitrosourea).\n   2. Small Molecule Inhibitor (anti-neoplastic agent): At least 7 days since the completion of therapy with a small molecule inhibitor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the Study Chair.\n   3. Immunotherapy: At least 4 weeks since the completion of any type of immunotherapy, e.g. tumor vaccines, CAR-T cells except for anti-GD2 Monoclonal antibodies (ex. naxitamab, dinutuximab, etc.) which should be at least 2 weeks since prior treatment with a monoclonal antibody.\n   4. XRT: At least 14 days since the last treatment except for radiation delivered with palliative intent to a non-target site.\n\n      Note: Participants with DIPG will be required to have had up front standard of care radiation. As above, participants with DIPG must be between 30-60 days post initial up- front radiation therapy.\n   5. Stem Cell Transplant:\n\n      1. Allogeneic: No evidence of active graft vs. host disease\n      2. Allo\u002FAuto: ≥ 45 days must have elapsed since transplant.\n   6. MIBG Therapy: At least 6 weeks since treatment with MIBG therapy.\n8. Participants must have a Lansky or Karnofsky Performance Scale score of \\>\u002F= 60\n9. Participants must have adequate organ function at the time of enrollment:\n\n   * Hematological: Hematological recovery as defined by ANC ≥750\u002FμL (unsupported- \\>24 hrs off G-CSF and 7 days off neulasta)\n   * Liver: Adequate liver function as defined by AST and ALT \\\u003C10x upper limit of normal\n   * Cardiac: all participants must have:\n\n     1. Normal serum Cardiac Troponin Concentration\n     2. Normal BNP (B-type natriuretic peptide) Level\n     3. A QTcF ≤ 470 msec (or EKG with no significant findings)\n     4. Normal ECHO defined as:\n\n     i. Shortening fraction of ≥ 27% by echocardiogram, or ii. Ejection fraction of ≥ 50% by echocardiogram or radionuclide angiogram\n   * Renal: Participants must have adequate renal function defined as:\n\n     1. For participants \\\u003C 17 years old: estimated Glomerular Filtration rate (eGFR) as calculated from the Bedside Schwartz equation (in units of mL\u002Fmin\u002F1.73 m2) or via radioisotope GFR of ≥ 70 mL\u002Fmin\u002F1.73 m2. The Bedside Schwartz equation is: \\[(0.413) X (Height in cm)\\] \u002F SCr\n     2. For participants ≥17 years old: estimated Glomerular Filtration rate (eGFR) as calculated from the Cockcroft and Gault formula (in units of mL\u002Fmin\u002F1.73 m2) or via radioisotope GFR of ≥ 70 mL\u002Fmin\u002F1.73 m2. The Cockcroft and Gault formula is: \\[(140-age) x (Wt in kg) x (0.85 if female)\\] \u002F (72 x SCr)\n10. Participants of childbearing potential must have a negative pregnancy test. Participants of childbearing potential must agree to use an effective birth control method. Participants who are lactating must agree to stop breast-feeding.\n11. Written informed consent in accordance with institutional and FDA guidelines must be obtained from all participants (or participants' legal representative).\n\nExclusion Criteria:\n\n1. BSA of \\\u003C0.25 m2\n2. Investigational Drugs: Participants who are currently receiving another investigational drug are excluded from participation.\n3. Anti-cancer Agents: Participants who are currently receiving other anticancer agents are not eligible. Participants must have fully recovered from the hematological and bone marrow suppression effects of prior chemotherapy.\n4. Infection: Participants who have an uncontrolled infection are not eligible until the infection is judged to be well controlled in the opinion of the investigator.\n5. Participants who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study, or in whom compliance is likely to be suboptimal, should be excluded.","26 Years",{"count":59,"type":23},289,[26,61],"PHASE2","The purpose of this study is to evaluate the investigational oral drug AMXT 1501 in combination with oral eflornithine (DFMO). An investigational drug is one that has not been approved by the U.S. Food \\& Drug Administration (FDA), or any other regulatory authorities around the world for use alone or in combination with any drug, for the condition or illness it is being used to treat.\n\nThe goals of this part of the study are:\n\n* Establish a recommended dose of AMXT 1501 in combination with DFMO\n* Test the safety and tolerability of AMXT 1501 in combination with DFMO\n* To determine the activity of study treatments chosen based on:\n* How each subject responds to the study treatment\n* How long a subject lives without their disease returning\u002Fprogressing",[64,65,66,30,67,68,69],"Atypical Teratoid\u002FRhabdoid Tumor","Embryonal Tumor With Multilayered Rosettes","Ewing Sarcoma","Osteosarcoma","Neuroblastoma","DIPG Brain Tumor",[71],"DFMO","RECRUITING",{"date":40,"type":41},{"date":75,"type":41},"2026-05-13",{"date":77,"type":23},"2035-05",{"name":79,"class":48},"Milton S. Hershey Medical Center",12,{"id":82,"slug":83,"hasResults":12,"nctId":84,"briefTitle":85,"officialTitle":86,"acronym":87,"eligibilityCriteria":88,"healthyVolunteers":12,"sex":18,"minAge":89,"maxAge":20,"enrollmentInfo":90,"targetDuration":4,"studyType":24,"phases":91,"briefSummary":92,"conditions":93,"keywords":4,"overallStatus":72,"whyStopped":4,"lastUpdateSubmitDate":94,"lastUpdatePostDateStruct":95,"startDateStruct":96,"completionDateStruct":98,"leadSponsor":100,"locationsCount":101},"100426787","phase-1-peach-trial--precision-medicine-and-adoptive-cellular-therapy-100426787","NCT04837547","PEACH TRIAL- Precision Medicine and Adoptive Cellular Therapy","PEACH TRIAL- Precision mEdicine and Adoptive Cellular tHerapy for the Treatment of Recurrent Neuroblastoma and Newly Diagnosed Diffuse Intrinsic Pontine Glioma (DIPG)","PEACH","Inclusion Criteria:\n\n* Subjects must have proven pediatric cancer with confirmation at diagnosis or at the time of recurrence\u002Fprogression and clinical determination of disease for which there is no known effective curative therapy or disease that is refractory to established proven therapies fitting into one of the following categories:\n* Disease Status:\n\nHigh Risk Neuroblastoma-\n\n1. Patients that have relapsed following standard of care therapy or having progressed during standard of care therapy and non-responsive\u002Fprogressive to accepted curative chemotherapy.\n2. Neuroblastoma must be age \\>12 months at enrollment\n\nDiffuse Intrinsic Pontine (or other brain stem) Glioma\n\n1. Newly-diagnosed patients willing to undergo biopsy\n2. Must be within 2 months of diagnosis and prior to starting radiation\n3. DIPG must be ≥ 3 years of age at enrollment\n\n   * All subjects must be age ≤ 30 years at enrollment\n   * Patient and\u002For parents\u002Fguardian willing to consent to biopsy for obtaining tumor material for confirmatory diagnosis and\u002For tumor RNA extraction and amplification.\n   * Subjects must have measurable disease as defined Per section 8 at the time of biopsy and tumor or bone marrow must be accessible for biopsy. Tumor or bone marrow samples submitted for analysis must contain \\>20% viable tumor tissue to qualify. Note: Subjects with NB who are expected to have no evidence of disease after surgical removal of their tumor are still eligible for this trial if their disease would normally require adjuvant chemotherapy treatment after surgery despite NED status.\n   * Current disease state must be one for which there is currently no known effective therapy\n   * Specimens will be obtained only in a non-significant risk manner and not solely for the purpose of investigational testing.\n   * Lansky or Karnofsky Score must be ≥ 60\n   * Bone Marrow:\n\n     1. ANC (Absolute neutrophil count) ≥ 1000\u002Fµl (unsupported- \\>24 hrs off G-CSF and 7 days off neulasta)\n     2. Platelets ≥ 100,000\u002Fµl (can be transfused)\n     3. Hemoglobin \\> 8 g\u002FdL (can be transfused)\n   * Renal: Serum creatinine ≤ upper limit of institutional normal.\n   * Adequate liver function must be demonstrated, defined as:\n\n     1. Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age AND\n     2. ALT (SGPT) ≤ 3 times upper limit of normal (ULN) for age\n     3. AST (SGOT) ≤ 3 times upper limit of normal (ULN) for age.\n   * Subjects with CNS disease currently taking steroids must have been on a stable dose of steroids for at least one week prior to their biopsy and must not have progressive hydrocephalus at enrollment.\n   * A negative serum pregnancy test is required for female participants of childbearing potential (≥13 years of age or after onset of menses)\n   * Both male and female post-pubertal study subjects need to agree to use one of the more effective birth control methods during treatment and for six months after treatment is stopped. These methods include total abstinence (no sex), oral contraceptives (\"the pill\"), an intrauterine device (IUD), levonorgestrel implants (Norplant), or medroxyprogesterone acetate injections (Depo-provera shots). If one of these cannot be used, contraceptive foam with a condom is recommended.\n   * Informed Consent: All subjects and\u002For legal guardians must sign informed written consent. Assent, when appropriate, will be obtained according to institutional guidelines\n   * Post-Biopsy: Patients with post-biopsy neurological deficits should have deficits that are stable for a minimum of 1 week prior to registration.\n\nExclusion Criteria:\n\n* Absence of tumor on biopsy specimen or a diagnosis other than NBL or glioma on biopsy\n* Known autoimmune or immunosuppressive disease or human immunodeficiency virus infection.\n* Subjects with significant renal, cardiac, pulmonary, hepatic or other organ dysfunction.\n* Prior allergic reaction to GM-CSF or Td.\n* Subjects who have received any cytotoxic chemotherapy within the last 7 days prior to biopsy or focal radiotherapy in the case of patients with diffuse intrinsic pontine (or other brain stem) gliomas\n* Subjects with NBL who have received any radiotherapy to the primary sample site within the last 14 days (radiation may be included in treatment decision after biopsy).\n* Subjects receiving any investigational drug concurrently.\n* Subjects with uncontrolled serious infections or a life-threatening illness (unrelated to tumor)\n* Subjects with any other medical condition, including malabsorption syndromes, mental illness or substance abuse, deemed by the Investigator to be likely to interfere with the interpretation of the results or which would interfere with a subject's ability to sign or the legal guardian's ability to sign the informed consent, and subject's ability to cooperate and participate in the study","1 Year",{"count":22,"type":23},[26],"A Phase I open-label, multicenter study, to evaluate the safety, feasibility, and maximum tolerated dose (MTD) of treating children with newly diagnosed DIPG or recurrent neuroblastoma with molecular targeted therapy in combination with adoptive cell therapy (Total tumor mRNA-pulsed autologous Dendritic Cells (DCs) (TTRNA-DCs), Tumor-specific ex vivo expanded autologous lymphocyte transfer (TTRNA-xALT) and Autologous G-CSF mobilized Hematopoietic Stem Cells (HSCs)).",[68,30],"2026-06-29",{"date":40,"type":41},{"date":97,"type":41},"2021-09-20",{"date":99,"type":23},"2032-09",{"name":47,"class":48},3,{"id":103,"slug":104,"hasResults":12,"nctId":105,"briefTitle":106,"officialTitle":107,"acronym":4,"eligibilityCriteria":108,"healthyVolunteers":12,"sex":18,"minAge":89,"maxAge":57,"enrollmentInfo":109,"targetDuration":4,"studyType":24,"phases":111,"briefSummary":112,"conditions":113,"keywords":124,"overallStatus":37,"whyStopped":4,"lastUpdateSubmitDate":137,"lastUpdatePostDateStruct":138,"startDateStruct":140,"completionDateStruct":141,"leadSponsor":143,"locationsCount":146},"100645242","phase-2-illuminate-a-clinical-study-evaluating-car-t-immune-cell-therapy-bcb-276-for-patients-with-diffuse-intrinsic-pontine-glioma-dipg-100645242","NCT07680439","Illuminate: A Clinical Study Evaluating CAR T Immune Cell Therapy (BCB-276) for Patients With Diffuse Intrinsic Pontine Glioma (DIPG).","A Phase 2 Pivotal Study of BCB-276, a B7-H3-Specific CAR T Cell Locoregional Immunotherapy for Diffuse Intrinsic Pontine Glioma","Inclusion Criteria:\n\n* Participants must be aged 1 and ≤ 26 years and weigh ≥10kg.\n* Diagnosis of Diffuse Intrinsic Pontine Glioma (DIPG) based on imaging, with or without biopsy confirmation consistent with high-grade glioma or diffuse midline glioma\n* Able to tolerate leukapheresis and other study procedures in the opinion of the Investigator.\n* Central Nervous System (CNS) reservoir catheter present prior to first dose of study drug.\n* Participant must have completed standard radiation therapy within 6 weeks of enrollment for participation.\n* Performance Status of ≥ 60; mild to moderate restriction or better. Lansky (under 16 years of age) or Karnofsky (16 years of age or older).\n* Adequate organ function and overall clinical status to participate, including stable or improving neurologic symptoms.\n* Participants of childbearing\u002Ffathering potential must agree to use highly effective contraception from the time of enrollment through 12 months following the last T cell infusion.\n* Participants with ventriculoperitoneal (VP) shunts need to have a programable system and be able to tolerate temporary adjustment of the shunt required for study treatment.\n* Participant must meet all other health and safety criteria defined in the study protocol.\n* Participant and\u002For authorized legal representative willing to provide consent\u002Fassent for study participation, including participation in the 15-year long term follow up period.\n\nExclusion Criteria:\n\nAn individual who meets any of the following criteria will be excluded from participation in this study:\n\n* Previous tumor-directed therapy or treatment-directed clinical study other than standard radiation with or without temozolamide.\n* Evidence of metastatic disease.\n* Requirement of high or increasing doses of corticosteroids prior to participation.\n* Severe swallowing difficulties or other significant clinical conditions that may interfere with participation.\n* Presence of an active malignancy other than DIPG.\n* Active or uncontrolled human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection based on protocol-required laboratory testing.\n* Pregnant or breastfeeding.\n* Presence of any condition that, in the Investigator's opinion, would prohibit the participant from undergoing treatment under this protocol.",{"count":110,"type":23},75,[61],"This study will evaluate BCB-276, an investigational B7-H3-targeted Chimeric Antigen Receptor (CAR) T cell therapy, in children and young adults with diffuse intrinsic pontine glioma (DIPG). DIPG is a rare and aggressive brain tumor with limited treatment options. CAR T cell therapy uses a patient's own immune cells that are changed in a laboratory to recognize and attack cancer cells. The purpose of this study is to determine whether BCB-276, when given after completion of standard radiation therapy, is safe and can improve survival for patients with DIPG.\n\nTo participate, individuals must be between 1 and 26 years of age when they join the study, have a diagnosis of DIPG, and enroll for treatment within 6 weeks of completing initial radiation therapy. Participants must not have received prior anti-cancer therapy beyond radiation with or without temozolomide prior to joining this study.\n\nBCB-276 is administered intraventricularly (into the fluid around the brain), which requires placement of a catheter for treatment. BCB-276 is given every 2 weeks at a research center over a period of several months (approximately 7-8 months). Participation includes travel to a study site, procedures to support treatment administration, sample collection, and ongoing monitoring for safety and effectiveness, with follow-up visits lasting up to about 2 years.",[30,114,33,115,116,117,118,119,120,121,122,123],"DIPG","CNS Tumor","Central Nervous System Tumor","Pediatric Cancer","Adult Cancer Patients","CNS Tumor, Childhood","CNS Tumor, Adult","Brainstem Glioma","Diffuse Midline Glioma","DMG",[125,126,127,128,129,130,32,35,131,132,133,134,135,136],"BCB-276","B7-H3-specific Chimeric Antigen Receptor [CAR] T cell therapy","B7-H3","B7-H3 CAR T","B7-H3 CAR T Cells","Chimeric antigen receptor T cells","Cell Therapy","Pediatric","Children","Adolescent","Young Adult","Adult","2026-06-25",{"date":139,"type":41},"2026-07-02",{"date":43,"type":23},{"date":142,"type":23},"2030-07",{"name":144,"class":145},"BrainChild Bio, Inc","INDUSTRY",6,{"id":148,"slug":149,"hasResults":12,"nctId":150,"briefTitle":151,"officialTitle":152,"acronym":4,"eligibilityCriteria":153,"healthyVolunteers":154,"sex":18,"minAge":89,"maxAge":155,"enrollmentInfo":156,"targetDuration":4,"studyType":24,"phases":158,"briefSummary":160,"conditions":161,"keywords":169,"overallStatus":72,"whyStopped":4,"lastUpdateSubmitDate":137,"lastUpdatePostDateStruct":172,"startDateStruct":173,"completionDateStruct":175,"leadSponsor":177,"locationsCount":179},"100541748","early-phase-1-lorlatinib-for-newly-diagnosed-high-grade-glioma-with-ros-or-alk-fusion-100541748","NCT06333899","Lorlatinib for Newly-Diagnosed High-Grade Glioma With ROS or ALK Fusion","A Pilot Study of Lorlatinib for Treatment of Children With Newly Diagnosed High-Grade Glioma With ROS-1 (ROS Proto-Oncogene 1, Receptor Tyrosine Kinase) or ALK (Anaplastic Lymphoma Kinase) Fusion","Inclusion Criteria:\n\n1. Patients must be ≥ 12 months and ≤ 21 years of age at the time of study enrollment on TarGeT-SCR.\n2. Diagnosis:\n\n   Patients with newly diagnosed high-grade glioma (HGG), including diffuse intrinsic pontine gliomas (DIPG), whose tumors harbor an ALK or ROS-1 fusion alteration are eligible. Patients must have had histologically verified high-grade glioma from diagnostic biopsy or resection. For the diagnosis of DIPG, patients must have a tumor with pontine epicenter and diffuse involvement of at least 2\u002F3 of the pons, with histopathology consistent with diffuse WHO Grade 2-4. All other HGGs must be Grade 3 or 4.\n3. Disease Status:\n\n   Patients with disseminated DIPG or HGG are eligible only if the patient is to receive chemotherapy only, i.e. no craniospinal RT is intended to be given. MRI of spine must be performed if disseminated disease is suspected clinically by the treating physicians. Patients with primary spinal tumors are eligible only if the patient is to receive either chemotherapy or focal radiation therapy, i.e., no craniospinal RT is intended to be given. Patients with leptomeningeal disease only, with no definitive identifiable primary tumor, and documented ALK or ROS-1 fusion, must be discussed with the Study Chair on a case-by-case basis.\n4. Performance Level:\n\n   Karnofsky ≥ 50% for patients \\> 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of age (See Appendix I). Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.\n5. Prior Therapy:\n\n   * Patients must not have received any prior anti-cancer chemotherapy.\n   * Prior use of corticosteroids is allowed (see below Exclusion Criteria)\n6. Organ Function Requirements 6.1 Adequate Bone Marrow Function Defined as:\n\n   * Peripheral absolute neutrophil count (ANC) ≥ 1000\u002FμL\n   * Platelet count ≥ 100,000\u002FμL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)\n   * Hemoglobin \\>8 g\u002FdL (may receive transfusions) 6.2 Adequate Renal Function Defined as:\n   * Serum creatinine within normal institutional limits OR Creatinine clearance or radioisotope GFR ≥ 70ml\u002Fmin\u002F1.73 m2 6.3 Adequate Liver Function Defined as:\n   * Total bilirubin ≤ 2 × institutional upper limit of normal\n   * AST(aspartate aminotransferase)\u002FALT(alanine transaminase) ≤ 2.5 × institutional upper limit of normal 6.4 Adequate Pulmonary Function Defined as: Pulse oximetry \\> 94% on room air if there is clinical indication for determination (e.g. dyspnea at rest).\n\n6.5Adequate Cardiac Function Defined as: QTc ≤ 470 msec (by Bazett formula) 6.6 Adequate Neurologic Function Defined as: Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled.\n\n6.7 Informed Consent: All patients and\u002For their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines\n\nExclusion Criteria:\n\n1. Pregnant or breast-feeding women will not be entered on this study due to unknown risks of fetal and teratogenic adverse events as seen in animal\u002Fhuman studies. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.\n\n   Females of reproductive potential must use an effective non-hormonal method of contraception, since lorlatinib can render hormonal contraceptives ineffective, during study treatment and for at least 6 months after the final dose. Males with female partners of reproductive potential must use effective contraception during treatment with lorlatinib and for 3 months after the final dose.\n2. Concomitant Medications\n\n   * Investigational Agents\u002FDrugs: Patients who have previously received or are currently receiving another investigational drug are not eligible.\n   * Anti-cancer Agents: Patients who have previously received or are currently receiving other anti-cancer agents, including chemotherapy, immunotherapy, monoclonal antibodies, biologic or targeted therapy, are not eligible\n3. Infection: Patients must not have any active, uncontrolled systemic bacterial, viral or fungal infection.\n4. Patients who have received prior solid organ transplantation are not eligible.\n5. Patients must not have malabsorption syndrome or other condition affecting oral absorption.