[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"atypical-teratoidrhabdoid-tumor\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:atypical-teratoidrhabdoid-tumor":27},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,4,0,[8,49,78,110],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":4,"eligibilityCriteria":15,"healthyVolunteers":11,"sex":16,"minAge":4,"maxAge":17,"enrollmentInfo":18,"targetDuration":4,"studyType":21,"phases":22,"briefSummary":25,"conditions":26,"keywords":34,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":37,"lastUpdatePostDateStruct":38,"startDateStruct":41,"completionDateStruct":43,"leadSponsor":45,"locationsCount":48},"100551831","phase-1-eflornithine-dfmo-and-amxt-1501-for-neuroblastoma-cns-tumors-and-sarcomas-100551831",false,"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.","ALL","26 Years",{"count":19,"type":20},289,"ESTIMATED","INTERVENTIONAL",[23,24],"PHASE1","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",[27,28,29,30,31,32,33],"Atypical Teratoid\u002FRhabdoid Tumor","Embryonal Tumor With Multilayered Rosettes","Ewing Sarcoma","Diffuse Intrinsic Pontine Glioma","Osteosarcoma","Neuroblastoma","DIPG Brain Tumor",[35],"DFMO","RECRUITING","2026-06-30",{"date":39,"type":40},"2026-07-01","ACTUAL",{"date":42,"type":40},"2026-05-13",{"date":44,"type":20},"2035-05",{"name":46,"class":47},"Milton S. Hershey Medical Center","OTHER",12,{"id":50,"slug":51,"hasResults":11,"nctId":52,"briefTitle":53,"officialTitle":54,"acronym":4,"eligibilityCriteria":55,"healthyVolunteers":11,"sex":16,"minAge":4,"maxAge":56,"enrollmentInfo":57,"targetDuration":4,"studyType":21,"phases":59,"briefSummary":60,"conditions":61,"keywords":4,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":68,"lastUpdatePostDateStruct":69,"startDateStruct":71,"completionDateStruct":73,"leadSponsor":75,"locationsCount":77},"100503471","phase-1-loc3car-locoregional-delivery-of-b7-h3-car-t-cells-for-pediatric-patients-with-primary-cns-tumors-100503471","NCT05835687","Loc3CAR: Locoregional Delivery of B7-H3-CAR T Cells for Pediatric Patients With Primary CNS Tumors","Loc3CAR: Locoregional Delivery of B7-H3-specific Chimeric Antigen Receptor Autologous T Cells for Pediatric Patients With Primary CNS Tumors","Inclusion Criteria: Screening Eligibility\n\n1. Age ≤ 21 years of age\n2. Primary CNS tumor\n3. For Cohort A, must have evidence of relapsed or refractory non-brainstem CNS tumor\n4. For Cohort B, must meet one of the following criteria:\n\n   * Adequate tumor tissue from primary tumor resection or biopsy for central pathology review (i.e., B7-H3 expression evaluation by immunohistochemistry \\[IHC\\] or H3K27M mutation if pontine lesion)\n   * Has a diagnosis of diffuse midline glioma that harbors a mutation associated with this entity (e.g. H3K27M)\n   * Has presumptive\u002Fsuspected brainstem high-grade neoplasm with available imaging for central imaging review\n5. Life expectancy of \\> 12 weeks\n6. Adult patient, parent or legal guardian can understand and is willing to sign a written informed consent document according to institutional guidelines\n\nExclusion Criteria: Screening Eligibility All Participants\n\n1\\. Participant has other clinically significant medical disorders (e.g. serious infections or significant cardiac, pulmonary, hepatic, psychiatric, or other organ dysfunction) that could compromise their ability to tolerate protocol therapy or would interfere with study procedure.\n\nInclusion Criteria: Procurement and T-cell Production Eligibility\n\n1. Age ≤ 21 years of age\n2. Primary CNS tumor with measurable or evaluable disease and meets criteria for either Cohort A or B:\n\n   * Cohort A: relapsed\u002Frefractory non-brainstem CNS primary tumor AND tumor is B7-H3 positive\n   * Cohort B: Diffuse midline glioma AND tumor is:\n\n     * B7-H3 positive if non-pontine\n     * OR H3K27-altered diffuse midline pontine glioma\n     * OR radiographically-confirmed classic\u002Ftypical DIPG\n3. Estimated life expectancy of \\>12 weeks\n4. Karnofsky or Lansky performance score ≥50\n5. Participant of childbearing\u002Fchild-fathering potential agrees to use contraception\n6. For females of childbearing age:\n\n   * Not pregnant with negative serum pregnancy test\n   * Not lactating with intent to breastfeed\n7. Chemotherapy\u002Fbiologic therapy must be discontinued ≥ 7 days prior to enrollment\n8. The last dose of antibody therapy (including check point inhibitor) must be at least 3 half-lives or 30 days, whichever is shorter, from the time of enrollment\n9. At least 30 days from most recent cell infusion prior to enrollment.