[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"medulloblastoma-childhood\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:medulloblastoma-childhood":27},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,11,0,[8,49,85,112,144,176,208,242,270,291,323],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":13,"acronym":14,"eligibilityCriteria":15,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":18,"enrollmentInfo":19,"targetDuration":4,"studyType":22,"phases":23,"briefSummary":25,"conditions":26,"keywords":33,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":37,"lastUpdatePostDateStruct":38,"startDateStruct":41,"completionDateStruct":43,"leadSponsor":45,"locationsCount":48},"100530974","phase-1-immunotherapy-for-malignant-pediatric-brain-tumors-employing-adoptive-cellular-therapy-impact-100530974",false,"NCT06193759","Immunotherapy for Malignant Pediatric Brain Tumors Employing Adoptive Cellular Therapy (IMPACT)","IMPACT","RECIPIENT SCREENING INCLUSION CRITERIA\n\n1. Diagnosis (select one group):\n\n   * Group A: New diagnosis of CNS embryonal tumors: medulloblastoma, embryonal tumor with multilayered rosettes, pineoblastoma, atypical teratoid\u002Frhabdoid tumor, and embryonal tumor, not otherwise specified (NOS).\n   * Group B: Radiographic evidence consistent with recurrent ependymoma, with planned or recent re-resection.\n2. Age:\n\n   * Group A: \\\u003C5 years of age at enrollment\n   * Group B: \\>1 year and \\\u003C30 years of age at enrollment\n3. Tissue:\n\n   o Group A: Availability of sufficient fresh or frozen tumor tissue (approximately 50 mg).\n\n   o Group B: Expectation of sufficient fresh or frozen tumor tissue, in the opinion of study PI or sub-I (based upon radiographic evidence of disease).\n4. Non-pregnant:\n\n   * Group A: N\u002FA\n   * Group B: For female of childbearing potential, must have negative pregnancy test.\n\n   Common to both groups:\n5. Karnofsky or Lansky score of ≥60%.\n6. Adequate organ function, defined below:\n\n   i. ANC ≥750\u002FµL. ii. Absolute lymphocyte count (ALC) \\>500\u002FμL. iii. Platelets ≥75K. iv. Bilirubin ≤3xULN. v. Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) \\\u003C5x upper limit of normal (ULN).\n\n   vi. Serum creatinine ≤1.0 mg\u002FdL or 1.5x ULN for age (whichever is higher). vii. Pulse oximetry \\>90% on room air.\n7. The patient (if ≥18 years old), or the patient's parent(s)\u002Flegal guardian(s) (if the patient is a minor), is capable of providing informed consent.\n8. Patient deemed to be of sufficient size to undergo MNC apheresis for TSA-T generation (Groups A and B) and PBSC rescue (Group A only).\n9. Patient is a surgical candidate for placement of a Rickham reservoir in the opinion of study PI or medically licensed sub-I.\n\nRECIPIENT INCLUSION CRITERIA FOR PROCUREMENT\n\n1\\. Karnofsky or Lansky score of ≥60%. 2. Adequate organ function, defined below: i. ANC ≥750\u002FµL. ii. Absolute lymphocyte count (ALC) \\>500\u002FμL. iii. Platelets ≥75K. iv. Bilirubin ≤3xULN. v. Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) \\\u003C5x upper limit of normal (ULN).\n\nvi. Serum creatinine ≤1.0mg\u002FdL or 1.5x ULN for age (whichever is higher). vii. Pulse oximetry \\>90% on room air. 3. Non-pregnant:\n\n* Group A: N\u002FA\n* Group B: For female of childbearing potential (if applicable), must have negative pregnancy test.\n\nRECIPIENT INCLUSION CRITERIA FOR INITIAL TSA-T ADMINISTRATION AND FOR ADDITIONAL INFUSIONS\n\n1. Applicable to TSA-T infusion #1 only: Group B participants must have histopathologic confirmation of recurrent ependymoma.\n2. Karnofsky or Lansky score of ≥60%.\n3. Adequate organ function, defined as below:\n\n   i. Bilirubin ≤3x ULN. ii. AST and ALT ≤5x ULN. iii. Serum creatinine ≤1.0mg\u002FdL or 1.5x ULN for age (whichever is higher). iv. Pulse oximetry \\>90% on room air.\n4. Applicable to TSA-T Infusion #1 only: Adequate count recovery, as described below, from prior therapies:\n\n   i. Absolute Neutrophil Count (ANC) \\>1000\u002FμL ii. Absolute Lymphocyte Count (ALC) \\>500\u002FμL\n5. Patients must have received their last dose of:\n\n   a. Myelosuppressive chemotherapy (if applicable) ≥14 days prior to TSA-T infusion b. Focal radiation (if applicable) ≥14 days prior to TSA-T infusion c. Craniospinal irradiation (if applicable) ≥28 days prior to TSA-T infusion\n6. Patients must have recovered from all acute effects of prior surgical intervention\u002Fs.