\n6. Patients must not be receiving any treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor or inducer. Discontinue strong CYP3A inducers for 3 plasma half-lives of the strong CYP3A inducer prior to treatment with loraltinib. Moderate inducers of CYP3A4 should be avoided\n7. Avoid concomitant use of lorlatinib with certain CYP3A substrates, for which minimal concentration changes may lead to serious therapeutic failures. If concomitant use is unavoidable, increase the CYP3A substrate dosage in accordance with approved product labeling.\n8. P-glycoprotein (P-gp) substrates: Lorlatinib is considered a moderate P-gp inducer. Co-administration of lorlatinib with P-gp substrates including but not limited to digoxin should be avoided as the concentration of these drugs may be reduced by lorlatinib.\n9. Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible.\n10. Patients with a known personal history of acute or chronic severe psychiatric disorders or current history of suicidal ideation and history of suicide attempt.",true,"21 Years",{"count":157,"type":23},15,[159],"EARLY_PHASE1","The goal of this study is to determine the response of the study drug loratinib in treating children who are newly diagnosed high-grade glioma with a fusion in ALK or ROS1. It will also evaluate the safety of lorlatinib when given with chemotherapy or after radiation therapy.",[162,30,163,164,36,165,166,167,168],"High Grade Glioma","Anaplastic Astrocytoma","Infant Type Hemispheric Glioma","Glioblastoma Multiforme","WHO Grade III Glioma","WHO Grade IV Glioma","Diffuse Midline Glioma, H3K27-altered",[170,171,162,30],"ALK fusion","ROS fusion",{"date":94,"type":41},{"date":174,"type":41},"2025-08-03",{"date":176,"type":23},"2035-06-01",{"name":178,"class":48},"Nationwide Children's Hospital",18,{"id":181,"slug":182,"hasResults":12,"nctId":183,"briefTitle":184,"officialTitle":185,"acronym":186,"eligibilityCriteria":187,"healthyVolunteers":12,"sex":18,"minAge":188,"maxAge":189,"enrollmentInfo":190,"targetDuration":4,"studyType":24,"phases":192,"briefSummary":193,"conditions":194,"keywords":4,"overallStatus":72,"whyStopped":4,"lastUpdateSubmitDate":199,"lastUpdatePostDateStruct":200,"startDateStruct":202,"completionDateStruct":204,"leadSponsor":206,"locationsCount":208},"100440030","phase-2-combination-therapy-for-the-treatment-of-diffuse-midline-gliomas-100440030","NCT05009992","Combination Therapy for the Treatment of Diffuse Midline Gliomas","A Combination Therapy Trial Using an Adaptive Platform Design for Children and Young Adults With Diffuse Midline Gliomas (DMGs) Including Diffuse Intrinsic Pontine Gliomas (DIPGs) at Initial Diagnosis, Post-Radiation Therapy and at Time of Progression","PNOC022","--COHORTS 1, 2, AND 3 CLOSED---\n\nINCLUSION CRITERIA:\n\nCOHORT 1A AND 1B:\n\n* New diagnosis of DMG with imaging and\u002For pathology consistent with a DMG, including spinal cord tumors. In cohort 1B, previous tumor tissue confirmation of DMG is mandatory and pathology must be consistent with a DMG including diffuse midline glioma Histone 3 lysine 27 - mutant (H3K27M); World Health Organization (WHO) grade III and IV H3 wildtype gliomas.\n* Must be within 6 weeks of diagnosis to begin standard of care radiation therapy on study.\n\nCOHORT 2A AND 2B:\n\n* Diagnosis of DMG with imaging and\u002For pathology consistent with a DMG, including spinal cord tumors, who have complete standard-of-care radiation therapy. In Cohort 2B, previous tumor tissue confirmation of DMG is mandatory and pathology must be consistent with a DMG including diffuse midline glioma H3K27M mutant; WHO grade III and IV H3 wildtype gliomas.\n* Participants must be within 4-14 weeks of completion of radiation. Radiation should have started within 6 weeks of diagnosis.\n\nCOHORT 3A AND 3B:\n\n* Diagnosis of recurrent DMG with imaging and\u002For pathology consistent with a DMG, including spinal cord tumors, who have complete standard-of-care radiation therapy. In cohort 3B, previous tumor tissue confirmation of DMG is mandatory and pathology must be consistent with a DMG including diffuse midline glioma H3K27M mutant; WHO grade III and IV H3 wildtype gliomas.\n* Participants must have evidence of progression and not have received any treatment for this progression and have not previously received re-irradiation.\n\nCOHORT 4A AND 4B:\n\n* Diagnosis of DMG with imaging and\u002For pathology consistent with a DMG, including spinal cord tumors. In cohort 4B\\^1, previous tumor tissue confirmation of DMG is mandatory and pathology must be consistent with a DMG diffuse midline glioma H3K27-altered.\n* Not currently eligible for any other clinical trials that include administration of ONC201.\n\nCohort 4A\\^1 and 4B\\^1 (participants with newly diagnosed DMG prior to radiation): Must be able to begin standard of care radiation therapy on study within 6 weeks of diagnosis.\n\nCohort 4A\\^2 and 4B\\^2 (participants with newly diagnosed DMG who have completed radiation): Participants must be within 4-14 weeks of completion of radiation and not have received additional therapy beyond completion of radiation therapy. Radiation should have started within 6 weeks of diagnosis.\n\nCohort 4A\\^3 and 4B\\^3 (participants with DMG at progression): Participants must have evidence of progression and not have received any treatment for this progression and have not previously received re-irradiation.\n\nCOHORT 5\n\n* Diagnosis of DMG with imaging and\u002For pathology consistent with a DMG, including spinal cord tumors. In cohort 5\\^1, previous tumor tissue confirmation of DMG is mandatory and pathology must be consistent with a DMG diffuse midline glioma H3K27-altered.\n* Not currently eligible for any other clinical trials that include administration of ONC201.\n* Multifocal and leptomeningeal disease will be eligible for Cohort 5.\n* Participant's tumor must demonstrate one of the following molecular alterations considered targetable by an approved agent:\n\n  * BRAFV600E\n  * PDGFRA (DNA point mutation or amplification with \\>=5 copy numbers)\n  * FGFR1 (DNA point mutation, gene fusions, or amplification with \\>=5 copy numbers)\n  * NF1\n\nCohort 5\\^1 (participants pre-radiation): Must be able to begin standard of care radiation therapy on study within 6 weeks of diagnosis.\n\nCohort 5\\^2 (participants post-radiation): Participants must be within 4-14 weeks of completion of radiation and not have received additional therapy beyond completion of radiation therapy. Radiation should have started within 6 weeks of diagnosis.\n\nCohort 5\\^3 (participants with progression): Participants must have evidence of progression and not have received any treatment for this progression and have not previously received re-irradiation.\n\nAll Cohorts (except Cohort 6):\n\n* Age 2 to 39 years\n* Participants must have recovered from all acute side effects of prior therapy and be beyond the window for expected ongoing acute toxicities. Any number of prior therapies are allowed.\n* Prior ONC201 exposure is allowed, except in participants who have participated in Chimerix trials investigating ONC201 in the upfront setting. Participants who participated in trials investigating ONC201 in the upfront setting will not be eligible at any time, with the exception if participants received ONC201 as part of PNOC022 or other expanded access programs such as German sources of ONC201.\n* Participant body weight must be above the minimum necessary for the participant to receive ONC201 (at least 10 kilograms (kg))\n* From the projected start of scheduled study treatment, the following time periods must have elapsed: At least 7 days after last dose of a biologic agent or beyond time during which adverse events are known to occur for a biologic agent, 5 half-lives from any investigational agent, 4 weeks from cytotoxic therapy (except 23 days for temozolomide and 6 weeks from nitrosoureas), 6 weeks from antibodies (21 days for bevacizumab when used for tumor-directed therapy, guidance on use for pseudo-progression is below), or, or 4 weeks (or 5 half-lives, whichever is shorter) from other anti-tumor therapies.\n\n  o The use of bevacizumab to control radiation therapy-induced edema is allowed (if used for tumor-directed therapy, please see required time period above).\n  * Dosing limitations are as follows:\n  * \\* Bevacizumab (or equivalent) for up to a maximum of 5 doses, dosing per institutional standard. There is no required washout period.\n* Prior use of temozolomide during radiation at maximum of the standard pediatric dosing (defined as 90 mg\u002Fm2 \u002Fdose continuously during radiation therapy for 42 days) or dexamethasone is allowed. Any other agent given throughout radiation therapy must be discussed with the study chairs prior to beginning the agent.\n* Corticosteroids: Participants who are receiving dexamethasone must be on a stable or decreasing dose for at least 3 days prior to baseline magnetic resonance imaging (MRI) scan.\n* The participant must have adequate organ function defined as:\n\n  * Peripheral absolute neutrophil count (ANC) \\>= 750\u002Fmm\\^3 (1.0g\u002Fl) AND\n  * Platelet count \\>= 75,000\u002Fmm\\^3 (100x10\\^9\u002Fl) (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).\n  * Creatinine clearance or radioisotope glomerular filtration rate (GFR) \\>= 70 mL\u002Fmin\u002F1.73 m\\^2 OR\n  * A serum creatinine within the normal limits for age\n  * Bilirubin (sum of conjugated + unconjugated) =\\\u003C 1.5 x upper limit of normal (ULN) for age AND\n  * Serum glutamate pyruvate transaminase (SGPT)(alanine aminotransferase (ALT)) =\\\u003C 3 x ULN AND\n  * Serum albumin \\>= 2 g\u002FDl\n  * No evidence of dyspnea at rest, no exercise intolerance due to pulmonary insufficiency, and a pulse oximetry of \\> 92% while breathing room air.\n  * Diarrhea \\\u003C grade 2 by Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0\n  * No history of congestive heart failure or family history of long QT syndrome.\n  * ECG must be obtained to verify the Corrected QT Interval (QTc). If an abnormal reading is obtained, the ECG should be repeated in triplicate. QTC \\\u003C 470 msec.\n  * Participants with history of congestive heart failure, at risk of having or have underlying cardiovascular disease, or with history of exposure to cardiotoxic drugs must have adequate cardiac function as determined by echocardiogram. Shortening fraction of \\>= 27%.\n  * Participants with seizure disorder may be enrolled if seizure disorder is well controlled\n* Females of child-bearing potential and males must agree to use adequate contraception.\n* Karnofsky \\>= 50 for participants \\> 16 years of age and Lansky \\>= 50 for participants =\\\u003C 16 years of age. Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.\n* Participants must be willing to provide adequate tissue. A minimum of 10-20 paraffin embedded unstained slides OR 1 block with tumor content of 40% or greater is required. Frozen tissue is also acceptable.\n\nCOHORT 6 Inclusion Criteria:\n\n* Diagnosis of newly diagnosed thalamic or pontine located DMG with imaging and\u002For pathology consistent with a DMG, excluding spinal cord tumors, who have completed standard-of-care radiation therapy. If archival tissue is available prior to first biopsy, participants must be willing to provide adequate tissue. A minimum of 10-20 paraffin embedded unstained slides OR 1 block with tumor content of 40% or greater is required.\n* Participants must be within 4-14 weeks of completion of radiation. Radiation should have started within 6 weeks of diagnosis.\n* Age 2-39 years.\n* Prior use of temozolomide during radiation at maximum of the standard pediatric dosing (defined as 90 mg\u002Fm2 \u002Fdose continuously during radiation therapy for 42 days) is allowed. Any other agent given throughout radiation therapy must be discussed with the study chairs prior to enrollment.\n* Participants must have recovered from all acute side effects of prior therapy and be beyond the window for expected ongoing acute toxicities. Washout requirements from prior therapy include:\n\n  * At least 7 days after last dose of a biologic agent or beyond time during which adverse events are known to occur for a biologic agent, 5 half-lives from any investigational agent, 4 weeks from cytotoxic therapy (except 30 days for temozolomide and 6 weeks from nitrosoureas), 6 weeks from antibodies (28 days for bevacizumab when used for tumor-directed therapy, guidance on use for pseudo-progression is below), or 4 weeks (or 5 half-lives, whichever is shorter) from other anti-tumor therapies.\n  * At least 4 weeks prior to study enrollment from last immune therapy\n* Corticosteroids: Participants treated with corticosteroids must be on stable or decreasing dose for at least 1 week prior to enrollment, with maximum dexamethasone dose 0.1 mg\u002Fkg\u002Fday dexamethasone equivalent at time of enrollment.\n* The participant must have adequate organ function defined as:\n\n  * Peripheral absolute neutrophil count (ANC) \\>= 750\u002Fmm3 (1.0g\u002Fl) and\n  * Platelet count \\>= 75,000\u002Fmm3 (100x109\u002Fl) (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment.\n  * Creatinine clearance or radioisotope GFR \\>= 70mL\u002Fmin\u002F1.73 m2 or\n  * A serum creatinine within the normal limits for age.\n  * Total bilirubin \\\u003C= 3 x upper limit of normal (ULN); in presence of Gilbert's syndrome, total bilirubin \\\u003C\u002F= 6 x ULN or direct bilirubin \\\u003C= 3 x ULN\n  * ALT \\\u003C= 5 x ULN\n  * AST \\\u003C= 5 x ULN.\n  * Serum albumin \\>= 2 g\u002FdL\n  * Diarrhea \\\u003C grade 2 by CTCAE v5.0.\n  * No history of congestive heart failure or family history of long QT syndrome.\n  * Participants with seizure disorder may be enrolled if seizure disorder is well controlled.\n* The effects of the study drugs on the developing human fetus are unknown. For this reason, females of child-bearing potential and males must agree to use adequate contraception.\n* Karnofsky \\>\u002F= 70 for Participants \\> 16 years of age and Lansky \\>\u002F= 70 for participants \\\u003C\u002F= 16 years of age. Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score\n\nEXCLUSION CRITERIA:\n\nCOHORT 1A AND 1B:\n\n* Prior exposure to radiation therapy.\n* Thalamic and Cerebellar H3K27M DMG.\n\nCOHORT 2A AND 2B:\n\n* For tumors that do not have a pontine or spinal cord epicenter the following specific exclusion criteria apply:\n* Thalamic and Cerebellar H3K27M DMG that has undergone standard radiation without concurrent therapy (other than temozolomide).\n\nCOHORT 1A AND 2A:\n\n• Deemed not appropriate for tissue resection\u002Fbiopsy.\n\nCOHORT 3A AND 3B:\n\n* Prior exposure to re-irradiation for tumor progression.\n* Thalamic and cerebellar H3K27M mutant DMG.\n\nCOHORT 4A AND 4B:\n\nCohort 4A\\^1and 4B\\^1: Prior exposure to radiation therapy Cohort 4A\\^3 and 4B\\^3: Prior exposure to re-irradiation for tumor progression\n\n* Thalamic and cerebellar H3K27M mutant DMG, except those who received ONC201\u002FONC026 from alternative source prior to 2024 or US patients enrolled while the accelerated approval new drug application for dordaviprone to treat recurrent H3 K27M-mutant diffuse glioma is under review by US FDA.\n* Cohort 4A\\^1and 4B\\^1: Prior exposure to radiation therapy\n* Cohort 4A\\^3 and 4B\\^3: Prior exposure to re-irradiation for tumor progression\n\nCOHORT 5:\n\n* Thalamic and cerebellar H3K27M mutant DMG, except those who received ONC201\u002FONC026 from alternative source prior to 2024 or US patients enrolled while the accelerated approval new drug application for dordaviprone to treat recurrent H3 K27M-mutant diffuse glioma is under review by US FDA.\n* Cohort 5\\^1: Prior exposure to radiation therapy\n* Cohort 5\\^3: Prior exposure to re-irradiation for tumor progression\n\nAll Cohorts (except Cohort 6):\n\n* Diagnosis of a histone H3 wildtype grade II diffuse astrocytoma.\n* Participants who are currently receiving another investigational drug. Investigational imaging agents or agents used to enhance tumor visibility on imaging or during tumor biopsy\u002Fresection should be discussed with the study chairs.\n* Participants who are currently receiving other anti-cancer agents.\n* Participants with a known disorder that affects their immune system, such as human immunodeficiency virus (HIV) or hepatitis B or C, or an auto-immune disorder requiring systemic cytotoxic or immunosuppressive therapy. Note: Participants that are currently using inhaled, intranasal, ocular, topical or other non-oral or non-intravenous (IV) steroids are not necessarily excluded from the study but need to be discussed with the study chair.\n* Participants with uncontrolled infection or other uncontrolled systemic illness.\n* Female participants of childbearing potential must not be pregnant or breast-feeding. Female participants of childbearing potential must have a negative serum or urine pregnancy test prior to the start of therapy (as clinically indicated).\n* Active illicit drug use or diagnosis of alcoholism.\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition as the agents used in study.\n* Evidence of disseminated disease, including diffuse leptomeningeal disease or evidence of CSF dissemination, with the exception of Cohort 5.\n* Known additional malignancy that is progressing or requires active treatment within 3 years of start of study drug.\n* Concomitant use of potent CYP3A4\u002F5 inhibitors during the treatment phase of the study and within 72 hours prior to starting study drug administration.\n* Concomitant use of potent CYP3A4\u002F5 inducers, which include enzyme inducing antiepileptic drugs (EIAEDs), during the treatment phase of the study and within 2 weeks prior to starting treatment. Concurrent corticosteroids is allowed.\n\nCOHORT 6 Exclusion Criteria:\n\n* • DMGs located outside the thalamus and pons including bilateral thalamic tumors.\n* Unacceptable anesthesia or surgery risk, as determined by the anesthesiologist or the neurosurgeon.\n* Evidence of significant mass effect\n* Evidence of herniation on imaging.\n* Participants with a known history coagulopathy that increases risk of bleeding or a history of clinically significant hemorrhage within 12 months of registration.\n* Participants must not require systemic anti-coagulation that cannot be halted for each intraoperative and perioperative biopsy time-period.\n* Participants with active viral infection or who are currently receiving antiviral treatment.\n* Participants with active, known, or suspected immunosuppressive disorders, such as acquired or congenital immune deficiency syndromes and autoimmune diseases.\n* This virus infects cells with a deficit in the RB gene. Therefore, participants with Li-Fraumeni Syndrome or a known germ line deficit in the retinoblastoma gene or its related pathway are excluded.\n* Participants must not have live or live-attenuated vaccinations within 30 days prior to DNX-2401 administration and while participating in the study. Killed vaccines are permitted.\n* Participants who are currently receiving another investigational drug. Investigational imaging agents or agents used to enhance tumor visibility on imaging or during tumor biopsy\u002Fresection should be discussed with the study chairs.\n* Participants with a known disorder that affects their immune system, such as HIV or Hepatitis B or C, or an auto-immune disorder requiring systemic cytotoxic or immunosuppressive therapy. Note: Participants who are currently using inhaled, intranasal, ocular, topical or other non-oral or non-IV steroids are not necessarily excluded from the study but need to be discussed with the study chair(s).\n* Participants with uncontrolled infection or other uncontrolled systemic illness.\n* Female participants of childbearing potential must not be pregnant or breast-feeding. Female participants of childbearing potential must have a negative serum or urine pregnancy test prior to the start of therapy (as clinically indicated).\n* Active illicit drug use or diagnosis of alcoholism.\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition as the agents used in the study.\n* Evidence of disseminated disease, including multi-focal disease, diffuse leptomeningeal disease or CSF dissemination.","2 Years","39 Years",{"count":191,"type":23},360,[61],"This phase II trial determines if the combination of ONC201 with different drugs is effective for treating participants with diffuse midline gliomas (DMGs). Despite years of research, little to no progress has been made to improve outcomes for participants with DMGs, and there are few treatment options. This trial will utilize an adaptive platform design in that the different treatment arms for each cohort will be opened and closed based on ongoing preclinical investigation as well as evolving outcome data from the trial.\n\nNovel agents will be continuously added to this study as pre-clinical data emerge to suggest additive or synergistic activity when combined ONC201. Should a novel agent not have an RP2D at the time of incorporation into this study, a phase 1 lead-in will be performed prior to initiation of combination therapy (via study amendment).",[30,195,196,197,198,166],"Diffuse Midline Glioma, H3 K27M-Mutant","Recurrent Diffuse Intrinsic Pontine Glioma","Recurrent Diffuse Midline Glioma, H3 K27M-Mutant","Recurrent WHO Grade III Glioma","2026-06-23",{"date":201,"type":41},"2026-06-26",{"date":203,"type":41},"2021-10-20",{"date":205,"type":23},"2029-06-30",{"name":207,"class":48},"University of California, San Francisco",32,{"id":210,"slug":211,"hasResults":12,"nctId":212,"briefTitle":213,"officialTitle":214,"acronym":4,"eligibilityCriteria":215,"healthyVolunteers":12,"sex":18,"minAge":216,"maxAge":189,"enrollmentInfo":217,"targetDuration":4,"studyType":24,"phases":219,"briefSummary":220,"conditions":221,"keywords":4,"overallStatus":72,"whyStopped":4,"lastUpdateSubmitDate":236,"lastUpdatePostDateStruct":237,"startDateStruct":239,"completionDateStruct":241,"leadSponsor":243,"locationsCount":245},"100528530","phase-2-study-of-olutasidenib-and-temozolomide-in-hgg-100528530","NCT06161974","Study of Olutasidenib and Temozolomide in HGG","Phase 2 Study of Olutasidenib With Temozolomide as Maintenance Therapy in Pediatric and Young Adult Patients Newly Diagnosed With High-Grade Glioma (HGG), Including Diffuse Intrinsic Pontine Glioma (DIPG), Which Harbor IDH1 Mutations","Criteria TarGeT-D study strata definitions\n\n* Stratum A: Patients with localized, intracranial, non-pontine, and non-thalamic IDH 1 mutant Astrocytoma, CNS WHO Grade 3.