\n10. All systemically administered corticosteroid therapy must be stable or decreasing for ≥1 week prior to enrollment, with a maximum dexamethasone dose of 2.8 mg\u002Fm\\^2\u002Fday\n11. Meets eligibility for apheresis, or has an apheresis product previously collected at a FACT-accredited program\n12. Adult patient, parent or legal guardian can understand and is willing to sign a written informed consent document according to institutional guidelines\n\nExclusion Criteria: Procurement and T-cell Production Eligibility\n\n1. Known primary immunodeficiency or acquired immunodeficiency.\n2. Known HIV positivity\n3. Severe intercurrent bacterial, viral or fungal infection (e.g. active hepatitis B or C infection or adenovirus infection).\n4. Rapidly progressive disease\n5. Known underlying medical condition for which participation in this trial would not be in the best interest of the participant or that could prevent, limit or confound protocol assessments.\n6. Adult patient, Parent, or legal guardian is unwilling or unable to provide consent for participation in a 15 year long-term follow up study.\n\nInclusion Criteria: Treatment Eligibility\n\nCohort A\n\n* Relapsed\u002Frefractory non-brainstem CNS primary tumor\n* Tumor must be considered B7-H3 positive\n\nCohort B\n\n* Diffuse Midline Glioma - Must meet one of the following criteria\n\n  * Tumor is considered B7-H3 positive\n  * H3K27-altered diffuse midline pontine glioma\n  * Radiographically-confirmed classic\u002Ftypical DIPG\n* Must complete standard radiation prior to Loc3CAR treatment and be a minimum of 6 weeks post-completion of radiation therapy\n\nAll participants\n\n1. Age ≤ 21 years old\n2. Primary CNS tumor with measurable or evaluable disease\n3. Available autologous T-cell product that has met GMP release criteria\n4. Participant has a CNS reservoir catheter (e.g., Ommaya) or programmable shunt\n5. First CAR T cell infusion is planned\u002Fscheduled ≥ 5 days from CNS surgery, including catheter placement\n6. The following treatments must be discontinued for the specified duration prior to treatment enrollment:\n\n   * Radiation therapy: ≥ 6 weeks\n   * Bevacizumab: ≥ 28 days\n   * Cytotoxic chemotherapy: ≥ 21 days\n   * Biologic agents: ≥ 7 days\n   * Antibody therapy: ≥ 3 half-lives or 30 days (whichever is shorter)\n   * Cellular therapy: ≥ 30 days\n   * Investigational agent: ≥ 3 half-lives or 30 days (whichever is shorter)\n   * Corticosteroids: All systemically administered therapy must be stable or decreasing for ≥ 1 week prior to enrollment, with a maximum dexamethasone dose of 2.8 mg\u002Fm\\^2\u002Fday. Corticosteroid physiologic replacement therapy for management of pituitary\u002Fadrenal axis insufficiency and\u002For topical administration (e.g. inhaled or dermatologic) is allowed.\n7. Estimated life expectancy of \\>8 weeks\n8. Karnofsky or Lansky performance score ≥ 50\n9. Echocardiogram with a left ventricular ejection fraction ≥ 50%\n10. Adequate renal function defined as calculated creatinine clearance or radioisotope GFR ≥ 50 mL\u002Fmin\u002F1.73m\\^2.\n11. Adequate pulmonary function defined as forced vital capacity (FVC) ≥50% of predicted value or pulse oximetry ≥90% on room air.\n12. Total Bilirubin ≤3 times the upper limit of normal for age.\n13. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤5 times the upper limit of normal for age.\n14. Hemoglobin \\>8.0 g\u002FdL (can be transfused).\n15. Platelet count \\>50,000\u002Fmm\\^3 (can be transfused).\n16. Absolute neutrophil count (ANC) ≥1000\u002FuL.\n17. Taking anti-seizure medication, or agrees to initiate anti-seizure medication prior to starting study therapy.\n18. Has recovered from all NCI CTAE grade III-IV, non-hematologic acute toxicities from prior therapy.