\n7. Group B female of childbearing potential or male capable of fathering a child (if applicable): Agree to use contraceptive measures during TSA-T treatment participation through 6 months following last administration of TSA-Ts\n8. Group B female of childbearing potential (if applicable), must have negative pregnancy test.\n9. Neurologic status: Patient must have a stable neurologic exam for 2 weeks, on a stable or decreasing dose of steroids, prior to administration of the first dose of TSA-T cells, and stability for 1 week prior to all subsequent infusions. The exams demonstrating stability must be performed by the study team, although these may occur via telemedicine if necessary. Patient must agree to a brief (\\\u003C72 hours) course of steroids if the PI or medically-licensed sub-I deems it clinically necessary in the context of clinical deterioration.\n10. Presence of a Rickham reservoir and catheter for intracerebroventricular administration of TSA-T therapy, placed \\>7 days prior to TSA-T infusion.\n11. For patients with programmable VP shunts: Able to tolerate the shunt being closed for at least 4 hours, in the opinion of study PI or medically licensed sub-I.\n\nEXCLUSION CRITERIA RECIPIENT SCREENING EXCLUSION CRITERIA\n\n1\\. Patients with uncontrolled infections. 2. Patients with known HIV infection. 3. Group A patients with medulloblastoma of the SHH subtype.\n\nRECIPIENT EXCLUSION CRITERIA FOR PROCUREMENT\n\n1\\. Patients with a fever above 38.0°C. 2. Patients with known HIV infection. 3. Prior immunotherapy with an investigational agent within the 28 days prior to planned date of procurement collection for TSA-T manufacturing.\n\n4\\. Patients who will be unable to tolerate the apheresis procedure, including inability to tolerate placement of apheresis line (if applicable), in the opinion of PI or medically licensed sub-I.\n\n5\\. Patients who have overly bulky tumors on imaging are ineligible. These include the following: i. Tumor with any evidence of herniation or significant midline shift. ii. Tumor with a significant brainstem component. iii. Patients who are deemed to have overly bulky tumor by the PI of the study.\n\nIf, due to complications during apheresis or subsequent manufacturing, procurement is repeated at a later date using peripheral whole blood collection, exclusion criterion #4 does not apply.\n\nRECIPIENT EXCLUSION CRITERIA FOR INITIAL AND SUBSEQUENT TSA-T INFUSIONS\n\n1. Patients with progressive disease based on most recent evaluation (for subsequent infusions).\n\n   a. Patients with progressive disease based on most recent evaluation may receive initial TSA-T infusion but would be ineligible if the tumor is found to be progressive before subsequent infusions\n2. Patients with uncontrolled infections.\n3. Patients who have overly bulky tumors on imaging are ineligible. These include the following:\n\n   i. Tumor with any evidence of herniation or significant midline shift. ii. Tumor with a significant brainstem component. iii. Patients who are deemed to have overly bulky tumor by the PI of the study.\n4. Patients who received ATG, Campath or other immunosuppressive T cell monoclonal antibodies within 28 days of TSA-T infusion.\n5. Patients receiving steroids (e.g., dexamethasone) at a dose of \\>0.05 mg\u002Fkg\u002Fday.\n6. Patients who have non-programmable VP shunts.","ALL","1 Year","30 Years",{"count":20,"type":21},12,"ESTIMATED","INTERVENTIONAL",[24],"PHASE1","This is an open-label phase 1 safety and feasibility study that will employ multi-tumor antigen specific cytotoxic T lymphocytes (TSA-T) directed against proteogenomically determined personalized tumor-specific antigens (TSA) derived from a patient's primary brain tumor tissues. Young patients with embryonal central nervous system (CNS) malignancies typically are unable to receive irradiation due to significant adverse effects and are treated with intensive chemotherapy followed by autologous stem cell rescue; however, despite intensive therapy, many of these patients relapse. In this study, individualized TSA-T cells will be generated against proteogenomically determined tumor-specific antigens after standard of care treatment in children less than 5 years of age with embryonal brain tumors. Correlative biological studies will measure clinical anti-tumor, immunological and biomarker effects.",[27,28,29,30,31,32],"Medulloblastoma, Childhood","Atypical Teratoid\u002FRhabdoid Tumor of CNS","Embryonal Tumor With Multilayered Rosettes","Pineoblastoma","Embryonal Brain Tumor Not Otherwise Specified","Ependymoma",[34,35],"Cellular