\n* Stratum B: Patients with localized, intracranial, non-pontine, and non-thalamic IDH 1 mutant Astrocytoma, CNS WHO Grade 4.\n* Stratum C: Patients with IDH-1 mutant DIPG, primary thalamic and spinal cord IDH-1 mutant HGG.\n\nInclusion Criteria:\n\n1. Inclusion criteria already met to enroll on TarGeT-SCR (central molecular and histopathologic screening) based on:\n\n   1.1) Age: patients must be ≥12 years and ≤39 years of age at the time of enrollment on TarGeT-SCR 1.2) Diagnosis:\n   * Patients with a newly-diagnosed IDH1-mutant HGG including DIPG are eligible. All patients must have tumor tissue from diagnostic biopsy or resection, without exceptions. The diagnosis of HGG, including DIPG, must have been confirmed through TarGeT-SCR.\n   * For the diagnosis of DIPG, patients must have a tumor with pontine epicenter and diffuse involvement of at least 2\u002F3 of the pons, and histopathology consistent with diffuse WHO Grade 2-4 glioma.\n   * All other HGG must be WHO Grade 3 or 4.\n\n   1.3) Disease status: There are no disease status requirements for enrollment\n   * Measurable disease is not required. Patients without measurable disease are eligible.\n   * Primary spinal tumor: Patients with a primary spinal HGG are eligible.\n   * Patient must not have metastatic disease.\n2. Inclusion criteria for assignment to TarGeT-D, for all strata:\n\n2.1 Presence of at Least One Relevant Actionable Somatic Mutation in IDH1 Gene, Detailed Here:\n\n* R132H, R132C, R132S, R132G or R132L.\n* Patients whose tumors harbor other alterations in addition to IDH1 mutation will potentially be eligible following consensus recommendation by the international multidisciplinary molecular screening committee.\n* Patients with IDH2 mutations are not eligible.\n* Patients with oligodendroglioma, IDH-mutant and 1p\u002F19q-codeleted are not eligible.\n\n2.2 Weight: Patients must weigh ≥35 Kg (77 lbs) at the time of enrollment on TarGeT-D.\n\n2.3 Performance Level: Karnofsky ≥ 50% for patients \\> 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of age. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.\n\n2.4 Prior Therapy 2.4.1 Surgery, radiation, and\u002For dexamethasone are permissible. Temozolomide administered concurrently with radiotherapy is permissible. Prior administration of bevacizumab is allowed, given at least 42-day washout period is completed prior to beginning treatment on TarGeT-D. No other prior anticancer therapy for HGG will be allowed.\n\n2.4.2 Radiation therapy requirements: RT, delivered via photon or proton beam, must have been administered at a standard dose including 54 Gy in 30 fractions for DIPG, 55-59.4 Gy in 30-33 fractions for other HGG or 45-54 Gy for primary spinal cord HGG. Any variances in the radiotherapy dose within 10% of the standard doses outlined above will be discussed with the Study Chair to confirm eligibility prior to study enrollment.\n\n2.4.3 Timing between diagnosis and start of RT: Patients must have started RT \\\u003C 42 calendar days of initial diagnosis defined as the date of diagnostic biopsy or resection; if a patient underwent two upfront surgeries (e.g., biopsy then resection or debulking), this is the date of the second surgery.\n\n* Patients in pre-maintenance phase must enroll and start treatment no later than 21 calendar days post-completion of RT.\n* Patients not in pre-maintenance phase must enroll and start treatment no later than 35 calendar days post-completion of RT.\n\n2.5 Organ Function Requirements 2.5.1 Adequate Bone Marrow Function Defined as:\n\n* Peripheral absolute neutrophil count (ANC) ≥ 1000\u002Fmm3.\n* Platelet count ≥ 100,000\u002Fmm3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).\n* Hemoglobin \\> 8 g\u002FdL (may be transfused). 2.5.2 Adequate Renal Function Defined as\n* Creatinine clearance or radioisotope GFR ≥ 70ml\u002Fmin\u002F1.73 m2 OR\n* Maximum serum creatinine based on age\u002Fgender as follows: 10 to \\\u003C 13 yrs=1.2 mg\u002FdL for males and females. 13 to \\\u003C 16 yrs=1.5 mg\u002FdL for males and 1.4 mg\u002FdL for females.\n\n2.5.3 Adequate Liver Function Defined as:\n\n* Total bilirubin must be ≤ 1.5 × institutional ULN.\n* AST(SGOT)\u002FALT(SGPT) \\\u003C 3 × institutional ULN.\n* Alkaline Phosphatase \\\u003C 3 × institutional ULN. 2.5.4 Adequate Neurologic Function Defined as:\n\n  * Patients with seizure disorder may be enrolled if well-controlled on anticonvulsants that are not a strong inducer or inhibitor of CYP3A4\u002F5.\n  * Patients must be able to swallow oral medications to be eligible for study enrollment.\n\n2.6. Informed consent: All patients and\u002For their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines.\n\nExclusion Criteria:\n\n1. Pregnancy or Breast-Feeding: Pregnant or breast-feeding women will not be entered on this study due to unknown potential risks of fetal and teratogenic adverse events as seen in animal studies. Pregnancy tests must be obtained in girls who are post-menarchal. Patients of childbearing or child fathering potential must agree to use one highly effective method of contraception while being treated on this study and for 3 months after completing therapy. A woman is considered of childbearing potential if she is fertile, following menarche and until becoming post-menopausal unless permanently sterile. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. A man is considered fertile after puberty unless permanently sterile by bilateral orchidectomy. Male participants should refrain from sperm donation throughout the duration of treatment and for 3 months after completion of therapy.\n\n   A highly effective contraception method is defined as one that results in a low failure rate (\\\u003C1% per year) when used consistently and correctly. The following are considered highly effective contraception methods:\n   * Combined estrogen and progesterone containing hormonal contraception associated with inhibition of ovulation.\n   * Progesterone-only hormonal contraception associated with inhibition of ovulation.\n   * Intra Uterine Device (IUD).\n   * Intra uterine hormone releasing system.\n   * Bilateral tubal occlusion.\n   * Vasectomized partner.\n   * Sexual abstinence (avoiding heterosexual intercourse).\n   * The following contraceptive measures are NOT considered effective:\n\n     * Progesterone-only hormonal contraception (birth control pill) that that does NOT stop ovulation.\n     * Male or female condom with or without spermicide.\n     * Cap, diaphragm, or sponge with spermicide.\n2. Using the following types of concomitant medications:\n\n   * Corticosteroids: Patients receiving corticosteroids are eligible. The use of corticosteroids must be reported.\n   * Investigational Drugs: Patients who are currently receiving another investigational drug are not eligible.\n   * Anti-cancer Agents: Concurrent anti-cancer agents are not allowed with the exception of temozolomide given concurrently with RT and as protocol-instructed post RT maintenance therapy after enrollment on TarGeT-D.\n   * Anticonvulsants: Patients who are receiving enzyme inducing anticonvulsants that are strong inducers of CYP3A4\u002F5 are not eligible.\n   * Strong CYP3A4\u002F5 inducers: Patients who are receiving strong inducers of CYP3A4\u002F5 are not eligible. Strong inducers of CYP3A4\u002F5 should be avoided from 14 days prior to or 5 half-lives (whichever is longer) enrollment to the end of the study.\n   * Patients who are receiving medications known to prolong QTc interval are not eligible\n   * Selective serotonin reuptake inhibitors (SSRIs) such as citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac), fluvoxamine (Luvox), paroxetine (Paxil), sertraline (Zoloft) should be used with caution but are not contraindicated.\n3. Other Criteria\n\n   * Infection: Patients who have an uncontrolled infection are not eligible.\n   * Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study are not eligible.\n   * Patients with known clinically significant active malabsorption syndrome or other condition that could affect absorption are not eligible.\n   * Patients with malignancy related to HIV or solid organ transplant: known history of HIV, HBV surface antigen positivity or positive HCV antibody are not eligible. Viral testing is not required unless clinically indicated in patients without a known history.\n   * Patients with prior or ongoing clinically significant illness, medical or psychiatric condition, that, in the investigator's opinion, could affect the safety of the participant, or could impair the assessment of study results are not eligible.\n   * Patients with any prior solid organ transplant are not eligible.\n   * Patients with secondary\u002Fradiation-related HGG are not eligible.\n   * Patients with metastatic\u002Fdisseminated HGG who have received CSI are not eligible.","12 Years",{"count":218,"type":23},60,[61],"The goal of this study is to determine the efficacy of the study drug olutasidenib to treat newly diagnosed pediatric and young adult patients with a high-grade glioma (HGG) harboring an IDH1 mutation.\n\nThe main question the study aims to answer is whether the combination of olutasidenib and temozolomide (TMZ) can prolong the life of patients diagnosed with an IDH-mutant HGG.",[162,222,223,224,30,166,167,225,195,226,227,228,229,230,231,232,233,234,235],"Astrocytoma","Astrocytoma, Grade III","Astrocytoma, Grade IV","Metastatic Brain Tumor","Thalamus Tumor","Spinal Tumor","IDH1 Mutation","IDH1 R132","IDH1 R132C","IDH1 R132H","IDH1 R132S","IDH1 R132G","IDH1 R132L","Oligodendroglioma","2026-06-10",{"date":238,"type":41},"2026-06-12",{"date":240,"type":41},"2025-02-01",{"date":242,"type":23},"2035-06",{"name":244,"class":145},"Rigel Pharmaceuticals",20,{"id":247,"slug":248,"hasResults":12,"nctId":249,"briefTitle":250,"officialTitle":251,"acronym":4,"eligibilityCriteria":252,"healthyVolunteers":12,"sex":18,"minAge":216,"maxAge":189,"enrollmentInfo":253,"targetDuration":4,"studyType":24,"phases":254,"briefSummary":255,"conditions":256,"keywords":4,"overallStatus":37,"whyStopped":4,"lastUpdateSubmitDate":260,"lastUpdatePostDateStruct":261,"startDateStruct":262,"completionDateStruct":264,"leadSponsor":266,"locationsCount":4},"100642450","phase-2-study-of-relatlimab-and-nivolumab-opdualag-in-replication-repair-deficient-hgg-and-dipg-100642450","NCT07644312","Study of Relatlimab and Nivolumab (Opdualag) in Replication Repair Deficient HGG and DIPG","Feasibility and Phase 2a Study of Relatlimab and Nivolumab (Opdualag™) in Adolescent and Young Adult Patients Newly Diagnosed With Replication Repair Deficient High-Grade Glioma (HGG), Including Diffuse Intrinsic Pontine Glioma (DIPG)","Inclusion Criteria:\n\n* Patients must be ≥12 years and ≤39 years of age at the time of enrollment on TarGeT-SCR.\n* Within the United States, patients must weight ≥ 40 kg at the time of enrollment. For all other countries, patients must weight ≥ 30 kg at the time of enrollment.\n\nDiagnosis:\n\n* Patients with newly-diagnosed HGG, including DIPG, are eligible. All patients mut have histologic confirmation from diagnostic biopsy or resection. The diagnosis of HGG, including DIPG must have been confirmed through TarGeT-SCR.\n* All HGGs must be WHO Grade 3 or 4. Note: WHO Grade 2 gliomas with pontine epicenter and diffuse involvement of at least 2\u002F3 of the pons are eligible.\n\nDisease Status:\n\n* Patients must be newly diagnosed.\n* Measurable disease is not required.\n* Patients with primary spinal tumors are eligible.\n* Patients should have no evidence of herniation or impending herniation, and no mass effect leading to severe midline shift.\n* Patients with prior malignancy are eligible.\n* Metastatic disease is excluded.\n* Disseminated or multifocal disease: discussion with Study Chairs is required. Patients with multifocal disease who received upfront CSI are not eligible.\n\nDemonstration of DNA replication repair deficiency (RRD) by fulfilling at least 2 of the following criteria:\n\n* Tumor mutational burden greater than or equal to 5 mutations\u002Fmegabase (Intermediate and high TMB)\n* Genetic diagnosis of germline Constitutional Mismatch Repair Deficiency (CMMRD), Lynch Syndrome, or Polymerase-Proofreading Deficiency (PPD)\n* Validated functional genomic assay (e.g. LOGIC) confirming mismatch repair (MMR) deficiency\n* Immunohistochemistry (IHC) demonstrating loss of protein expression of any of the 4 MMR genes\n\nPerformance Level: Karnofsky ≥ 50 for patients \\> 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of age\n\nPrior Therapy for HGG:\n\n* Surgery, RT, and\u002For dexamethasone are permissible. Temozolomide administration is highly discouraged with concurrent RT, but permissible. Anti-VEGF treatment used for vasogenic edema or steroid weaning is permitted. No other prior anticancer therapy for HGG will be allowed. Anti-VEGF use is well-established to not impact outcomes in HGG and is not considered as oncologic treatment but rather as a supportive measure to minimize steroid use in this setting. Discussion with Study Chairs is highly recommended.\n* RT requirements: Patients must have received photon or proton focal RT and administered at a standard dose, including:\n* 54 Gy in 30 fractions for DIPG\n* 54-59.4 Gy in 30-33 fractions for other HGG\n* 45-54 Gy for primary spinal cord HGG Note: Variances in RT dose within 10% of standard doses listed above are acceptable.\n* Timing between diagnosis and start of RT: Patients must have started RT \\\u003C 42 calendar days from initial diagnosis.\n* Timing post-RT: The earliest patent can begin protocl treatment is 28 days post-completion of RT. It is recommended treatment should begin within 25 days, however patients must start treatment on TarGeT-F no later than 8 weeks post-completion of RT.\n\nOrgan Function Requirements:\n\n* ANC ≥ 1000\u002Fmm3\n* Platelet count ≥ 100,000\u002Fmm3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).\n* Hemoglobin \\> 8g\u002FdL (may be transfused)\n* Creatinine clearance or radioisotope GFR≥ 70 mL\u002Fmin\u002F1.73 m2 OR serum creatinine based on age\u002Fgender as follows:\n\n  10 to \\\u003C 13 years: 1.2 mg\u002FdL for males and females 13 to \\\u003C 16 years: 1.5 mg\u002FdL for males and 1.4 mg\u002FdL for females\n  * 16 years: 1.7 mg\u002FdL for males and 1.4 mg\u002FdL for females\n* AST\u002FALT \\\u003C 3 times the ULN. For the purpose of this study, the ULN for ALT and AST is 45 U\u002FL.\n* Ejection fraction greater than or equal to 50% as measured by echocardiogram or multiple-gated acquisition\n* QTc ≤ 480 msec (by Bazett formula)\n* Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled.\n* TSH within institutional guidelines for normal range.\n\nExclusion Criteria:\n\n* Pregnant or breastfeeding patients are excluded.\n* Patients with uncontrolled infection.\n* Patients with bone marrow failure syndrome.\n* Participants who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.\n* Inflammatory bowel disease\n* Moderate to severe pulmonary conditions defined by need for medical intervention and\u002For limiting activities of daily living or shortness of breath with limited exertion.\n* Personal history of pneumonitis.\n* Cardiac conditions.\n* Patients with a history of severe or life-threatening adverse dermatologic reactions such as SJS or toxic epidermal necrolysis, or other severe reactions that have been associated with prior immune checkpoint inhibitor therapy.\n* Active tuberculosis\n* Active autoimmune disease requiring systemic treatment in the past 2 years\n* Chronic HBV infections with active disease\n* Personal known history of HPC who have not completed curative antiviral treatment\n* Personal known history of HIV\n* Receipt of any organ transplantation\n* Treated with other malignancy within 1 year prior to enrollment with the exception of the following: curatively treated basal cell carcinoma, squamous cell carcinoma of the skin, and in situ cervical cancer.\n* Receipt of a live or live-attenuated vaccine within 4 weeks prior to enrollment\n* Previous treatment with relatlimab\n* Patients with ongoing or clinically significant illness, medical or psychiatric conditions that, in the investigator's opinion, could affect the safety of the participant, or could impair assessment of the study's results are not eligible.",{"count":80,"type":23},[61],"The goal of this study is to further evaluate feasibility and tolerability of Opdualag for patients with replication repair deficient HGG, including DIPG.",[162,30,257,258,259],"WHO Grade 3 Glioma","WHO Grade 4 Glioma","Replication Repair Deficient","2026-06-08",{"date":238,"type":41},{"date":263,"type":23},"2027-03-01",{"date":265,"type":23},"2038-03-01",{"name":178,"class":48},{"id":268,"slug":269,"hasResults":12,"nctId":270,"briefTitle":271,"officialTitle":272,"acronym":4,"eligibilityCriteria":273,"healthyVolunteers":12,"sex":18,"minAge":274,"maxAge":189,"enrollmentInfo":275,"targetDuration":4,"studyType":277,"phases":4,"briefSummary":278,"conditions":279,"keywords":4,"overallStatus":72,"whyStopped":4,"lastUpdateSubmitDate":260,"lastUpdatePostDateStruct":280,"startDateStruct":281,"completionDateStruct":283,"leadSponsor":285,"locationsCount":286},"100503755","targeted-pediatric-high-grade-glioma-therapy-100503755","NCT05839379","Targeted Pediatric High-Grade Glioma Therapy","Molecularly-Guided Phase II Umbrella Trial for Children, Adolescents, and Young Adults Newly Diagnosed With High-Grade Glioma, Including Diffuse Intrinsic Pontine Glioma","Inclusion Criteria:\n\n1. Age: Patients must be ≥12 months and ≤39 years of age at the time of enrollment onto this screening protocol.\n2. Diagnosis: Patients with newly diagnosed HGG, including DIPG are eligible. Diagnosis must have histologic confirmation from biopsy or resection. The diagnosis of HGG must have been confirmed by pathology review at the local site. For the diagnosis of DIPG, patients must have a tumor with pontine epicenter and diffuse involvement of at least 2\u002F3 of the pons, with histopathology consistent with diffuse WHO grade 2-4 glioma (eg, diffuse astrocytoma, anaplastic astrocytoma, glioblastoma, H3K27-altered diffuse midline glioma). For all other tumors, histologic grade must be WHO grade 3-4.\n3. Disease Status: There are no disease status requirements for enrollment.\n\n   * Measurable disease is not required. Patients without measurable disease are eligible.\n   * Patients with metastatic\u002Fdisseminated or multifocal disease or gliomatosis cerebri are eligible.\n   * Patients with a primary spinal tumor are eligible.\n   * Patients with secondary, radiation related HGG are eligible.\n4. Prior Therapy for HGG: Surgery, radiation, and\u002For dexamethasone are permissible. Temozolomide concurrent with radiation is permissible. Prior administration of avastin\u002Fbevacizumab is allowed (individual treatment arms have different washout period requirements, check individual arm eligibility). No other prior anticancer therapy for HGG will be allowed.\n\n   * Participants screening for assignment to TarGeT-L may not have received radiation.\n\n   Timing from surgery to start of RT: For patients who have started RT, radiation must have started \\\u003C42 days from definitive surgery or biopsy, however it is strongly recommended patients start RT within 31 days from definitive surgery (if patient had two surgeries, radiation must have started within 31 days from second surgery).\n5. Tumor Sample Availability OR results from previous molecular profiling\u002Ftargeted sequencing\n\n   * If a patient screens through OPTION #1, tumor sample in addition to normal comparator tissue (peripheral blood, saliva, or buccal swab) must be submitted for comprehensive molecular screening at the time of screening enrollment.\n   * If a patient screens through OPTIONS #2 or #3, results from previously performed molecular profiling must be submitted following enrollment. It is highly recommended that results be uploaded within 7 days of enrollment (if results are available at time of enrollment) or within 7 days of results becoming available (if pending at time of enrollment) to allow adequate time for central review.\n6. Informed Consent: All patients and\u002For their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines.\n7. Enrollment timeline: Patients are eligible to enroll on the TarGeT-SCR anytime between diagnosis and the following specific timepoints post completion of RT (if relevant)\n\n   * Patients screening through OPTION #1 are eligible to enroll anytime between diagnosis and 10 days post RT (if completing RT).\n   * Patients screening through OPTIONS #2 or #3 are eligible to enroll anytime between diagnosis and 21 days post RT (if completing RT).\n   * Participants screening for TarGeT-L (lorlatinib) are eligible to enroll on TarGeT-SCR anytime between diagnosis and 31 days post definitive surgery (to allow time for molecular review).