\n19. Male participants of child-fathering potential agree to use contraception\n20. Female participants of childbearing potential:\n\n    * Negative serum pregnancy test within 7 days prior to infusion\n    * Not lactating with intent to breastfeed\n    * If sexually active, agrees to use birth control until 3 months after T-cell infusion. Male partners should use a condom\n21. Adult patient, parent or legal guardian can understand and is willing to sign a written informed consent document according to institutional guidelines\n\nExclusion Criteria: Treatment Eligibility-All Participants\n\n1. Participant has a non-programmable ventricular shunt that could compromise study therapy\n2. Participant has a reservoir catheter or shunt in a location that could compromise study therapy or patient safety\n3. Known primary immunodeficiency or acquired immunodeficiency.\n4. Known HIV positivity\n5. Severe intercurrent bacterial, viral or fungal infection\n6. Myocardial infarction, unstable angina, New York Heart Association class III and IV congestive heart failure, myocarditis, or ventricular arrhythmias requiring medication within 6 months prior to study entry\n7. Receiving therapy as outlined above during the 'wash-out' period\n8. Rapidly progressing disease\n9. Received any live vaccines within 30 days\n10. Known underlying medical condition for which participation in this trial would not be in the best interest of the participant or that could prevent, limit or confound protocol assessments\n11. Adult patient, Parent, or legal guardian is unwilling or unable to provide consent for participation in a 15 year long-term follow up study\n12. Evidence of uncontrolled hypertension. Anti-hypertensive medications are permitted if on a stable dose.\n13. Uncontrolled seizures","21 Years",{"count":58,"type":20},48,[23],"Loc3CAR is a Phase I clinical trial evaluating the use of autologous B7-H3-CAR T cells for participants ≤ 21 years old with primary CNS neoplasms. B7-H3-CAR T cells will be locoregionally administered via a CNS reservoir catheter. Study participants will be divided into two cohorts: cohort A with B7-H3-positive relapsed\u002Frefractory non-brainstem primary CNS tumors, and cohort B with diffuse midline gliomas (DMG). Participants will receive four (4) B7-H3-CAR T cell infusions over a 4 week period. The purpose of this study is to find the maximum (highest) dose of B7-H3-CAR T cells that are safe to give patients with primary brain tumors.\n\nPrimary objectives\n\n* To determine the safety, maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) for the locoregional delivery of autologous B7-H3-CAR T cells in patients ≤ 21 years of age with recurrent\u002Frefractory B7-H3+ primary CNS tumors (Cohort A) or DMG (Cohort B).\n\nSecondary objectives\n\n* To assess the efficacy, defined as sustained objective response, a partial response (PR) or complete response (CR) observed anytime on active treatment with B7-H3-CAR T cells in patients with relapsed\u002Frefractory B7-H3+ primary CNS tumors (Cohort A) or DMG (Cohort B).\n* To characterize and monitor neurologic toxicities in patients while on study (Cohort A and B).",[62,27,63,64,65,66,67],"Central Nervous System Neoplasms","Diffuse Midline Glioma, H3 K27M-Mutant","Ependymoma","High Grade Glioma","Glioblastoma","Medulloblastoma","2026-05-01",{"date":70,"type":40},"2026-05-05",{"date":72,"type":40},"2023-04-27",{"date":74,"type":20},"2028-03",{"name":76,"class":47},"St. Jude Children's Research Hospital",1,{"id":79,"slug":80,"hasResults":11,"nctId":81,"briefTitle":82,"officialTitle":83,"acronym":4,"eligibilityCriteria":84,"healthyVolunteers":11,"sex":16,"minAge":85,"maxAge":17,"enrollmentInfo":86,"targetDuration":4,"studyType":21,"phases":88,"briefSummary":89,"conditions":90,"keywords":99,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":101,"lastUpdatePostDateStruct":102,"startDateStruct":104,"completionDateStruct":106,"leadSponsor":108,"locationsCount":77},"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","1 Year",{"count":87,"type":20},90,[23],"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.",[91,30,92,64,93,94,27,95,96,97,98],"Central Nervous System Tumor","Diffuse Midline Glioma","Medulloblastoma, Childhood","Germ Cell Tumor","Primitive Neuroectodermal Tumor","Choroid Plexus Carcinoma","Pineoblastoma, Childhood","Glioma",[100],"CNS, CAR T cell, B7-H3, pediatric, young adult, brain tumor, DIPG, DMG","2026-04-07",{"date":103,"type":40},"2026-04-13",{"date":105,"type":40},"2019-12-11",{"date":107,"type":20},"2042-05",{"name":109,"class":47},"Seattle Children's