Therapy","Pediatric Brain Tumors","RECRUITING","2026-06-15",{"date":39,"type":40},"2026-06-17","ACTUAL",{"date":42,"type":40},"2024-09-20",{"date":44,"type":21},"2032-12-29",{"name":46,"class":47},"Children's National Research Institute","OTHER",1,{"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":22,"phases":59,"briefSummary":61,"conditions":62,"keywords":74,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":76,"lastUpdatePostDateStruct":77,"startDateStruct":79,"completionDateStruct":81,"leadSponsor":83,"locationsCount":20},"100588487","early-phase-1-pilot-study-of-it-topotecan-and-maintenance-chemotherapy-for-hr-ebts-in-children--6-years-post-consolidation-100588487","NCT06942039","Pilot Study of IT Topotecan and Maintenance Chemotherapy for HR-EBTs in Children \u003C 6 Years, Post Consolidation","A Pilot Study of Intrathecal Topotecan and Maintenance Chemotherapy in the Post-consolidation Setting for the Treatment of High-risk Embryonal Central Nervous System Tumours in Children Less Than 6 Years of Age","Inclusion Criteria:\n\n1. Tumor Tissue Sample\n2. Age: Patient must be aged ≥ 0 years to ≤ 6 years at the time of definitive confirmation of histologic diagnosis of eligible CNS tumor.\n3. Diagnoses. Participants must have Central nervous system (CNS) HR-EBT including atypical teratoid rhabdoid tumour (ATRT), group 3 and group 4 medulloblastoma (MB), pineoblastoma, CNS neuroblastoma, embryonal tumor with multi-layered rosettes (ETMR including embryonal tumor with abundant neuropil and true rosettes (ETANTR), ependymoblastoma and ETMR not otherwise specified), medulloepithelioma, CNS embryonal tumor with rhabdoid features (INI-1 intact) and CNS embryonal tumor, not otherwise specified. Metastatic disease included. Any extent of resection included.\n4. Cranial and Spine MRI. A baseline MRI brain and spine with and without contrast is required for all patients. cranial MRI (with and without gadolinium) must be done pre-operatively. Post-operatively, cranial MRI (with and without gadolinium) must be done.\n5. Lumbar Puncture (LP) CSF for cytopathology (strongly recommended but not mandatory; if medically feasible). A baseline LP CSF cytology either pre-operatively or post-operatively at least 10 days after definitive surgery for all patients if medically feasible (This is not mandatory and will not make the patient ineligible).\n6. Life expectancy: Patients must have a life expectancy of greater than 8 weeks from diagnosis.\n7. Performance level: Patients must have a performance status corresponding of a Lansky score ≥ 50.\n8. Organ Function Requirements: Participants must have normal organ and marrow function as defined below:\n\nAdequate renal function defined as:\n\n\\- Creatinine clearance (12-24-hour urine collection) or radioisotope glomerular filtration rate (GFR) ≥ 60 ml\u002Fmin\u002F1.73m2\n\nAdequate cardiac function defined as:\n\n* Shortening fraction of ≥ 27% by echocardiogram, or\n* Ejection fraction of ≥ 47% by radionuclide angiogram.\n\nAdequate pulmonary function defined as:\n\n\\- No evidence of dyspnea at rest and a pulse oximetry \\> 94% on room air.\n\nAdequate Bone Marrow Function defined as:\n\n* Peripheral absolute neutrophil count (ANC) \\> 1000\u002FμL\n* Platelet Count \\> 100,000\u002FμL (without transfusion for 3 days)\n* Hemoglobin greater than 8 gm\u002FdL (may have received red blood cell (RBC) transfusions)\n\nAdequate liver function defined as:\n\n* Total bilirubin ≤ 1.5X upper limit of normal (ULN) within normal institutional limits for age (patients with documented Gilbert's Disease may be enrolled with Study Chair approval and total bilirubin ≤ 2.0 × ULN)\n* Alanine Aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 100 U\u002FL\n\nExclusion criteria:\n\n1. Patients who are receiving any other conventional anti-cancer agents or investigational agents.\n2. Patients who received previous therapy including radiotherapy or chemotherapy other than corticosteroids.\n3. Presence of another malignancy, except if the other primary malignancy is neither currently clinically significant nor requiring active intervention.\n4. Concomitant medications restrictions: Concurrent use of enzyme inducing anticonvulsants (e.g. phenytoin, phenobarbital, and carbamazepine), selected strong inhibitors of cytochrome P450 3A4 include azole antifungals, such as fluconazole, voriconazole, itraconazole, ketoconazole, and strong inducers include drugs such as rifampin, phenytoin, phenobarbitol, carbamazepine, and St. John's wort or CYP450 3A4 stimulators or inhibitors.