\n\nHowever, it is important to note the following:\n\n* For treatment protocols that include targeted therapy administered concurrently with RT, patients must start treatment within 10 calendar days of starting RT.\n* For treatment protocols that only include maintenance\u002Fadjuvant therapy (no systemic therapy given concurrently with radiation), patients must start treatment by 35 days post RT\n\n  #SCREENING OPTIONS\n* OPTION1: Molecular screening through CONNECT TarGeT Clinical Testing Laboratories\n* OPTION2: Molecular screening through a national comprehensive tumor profiling program\n* OPTION3: Clinically validated targeted sequencing or focused profiling\n\nExclusion Criteria:\n\n-Tumors that do not meet HGG and DIPG diagnoses specified above","12 Months",{"count":276,"type":23},350,"OBSERVATIONAL","The goal of this study is to perform genetic sequencing on brain tumors from children, adolescents, and young adult patients who have been newly diagnosed with a high-grade glioma. This molecular profiling will decide if patients are eligible to participate in a subsequent treatment-based clinical trial based on the genetic alterations identified in their tumor.",[162,30,163,36,165,195,225,166,167],{"date":236,"type":41},{"date":282,"type":41},"2024-08-02",{"date":284,"type":23},"2034-08-28",{"name":178,"class":48},21,{"id":288,"slug":289,"hasResults":12,"nctId":290,"briefTitle":291,"officialTitle":292,"acronym":4,"eligibilityCriteria":293,"healthyVolunteers":12,"sex":18,"minAge":274,"maxAge":189,"enrollmentInfo":294,"targetDuration":4,"studyType":24,"phases":296,"briefSummary":297,"conditions":298,"keywords":4,"overallStatus":72,"whyStopped":4,"lastUpdateSubmitDate":300,"lastUpdatePostDateStruct":301,"startDateStruct":303,"completionDateStruct":305,"leadSponsor":306,"locationsCount":245},"100504051","phase-2-study-of-ribociclib-and-everolimus-in-hgg-and-dipg-or-ribociclib-and-temozolomide-in-dhg-h3g34-mutant-100504051","NCT05843253","Study of Ribociclib and Everolimus in HGG and DIPG or Ribociclib and Temozolomide in DHG, H3G34-mutant","Phase 2 Study of Ribociclib-Containing Post-Radiotherapy Combinations in Pediatric and Young Adult Patients Newly Diagnosed With High-Grade Glioma, Including Diffuse Intrinsic Pontine Glioma: Ribociclib and Everolimus for HGG\u002FDIPG Which Harbor Alterations of the Cell Cycle and\u002For PI3K\u002FmTOR Pathways AND Ribociclib and Temozolomide for DHG, H3G34-mutant","TarGeT-A study strata definitions Part1: Initial Feasibility Study for the combination of ribociclib PfOS formulation with everolimus: Enrollment on this cohort will be limited to patients aged \\\u003C21 years with primary intracranial localized HGG and DIPG\n\nPart 2\n\n* Stratum A: Patients with localized, intracranial, non-pontine, and non-thalamic HGG (who do not meet criteria for strata C-D)\n* Stratum B: Patients with DIPG\n* Stratum C: Patients with primary thalamic, spinal cord, and\u002For secondary\u002Fradiation-related HGG.\n* Stratum D: Patients with metastatic\u002Fdisseminated HGG, multifocal HGG, and\u002For gliomatosis cerebri who received CSI.\n\nStratum E\n\n* Stratum E: Patients with localized DHG, H3G34-mutant.\n\nInclusion Criteria:\n\n1. Inclusion criteria already met to enroll on TarGeT-SCR (central molecular and histopathologic screening) based on:\n\n   1.1) Age: patients must be ≥12 months and ≤39 years of age at the time of enrollment on TarGeT-SCR. For the Part 1 Initial Feasibility Cohort (receiving ribociclib and everolimus) only: patients must be \\\u003C21 years of age at the time of enrollment on this protocol.\n\n   1.2) Diagnosis: patients with newly-diagnosed HGG, including DIPG are eligible. All patients must have histologic confirmation tumor tissue from diagnostic biopsy or resection, without exceptions. The diagnosis of HGG, including DIPG, must have been confirmed through TarGeT-SCR:\n   * For the diagnosis of DIPG, patients must have a tumor with pontine epicenter and diffuse involvement of at least 2\u002F3 of the pons, with histopathology, consistent with diffuse WHO grade 2-4 glioma\n   * All other HGGs must be WHO grade 3 or 4.\n\n   1.3) Disease status: There are no disease status requirements for enrollment\n   * Patients without measurable disease are eligible.\n   * Patients with metastatic or multifocal disease or gliomatosis cerebri who received upfront CSI are eligible\n   * Patients with a primary spinal HGG are eligible\n   * Patients with secondary, radiation-related HGG are eligible.\n2. Inclusion criteria for assignment to TarGeT-A, for all strata:\n\n2.1) Presence of at least one relevant actionable somatic alteration, detailed here:\n\n* Pathogenic alterations presumed to cause activation of cell cycle:\n* Amplification of CDK4 or CDK6\n* Deletion of CDKN2A, CDKN2B, or CDKN2C\n* Amplification of CCND1 or CCND2\n* Pathogenic alterations presumed to cause activation of the PI3K\u002FmTOR pathway:\n* Deletion or mutation of PTEN\n* Mutation or amplification of PIK3CA\n* Mutation of PIK3R1\n* Deletion or mutation of TSC1 or TSC2\n* Patients with evidence of homozygous (biallelic) RB1 loss by sequencing are excluded from TarGeT-A\n* Patients whose tumors harbor other alterations suspected to activate the cell cycle and\u002For PI3K\u002FmTOR pathway could potentially also be eligible, but only following consensus recommendation by the international multidisciplinary molecular screening committee.\n* For Stratum E: H3G34 (R\u002FV) mutation\n\n2.2) Performance Level: Karnofsky ≥ 50% for patients \\> 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of ag. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.\n\n2.3) Prior Therapy for HGG:\n\n* Surgery, RT, dexamethasone are permissible. Temozolomide administered concurrently with RT is permissible. Avastin\u002Fbevacizumab use is permitted given the last dose was administered \\> 21 days prior to enrollment. No other prior anticancer therapy for HGG will be allowed.\n* Patients must have received photon or proton RT.\n* Patients must have started RT \\\u003C 42 calendar days from initial diagnosis defined as the date of diagnostic biopsy or resection. If a patient underwent 2 upfront surgeries (e.g., biopsy then resection or debulking), this is the date of the second surgery.\n* RT delivered via photon or proton beam, must have been administered at a standard dose including (54 Gy in 30 fractions for DIPG, 54-59.4 Gy in 30-33 fractions), 45 Gy-54 Gy for primary spinal disease, and\u002For 36 Gy-39.6 Gy craniospinal for patients with spinal or leptomeningeal metastatic disease with supplemental boost to 45-54 Gy for metastasis within the thecal sac and 54 Gy-60 Gy for intracranial metastasis. Any variances in the radiotherapy dose within 10% of the standard doses outlined above will be discussed with the Sponsor-Investigator to confirm eligibility prior to study enrollment.\n* Patients must enroll and start treatment No later than 35 calendar days post-completion of RT. The earliest patients can begin protocol treatment is 28 calendar days post-completion of RT.\n\n2.4) Organ Function Requirements\n\n2.4.1) Adequate Bone Marrow Function Defined as:\n\n* Peripheral absolute neutrophil count (ANC) ≥ 1000\u002Fmm3\n* Platelet count ≥ 100,000\u002Fmm3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)\n* Hemoglobin \\>8 g\u002FdL (may be transfused)\n\n2.4.2) Adequate Renal Function Defined as:\n\n* Creatinine clearance or radioisotope GFR ≥ 70ml\u002Fmin\u002F1.73 m2 OR\n* Maximum serum creatinine based on (Schwartz et al. J. Peds, 106:522, 1985) age\u002Fgender as follows: 1 to \\\u003C 2 years=0.6 mg\u002FdL for males and females; 2 to \\\u003C 6 years=0.8 mg\u002FdL for males and females; 6 to \\\u003C 10 years= 1.0 mg\u002FdL for males and females; 10 to \\\u003C 13 years=1.2 mg\u002FdL for males and females. 13 to \\\u003C 16 years=1.5 mg\u002FdL for males and 1.4 mg\u002FdL for females.\n\n2.4.3) Adequate Liver Function Defined as:\n\n* Total bilirubin must be ≤ 1.5 times institutional upper limit of normal for age\n* AST(SGOT)\u002FALT(SGPT) ≤ 3 times institutional upper limit of normal\n* Serum albumin ≥ 2g\u002FdL\n\n2.4.4) Adequate Cardiac Function Defined as:\n\n* Ejection fraction of ≥ 50% by echocardiogram\n* QTc ≤ 450 msec (by Bazett formula)\n\n2.4.5) Adequate Neurologic Function Defined as: Patients with seizure disorder may be enrolled if well-controlled on anticonvulsants that are not strong inducers or inhibitors of CYP3A4\u002F5.\n\n2.4.6) Adequate Pulmonary Function Defined as: No evidence of dyspnea at rest, and a pulse oximetry \\>94% on room air if there is clinical indication for determination.\n\n2.5) Ability to take medications by mouth: For ribociclib and everolimus strata, patients must be able to take study medications by mouth as administration via NG\u002FNJ\u002FG tube is not allowed.\n\n2.6) Informed Consent: All patients and\u002For their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines\n\n2.7) Contraception: Male and female patients of childbearing potential must be willing to use a highly effective contraception method.\n\nExclusion Criteria\n\n1. Pregnant or Breast-Feeding Pregnant or breast-feeding women will not be entered on this study due to known potential risks of fetal and teratogenic adverse events as seen in animal\u002Fhuman studies. Pregnancy tests must be obtained in girls who are post-menarchal. Patients of childbearing or child fathering potential must agree to use at least one highly effective method of contraception while being treated on this study and for 3 months after completing therapy. A woman is considered of childbearing potential if she is fertile, following menarche and until becoming post-menopausal unless permanently sterile. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. A man is considered fertile after puberty unless permanently sterile by bilateral orchidectomy. Male participants should refrain from sperm donation throughout the duration of treatment and for 3 months after completion of therapy\n\n   A highly effective contraception method is defined as one that results in a low failure rate (\\\u003C1% per year) when used consistently and correctly. The following are considered highly effective contraception methods:\n   * Combined estrogen and progesterone containing hormonal contraception associated with inhibition of ovulation.\n   * Progesterone-only hormonal contraception associated with inhibition of ovulation.\n   * Intra Uterine Device (IUD)\n   * Intra Uterine hormone releasing system\n   * Bilateral tubal occlusion\n   * Vasectomized partner\n   * Sexual abstinence (avoiding having heterosexual intercourse) The following contraceptive measures are NOT considered effective\n   * Progesterone-only hormonal contraception (birth control pill) that that does NOT stop ovulation\n   * Male or female condom with or without spermicide\n   * Cap, diaphragm or sponge with spermicide\n2. Concomitant Medications\n\n   * Patients receiving corticosteroids are eligible. The use of corticosteroids must be reported.\n   * Patients who are currently receiving another investigational drug are not eligible.\n   * Patients who are currently receiving other anti-cancer agents are not eligible, with the exception of temozolomide given concurrently with RT only.\n   * Patients who are receiving enzyme inducing anticonvulsants that are strong inducers or inhibitors of CYP3A4\u002F5 are not eligible.\n   * Patients who are receiving strong inducers or inhibitors of CYP3A4\u002F5 are not eligible and should be avoided from 14 days prior to enrollment to the end of the study.\n   * Patients who are receiving medications known to prolong QTc interval are not eligible.\n   * Patients who are receiving therapeutic anticoagulation with warfarin or other coumadin-derived anticoagulants are not eligible. Therapy with heparin, low molecular weight heparin (LMWH), or fondaparinux is allowed as long as the patient has adequate coagulation defined as aPTT \\\u003C 1.5Xs ULN and INR \\\u003C 1.5.\n3. Patients who have an uncontrolled infection are not eligible.\n4. Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study are not eligible.\n5. Patients with known clinically significant active malabsorption syndrome or other condition that could affect absorption are not eligible.\n6. Patients with prior or ongoing clinically significant medical or psychiatric condition that, in the investigator's opinion, could affect the safety of the subject, or could impair the assessment of study results are not eligible.",{"count":295,"type":23},120,[61],"The goal of this study is to determine the efficacy of the 1) ribociclib and everolimus to treat pediatric and young adult patients newly diagnosed with a high-grade glioma (HGG), including DIPG, that have genetic changes in pathways (cell cycle, PI3K\u002FmTOR) that these drugs target or 2) ribociclib and temozolomide to treat pediatric and young adult patients newly diagnosed with diffuse hemispheric glioma (DHG), H3G34-mutant.\n\nThe main question the study aims to answer is whether the combinations of ribociclib and everolimus or ribociclib and temozolomide can prolong the life of patients diagnosed with HGG\u002FDIPG or DHG H3G34-mutant.",[162,30,163,36,165,195,225,166,167,299],"Diffuse Hemispheric Glioma, H3 G34-Mutant","2026-05-27",{"date":302,"type":41},"2026-05-29",{"date":304,"type":41},"2024-08-22",{"date":284,"type":23},{"name":178,"class":48},{"id":308,"slug":309,"hasResults":12,"nctId":310,"briefTitle":311,"officialTitle":312,"acronym":4,"eligibilityCriteria":313,"healthyVolunteers":12,"sex":18,"minAge":314,"maxAge":315,"enrollmentInfo":316,"targetDuration":4,"studyType":24,"phases":318,"briefSummary":319,"conditions":320,"keywords":321,"overallStatus":72,"whyStopped":4,"lastUpdateSubmitDate":75,"lastUpdatePostDateStruct":322,"startDateStruct":324,"completionDateStruct":326,"leadSponsor":328,"locationsCount":49},"100639343","phase-2-a-study-of-vrt106-in-combination-with-radiotherapy-in-adult-patients-with-diffuse-midline-glioma--diffuse-intrinsic-pontine-glioma-100639343","NCT07589257","A Study of VRT106 in Combination With Radiotherapy in Adult Patients With Diffuse Midline Glioma \u002F Diffuse Intrinsic Pontine Glioma","A Single-Arm, Open-Label, Multicenter Phase II Clinical Study of VRT106 in Combination With Radiotherapy in Adult Patients With Diffuse Midline Glioma \u002F Including Diffuse Intrinsic Pontine Glioma","Inclusion Criteria:\n\n* Voluntary signing of the Informed Consent Form (ICF), indicating understanding of the study and willingness and ability to comply with all study procedures.\n* Male or female adults aged 18 to 75 years at the time of signing the ICF.\n* Histologically or cytologically confirmed H3 K27-altered diffuse midline glioma (DMG), or a diagnosis of DIPG based on brain contrast-enhanced MRI: tumor originating in the pons, occupying \\>50% of the pons volume, with diffuse brainstem enlargement.\n* Karnofsky Performance Status (KPS) score ≥ 60.\n* Expected survival time ≥ 3 months.\n\nExclusion Criteria:\n\n* Individuals with extracranial metastases.\n* Presence of spinal cord tumors or evidence of leptomeningeal disease dissemination.\n* Active hemorrhage detected on cranial MRI scan prior to enrollment.\n* Inability to undergo cranial MRI scanning (e.g., due to contraindications or incompatible implants).\n* Prior receipt of oncolytic virus therapy or other gene therapy agents.","18 Years","75 Years",{"count":317,"type":23},10,[61],"To Evaluate the Preliminary Efficacy and Safety\u002FTolerability of VRT106 Combined with Radiotherapy in Adult Patients with DMG\u002FDIPG",[195,30],[195,30],{"date":323,"type":41},"2026-05-15",{"date":325,"type":23},"2026-05-07",{"date":327,"type":23},"2028-12-31",{"name":329,"class":145},"Guangzhou Virotech Pharmaceutical Co., Ltd.",{"id":331,"slug":332,"hasResults":12,"nctId":333,"briefTitle":334,"officialTitle":335,"acronym":4,"eligibilityCriteria":336,"healthyVolunteers":12,"sex":18,"minAge":337,"maxAge":189,"enrollmentInfo":338,"targetDuration":4,"studyType":24,"phases":339,"briefSummary":340,"conditions":341,"keywords":343,"overallStatus":72,"whyStopped":4,"lastUpdateSubmitDate":325,"lastUpdatePostDateStruct":344,"startDateStruct":346,"completionDateStruct":348,"leadSponsor":350,"locationsCount":351},"100446672","phase-2-pep-cmv-vaccine-targeting-cmv-antigen-to-treat-newly-diagnosed-pediatric-hgg-and-dipg-and-recurrent-medulloblastoma-100446672","NCT05096481","PEP-CMV Vaccine Targeting CMV Antigen to Treat Newly Diagnosed Pediatric HGG and DIPG and Recurrent Medulloblastoma","Phase 2 Trial of a Novel Peptide Vaccine (PEP-CMV) Targeting CMV Antigen for Newly Diagnosed Pediatric High-grade Glioma and Diffuse Intrinsic Pontine Glioma and Recurrent Medulloblastoma","Inclusion Criteria for patients with recurrent \u002Fprogressive medulloblastoma (stratum I)\n\n1. Age: Patients must be ≥3 and ≤39 years of age at the time of study enrollment\n2. Diagnosis: Patients must have a diagnosis of medulloblastoma that is recurrent, progressive or refractory. All patients must have histological verification of a medulloblastoma, at original diagnosis or relapse.\n\n   • Patients must have measurable disease defined as a lesion that can be measured in two perpendicular diameters on MRI.\n3. Metastatic Disease: Patients with M+ disease are eligible.\n4. Performance Status:\n\n   Karnofsky ≥ 50% for patients \\>16 years of age or Lansky ≥ 50 for patients ≤ 16 years of age. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.\n5. Prior Therapy:\n\n   1. Radiotherapy: prior radiotherapy requirements Patients must have received prior disease-directed therapy including radiotherapy for their initial diagnosis of medulloblastoma unless patients are less than 4 years of age at the time of enrollment.\n\n      For those less than 4 years of age at the time of enrollment, prior disease directed therapy does not have to include prior radiotherapy.\n\n      Patients must have had their last fraction of:\n      * Craniospinal irradiation, total body irradiation or radiation to ≥ 50% of pelvis \\> 3 months prior to enrollment.\n      * Focal irradiation \\> 4 weeks prior to enrollment\n   2. Myelosuppressive anticancer therapy: Patients must have received their last dose of myelosuppressive anticancer therapy at least 21 days prior to enrollment\n   3. Immunotherapy: Patients must have received their last dose of any immunotherapy agents at least 30 days prior to enrollment\n   4. Non-myelosuppressive anticancer agents: Patients must have received their last dose of non-myelosuppressive anticancer agents at least 7 days prior to study enrollment.\n   5. Antibodies: Patients must have received their last dose of any antibodies at least 21 days prior to enrollment.\n   6. Hematopoietic growth factors: Patients must have received their last dose of hematopoietic growth factors at least 14 days prior to enrollment for a long-acting growth factor (e.g. pegfilgrastim) or 7 days prior to enrollment for short-acting growth factor.\n   7. Autologous stem cell infusion: At least 90 days must have elapsed after an autologous stem cell infusion\n6. Organ Function Requirements:\n\n   1. Adequate bone marrow function defined as:\n\n      * ANC (Absolute neutrophil count) ≥ 1000\u002Fµl.\n      * Platelets ≥ 100,000\u002Fµl. (may be supported)\n      * Hemoglobin \\> 8 g\u002FdL. (may be supported)\n   2. Adequate Renal Function defined as: Creatinine clearance or radioisotope GFR ≥ 70ml\u002Fmin\u002F1.73 m2 or A serum creatinine based on age\u002Fgender as follows:\n\n      Age: Maximum Serum Creatinine (mg\u002FdL)\n      * 2 to \\\u003C 6 years: 0.8 (Male) 0.8 (Female)\n      * 6 to \\\u003C 10 years: 1 (Male) 1 (Female)\n      * 10 to \\\u003C 13 years: 1.2 (Male) 1.2 (Female)\n      * 13 to \\\u003C 16 years: 1.5 (Male) 1.4 (Female)\n      * ≥ 16 years: 1.7 (Male) 1.4 (Female)\n   3. Adequate Liver Function Defined as\n\n      * Total bilirubin ≤1.5 times institutional ULN\n      * AST(SGOT) ≤3 × institutional upper limit of normal\n      * ALT(SGPT) ≤3 × institutional upper limit of normal\n   4. Adequate Neurological Function Defined as\n\n      * Patients with neurological deficits should have deficits that are stable for a minimum of 2 weeks prior to enrollment.\n      * Patients with current seizure disorders may be enrolled if seizures are well- controlled on antiepileptic therapies.\n   5. Patients of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study and for three months after drug cessation.\n   6. Signed informed consent according to institutional guidelines must be obtained prior to enrollment.\n\nInclusion Criteria for Patients with Newly-Diagnosed High-Grade Gliomas (HGG) (stratum II, NOT CURRENTLY ENROLLING) and Newly-Diagnosed (DIPG) (stratum III)\n\n1. Age: Patients must be ≥3 and ≤39 years of age at the time of study enrollment\n2. Diagnosis\n\n   1. Stratum II (NOT CURRENTLY ENROLLING): patients must have histologically confirmed, newly-diagnosed HGG (such as anaplastic astrocytoma, glioblastoma, H3K27-altered DMG).\n\n      * Patients with a newly-diagnosed HGG must enroll within 6 weeks of their final dose of standard radiation therapy with or without chemotherapy.\n      * Patients with primary spinal cord tumors are eligible\n   2. Stratum III: Patients with a newly-diagnosed DIPG:\n\n      * Patients with a radiographically typical DIPG, defined as a tumor with a pontine epicenter and diffuse involvement of more than 2\u002F3 of the pons, are eligible without histologic confirmation.