Hospital",{"id":111,"slug":112,"hasResults":11,"nctId":113,"briefTitle":114,"officialTitle":115,"acronym":4,"eligibilityCriteria":116,"healthyVolunteers":11,"sex":16,"minAge":117,"maxAge":56,"enrollmentInfo":118,"targetDuration":4,"studyType":21,"phases":120,"briefSummary":121,"conditions":122,"keywords":131,"overallStatus":135,"whyStopped":4,"lastUpdateSubmitDate":136,"lastUpdatePostDateStruct":137,"startDateStruct":139,"completionDateStruct":141,"leadSponsor":143,"locationsCount":145},"100622970","phase-1-b7-h3cd28zcart-in-cns-neoplasms-100622970","NCT07390539","B7-H3.CD28Z.CART in CNS Neoplasms","A Phase 1\u002F1b Study of Autologous b7-h3 Chimeric Antigen Receptor t Cells (b7-h3.cd28z.Cart) in Children and Young Adults With Recurrent or Progressive Cns Neoplasms Expressing b7-h3 Target","Pre-screening Inclusion Criteria:\n\n* Participants must have histologically and\u002For molecularly confirmed CNS embryonal tumor (see eligible tumor types below), OR ependymoma that is recurrent\u002Fprogressive following standard of care treatment.\n\n  --Eligible CNS embryonal tumor types include:\n  * Medulloblastoma\n  * Atypical Teratoid Rhabdoid Tumor (ATRT)\n  * Embryonal Tumor with Multilayered Rosettes (ETMR) Pineoblastoma\n  * Other CNS embryonal tumor types, at the discretion of the study chair (or designee)\n* Participants must have adequate pre-trial tumor material available to determine B7- H3 expression status. Tumor tissue from the most recent resection or biopsy of recurrent disease is preferred. If unavailable, tumor tissue from prior recurrences or from time of initial diagnosis is acceptable. Biopsies will not be performed for participation in this research trial or for research purposes.\n* Pre-screening IHC Consent: All participants ≥ 18 years of age must be able to give informed consent. For participants \\\u003C18 years of age, their legal authorized representative (LAR) (i.e. parent or guardian) must give informed consent. Pediatric participants will be included in age-appropriate discussion and written assent will be obtained for those ≥10 years of age, where appropriate. If a minor becomes of age during participation of this study, they will be asked to reconsent as an adult.\n\nInclusion Criteria:\n\n* Participants must have histologically and\u002For molecularly confirmed CNS embryonal tumor (see eligible tumor types below), OR ependymoma that is recurrent\u002Fprogressive following standard of care treatment.\n\n  --Eligible CNS embryonal tumor types include:\n  * Medulloblastoma\n  * Atypical Teratoid Rhabdoid Tumor (ATRT)\n  * Embryonal Tumor with Multilayered Rosettes (ETMR)\n  * Pineoblastoma\n  * Other CNS embryonal tumor types, at the discretion of the study chair (or designee)\n* B7-H3 expression: Demonstration of B7-H3 expression with H score greater than 100 by immunohistochemistry (IHC) is required.\n* Age: greater than or equal to two (2) years of age and less than or equal to 21 years of age. The first participant treated at each dose level within each stratum (Standard Risk and High Risk) will be ≥ 6 years of age when feasible.\n* Disease status: Participants must have evaluable disease in the central nervous system to be eligible. Evaluable disease includes either measurable OR non-measurable disease, defined as follows:\n\n  --Measurable disease (contrast-enhancing or non-enhancing tumor)\n  * Clearly defined lesional margins with two perpendicular diameters of at least 10mm, OR\n  * At least two times (in both perpendicular diameters) the MRI slice thickness, plus the interslice gap\n\n    --Non-measurable disease (tumor that is too small to be accurately measured)\n  * Lesion that is measurable in only one perpendicular dimension, OR\n  * Lesion that is less than 10mm in at least one perpendicular dimension, OR\n  * Lesion that is less than two times the MRI slice thickness, plus the interslice gap\n  * Note: Leptomeningeal (LM) disease is considered non-measurable but evaluable.\n* Performance status: Karnofsky performance status ≥60% for participants ≥16 years of age and Lansky performance status ≥60% for participants \\\u003C16 years of age (see APPENDIX A PERFORMANCE STATUS CRITERIA). NOTE: Participants with neurologic deficits must have a stable neurologic exam for seven (7) days prior to enrollment. 