\n      * Patients with brainstem lesions that do not meet these radiographic criteria will be eligible if there is histologic confirmation of an infiltrating astrocytoma WHO grades II-IV.\n3. Metastatic Disease: Patients with M+ disease are eligible.\n4. Performance Status:\n\n   Karnofsky ≥ 50 for patients \\> 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of age (See Appendix I). Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.\n5. Prior Therapy requirements: Patients must have received no prior therapy other than surgery, radiation, chemotherapy during radiotherapy and\u002For steroids (dexamethasone with goal to wean dexamethasone throughout protocol therapy).\n\n   Patients with a newly diagnosed high-grade glioma or DIPG must enroll within 6 weeks of their final dose of standard of care radiation therapy with or without chemotherapy.\n   1. Patients with HGG or DIPG are permitted, but not required, to have received chemotherapy during radiation. Bevacizumab is permitted prior to enrollment in patients with DIPG or HGG. Patients must have received their last dose of bevacizumab at least 14 days prior to enrollment.\n   2. For HGG patients, Patients must have received radiotherapy at a standard dose of 54-59.4 Gy in 1.8 Gy fractions for approximately 6 weeks with an acceptable variance of 10%. Radiation therapy must have begun no later than 42 days after the date definitive surgery.\n   3. For patients with DIPG, Patients must have received radiotherapy at a standard dose of radiotherapy of 54 Gy in 1.8 Gy daily fractions for approximately 6 weeks with an acceptable variance rate of 10%. Radiation therapy must have begun no later than 42 days after the date of radiographic diagnosis or biopsy\n   4. For patients with spinal cord HGG: Patients must have received radiotherapy at a standard dose of 45-54 Gy in 1.8 Gy fractions for approximately 6-7 weeks with an acceptable variance of 10%\n   5. For patients with metastatic disease: Patients may have received standard dose CSI\n6. Organ Function Requirements:\n\n   1. Adequate bone marrow function defined as • ANC (Absolute neutrophil count) ≥ 1000\u002Fµl.\n\n      • Platelets ≥ 100,000\u002Fµl. (may be supported)\n\n      • Hemoglobin \\> 8 g\u002FdL. (may be supported)\n   2. Adequate Renal Function defined as: Creatinine clearance or radioisotope GFR ≥ 70ml\u002Fmin\u002F1.73 m2 or A serum creatinine based on age\u002Fgender as follows:\n\n      Age: Maximum Serum Creatinine (mg\u002FdL)\n\n      • 2 to \\\u003C 6 years: 0.8 (Male) 0.8 (Female)\n\n      • 6 to \\\u003C 10 years: 1 (Male) 1 (Female)\n\n      • 10 to \\\u003C 13 years: 1.2 (Male) 1.2 (Female)\n\n      • 13 to \\\u003C 16 years: 1.5 (Male) 1.4 (Female)\n\n      • ≥ 16 years: 1.7 (Male) 1.4 (Female)\n   3. Adequate Liver Function Defined as:\n\n      • Total bilirubin ≤1.5 times institutional ULN\n      * AST(SGOT) ≤3 × institutional upper limit of normal\n      * ALT(SGPT) ≤3 × institutional upper limit of normal\n   4. Adequate Neurological Function Defined as:\n\nPatients with neurological deficits should have deficits that are stable for a minimum of 1 week prior to enrollment.\n\nd. Patients of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study.\n\ne. Signed informed consent according to institutional guidelines must be obtained prior to registration and for 3 months after drug cessation.\n\nExclusion Criteria for all strata:\n\n1. Pregnancy or Breast-Feeding:\n\n   1. Pregnant or breast-feeding women will not be entered on this study due to known or unknown risks of fetal and teratogenic adverse events as seen in animal\u002Fhuman studies. Pregnancy tests must be obtained in girls who are post-monarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.\n   2. Pregnancy Prevention Patients of childbearing or child fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study and for 3 months after drug cessation.\n2. Study Specific:\n\n   1. Active infection requiring treatment\n   2. Patients with malignancy related to HIV or solid organ transplant: known history of HIV, HBV surface antigen positivity or positive HCV antibody are not eligible. Viral testing is not required unless clinically indicated in patients without a known history\n   3. Known immunosuppressive disease\n   4. Patients with active renal, cardiac (congestive cardiac failure, myocardial infarction, myocarditis), or moderate to severe pulmonary problems generally defined by need for medical intervention (e.g., oxygen, medications) and\u002For limiting activities of daily living (generally CTCAE Grade 2 or higher) or shortness of breath with limited exertion are not eligible. Pulmonary conditions include (but are not limited to) COPD, asthma, and hemi-pneumectomy\n   5. Patients receiving concomitant immunosuppressive agents for medical conditions; inhaled corticosteroids for asthma are allowed.\n   6. Patients receiving concomitant tumor-directed therapy\n   7. Patients receiving any other investigational drug therapy.\n   8. Patients on dexamethasone \\> 0.1 mg\u002FKg\u002Fday up to maximum dose of 4 mg\u002Fday or equivalent.\n   9. Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction).\n   10. Patients with inability to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy\n   11. Patients at high risk for imminent neurologic decline due to extensive bulk disease, midline shift, or herniation on MRI. These patients should be discussed with the study chairs.","3 Years",{"count":295,"type":23},[61],"This study will address the question of whether targeting CMV antigens with PEP-CMV can serve as a novel immunotherapeutic approach in pediatric patients with newly-diagnosed high-grade glioma (HGG) or diffuse intrinsic pontine glioma (DIPG) as well as recurrent medulloblastoma (MB).\n\nPEP-CMV is a vaccine mixture of a peptide referred to as Component A. Component A is a synthetic long peptide (SLP) of 26 amino acid residues from human pp65. The SLPs encode multiple potential class I, class II, and antibody epitopes across several haplotypes. Component A will be administered as a stable water:oil emulsion in Montanide ISA 51.\n\nFunding Source - FDA OOPD",[162,30,342],"Recurrent Medulloblastoma",[162,30,342,35],{"date":345,"type":41},"2026-05-11",{"date":347,"type":41},"2024-07-18",{"date":349,"type":23},"2030-06-15",{"name":178,"class":48},13,{"id":353,"slug":354,"hasResults":12,"nctId":355,"briefTitle":356,"officialTitle":357,"acronym":4,"eligibilityCriteria":358,"healthyVolunteers":12,"sex":18,"minAge":274,"maxAge":359,"enrollmentInfo":360,"targetDuration":4,"studyType":24,"phases":362,"briefSummary":363,"conditions":364,"keywords":367,"overallStatus":72,"whyStopped":4,"lastUpdateSubmitDate":376,"lastUpdatePostDateStruct":377,"startDateStruct":379,"completionDateStruct":381,"leadSponsor":383,"locationsCount":49},"100370165","phase-1-c7r-gd2car-t-cells-for-patients-with-gd2-expressing-brain-tumors-gail-b-100370165","NCT04099797","C7R-GD2.CAR T Cells for Patients With GD2-expressing Brain Tumors (GAIL-B)","Phase I Study of Autologous T Lymphocytes Expressing GD2-specific Chimeric Antigen and Constitutively Active IL-7 Receptors for the Treatment of Patients With GD2-expressing Brain Tumors (GAIL-B)","Procurement Inclusion Criteria:\n\nCohort 1:\n\n1. Histologically confirmed, GD2-expressing newly diagnosed DMG\u002FHGG (including pontine) or confirmation of H3K27 alteration if sufficient tissue for GD2 staining by IHC is not available. Newly diagnosed is defined as prior to radiographic progression or recurrence.\n\n   OR\n\n   Histologically confirmed, GD2-expressing recurrent, refractory, or progressive DMG\u002FHGG (except pontine) or confirmation of positive H3K27 alteration if sufficient tissue for GD2 staining by IHC is not available.\n\n   OR\n\n   Recurrent, refractory, or progressive high-grade CNS tumor with confirmed GD2-expression. Examples include: medulloblastoma \"CNS embryonal tumors, AT\u002FRT, ependymal tumors, diffuse gliomas or glioneuronal tumors.\n\n   Cohort 2:\n\n   Recurrent, refractory, or progressive pontine HGG with confirmed GD2-expression or H3K27-altered DMG\n2. Tumors less than 5 cm in maximum dimension at enrollment\n\n   1. Tumors with ≤25% increase in size (on any dimension) on MRI 4-8 weeks post-radiotherapy remain eligible for study\n   2. Tumors with \\>25% increase in size on post-radiation imaging may be reassessed with repeat MRI in 4-6 weeks, and are eligible if tumor size is subsequently ≤ 25% increased compared with pre-irradiation MRI.\n   3. Tumors with sizes between 5 and 5.5 cm are eligible if the tumor was surgically debulked\n3. Measurable disease on at least 2 dimensions on MRI\n4. Age 12 months to 25 years\n5. Functional score (Karnofsky\u002FLansky) ≥ 50 expected at infusion (≥60 for cohort 2)\n\nProcurement Exclusion Criteria:\n\n1. Patients who are pregnant or breast feeding\n2. Any patient with other risk factors for whom administration of investigational agent is deemed not in the patient's best interest, in the opinion of the investigator.\n\nTreatment Inclusion Criteria\n\nCohort 1:\n\n1. Histologically confirmed, GD2-expressing newly diagnosed DMG\u002FHGG (including pontine) or confirmation of H3K27 alteration if sufficient tissue for GD2 staining by IHC is not available. Newly diagnosed is defined as prior to radiographic progression or recurrence.\n\n   OR\n\n   Histologically confirmed, GD2-expressing recurrent, refractory, or progressive DMG\u002FHGG (except pontine) or confirmation of positive H3K27 alteration if sufficient tissue for GD2 staining by IHC is not available.\n\n   OR\n\n   Recurrent, refractory, or progressive high -grade CNS tumor with confirmed GD2-expression. Examples include: medulloblastoma, CNS embryonal tumors, AT\u002FRT, ependymal tumors, diffuse gliomas, or glioneuronal tumors.\n\n   Cohort 2:\n\n   Recurrent, refractory, or progressive pontine H3K27-altered for DMG or HGG with confirmed GD2-expression.\n2. Tumors less than 5 cm in maximum dimension at enrollment\n\n   1. Tumors with ≤25% increase in size (on any dimension) on MRI 4-8 weeks post-radiotherapy remain eligible for study\n   2. Tumors with \\>25% increase in size on post-radiation imaging may be reassessed with repeat MRI in 4-6 weeks, and are eligible if tumor size is subsequently ≤ 25% increased compared pre-irradiation MRI\n   3. Tumors with sizes between 5 and 5.5 cm are eligible if the tumor was surgically debulked\n3. Measurable disease on at least 2 dimensions on MRI\n4. Central line (PICC or other) and Ommaya reservoir or VP shunt in place or planned to be placed. Central line\u002FPICC may be omitted for cycles that do not include lymphodepletion\n5. Age 12 months to 25 years\n6. Functional score (Karnofsky\u002FLansky) ≥ 50 (≥60 for cohort 2)\n7. Patients must have completed standard of care radiation therapy at least 4 weeks prior to administration of investigational agent. If bevacizumab was administered for management of radiation necrosis, therapy must be completed at least 4 weeks prior to administration of investigational agent.\n8. Stable neurologic exam for 7 days prior to enrollment\n9. Stable or decreasing dose of steroids (max. allowable dose of dexamethasone is 0.1 mg\u002Fkg\u002Fday over the past 7 days prior to infusion of investigational therapy)\n10. Organ function:\n\n    1. ANC \\> 1000 cells\u002Ful\n    2. Platelet count \\> 100,000 cells\u002Ful\n    3. Total bilirubin \\\u003C 1.5x ULN\n    4. ALT and AST \\\u003C 5x ULN\n    5. Serum creatinine or kidney within 2x ULN for age\n\nTreatment Exclusion Criteria\n\n1. Patients who received any other forms of immunotherapy ≤ 42 days before administration of investigational agent\n2. Patients who received colony-stimulating factors within 14 days prior to administration of lymphodepletion\n3. Patients receiving any concurrent anti-cancer therapy (treatment must occur at least three half-lives following prior anti-cancer therapy)\n4. Patients who are pregnant or breast feeding\n5. Any patient with other risk factors for whom administration of investigational agent is deemed not in the patient's best interest, in the opinion of the investigator.","25 Years",{"count":361,"type":23},56,[26],"In this study, there are two treatment groups called Cohort 1 and Cohort 2. Cohort 1 is for patients with diffuse midline glioma, diffuse intrinsic pontine glioma, medulloblastoma, or another rare high-grade glioma that expresses GD2. Cohort 2 is for patients with a type of cancer called progressive diffuse intrinsic pontine glioma that expresses GD2.\n\nBecause there is no standard treatment at this time, patients are asked to volunteer in a gene transfer research study using special immune cells called T cells. T cells are a type of white blood cell that help the body fight infection.\n\nThis research study combines two different ways of fighting cancer: antibodies and T cells. Both antibodies and T cells have been used to treat cancer patients. They have shown promise but have not been strong enough to cure most patients.\n\nResearchers have found from previous research that they can put a new antibody gene into T cells that will make them recognize cancer cells and kill them. GD2 is a protein found on several different cancers. Researchers testing brain cancer cells found that many of these cancers also have GD2 on their surface.\n\nIn a study for neuroblastoma in children, a gene called a chimeric antigen receptor (CAR) was made from an antibody that recognizes GD2. This gene was put into the patients own T cells and given back to 11 patients. The cells did grow for a while but started to disappear from the blood after 2 weeks. The researchers think that if T cells are able to last longer they may have a better chance of killing tumor cells.\n\nIn this study, a new gene will be added to the GD2 T cells that can potentially cause the cells to live longer. T cells need substances called cytokines to survive. The gene C7R has been added that gives the cells a constant supply of cytokine and helps them to survive for a longer period of time.\n\nIn other studies using T cells researchers found that giving chemotherapy before the T cell infusion can improve the amount of time the T cells stay in the body and therefore the effect the T cells can have. This is called lymphodepletion and it will allow the T cells to expand and stay longer in the body and potentially kill cancer cells more effectively.\n\nAfter treating 11 patients, the largest safe dose of GD2-CAR T cells given in the vein (IV) was determined. We are now combining an IV infusion with an infusion directly into the brain through the Ommaya reservoir or programmable VP shunt. The goal is to find the largest safe dose of GD2-C7R T cells that can be administered in this way.\n\nPatients will now be assigned to Cohort 1 and 2 based on their tumor type.\n\nThe GD2.C7R T cells are an investigational product not approved by the FDA.\n\nThe purpose of this study is to combine infusions into the vein in the first treatment cycle with infusions directly into the cerebrospinal fluid (CSF) in the brain (intracerebroventricularly) through the ommaya reservoir or programmable VP shunt for infusions cycles 2-24. The goal is to find the largest safe dose of GD2-C7R T cells that can be administered in this way, and additionally to evaluate how long they can be detected in the blood and CSF and what affect they have on brain cancer.",[30,162,365,366],"Embryonal Tumor","Ependymal Tumor",[368,369,370,34,35,371,372,114,373,374,375],"Gene Therapy","CAR T-cells","chimeric antigen receptor","Glioma","Brain tumor","ETMRs","Medulloepithelioma","Atypical teratoid\u002Frhabdoid tumors","2026-04-23",{"date":378,"type":41},"2026-04-27",{"date":380,"type":41},"2020-02-03",{"date":382,"type":23},"2041-02",{"name":384,"class":48},"Baylor College of Medicine",{"id":386,"slug":387,"hasResults":12,"nctId":388,"briefTitle":389,"officialTitle":390,"acronym":4,"eligibilityCriteria":391,"healthyVolunteers":12,"sex":18,"minAge":89,"maxAge":57,"enrollmentInfo":392,"targetDuration":4,"studyType":24,"phases":394,"briefSummary":395,"conditions":396,"keywords":403,"overallStatus":72,"whyStopped":4,"lastUpdateSubmitDate":405,"lastUpdatePostDateStruct":406,"startDateStruct":408,"completionDateStruct":410,"leadSponsor":412,"locationsCount":49},"100376708","phase-1-study-of-b7-h3-specific-car-t-cell-locoregional-immunotherapy-for-diffuse-intrinsic-pontine-gliomadiffuse-midline-glioma-and-recurrent-or-refractory-pediatric-central-nervous-system-tumors-100376708","NCT04185038","Study of B7-H3-Specific CAR T Cell Locoregional Immunotherapy for Diffuse Intrinsic Pontine Glioma\u002FDiffuse Midline Glioma and Recurrent or Refractory Pediatric Central Nervous System Tumors","Phase 1 Study of B7-H3-Specific CAR T Cell Locoregional Immunotherapy for Diffuse Intrinsic Pontine Glioma\u002FDiffuse Midline Glioma and Recurrent or Refractory Pediatric Central Nervous System Tumors","Inclusion Criteria:\n\n1. Age ≥ 1 and ≤ 26 years\n2. Diagnosis of refractory or recurrent CNS disease for which there is no standard therapy, or diagnosis of DIPG or DMG at any time point following completion of standard therapy\n3. Able to tolerate apheresis, or has apheresis product available for use in manufacturing\n4. CNS reservoir catheter, such as an Ommaya or Rickham catheter\n5. Life expectancy ≥ 8 weeks\n6. Lansky or Karnofsky score ≥ 60\n7. If patient does not have previously obtained apheresis product, patient must have discontinued, and recovered from acute toxic effects of, all prior chemotherapy, immunotherapy, and radiotherapy and discontinue the following prior to enrollment:\n\n   1. ≥ 7 days post last chemotherapy\u002Fbiologic therapy administration\n   2. 3 half lives or 30 days, whichever is shorter post last dose of anti-tumor antibody therapy\n   3. Must be at least 30 days from most recent cellular infusion\n   4. All systemically administered corticosteroid treatment therapy must be stable or decreasing within 1 week prior to enrollment with maximum dexamethasone dose of 2.5 mg\u002Fm2\u002Fday. Corticosteroid physiologic replacement therapy is allowed.\n8. Adequate organ function\n9. Adequate laboratory values\n10. Patients of childbearing\u002Ffathering potential must agree to use highly effective contraception\n\nExclusion Criteria:\n\n1. Presence of Grade ≥ 3 cardiac dysfunction or symptomatic arrhythmia requiring intervention\n2. Presence of primary immunodeficiency\u002Fbone marrow failure syndrome\n3. Presence of clinical and\u002For radiographic evidence of impending herniation\n4. Presence of \\>Grade 3 dysphagia\n5. Presence of active malignancy other than the primary CNS tumor under study\n6. Presence of active severe infection\n7. Receiving any anti-cancer agents or chemotherapy\n8. Pregnant or breastfeeding\n9. Subject and\u002For authorized legal representative unwilling or unable to provide consent\u002Fassent for participation in the 15 year follow up period\n10. Presence of any condition that, in the opinion of the investigator, would prohibit the patient from undergoing treatment under this protocol",{"count":393,"type":23},90,[26],"This is a Phase 1 study of central nervous system (CNS) locoregional adoptive therapy with autologous CD4+ and CD8+ T cells lentivirally transduced to express a B7H3-specific chimeric antigen receptor (CAR) and EGFRt. CAR T cells are delivered via an indwelling catheter into the tumor resection cavity or ventricular system in children and young adults with diffuse intrinsic pontine glioma (DIPG), diffuse midline glioma (DMG), and recurrent or refractory CNS tumors.\n\nA child or young adult meeting all eligibility criteria, including having a CNS catheter placed into the tumor resection cavity or into their ventricular system, and meeting none of the exclusion criteria, will have their T cells collected. The T cells will then be bioengineered into a second-generation CAR T cell that targets B7H3-expressing tumor cells. Patients will be assigned to one of 3 treatment arms based on location or type of their tumor. Patients with supratentorial tumors will be assigned to Arm A, and will receive their treatment into the tumor cavity. Patients with either infratentorial or metastatic\u002Fleptomeningeal tumors will be assigned to Arm B, and will have their treatment delivered into the ventricular system. The first 3 patients enrolled onto the study must be at least 15 years of age and assigned to Arm A or Arm B. Patients with DIPG will be assigned to Arm C and have their treatment delivered into the ventricular system. The patient's newly engineered T cells will be administered via the indwelling catheter for two courses. In the first course patients in Arms A and B will receive a weekly dose of CAR T cells for three weeks, followed by a week off, an examination period, and then another course of weekly doses for three weeks. Patients in Arm C will receive a dose of CAR T cells every other week for 3 weeks, followed by a week off, an examination period, and then dosing every other week for 3 weeks. Following the two courses, patients in all Arms will undergo a series of studies including MRI to evaluate the effect of the CAR T cells and may have the opportunity to continue receiving additional courses of CAR T cells if the patient has not had adverse effects and if more of their T cells are available.