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* Life expectancy of greater than 12 weeks\n* Prior therapy: Participants must have received prior standard of care therapy, including maximal safe surgical resection, radiation therapy and\u002For standard chemotherapy, and is recovered from all acute treatment-related toxicities (defined as ≤ Grade 1 or stable) from all prior therapy before entering this study There is no upper limit to the number of prior therapies allowed, but must have received all standard curative options for their tumor type.\n* Participants must meet the following washouts prior to enrollment:\n\n  * Radiation therapy - Participants must have had their last fraction of:\n\n    ---Craniospinal irradiation, whole brain radiation therapy, or radiation therapy to \\>50% of the pelvis or spine \\>28 days prior to enrollment\n\n    ---Focal irradiation (small port) \\>14 days prior to enrollment\n  * At least 14 days since any prior cytotoxic chemotherapy\n  * At least 7 days since any biologic antineoplastics, tyrosine kinase inhibitor, targeted agent\n  * At least 21 days or 5 half-lives (whichever is shorter) since any investigational antineoplastic or disease-directed agent (but at least 28 days from prior investigational antineoplastic vaccine therapy)\n  * At least 21 days since any monoclonal antibody therapy\n  * At least 90 days since any systemic inhibitor\u002Fstimulatory immune checkpoint therapy\n  * At least 28 days from prior autologous stem cell transplantation, with no ongoing toxicities\n  * At least 14 days after peg-filgrastim and 7 days for hematopoietic growth factor support\n* Steroid use: Must not require concurrent systemic steroid therapy, although physiologic corticosteroid replacement therapy for management of pituitary\u002Fadrenal insufficiency and\u002For topical administration (e.g. inhaled or dermatologic) is allowed. Use of topical, ocular, intranasal, or inhaled corticosteroids are permitted per PI\n\ndiscretion.\n\n* Participants must have adequate organ function, as defined below\n\n  --Adequate bone marrow function\n  * Hemoglobin ≥ 8 g\u002FdL\n  * Absolute neutrophil count (ANC) ≥ 1000 cells\u002FuL\n  * Absolute lymphocyte count (ALC) ≥ 150 cells\u002FuL\n  * Platelets ≥100,000\u002FuL (unsupported, defined as no platelet transfusion within 4 days)\n* Adequate renal function defined as creatinine within normal limits for age OR creatinine clearance (as estimated by Cockcroft Gault Equation for participants ≥ 18yo and Bedside Schwartz for participants \\\u003C18yo) ≥70mL\u002Fmin\n\n  * Maximum Serum Creatinine mg\u002FDL ---6 months to 1 year Male 0.5 Female 0.5 ---1 to \\\u003C 2 years Male 0.6 Female 0.6 ---2 to \\\u003C 6 years Male 0.8 Female 0.8\n\n    * 6 to \\\u003C 10 years Male 1 Female 1\n    * 10 to \\\u003C 13 years Male 1.2 Female 1.2\n    * 13 years to \\\u003C 16 years Male 1.5 Female 1.4\n\n      * 16 years Male 1.7 Female 1.4\n* Adequate hepatic function\n\n  * Serum ALT\u002FAST ≤3.0 upper limit of normal (ULN)\n  * Total bilirubin ≤1.5mg\u002FdL, except in subjects with confirmed Gilbert's syndrome\n* Adequate cardiac function\n\n  --Ejection fraction ≥50% or fractional shortening ≥28%, measured by echocardiography\n* Adequate pulmonary function\n\n  * No evidence of dyspnea at rest\n  * Pulse oximetry \\>92% whilst breathing room air\n* Adequate neurologic function\n\n  * Participants with seizure disorders on anticonvulsants may be enrolled if seizures are well controlled (no seizure activity within 7 days prior to enrollment)\n  * Nervous system disorders (CTCAE v6.0) resulting from prior therapy must be ≤ Grade 2, with the exception of decreased tendon reflex (DTR; any Grade eligible). Participants with neurological deficits should be stable for a minimum of 7 days prior to enrollment. (A baseline detailed neurological exam should clearly document the neurological status of the participant prior at enrollment).\n* Females of childbearing potential must have a negative serum or urine pregnancy test (females who have undergone surgical sterilization are not considered to be of childbearing potential)\n* Participants of childbearing or child-fathering potential must be willing to practice birth control from the time of enrollment on this study and for one year after receiving the preparative lymphodepletion regimen, or for as long as B7- H3.CD28Z.CART cells are detectable in peripheral blood or CSF, whichever is later.