\n\nThe hypothesis is that an adequate amount of B7H3-specific CAR T cells can be manufactured to complete two courses of treatment with 3 or 2 doses given on a weekly schedule followed by one week off in each course. The other hypothesis is that B7H3-specific CAR T cells can safely be administered through an indwelling CNS catheter or delivered directly into the brain via indwelling catheter to allow the T cells to directly interact with the tumor cells for each patient enrolled on the study. Secondary aims of the study will include evaluating CAR T cell distribution with the cerebrospinal fluid (CSF), the extent to which CAR T cells egress or traffic into the peripheral circulation or blood stream, and, if tissues samples from multiple timepoints are available, also evaluate disease response to B7-H3 CAR T cell locoregional therapy.",[116,30,122,397,398,399,64,400,401,402,371],"Ependymoma","Medulloblastoma, Childhood","Germ Cell Tumor","Primitive Neuroectodermal Tumor","Choroid Plexus Carcinoma","Pineoblastoma, Childhood",[404],"CNS, CAR T cell, B7-H3, pediatric, young adult, brain tumor, DIPG, DMG","2026-04-07",{"date":407,"type":41},"2026-04-13",{"date":409,"type":41},"2019-12-11",{"date":411,"type":23},"2042-05",{"name":413,"class":48},"Seattle Children's Hospital",{"id":415,"slug":416,"hasResults":12,"nctId":417,"briefTitle":418,"officialTitle":419,"acronym":4,"eligibilityCriteria":420,"healthyVolunteers":12,"sex":18,"minAge":274,"maxAge":189,"enrollmentInfo":421,"targetDuration":4,"studyType":24,"phases":423,"briefSummary":424,"conditions":425,"keywords":428,"overallStatus":37,"whyStopped":4,"lastUpdateSubmitDate":431,"lastUpdatePostDateStruct":432,"startDateStruct":434,"completionDateStruct":436,"leadSponsor":438,"locationsCount":4},"100608845","phase-2-study-of-tovorafenib-in-high-grade-glioma-and-diffuse-intrinsic-pontine-glioma-dipg-100608845","NCT07206849","Study of Tovorafenib in High-Grade Glioma and Diffuse Intrinsic Pontine Glioma (DIPG)","A Phase 2 Study of Tovorafenib in Pediatric and Young Adult Patients Newly Diagnosed With High-Grade Glioma (HGG), Including Diffuse Intrinsic Pontine Glioma (DIPG), Which Harbor Alterations in the Mitogen-Activated Protein Kinase (MAPK) Pathway","Inclusion Criteria:\n\n* Patient must have previously enrolled on TarGeT-SCR.\n\n  1. Age Patients must be ≥12 months and ≤39 years of age at the time of enrollment on TarGeT-SCR.\n  2. Body Surface Area (BSA) Patients must have a BSA \\>0.3m2.\n  3. Diagnosis:\n\n     * Patients with a newly-diagnosed HGG, including DIPG, which harbor alterations in the MAPK pathway are eligible. All patients must have tumor tissue from diagnostic biopsy or resection. The diagnosis of HGG, including DIPG, must have been confirmed through TarGeT-SCR.\n     * For the diagnosis of DIPG, patients must have a tumor with pontine epicenter and diffuse involvement of at least 2\u002F3 of the pons, with histopathology consistent with diffuse WHO Grade 2-4 glioma.\n     * All other HGGs must be WHO Grade 3 or 4.\n  4. Disease Status\n\n     • Patients must be newly diagnosed and enroll and start treatment within 35 days of completion of radiotherapy.\n\n     • Measurable disease is not required. Patients without measurable disease are eligible.\n     * Patients with primary spinal tumors are eligible.\n     * Patients with secondary or radiation-induced HGG are eligible.\n  5. TarGeT-B Strata Definitions\n\n     Patients must be able to be assigned to one of the strata below:\n\n     • Stratum A: Patients with intracranial, localized, non-pontine, and non-thalamic HGG harboring a BRAFV600 mutation (who do not meet criteria for Strata B or C).\n     * Stratum B: Patients with DIPG\u002FDMG as defined in Section 4.1.3 OR patients with localized, non-pontine, non-thalamic HGG harboring a MAPK alteration not included in Stratum A (KIAA1549:BRAF fusion, KRAS\u002FNRAS, CRAF\u002FRAF1, other RAF mutation, or FGFR alteration) OR patients with primary spinal tumors.\n     * Stratum C: Patients with metastatic HGG (including metastatic DIPG\u002FDMG) harboring a MAPK alteration (BRAFV600, KIAA1549:BRAF fusion, KRAS\u002FNRAS, CRAF\u002FRAF1, other RAF mutation, or FGFR alteration).\n  6. Presence of at least one relevant actionable somatic alteration:\n\n     • MAPK pathway alteration(s): BRAFV600 mutation (Strata A or C)\n     * KIAA1549:BRAF fusion (Strata B or C)\n     * KRAS\u002FNRAS alteration (Strata B or C)\n     * CRAF\u002FRAF1 alteration (Strata B or C)\n     * other RAF mutations (Strata B or C)\n     * FGFR alteration (Strata B or C)\n  7. Performance Level:\n\n     Karnofsky ≥ 50 for patients \\> 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of age (Appendix I). Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.\n  8. Prior Therapy for HGG:\n\n     o Surgery, radiation (RT), and\u002For dexamethasone are permissible. Temozolomide administered concurrently with RT is permissible but discouraged for patients with DIPG\u002FDMG. No other prior anticancer therapy for HGG will be allowed.\n\n     o Radiation therapy requirements: Patients must have received photon or proton focal radiotherapy if enrolling on Stratum A or B. Patients must have received craniospinal irradiation if enrolling on Stratum C.\n\n     o Radiotherapy, delivered photon or proton beam, must have been administered at a standard dose, including:\n\n     o 54 Gy in 30 fractions for DIPG\n\n     o 54-59.4 Gy in 30-33 fractions for other HGG\n\n     o 45-54 Gy for primary spinal cord HGG\n\n     o And\u002For 36-39.6 Gy craniospinal for patients with spinal or leptomeningeal metastatic disease with supplemental boost to 45-54 Gy for metastasis within the thecal sac and 54-60 Gy for intracranial metastasis.\n\n     o Any variances in the radiotherapy dose within 10% of standard doses outlined above will be discussed with the Sponsor-Investigator to confirm eligibility prior to study enrollment.\n\n     o Timing between diagnosis and start of RT: Patients must have started RT within 31 calendar days of initial diagnosis which is defined as the date of diagnostic biopsy or resection. If a patient underwent two upfront surgeries e.g., biopsy then resection or debulking, this is the date of the second surgery.\n     * Timing post-RT: Patients must enroll and start treatment on TarGeT-B no later than 35 calendar days post-completion of RT. The earliest patients can begin protocol treatment is 28 calendar days post-completion of RT.\n  9. Organ Function Requirements\n* Adequate Bone Marrow Function Defined as:\n\n  • Peripheral absolute neutrophil count (ANC) \\>= 1000\u002Fmm3.\n\n  • Platelet count \\>= 100,000\u002Fmm3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).\n\n  • Hemoglobin \\>8 g\u002FdL (may be transfused).\n* Adequate Renal Function Defined as:\n\nCreatinine clearance or radioisotope GFR \\> 70ml\u002Fmin\u002F1.73 m2 OR serum creatinine based on age\u002Fgender as follows:\n\nMaximum Serum Creatinine (mg\u002FdL) Age Male Female 1 to \\\u003C 2 years 0.6 0.6 2 to \\\u003C 6 years 0.8 0.8 6 to \\\u003C 10 years 1 1 10 to \\\u003C 13 years 1.2 1.2 13 to \\\u003C 16 years 1.5 1.4\n\n* 16 years 1.7 1.4 The threshold creatinine values in this table were derived from the Schwartz formula for estimating GFR (Schwartz et al. J. Peds, 106:522, 1985) utilizing child length and stature data published by the CDC.\n\n  * Adequate Liver Function Defined as:\n\n    * Total bilirubin ≤ 1.5 times institutional upper limit of normal (ULN).\n    * Aspartate aminotransferase (AST)\u002Falanine aminotransferase (ALT) \\\u003C 3 times the ULN.\n    * Serum albumin ≥ 2g\u002FdL.\n  * Adequate Cardiac Function Defined as:\n\n    • Left Ventricular Ejection fraction of ≥ 50% as measured by echocardiogram or multiple-gated acquisition (MUGA).\n    * QTc ≤ 450 msec (by Bazett formula).\n  * Adequate Neurologic Function Defined as:\n\n    * Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled (see Appendix II).\n  * Normal Thyroid Function Defined as:\n\n    • Free throxine (T4) within institutional guidelines for normal range. It is acceptable for patient to be on thyroid supplementation as long as free T4 is within institutional guidelines for normal range prior to starting treatment.\n\n    10\\) Informed Consent All patients and\u002For their parents or legally authorized representatives must sign a written Informed Consent and Assent, when appropriate, will be obtained according to institutional guidelines.\n\nExclusion Criteria:\n\n1. Pregnancy or breastfeeding.\n2. Other Exclusion Criteria\n\n   • Patients with neurofibromatosis type 1 (NF-1) are not eligible for this study.\n\n   • Infection: Patients who have an uncontrolled infection are not eligible.\n\n   • Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study are not eligible.\n\n   • Patients with uncontrolled GI disease or other condition that could affect absorption or predispose participant to gastrointestinal ulceration are not eligible.\n3. Concomitant Medications • Corticosteroids: Patients receiving corticosteroids are eligible, but the use of corticosteroids must be reported.\n\n   • Investigational Agents\u002FDrugs: Patients who are currently receiving another investigational drug are not eligible. This includes targeted agents, monoclonal antibodies, herbal supplements, or other investigational agents other than tovorafenib.\n\n   • Anti-cancer Agents: Patients who are currently receiving other anti-cancer agents are not eligible with the exception of temozolomide given concurrently with radiotherapy.\n\n   • Anticonvulsants: Patients who are receiving enzyme-inducing anticonvulsants as listed in Appendix II, are not eligible.\n\n   • Patients who are receiving medications known to prolong QTc interval as listed in Appendix III are not eligible.\n\n   • As tovorafenib is a substrate of CYP2C8, patients should not take strong inhibitors or inducers of CYP2C8 (See Appendix VI), as they could alter the drug's pharmacokinetics. Medications that are substrates of CYP2C8 or CYP3A4 are allowed but should be used with caution.\n\n   • Medications that are substrates of breast cancer resistance protein (BCRP) with a narrow therapeutic index are prohibited during this study (Appendix IV).\n   * Patients who are receiving duloxetine, alosetron, or theophylline (CYP1A2 inhibitors) are not eligible.\n   * Patients on beta-blockers are not eligible.\n   * Selective serotonin reuptake inhibitors (SSRIs) such as citalopram (Celexa), escitalopram (Lexapro), Fluoxetine (Prozac), fluvoxamine (Luvox), paroxetine (Paxil), sertraline (Zoloft) should be used with caution but are not contraindicated.\n   * Anticoagulants: patients who are receiving therapeutic anticoagulants including warfarin, low-molecular weight heparin are not eligible.\n\n5\\) Patients with prior or ongoing clinically significant medical or psychiatric condition that, in the investigator's opinion, could affect the safety of the participant, or could impair the assessment of study results are not eligible.",{"count":422,"type":23},79,[61],"The goal of this study is to determine the efficacy of the study drugs tovorafenib to treat pediatric and young adult patients newly diagnosed with a high-grade glioma (HGG), including DIPG, that have genetic changes in pathways (MAPK) that this drug targets.\n\nThe main question the study aims to answer is whether tovorafenib can prolong the life of patients diagnosed with HGG, including DIPG.",[426,427,30,162,257,258,225],"High Grade Glioma (HGG) of the Brain With BRAF Aberration","High Grade Glioma (III or IV)",[429,430],"tovorafenib","high grade glioma","2026-04-03",{"date":433,"type":41},"2026-04-08",{"date":435,"type":23},"2026-05",{"date":437,"type":23},"2037-05",{"name":178,"class":48},{"id":440,"slug":441,"hasResults":12,"nctId":442,"briefTitle":443,"officialTitle":444,"acronym":4,"eligibilityCriteria":445,"healthyVolunteers":12,"sex":18,"minAge":274,"maxAge":314,"enrollmentInfo":446,"targetDuration":4,"studyType":24,"phases":448,"briefSummary":449,"conditions":450,"keywords":451,"overallStatus":72,"whyStopped":4,"lastUpdateSubmitDate":460,"lastUpdatePostDateStruct":461,"startDateStruct":463,"completionDateStruct":465,"leadSponsor":467,"locationsCount":101},"100434949","phase-1-rhsc-dipgvax-plus-checkpoint-blockade-for-the-treatment-of-newly-diagnosed-dipg-and-dmg-100434949","NCT04943848","rHSC-DIPGVax Plus Checkpoint Blockade for the Treatment of Newly Diagnosed DIPG and DMG","A Phase I Clinical Trial of Neo-antigen Heat Shock Protein Vaccine (rHSC-DIPGVax) in Combination With Checkpoint Blockade for the Treatment of Diffuse Intrinsic Pontine Glioma (DIPG) and Diffuse Midline Glioma in Childhood","Inclusion Criteria:\n\n* Subjects with newly diagnosed typical or non-typical, biopsy-proven DIPG or DMG are eligible for study enrollment. Biopsy is not required for subjects with radiographically typical DIPG meeting imaging criteria. Biopsy is required for DMG's and non-radiographically typical DIPG. Histone mutation must be confirmed by pathology report. Radiographically typical DIPG defined as a tumor with a pontine epicenter and diffuse involvement of more than 2\u002F3 of the pons.\n\n  = Subjects ages \\> or = to 12 months and \\\u003C or = 18 years (\"Lead In\", Part A, and Part B require first three patients be \\> or = to 12 years of age)\n* BSA \\> or = 0.35m2 at the time of study enrollment\n* Performance score: Karnofsky \\>50% of subjects \\>16 years of age and Lansky \\> or = 50 for subjects \\\u003C or = 16 years of age. Subjects who are unable to walk because of paralysis but are up in a wheelchair will be considered ambulatory for the purpose of assessing the performance score.\n* Must start radiation therapy within 42 days from date of diagnostic imaging. C1D1 must be within 42 days to 70 days post radiation (6-10 weeks). Patients CANNOT receive temozolomide during radiation\n* Corticosteroids should be weaned as tolerated after radiation therapy with the goal of \\\u003C or = 0.5mg\u002Fkg\u002Fday for a minimum of 7 days prior to enrollment.\n* Subjects must have measurable disease\n\nExclusion Criteria:\n\n* Patients cannot receive temozolomide during radiation\n* Disseminated disease\n* Subjects who have received any cancer therapy except for radiation\n* Autoimmune or immune disorders\n* Active respiratory disorder or infection\n* Active viral infection",{"count":447,"type":23},36,[26],"This is a phase I, open label, plus expansion clinical trial evaluating the safety and tolerability of rHSC-DIPGVax in combination with BALSTILIMAB and ZALIFRELIMAB. rHSC-DIPGVax is an off-the-shelf neo-antigen heat shock protein containing 16 peptides reflecting neo-epitopes found in the majority of DIPG and DMG tumors. Newly diagnosed patients with DIPG and DMG who have completed radiation six to ten weeks prior to enrollment are eligible.",[30,195],[35,452,453,114,454,455,123,456,457,458,459],"Cancer vaccine","Checkpoint blockade","Diffuse intrinsic pontine glioma","High grade glioma","Diffuse midline glioma","rHSC-DIPGVax","Balstilimab","Zalifrelimab","2026-03-16",{"date":462,"type":41},"2026-03-17",{"date":464,"type":41},"2022-01-10",{"date":466,"type":23},"2027-09",{"name":468,"class":48},"Ann & Robert H Lurie Children's Hospital of Chicago",{"id":470,"slug":471,"hasResults":12,"nctId":472,"briefTitle":473,"officialTitle":474,"acronym":4,"eligibilityCriteria":475,"healthyVolunteers":12,"sex":18,"minAge":4,"maxAge":155,"enrollmentInfo":476,"targetDuration":4,"studyType":24,"phases":477,"briefSummary":478,"conditions":479,"keywords":480,"overallStatus":72,"whyStopped":4,"lastUpdateSubmitDate":460,"lastUpdatePostDateStruct":485,"startDateStruct":487,"completionDateStruct":489,"leadSponsor":491,"locationsCount":286},"100412811","early-phase-1-a-pilot-study-of-larotrectinib-for-newly-diagnosed-high-grade-glioma-with-ntrk-fusion-100412811","NCT04655404","A Pilot Study of Larotrectinib for Newly-Diagnosed High-Grade Glioma With NTRK Fusion","A Pilot and Surgical Study of Larotrectinib for Treatment of Children With Newly-Diagnosed High-Grade Glioma With NTRK Fusion","Inclusion Criteria:\n\n* Age: Patients ≤ 21 years of age (birth to 21 years of age) at the time of study enrollment will be eligible.\n* Diagnosis: Patients with newly-diagnosed high-grade (HGG), including diffuse intrinsic pontine gliomas (DIPG), whose tumors are documented in a CLIA\u002FCAP certified lab (or clinically equivalent method considered standard in non-US sites) to harbor an NTRK fusion alteration by FISH, PCR, or next generation sequencing are eligible. Patients must have had histologically verified high-grade glioma such as anaplastic astrocytoma, glioblastoma, or H3 K27-mutant diffuse midline glioma verified at a CONNECT site.\n\nFor sites that do not have CLIA-certified equivalent (certified laboratory) to assess NTRK fusion, testing will be conducted centrally at NCH. NTRK testing will be performed by NGS using targeted RNA-sequencing (Archer Solid Tumor analysis) Please submit 10 unstained sections on charged slides at 10uM thickness, or 10 scrolls cut at 10uM thickness, along with submission of an H\\&E slide. Formalin-fixed paraffin embedded (FFPE) tissue block and FFPE tissue scroll specimens must contain minimum of 25% tumor Snap-frozen tissue specimens are also acceptable and they must contain a minimum of 10% tumor. Please note that turn-around time for this test is up to 21 days.\n\n* Disease Status: Patients with disseminated DIPG or HGG are eligible only if the patient is to receive chemotherapy only, i.e. no craniospinal RT is intended to be given. MRI of spine must be performed if disseminated disease is suspected clinically by the treating physicians. Patients with primary spinal tumors are eligible only if the patient is to receive either chemotherapy or focal radiation therapy, i.e. no craniospinal RT is intended to be given. Patients with leptomeningeal disease only, with no definitive identifiable primary tumor, and documented NTRK fusion, must be discussed with the Study Chair on a case-by-case basis.\n* Surgical Cohort ONLY: Patients with newly-diagnosed HGG with NTRK fusions who have undergone prior biopsy and for whom further resection is indicated for a more definitive surgery at an enrolling site will be eligible to enroll onto the surgical study. DIPG patients are not eligible for the surgical cohort.\n* Performance Level: Karnofsky ≥ 50% for patients \\> 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of age (See Appendix I). Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.\n* Prior Therapy: Patients must not have received any prior anti-cancer chemotherapy. Prior use of corticosteroids are allowed (see below Exclusion Criteria)\n* Organ Function Requirements: Adequate Bone Marrow Function Defined as:\n\nPeripheral absolute neutrophil count (ANC) ≥ 1000\u002Fmm3 Platelet count ≥ 100,000\u002Fmm3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) Hemoglobin \\>8 g\u002FdL (may receive transfusions)\n\n\\- Adequate Renal Function Defined as: Serum creatinine within normal institutional limits, or Creatinine clearance or radioisotope GFR ≥ 70ml\u002Fmin\u002F1.73 m2\n\n\\- Adequate Liver Function Defined as: Total bilirubin ≤ 2.5 × institutional upper limit of normal AST(SGOT)\u002FALT(SGPT) ≤ 2.5 × institutional upper limit of normal\n\n\\- Adequate Pulmonary Function Defined as: Pulse oximetry \\> 94% on room air if there is clinical indication for determination (e.g. dyspnea at rest).\n\n\\- Adequate Neurologic Function Defined as: Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled. See Section 5.5.2 and Appendix III for EIAED guidelines.\n\n\\- Informed Consent: All patients and\u002For their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines.\n\nExclusion Criteria:\n\n* Pregnancy or Breast-Feeding: Pregnant or breast-feeding women will not be entered on this study due to unknown risks of fetal and teratogenic adverse events as seen in animal\u002Fhuman studies. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.\n* Concomitant Medications Investigational Drugs: Patients who have previously received or are currently receiving another investigational drug are not eligible.\n\nAnti-cancer Agents: Patients who have previously received or are currently receiving other anti-cancer agents, including chemotherapy, immunotherapy, monoclonal antibodies, biologic or targeted therapy, are not eligible\n\n* Infection: Patients must not have any active, uncontrolled systemic bacterial, viral or fungal infection.\n* Patients who have received prior solid organ transplantation are not eligible.\n* Patients must not have malabsorption syndrome or other condition affecting oral absorption.\n* Patients must not be receiving any treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor or inducer. (See Appendix III.) Strong inducers or inhibitors of CYP3A4 should be avoided from 7 days prior to enrollment to the end of the study.\n* Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible.",{"count":157,"type":23},[159],"This is a pilot study that will evaluate disease status in children that have been newly diagnosed high-grade glioma with TRK fusion. The evaluation will occur after 2 cycles of the medication (Larotrectinib) have been given.