\n* Participant or parent of participant or legally recognized representative must be able to sign a written informed consent document. Pediatric participants will be included in age-appropriate discussion and written assent will be obtained for those ≥10 years of age, where appropriate.\n\nExclusion Criteria:\n\n* Participants with bulky tumor are ineligible. Bulky tumor is defined as:\n\n  * Tumor with diameter of \\>5cm in one dimension on T2\u002FFLAIR sequence\n  * Tumor with evidence of clinically significant midline shift or uncal herniation\n  * Tumor that, in opinion of the site investigator, shows significant mass effect in either the brain or spine\n* Participants with clinical or radiological evidence of brain herniation.\n* Participants who have received other B7-H3 targeted cellular therapies. Other prior cellular therapies are eligible, including immune checkpoint inhibition and vaccine therapy. These prior therapies should be discussed with the study chair (or designee) prior to participant enrollment.\n* Concurrent illness\n\n  * Participants with any prior immunodeficiency or history of autoimmune disease requiring systemic steroids\u002F immunosuppressive medication\u002F disease-modifying agents within the last two (2) years.\n  * Uncontrolled (Grade 3) bacterial, viral, fungal, or other infection.\n  * Ongoing infection with HIV or hepatitis B (HBsAg positive) or hepatitis C virus (anti-HCV positive). A history of hepatitis B or hepatitis C is permitted if the viral load is undetectable per quantitative PCR and\u002For nucleic acid testing.\n  * Evidence of severe or uncontrolled systemic disease (e.g. Grade 3 significant cardiac, pulmonary, hepatic, renal or other organ dysfunction) that in the judgement of the principal investigator is likely to interfere with assessment of safety or efficacy of the investigational regimen and its requirements.\n  * Known sensitivity or allergy to any of the agents\u002Freagents used in this study (i.e. DSMO, cyclophosphamide, fludarabine)\n  * History of severe hypersensitivity reaction to compounds of similar chemical or biologic compositions to any agent used in the study or in the manufacturing of cells.\n* Concomitant medications\n\n  * Current systemic corticosteroid therapy\n  * Note, physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency will be allowed.\n  * Participants who are receiving any other anti-cancer or investigational drug therapy are ineligible.\n  * Participants who have received the last vaccination of a live vaccine ≤ 30 days prior to the start of treatment are ineligible.\n  * Ongoing use of dietary supplements, alternative therapies or extreme diets, or any medication not approved by the study chair (or designee).\n* Any other condition which in the principal investigator's opinion makes the individual clinically unsuitable to participate in this trial, or which would jeopardize compliance with the protocol, or would make it difficult to interpret adverse events or study data.","2 Years",{"count":119,"type":20},70,[23],"The purpose of this research study is to test the safety and effectiveness of a cell therapy at different doses for children and young adults with recurrent or progressive brain tumors. Recurrent\u002Frecurred means a tumor that has gone away and then came back. This cell therapy is called B7- H3.CD28Z.CART, referred to as B7-H3 CAR T cells. B7-H3 is a protein that is over-expressed on many tumor cells, making it a good target for cancer cell therapy.\n\nThe names of the study investigational therapies involved in this study are:\n\n* Fludarabine (a type of chemotherapy)\n* Cyclophosphamide (a type of chemotherapy)\n* B7-H3 CAR T cells (a type of cellular therapy)",[62,123,124,125,126,67,93,127,128,64,27,28,129,130],"Brain Tumor","Brain Tumor, Recurrent","Brain Tumor, Pediatric","Brain Tumor Adult","Medulloblastoma, Adult","Medulloblastoma Recurrent","Pineoblastoma","Leptomeningeal Disease",[62,123,125,132,133,67,93,127,128,64,27,134,129,130],"Brain Tumor, Adult","Brain Tumor Recurrent","Embryonal Tumor with Multilayered Rosettes","NOT_YET_RECRUITING","2026-01-28",{"date":138,"type":40},"2026-02-05",{"date":140,"type":20},"2026-07",{"date":142,"type":20},"2032-08-31",{"name":144,"class":47},"Robbie Majzner",2]