\n\nThe study will also evaluate the safety of larotrectinib when given with chemotherapy in your children; as well as the safety larotrectinib when given post-focal radiation therapy.",[162,30],[481,482,483,484],"NTRK gene fusion","BABYPOG","HIT-SKK","Larotrectinib",{"date":486,"type":41},"2026-03-18",{"date":488,"type":41},"2021-04-08",{"date":490,"type":23},"2036-12-01",{"name":178,"class":48},{"id":493,"slug":494,"hasResults":12,"nctId":495,"briefTitle":496,"officialTitle":497,"acronym":498,"eligibilityCriteria":499,"healthyVolunteers":12,"sex":18,"minAge":500,"maxAge":4,"enrollmentInfo":501,"targetDuration":4,"studyType":24,"phases":503,"briefSummary":505,"conditions":506,"keywords":507,"overallStatus":72,"whyStopped":4,"lastUpdateSubmitDate":511,"lastUpdatePostDateStruct":512,"startDateStruct":514,"completionDateStruct":516,"leadSponsor":518,"locationsCount":520},"100475900","phase-3-biological-medicine-for-diffuse-intrinsic-pontine-glioma-dipg-eradication-20-100475900","NCT05476939","Biological Medicine for Diffuse Intrinsic Pontine Glioma (DIPG) Eradication 2.0","Biological Medicine for Diffuse Intrinsic Pontine Glioma (DIPG) Eradication","BIOMEDE 2","Eligibility criteria for the inclusion (registration) in BIOMEDE 2.0 study:\n\n* Diagnosis Criteria:\n\n  * Diagnosis of DIPG (clinical and radiological). As biopsy is not standard for these tumors, an informed consent is required for the necessary histological verification. \\[Biopsy-part of BIOMEDE 2.0 trial\\]. OR\n  * Histological diagnosis of DIPG (i.e. H3K28M or EZHIP positive Diffuse Midline Glioma located in the pons) in case the tumor biopsy was performed before study entry. The diagnosis will be defined by 1\u002F diffuse glioma, 2\u002F H3K28M mutation or loss of H3K28 trimethylation together with EZHIP overexpression. In this situation, patient will sign the consent after the diagnosis to allow central review and biomarkers assessment thereafter. OR\n  * Molecular diagnosis of DIPG (i.e. H3K28M) in case a liquid biopsy (CSF or blood) was performed before study entry, in a patient who could not undergo a tumor biopsy because it was too dangerous according to the patient's clinical condition. The diagnosis will be defined by 1\u002F DIPG, 2\u002F H3K28M mutation. In this situation, patient will sign the consent after the diagnosis to allow collection of the molecular report. OR\n  * Non-DIPG diffuse midline gliomas (ND-DMG), H3K28M mutant or with H3K28 trimethylation loss together with EZHIP overexpression, will be eligible for the trial after biopsy or surgery. As biopsy and surgery is considered as standard practice for these locations, informed consent for the biopsy will not be necessary. Patient will sign the consent after the diagnosis to allow central review and biomarkers assessment thereafter. OR\n  * Non-DIPG diffuse midline gliomas (ND-DMG) will be eligible for the trial before the biopsy in case the diagnosis is clinically or radiologically suspected. Informed consent for the biopsy and molecular analysis will be necessary. Then, if the central pathology review concludes to a ND-DMG with H3K28M mutant or H3K28 trimethylation loss together with EZHIP overexpression, these patients will be eligible for the treatment part of the trial.\n* Eligible for a biopsy, or biopsy material available for the biomarker assessment.\n* Age \\> 6 months, with no upper age limit. Children between 6 months and 3 years will be discussed on a case by case basis for inclusion in the study for the feasibility of the stereotactic biopsy.\n* Eligible for cerebral or craniospinal radiotherapy.\n* Tumor at diagnosis: no prior chemotherapy for the present cancer; no prior cerebral radiation therapy even for another neoplasm. Surgery is allowed when performed for diagnostic or therapeutic purpose.\n* Metastatic diseases or spinal tumors allowed; in this case, patients would receive craniospinal or spinal radiotherapy and medical treatment (everolimus or ONC201) will be postponed and only started after the end of radiotherapy.\n* Patients must be affiliated to a social security system or beneficiary of the same according to local requirements.\n* Written informed consent from parents\u002Flegal representative, patient, and age-appropriate assent before any study-specific procedures are conducted according to local, regional or national guidelines.\n\nNon eligibility criteria for the inclusion (registration) in BIOMEDE 2.0 study:\n\n* Uncontrolled spontaneous massive intratumor bleeding. Patients with post-operative bleeding will be allowed to enter the study provided the hemorrhage is controled. Same rule applies for the other post-operative complications (infection, CSF leakage, absence of wound closure, subdural collection…).\n* Any other concomitant anti-cancer treatment not foreseen by this protocol is not allowed, except corticosteroids and Bevacizumab which are allowed during the protocol. Bevacizumab is not allowed before and until 15 days after the surgery. The use of bevacizumab and corticosteroids will be taken into account when judging the possibility of progression\u002Fpseudoprogression.\n* Any other cancer diagnosed during the last 5 years.\n* Uncontrolled intercurrent illness or active infection.\n* Any other co-morbid condition that in the investigator's opinion would impair study participation.\n* Unable for medical follow-up (geographic, social or mental reasons).\n* Patient previously treated with irradiation on the brainstem for another neoplasm.\n* Participation in another clinical study with an investigational product while on study treatment.\n* Patient under guardianship or deprived of his\u002Fher liberty by a judicial or administrative decision or incapable of giving his\u002Fher consent.\n\nEligibility criteria for the randomization in BIOMEDE 2.0 study:\n\n* Patient enrolled in the BIOMEDE 2.0 study.\n* Life expectancy \\> 12 weeks after the start of study treatment.\n* Histological diagnosis of DIPG (as per the WHO criteria) confirmed by central pathology review, OR Typical radiology of a DIPG (mandatory central radiological review) as well as the short clinical history (less than three months of pre-existing symptoms) in case of suspected DIPG but no histological confirmation (tumor biopsy performed but not informative), or suspected DIPG with detection of H3K28M mutation in the CSF or blood (ctDNA analysis in the CSF or blood), OR Histological diagnosis of ND-DMG confirmed by central pathology review, with mutation in the histone H3.1, H3.2, H3.3 genes, or loss of H3K28me3 and EZHIP overexpression by immunohistochemistry.\n* Karnofsky performance status scale or Lansky Play Scale \\> 50%. The PS should not take the neurologic deficit per se into account. NB: Children and adults with a worse performance status due to glioma-related motor paresis can be included.\n* Highly effective and appropriate contraception for patients (male and female) of reproductive potential during their entire participation in the study and during 6 months after the end of treatment.\n* Negative pregnancy test (serum beta-HCG or urinary test) evaluated within one week prior randomization in sexually active females of reproductive potential.\n* Absolute neutrophil count \\> 1.0 x 10\\^9\u002Fl, Platelets \\> 100 x 10\\^9\u002Fl.\n* Total bilirubin \\\u003C 1.5 x ULN, AST and ALT\\\u003C 2.5 x ULN.\n* Serum creatinine \\\u003C 1.5 X ULN for age. If serum creatinine \\> 1.5 x ULN, creatinine clearance must be \\> 70 ml\u002Fmin\u002F1.73 m² (as per local practice).\n* Normal coagulation tests within the local reference ranges.\n* Written informed consent from parents\u002Flegal representative, patient, and age-appropriate assent before randomization according to local, regional or national guidelines.\n\nNon Eligibility criteria for the randomization in BIOMEDE 2.0 study:\n\n* Current organ toxicity \\> grade 2 according to the NCI-CTCAE version 5.0, especially cardiovascular or renal disease (including but not limited to: congenital long QT syndrome, nephrotic syndrome, glomerulopathy, uncontrolled high blood pressure despite adequate treatment).\n* Patients with the following cardiac history cannot take ONC201:\n\n  * Prolongation of QT\u002FQTcF interval (QTc interval \\> 480 milliseconds) preferably using Frederica's QT correction formula on two ECGs separated by at least 48 hours.\n  * A history of Torsades de pointes or heart failure, hypokalemia, or family history of prolonged QT Syndrome.\n  * Required concomitant use of medication(s) known to prolong the QT\u002FQTc interval.\n\nIn this case, patients will be treated in the Everolimus arm without randomization (except if contra-indication to Everolimus).\n\n* Pregnant or breastfeeding women.\n* Patients with chronic HBV disease compatible with the trial are not excluded from the study. These patients randomized to everolimus treatment will have regular viral load monitoring throughout the study.\n* Patients taking strong P450 inhibitors or inducers or PgP inhibitors are not excluded from the study but drug concentration of everolimus should be monitored carefully to avoid toxicity. Preferably alternative medications should be considered.\n* Patient with known congenital galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption will not be randomized and will be treated in the ONC201 arm (except if contra-indication to ONC201).\n* Patients with known hypersensitivity to any component of Everolimus (active substance, other rapamycin derivatives or excipients) will not be randomized and will be treated in the ONC201 arm (except if contra-indication to ONC201).\n* Patients with known hypersensitivity to any component of ONC201 (drug product or excipients) will not be randomized and will be treated in the Everolimus arm (except if contra-indication to Everolimus).","6 Months",{"count":502,"type":23},433,[504],"PHASE3","The BIOMEDE 2.0 study is the second stage of the BIOMEDE multi-arm, multistage rolling programme (adaptive platform protocol).\n\nIt is a multicenter, randomized, open-label, controlled phase-3 trial evaluating efficacy of ONC201 in comparison with everolimus (primary objective based on internal comparison) and subsequently to historical controls.\n\nTwo treatment groups will be compared. A switch between treatment groups is allowed after confirmation of the disease progression (real-time central review blinded to the treatment arm allocation). Study treatment will be continued until centrally confirmed disease progression (either radiologically or histologically), unacceptable toxicity or consent withdrawal.\n\nThe final conclusion of the trial will be successful for ONC201, if ONC201 is found significantly superior to everolimus in terms of centrally-reviewed PFS (Progression-free survival) from randomization (internal comparison) either overall, considering ND-DMG and DIPG-patients together, or in the subgroup of ND-DMG patients alone. In other cases, Everolimus will remain the standard arm unless it appears associated with an excess of toxicity compared to ONC201 which could then be discussed as a new standard.",[30,195,168],[133,508,509,510],"Adolescents","Adults","Newly diagnosed","2026-02-03",{"date":513,"type":41},"2026-02-05",{"date":515,"type":41},"2022-09-29",{"date":517,"type":23},"2031-09",{"name":519,"class":48},"Gustave Roussy, Cancer Campus, Grand Paris",50,{"id":522,"slug":523,"hasResults":12,"nctId":524,"briefTitle":525,"officialTitle":526,"acronym":4,"eligibilityCriteria":527,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":155,"enrollmentInfo":528,"targetDuration":4,"studyType":24,"phases":529,"briefSummary":530,"conditions":531,"keywords":532,"overallStatus":72,"whyStopped":4,"lastUpdateSubmitDate":543,"lastUpdatePostDateStruct":544,"startDateStruct":546,"completionDateStruct":548,"leadSponsor":550,"locationsCount":49},"100497836","phase-1-fus-etoposide-for-dmg-100497836","NCT05762419","FUS Etoposide for DMG","A Feasibility Study Examining the Use of Non-Invasive Focused Ultrasound (FUS) With Oral Etoposide Administration in Children With Progressive Diffuse Midline Glioma (DMG)","Inclusion Criteria:\n\n* Ages 4 - 21 years\n* Radiological diagnosis of Diffuse Midline Glioma with tumor involving the pons (intrinsic, pontine based infiltrative lesion; hypointense on T1 weighted images (T1WIs) and hyperintense in T2 sequences, with mass effect on the adjacent structures and occupying at least 50% of the pons), thalami, and\u002For histological confirmation of H3K27M mutation of pontine or thalamic glioma. Subjects must have evidence of clinical and\u002For radiographic progression of disease.\n* Lansky performance status score of at least 60 for subjects 16 years of age or younger.\n* Karnofsky performance status of at least 60 for subjects greater than 16 years of age\n* Organ Function:\n\n  * Adequate hematologic function defined as:\n\n    * Peripheral absolute neutrophil count ≥ 1,500\u002FµL\n    * Platelet count ≥ 100,000\u002FµL\n    * Partial thromboplastin time (PTT) and activated partial thromboplastin time (APTT): within normal institutional limits\n  * Adequate renal function defined as:\n\n    * Potassium and magnesium levels within institutional limits\n    * Serum creatinine below the institutional upper limit of normal (ULN) for age and gender, or creatinine clearance: ≥ 60 mL\u002Fmin\u002F1.73m2\n  * Adequate hepatic function defined as:\n\n    * Total bilirubin below the institutional ULN for age\n    * Aspartate aminotransferase (AST)\u002Falanine aminotransferase (ALT) ≤ 2.5 × institutional ULN\n* Prior Therapy:\n\n  * Subjects must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment.\n  * Cytotoxic chemotherapy or anti-cancer agents known to be myelosuppressive: at least 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy.\n  * Anti-cancer agents not known to be myelosuppressive: at least 7 days must have elapsed from last dose of agent.\n  * Antibodies: at least 21 days must have elapsed from infusion of last dose of antibody.\n  * Interleukins, interferons, and cytokines: at least 21 days must have elapsed since the completion of interleukins, interferon, or cytokines.\n  * Stem cell infusions: at least 42 days must have elapsed after completion of an autologous stem cell infusion, and at least 84 days must have elapsed after completion of an allogeneic stem cell infusion.\n  * Cellular therapy: at least 42 days must have elapsed since the completion of any type of cellular therapy\n  * Radiotherapy (XRT): at least 1 month must have elapsed after local XRT.\n  * Subjects must be on a stable or decreasing dose of steroids, as well as stable dose of anti-seizure medication for at least 1 week.\n* Subject able to give consent\n\nExclusion Criteria:\n\n* Subjects that have previously received etoposide therapy\n* Subjects unable to tolerate study procedures and\u002For anesthesia based on the opinion of the principal investigator\n* Uncontrolled seizure disorder\n* Pregnancy or Breast-Feeding: pregnant or breast-feeding women will not be entered on this study, since there is yet no available information regarding human fetal or teratogenic toxicities; a pregnancy test must be obtained in girls who are post-menarchal. Males with female partners of reproductive potential or females of reproductive potential may not participate unless they have agreed to use two effective methods of birth control- including a medically accepted barrier method of contraception (e.g., a male or female condom) for the entire period in which they are receiving protocol therapy and for at least 1 month following their last study treatment requirement. Abstinence is an acceptable method of birth control. Women of childbearing potential will be provided a routine quantitative beta-human chorionic gonadotropin (B-hCG) test during the pre-study phase, prior to enrollment and each cycle.\n* Concomitant medications: subjects who are currently receiving another investigational drug or other anti-cancer agents are not eligible.\n* Screening EKG with a QTc \\> 450 msec.\n* Subjects with evidence of active systemic infection\n* Subjects with a documented allergy to compounds of similar chemical or biologic composition to etoposide or gadolinium compounds\n* Subjects with implanted metallic or electrical devices\n* Subjects with uncontrollable hypertension\n* Subjects with a documented bleeding disorder\n* Subjects with history of structural cardiac anomalies or arrhythmias\n* Subjects with history of unprovoked stroke or signs of stroke in the area of FUS target\n* Subjects with SARS-CoV-2 infection requiring hospitalization in the past month and requires anticoagulation as per the Columbia University Irving Medical Center (CUIMC) institutional \"Anticoagulation for COVID-19 Positive Pediatric Inpatients\" guidelines (See Appendix B)\n* Subjects with coagulopathy or under anticoagulant therapy.\n* Subjects with signs of impending herniation or an acute or previous intratumoral hemorrhage\n* Subjects with spinal cord diffuse midline glioma\n* Subjects receiving a drug where CNS toxicity is reasonably suspected",{"count":317,"type":23},[26],"The blood brain barrier (BBB) prevents some drugs from successfully reaching the target tumor. Focused Ultrasound (FUS) using microbubbles and neuro-navigator controlled sonication is a non-invasive method of temporarily opening up the blood brain barrier to allow a greater concentration of the drug to reach into the brain tumor. This may improve response and may also reduce system side effects in the patient.\n\nThe primary purpose of this study is to evaluate the feasibility of safely opening the blood brain barrier in children with progressive diffuse midline gliomas (DMG) treated with oral etoposide using focused ultrasound with microbubbles and neuro-navigator-controlled sonication.\n\nFor the purpose of the study, the investigators will be opening up the blood brain barrier temporarily in one or two locations around the tumor using the non-invasive focused ultrasound technology, and administrating oral etoposide in children with progressive diffuse midline glioma.",[30,195],[533,534,535,536,537,114,123,371,538,539,540,541,30,542],"bood brain barrier","diffuse midline glioma","focused ultrasound","pontine glioma","thalamic glioma","Brain Diseases","Nervous System Neoplasms","Central Nervous System Neoplasm","Etoposide","Brain Neoplasms","2026-01-26",{"date":545,"type":41},"2026-01-28",{"date":547,"type":41},"2023-06-05",{"date":549,"type":23},"2027-12",{"name":551,"class":48},"Columbia University",{"id":553,"slug":554,"hasResults":12,"nctId":555,"briefTitle":556,"officialTitle":557,"acronym":4,"eligibilityCriteria":558,"healthyVolunteers":154,"sex":18,"minAge":89,"maxAge":155,"enrollmentInfo":559,"targetDuration":4,"studyType":24,"phases":560,"briefSummary":561,"conditions":562,"keywords":4,"overallStatus":72,"whyStopped":4,"lastUpdateSubmitDate":566,"lastUpdatePostDateStruct":567,"startDateStruct":569,"completionDateStruct":571,"leadSponsor":573,"locationsCount":49},"100512774","phase-1-treatment-of-relapsedrefractory-intracranial-glioma-in-patients-under-22-years-of-age-100512774","NCT05956821","Treatment of Relapsed\u002FRefractory Intracranial Glioma in Patients Under 22 Years of Age","Phase I\u002FII Trial of Repeat Dosing of Super-Selective Intraarterial Infusion of Erbitux (Cetuximab) and Avastin (Bevacizumab) for Treatment of Relapsed\u002FRefractory Intracranial Glioma in Patients Under 22 Years of Age","Inclusion Criteria:\n\n* Documented histologic diagnosis of relapsed or refractory glioblastoma multiforme (GBM), anaplastic astrocytoma (AA), fibrillary astrocytomas (FA), pilomyxoid astrocytoma (PXA), oligodendroglioma, or anaplastic mixed oligoastrocytoma (AOA), or radiologically diagnosed diffuse intrinsic brainstem glioma (DIPG)\n* Must have at least one confirmed and evaluable tumor site\n* Must have a Karnofsky or Lansky performance status ≥60%.\n* No chemotherapy for three weeks prior to treatment\n* Patients must have adequate hematologic reserve with absolute neutrophils≥1000\u002Fmm3 and platelets ≥100,000\u002F mm3\n* Pre-enrollment chemistry parameters must show: bilirubin\\\u003C1.5x the institutional upper limit of normal (IUNL); Aspartate Aminotransferase( AST) or Alanine transaminase (ALT)\\\u003C2.5x IUNL and creatinine\\\u003C1.5x IUNL\n* Pre-enrollment coagulation parameters (PT and PTT) must be ≤1.5x the IUNL\n* Growth factor(s): Must not have received within 1 week of entry onto this study\n* Steroids: Systemic corticosteroid therapy is permissible in patients with Central Nervous System (CNS) tumors for treatment of increased intracranial pressure or symptomatic tumor edema. Patients with CNS tumors who are receiving dexamethasone must be on a stable or decreasing dose for at least 1 week prior to study entry.\n* Patients of reproductive age must agree to use a medically effective method of contraception during and for a period of three months after the treatment period. A pregnancy test will be performed on each premenopausal female of childbearing potential immediately prior to entry into the research study\n* Patients or their parents\u002Fguardians must be able to understand and give written informed consent. Informed consent must be obtained at the time of patient screening\n* Because of known concerns with Avastin and wound healing, craniotomy patients are eligible for the treatment if they have had a craniotomy greater than two weeks prior to Intra-Arterial (IA) therapy. Craniotomy or major procedure after SIACI Avastin therapy should wait 4 weeks. Minor surgeries may be performed after two weeks\n\nExclusion Criteria:\n\n* Females who are pregnant or lactating\n* Females of childbearing potential and fertile men will be informed as to the potential risk of procreation while participating in this research trial and will be advised that they must use effective contraception during and for a period of three months after the treatment period. If they do not agree, they will be ineligible for the study\n* Patients with significant concurrent medical or psychiatric conditions that would place them at increased risk or affect their ability to receive or comply with treatment or post-treatment clinical monitoring",{"count":245,"type":23},[26,61],"This study assesses the safety and efficacy of repeat monthly dosing of super-selective intra-arterial cerebral infusion (SIACI) of cetuximab and bevacizumab in patients \\\u003C 22 years of age.",[165,163,563,235,564,30,69,565],"Fibrillary Astrocytomas","Diffuse Intrinsic Brainstem Glioma","H3 K27M","2025-12-04",{"date":568,"type":41},"2025-12-08",{"date":570,"type":41},"2025-06-19",{"date":572,"type":23},"2029-12-01",{"name":574,"class":48},"University of Miami",{"id":576,"slug":577,"hasResults":12,"nctId":578,"briefTitle":579,"officialTitle":579,"acronym":4,"eligibilityCriteria":580,"healthyVolunteers":12,"sex":18,"minAge":4,"maxAge":4,"enrollmentInfo":581,"targetDuration":4,"studyType":277,"phases":4,"briefSummary":583,"conditions":584,"keywords":4,"overallStatus":72,"whyStopped":4,"lastUpdateSubmitDate":585,"lastUpdatePostDateStruct":586,"startDateStruct":588,"completionDateStruct":590,"leadSponsor":592,"locationsCount":49},"100293588","international-diffuse-intrinsic-pontine-glioma-dipgdiffuse-midline-glioma-dmg-registry-and-repository-100293588","NCT03101813","International Diffuse Intrinsic Pontine Glioma (DIPG)\u002FDiffuse Midline Glioma (DMG) Registry and Repository","Inclusion Criteria:\n\n* All patients of any age (living or deceased) with a diagnosis (either current or past) of a DIPG\u002FDMG tumor\n* Unless the patient is deceased, all patients and\u002For one parent or legal guardian must provide written informed consent as well as HIPAA\u002Frelease of information consent.",{"count":582,"type":23},1500,"Doctors and other medical scientists want learn about the biology of DIPG\u002FDMG and to develop better ways to diagnose and treat patients with DIPG\u002FDMG. To do this, they need more information about the characteristics of DIPG\u002FDMG tumors. Therefore, they want to establish a central location for clinical information and tumor tissue collected from DIPG\u002FDMG patients.\n\nThe purposes of this study are:\n\n* To enroll patients diagnosed with DIPG\u002FDMG in the International DIPG\u002FDMG Registry and Repository.\n* To provide a central location for clinical information, scans, and tissue samples from patients with DIPG\u002FDMG enrolled in the registry.\n* To collect tissue samples in order to study how DIPG\u002FDMG works on the molecular level. Researchers may use the tissue samples to study molecules such as proteins and DNA. Proteins are needed for the body to function properly and DNA is the molecule that carries our genetic information. Other researchers will be able to use the stored samples in the future to learn more about DIPG\u002FDMG. The information researchers get from the research studies will be kept in the registry along with the clinical information.\n* To help investigators around the world to work together to make more consistent diagnosis and better design of future research studies. We hope this will lead to better treatments for DIPG\u002FDMG in the future.",[30,195,122],"2025-10-16",{"date":587,"type":41},"2025-10-20",{"date":589,"type":41},"2012-06",{"date":591,"type":23},"2047-06",{"name":593,"class":48},"Children's Hospital Medical Center, Cincinnati",{"id":595,"slug":596,"hasResults":12,"nctId":597,"briefTitle":598,"officialTitle":598,"acronym":599,"eligibilityCriteria":600,"healthyVolunteers":12,"sex":18,"minAge":188,"maxAge":359,"enrollmentInfo":601,"targetDuration":4,"studyType":24,"phases":602,"briefSummary":603,"conditions":604,"keywords":606,"overallStatus":72,"whyStopped":4,"lastUpdateSubmitDate":609,"lastUpdatePostDateStruct":610,"startDateStruct":612,"completionDateStruct":614,"leadSponsor":616,"locationsCount":618},"100564069","phase-1-atovaquone-combined-with-radiation-in-children-with-malignant-brain-tumors-100564069","NCT06624371","Atovaquone Combined With Radiation in Children With Malignant Brain Tumors","AflacBT2303","Inclusion Criteria:\n\n-Stratum 1\n\n* Newly diagnosed pHGG\u002FDMG\u002FDIPG Patients must have histologically confirmed pediatric high-grade glioma (pHGG, WHO Grade 3 or 4) or diffuse midline glioma with altered H3K27 (DMG, WHO Grade 4). Primary pHGG or DMG spinal tumors are eligible. Diffuse intrinsic pontine glioma (DIPG) defined by MRI does not require histological confirmation.\n* Weight \\> 10kg\n* Karnofsky and Lansky performance score \\> 50%\n* Patients with stable seizures (e.g., no seizures for ≥ 7 days and not requiring escalation or addition of anti-epileptic drugs) will be eligible.\n* Adequate liver function defined as:\n\n  * Total bilirubin ≤ 2x upper limit of normal (ULN) and\n  * AST (SGOT) and ALT (SGPT) ≤ 225 U\u002FL (5x the ULN). The ULN for AST and ALT will be 45 U\u002FL.\n* Patients must have normal organ and marrow function as defined below:\n\n  * absolute neutrophil count \\> 1,000\u002FmcL\n  * platelets \\> 100,000\u002FmcL\n  * hemoglobin \\> 8g\u002FdL\n  * Total bilirubin within normal institutional limits\n  * AST(SGOT)\u002FALT(SGPT) \\\u003C 5 x (\\\u003C10 x if taking steroids) the institutional upper limit of normal\n  * creatinine within normal institutional limits for age 2 OR\n  * creatinine clearance \\> 60mL\u002Fmin\u002F1.73 m for patients with creatinine levels above institutional normal\n\nStratum 2\n\n* Relapsed, progressive pHGG\u002FDMG\u002FDIPG and medulloblastoma (MB) or pHGG\u002FDMG\u002FDIPG after completion of standard radiation therapy without prior atovaquone exposure and before progression. Patients with metastatic disease are allowed for Stratum 2 only.\n\n  --Measurable disease is not necessary for enrollment study.\n* Patients must have previously undergone standard-of-care treatment including surgery, radiation, and\u002For first-line adjuvant chemotherapy before the experimental treatment (atovaquone).\n* Patients must have recovered from the acute treatment-related toxicities (defined as \\\u003C grade 1 if not defined in eligibility criteria) of all prior chemotherapy, immunotherapy or radiotherapy prior to entering this study. There is no upper limit to the number of prior therapies that is allowed.\n* Age \\> 2 to 25 years\n* Weight \\> 10kg\n* Karnofsky and Lansky performance score \\> 50%\n* Patients with stable seizures (e.g., no seizures for ≥ 7 days and not requiring escalation or addition of anti-epileptic drugs) will be eligible.\n* Patients must have normal organ and marrow function as defined above for Stratum 1\n* Adequate liver function is defined as:\n\n  1. Total bilirubin ≤ 2x upper limit of normal (ULN) and\n  2. AST (SGOT) and ALT (SGPT) ≤ 225 U\u002FL (5x the ULN). The ULN for AST and ALT will be 45 U\u002FL.\n\nExclusion Criteria:\n\nStratum 1\n\n* Chronic systemic concurrent illness\n* Concurrent or history of anti-cancer therapy other than RT\n* Patients with metastatic tumor are excluded for Stratum 1 only.\n* Patients with uncontrolled seizures or seizure requiring escalation or addition of anti-epileptic drugs are excluded.\n* Patients must fully recover from all acute effects of prior surgical intervention.\n* History of allergic reactions to atovaquone or attributed to compounds of similar chemical or biological composition to atovaquone.\n* Symptomatic intratumoral hemorrhage, or asymptomatic intratumoral hemorrhage larger than punctate foci, at any time prior to enrollment.\n* Pregnant or breast-feeding women will not be entered into this study as there may be fetal risks or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method during treatment and for 3 months after stopping treatment. This should be documented in the electronic medical records as part of the consent discussion.\n\nStratum 2\n\n* Concurrent illness\n* Patients must have recovered from all prior therapy as follows:\n\n  1. Patients must have received their last dose of known myelosuppressive anticancer therapy at least three (3) weeks before study enrollment or at least six (6) weeks if prior nitrosourea.\n  2. Biologic or investigational agent (anti-neoplastic): Patient must have received their last dose of the investigational or biologic agent ≥ 7 days before study enrollment.\n  3. Antibodies: ≥ 21 days must have elapsed from an infusion of the last dose of antibody and toxicity related to prior antibody therapy must be recovered to Grade ≤ 1. Agents with prolonged half-lives: At least three half-lives must have elapsed before enrollment.\n  4. Immunotherapy: Patient must have completed immunotherapy (e.g. tumor vaccines, oncolytic viruses. etc.) at least 42 days before enrollment.\n  5. Radiation: Patients must have had their last fraction of • Craniospinal irradiation ≥ 3 months before enrollment. • Other substantial bone marrow irradiation ≥ 6 weeks before enrollment • Local or palliative XRT (small port) ≥ 2 weeks.\n  6. Stem Cell Transplant: Patient must be ≥ 12 weeks since autologous bone marrow\u002Fstem cell transplant before enrollment. Patients with uncontrolled seizures or seizure requiring escalation or addition of anti-epileptic drugs are excluded.\n* Patients must fully recover from all acute effects of prior surgical intervention.\n* History of allergic reactions to atovaquone or attributed to compounds of similar chemical or biological composition to atovaquone.\n* Pregnant or breast-feeding women will not be entered into this study as there may be fetal risks or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method during treatment and for 3 months after stopping treatment. This should be documented in the electronic medical records as part of the consent discussion.",{"count":179,"type":23},[26],"The goal of this interventional study is to Assess the safety and tolerability of atovaquone in combination with standard radiation therapy (RT) for the treatment of pediatric patients with newly diagnosed pediatric high-grade glioma\u002Fdiffuse midline glioma\u002Fdiffuse intrinsic pontine glioma (pHGG\u002FDMG\u002FDIPG).\n\nThe secondary aim is to assess the safety and tolerability of longer-term atovaquone treatment for pediatric patients with relapsed or progressed pHGG\u002FDMG\u002FDIPG and medulloblastoma (MB) or pHGG\u002FDMG\u002FDIPG after completion of RT and before progression.",[29,605,30,195],"Medulloblastoma",[607,608],"Atovaquone","Progression-free survival","2025-07-21",{"date":611,"type":41},"2025-07-22",{"date":613,"type":41},"2025-03-28",{"date":615,"type":23},"2027-10",{"name":617,"class":48},"Emory University",2,{"id":620,"slug":621,"hasResults":12,"nctId":622,"briefTitle":623,"officialTitle":624,"acronym":625,"eligibilityCriteria":626,"healthyVolunteers":12,"sex":18,"minAge":89,"maxAge":314,"enrollmentInfo":627,"targetDuration":4,"studyType":24,"phases":629,"briefSummary":630,"conditions":631,"keywords":632,"overallStatus":72,"whyStopped":4,"lastUpdateSubmitDate":638,"lastUpdatePostDateStruct":639,"startDateStruct":641,"completionDateStruct":643,"leadSponsor":645,"locationsCount":49},"100533110","phase-1-safety-and-efficacy-of-loco-regional-b7h3-il-7ra-car-t-cell-in-dipg-100533110","NCT06221553","Safety and Efficacy of Loco-regional B7H3 IL-7Ra CAR T Cell in DIPG","Safety and Efficacy of Intraventricular Infusion of B7H3 With IL-7 Receptor Alpha Signaling Chimeric Antigen Receptor T Cell in Diffuse Intrinsic Pontine Glioma","CMD03DIPG","Inclusion Criteria:\n\n1. Participants must have diffuse intrinsic pontine glioma at any timepoint following completion of standard radiotherapy\n2. Age 1-18 years\n3. Sex: Male or female\n4. CNS reservoir catheter, such as an Ommaya or Rickham catheter, present in the proper location for CNS-directed therapy\n5. Performance status: Lansky or Karnofsky score \\>= 60\n6. Life expectancy \\>= 8 weeks\n7. Normal organ function:\n\n   7.1 AST (SGOT) \\< 5 times the upper limit of normal (ULN) 7.2 ALT (SGPT) \\< 5 times the upper limit of normal (ULN) 7.3 Total bilirubin \\< 3 times the upper limit of normal (ULN) 7.4 Creatinine \\< 5 times the upper limit of normal (ULN) 7.5 SpO2 room air \\>=90%\n8. Prior therapy wash-out before planned leukapheresis 8.1 \\>= 7 days post last chemotherapy\u002Fbiologic therapy administration 8.2 3 half-lives or 30 days, whichever is shorter after the last dose of antitumor antibody therapy 8.3 At least 30 days from most recent cellular infusion 8.4 All systemically administered corticosteroid treatment therapy must be stable or decreasing within 1 week prior to enrollment with a maximum dexamethasone dose of 2.5 mg\u002Fm2\u002Fday. Corticosteroid physiologic replacement therapy is allowed\n9. Participants and\u002For legal guardians must have the ability to understand and willingness to sign a written informed consent and\u002For assent document\n\nExclusion Criteria:\n\n1. Presence of \\>= grade 3 cardiac dysfunction or symptomatic arrythmia requiring intervention\n2. Presence of primary immunodeficiency or bone marrow failure syndrome\n3. Presence of clinical and\u002For radiographic evidence of impending herniation of CNS\n4. Presence of \\> Grade 3 dysphagia\n5. History of active malignancy other than nonmelanoma skin cancer and carcinoma in situ (e.g., cervix, bladder, breast).\n6. Presence of uncontrolled intercurrent illness including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, pulmonary abnormalities, or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements.\n7. Pregnant or breastfeeding women were excluded from this study because CAR-T-cell therapy may be associated with the potential for teratogenic or abortifacient effects. Women of childbearing potential must have a negative serum pregnancy test. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with CAR-T cells, breastfeeding should be discontinued. These potential risks may also apply to other agents used in this study. Participants of childbearing or child-fathering potential must be willing to practice birth control from the time of enrollment in this study and for four months after receiving CAR-T-cell infusion.\n8. Serologic status reflecting active HIV, hepatitis B or C infection. Participants who are positive for hepatitis B core antibody, hepatitis B surface antigen or hepatitis C antibody must have negative PCR prior to enrollment.",{"count":628,"type":23},9,[26],"A Phase 1 clinical trial to evaluate the safety and early efficacy of CAR T-cell with IL-7Ra signal targeting B7H3 in children with diffuse intrinsic pontine glioma (DIPG) patients after complete standard treatments.",[69,30],[633,114,634,635,636,637],"CAR T cell","B7H3","IL-7 receptor alpha","Chimeric antigen receptor T cell","Adoptive cellular therapy","2025-03-27",{"date":640,"type":41},"2025-03-30",{"date":642,"type":41},"2024-03-01",{"date":644,"type":23},"2026-09-01",{"name":646,"class":48},"Chulalongkorn University",{"id":648,"slug":649,"hasResults":12,"nctId":650,"briefTitle":651,"officialTitle":652,"acronym":4,"eligibilityCriteria":653,"healthyVolunteers":12,"sex":18,"minAge":500,"maxAge":20,"enrollmentInfo":654,"targetDuration":4,"studyType":24,"phases":656,"briefSummary":657,"conditions":658,"keywords":661,"overallStatus":72,"whyStopped":4,"lastUpdateSubmitDate":667,"lastUpdatePostDateStruct":668,"startDateStruct":670,"completionDateStruct":672,"leadSponsor":674,"locationsCount":49},"100462233","phase-1-gd2-car-t-cells-for-pediatric-brain-tumours-100462233","NCT05298995","GD2-CAR T Cells for Pediatric Brain Tumours","Phase I Study of Anti-GD2 Chimeric Antigen Receptor-Expressing T Cells in Pediatric and Young Adult Patients Affected by Relapsed\u002FRefractory Central Nervous System Tumors","Inclusion Criteria:\n\n1. Imaging assessments performed within 14 days of start of treatment\n2. Age: 6months-30years\n3. Measurable or evaluable disease on at least 2 dimensions on MRI at the time of treatment enrollment\n4. Karnofsky\u002FLansky≥60\n5. Recoverfromthetoxiceffectsofpreviousradiationandchemotherapies:grade4and or 3 non-hematologic toxicities must have resolved to grade ≤ 2; in presence of chronic complications (i.e. treatment-associated thrombocytopenia), patient must be clinically stable, according to the opinion of the treating physicians, and meet all other eligibility criteria\n6. Positioning of an implantable intraventricular access device (CodmanHolterRickham reservoir, Integra LifeSciences, NJ, U.S.A) and a microdialysis probe (71 high cutoff microdialysis bolt catheter, M Dialysis AB, Stockholm Sweden)\n7. Written and signed informed consent from patients, parents or legal guardians. For subjects \\\u003C 18 year-old their legal guardian must give informed consent. In addition, pediatric subjects will be included in age-appropriate discussion and written informed assent will be obtained for those greater than or equal to 7 years of age, when appropriate\n8. Patients of childbearing or child-fathering potential must be willing to practice birth control from the time of enrollment on this study and for four months after receiving the preparative regimen\n9. Females of childbearing potential must have a negative pregnancy test because of the potentially dangerous effects on the fetus\n\nExclusion Criteria:\n\n1. Pregnant or lactating women\n2. Severe,uncontrolledactiveinfections\n3. HIV or active HCV and\u002For HBV infection\n4. Rapidly progressive disease with life expectancy \\\u003C 6 weeks\n5. Historyofgrade3or4hypersensitivitytomurineprotein-containingproducts\n6. Hepatic function: inadequate liver function defined as total bilirubin \\> 4x upper limit of normal (ULN) or transaminase (ALT and AST) \\> 6 x ULN based on age and laboratory specific normal ranges\n7. Renal function: serum creatinine \\> 3x ULN for age\n8. Blood oxygen saturation \\\u003C 90%\n9. Cardiac function: left ventricular ejection fraction lower than 45% by ECHO\n10. Marrow function: absolute neutrophils count (ANC) lower than 500\u002Fmm3 and\u002For platelets lower than 20.000 (not reached by transfusion)\n11. Congestive heart failure, cardiac arrhythmia, psychiatric illness, or social situations that would limit compliance with study requirements or in the opinion of the principal investigator (PI) would pose an unacceptable risk to the subject. 12.Concurrent or recent prior therapies, before infusion:\n\n    1. If receiving glucocorticoids, patient must be on a stable or weaning dose for at least 7 days prior to infusion. Recent or current use of inhaled\u002Ftopical\u002Fnon- absorbable steroids is not exclusionary. Subjects receiving steroid therapy at physiologic replacement doses only are allowed provided there has been no increase in dose for at least 2 weeks prior to starting apheresis\n    2. Systemic chemotherapy in the 3 weeks preceding infusion\n    3. Immunosuppressive agents less than or equal to 30 days\n    4. Radiation therapy must have been completed at least 6 weeks prior to enrollment\n    5. Otheranti-neoplasticinvestigationalagentscurrentlyorwithin30dayspriorto start of protocol therapy\n\n13.Patient-derived GD2-CART01 production failure: vitality \\\u003C80%, CD3+ cells \\\u003C80%, CD3+ CAR+ cells \\\u003C20%, CD3+ CAR+ antitumor activity \\\u003C60% in functional co-culture assay at an Effector: Target ratio 1:1, viable CAR+ cells upon AP1903 exposition \\>20%, RCR positivity, Vector Copy Number \\>10, non-sterility, endotoxin contamination (\\> 1 EU\u002Fml)",{"count":655,"type":23},54,[26],"The purpose of this study is to test the safety and efficacy of iC9-GD2-CAR T-cells, a third generation (4.1BB-CD28) CAR T cell treatment targeting GD2 in paediatric or young adult patients affected by relapsed\u002Frefractory malignant central nervous system (CNS) tumors. In order to improve the safety of the approach, the suicide gene inducible Caspase 9 (iC9) has been included.",[659,398,365,162,122,30,660],"Brain Tumor, Pediatric","Brain Tumor Adult",[662,430,663,122,30,633,664,35,665,666],"Brain tumors","medulloblastoma","GD2-antigen","Pediatric Central Nervous System tumours","Central nervous system tumour young adults","2025-02-03",{"date":669,"type":41},"2025-02-05",{"date":671,"type":41},"2023-11-09",{"date":673,"type":23},"2038-11",{"name":675,"class":48},"Bambino Gesù Hospital and Research Institute",{"id":677,"slug":678,"hasResults":12,"nctId":679,"briefTitle":680,"officialTitle":680,"acronym":4,"eligibilityCriteria":681,"healthyVolunteers":12,"sex":18,"minAge":4,"maxAge":155,"enrollmentInfo":682,"targetDuration":4,"studyType":277,"phases":4,"briefSummary":684,"conditions":685,"keywords":686,"overallStatus":72,"whyStopped":4,"lastUpdateSubmitDate":692,"lastUpdatePostDateStruct":693,"startDateStruct":695,"completionDateStruct":697,"leadSponsor":699,"locationsCount":49},"100141042","molecular-analysis-of-samples-from-patients-with-diffuse-intrinsic-pontine-glioma-and-brainstem-glioma-100141042","NCT01106794","Molecular Analysis of Samples From Patients With Diffuse Intrinsic Pontine Glioma and Brainstem Glioma","Inclusion Criteria:\n\n* Patients of any age with clinical and radiologic diagnosis of diffuse intrinsic pontine glioma\n* Patients with other high-grade gliomas originating in the brainstem\n* Patients with focal gliomas (WHO grade I\u002FII) of the brainstem\n\nExclusion Criteria:\n\n* Patients with any type of infiltrative low grade (WHO grade I and II) or high grade glioma (WHO grade III and IV) originating outside the brainstem\n* Patients harboring primary brainstem tumors with other histologic diagnoses (e.g., PNET)",{"count":683,"type":23},100,"The purpose of this study is to prospectively collect specimens from pediatric patients with diffuse intrinsic pontine glioma or brainstem glioma, either during therapy or at autopsy, in order to characterize the molecular abnormalities of this tumor.",[30,121],[687,114,688,689,690,691],"diffuse intrinsic pontine glioma","childhood brainstem glioma","pediatric brainstem glioma","brainstem glioma","BSG","2024-08-19",{"date":694,"type":41},"2024-08-20",{"date":696,"type":41},"2010-04",{"date":698,"type":23},"2030-04",{"name":700,"class":48},"Children's National Research Institute"]