\n5. Other uncontrollable medical disease: Patient has a severe and uncontrollable medical disease (i.e., uncontrolled diabetes, hyperglycemia, chronic renal disease or active uncontrolled infection), has chronic liver disease (i.e., chronic active hepatitis and cirrhosis), hypercholesterolemia (serum cholesterol \\>300 mg\u002FdL), intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, active hyperparathyroidism, or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements.\n6. Patients who have a known diagnosis of human immunodeficiency virus (HIV) infection, hepatitis B or C.\n7. Ineligible diagnoses for study entry by neuropathology: This includes sonic hedgehog (SHH) and wingless (WNT) MBs, all ependymomas, all choroid plexus carcinomas, all high grade glial and glio-neuronal tumors, all diffuse midline gliomas, all primary CNS germ cell tumors, all primary CNS sarcomas, all primary or metastatic CNS lymphomas and solid leukemic lesions (chloromas, granulocytic sarcomas).\n8. The participant or parent(s)\u002Fguardian(s) cannot comply with the study visit schedule and other protocol requirements, in the investigator's opinion.\n\nAll patients must meet inclusion\u002Fexclusion criteria prior to starting any protocol therapy.","6 Years",{"count":58,"type":21},15,[60],"EARLY_PHASE1","Pilot study to determine feasibility of adding intrathecal chemotherapy and maintenance therapy after high dose chemotherapy for treatment of newly diagnosed HR-EBTs in patients less than 6 years of age.",[63,64,65,27,66,67,30,68,29,69,70,71,72,73],"CNS Embryonal Tumor","CNS, Medulloblastoma","Atypical Teratoid Rhabdoid Tumor","Medulloblastoma, Group 3","Medulloblastoma, Group 4","Neuroblastoma","Embryonal Tumor With Abundant Neuropil and True Rosettes","Ependymoblastoma","Medulloepithelioma","CNS Embryonal Tumor With Rhabdoid Features","CNS Embryonal Tumor, Nos",[75],"HR-EBT","2026-06-05",{"date":78,"type":40},"2026-06-08",{"date":80,"type":40},"2025-09-23",{"date":82,"type":21},"2032-12-31",{"name":84,"class":47},"C17 Council",{"id":86,"slug":87,"hasResults":11,"nctId":88,"briefTitle":89,"officialTitle":90,"acronym":91,"eligibilityCriteria":92,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":93,"enrollmentInfo":94,"targetDuration":4,"studyType":22,"phases":96,"briefSummary":98,"conditions":99,"keywords":4,"overallStatus":102,"whyStopped":4,"lastUpdateSubmitDate":103,"lastUpdatePostDateStruct":104,"startDateStruct":106,"completionDateStruct":108,"leadSponsor":110,"locationsCount":48},"100619556","phase-1-liothyronine-in-combination-with-bit-regimen-for-medulloblastoma-with-or-without-minimal-residual-disease-100619556","NCT07346157","Liothyronine in Combination With BIT Regimen for Medulloblastoma With or Without Minimal Residual Disease","PNOC044: Liothyronine (L-T3) in Combination With Bevacizumab, Irinotecan and Temozolomide (BIT) for Progressive or Relapsed Medulloblastoma (Cohort 1) or as Monotherapy for Medulloblastoma With Minimal Residual Disease (Cohort 2)","PNOC044","Inclusion Criteria:\n\n1. Phase 1 and Phase 2, Cohort 1:\n\n   Participants must have histologically confirmed medulloblastoma that is relapsed\u002Fprogressive following standard upfront therapy. Tissue confirmation of medulloblastoma diagnosis is required at diagnosis and not required at the time of relapse for entry into the study.\n2. Phase 2, Cohort 2: Participants must have cerebrospinal fluid (CSF) with cell-free deoxyribonucleic acid (cf-DNA) + assessed in a Chemiluminescent immunoassay (CLIA)-certified or protocol-approved laboratory. After entry into the study, another CSF sample will be collected and analyzed centrally prior to initiation of protocol therapy to verify cf-DNA positivity.\n3. Evidence of Disease:\n\n   Phase 1 and Phase 2, Cohort 1:\n\n   Participants may have either Measurable or Evaluable Disease Measurable Disease: Participants must have clear residual disease at the time of enrollment, defined as tumor that is measurable in two perpendicular dimensions on MRI Evaluable Disease: Diffuse leptomeningeal disease OR clear MRI evidence of disease that may not be measurable in two perpendicular dimensions.\n\n   Phase 2, Cohort 2:\n\n   For cf-DNA positive cohort: Participants are not required to have measurable or evaluable disease but must have cf-DNA positivity in a CLIA-certified or protocol-approved laboratory, as above.\n4. Prior Therapy: Participants must have received standard upfront therapy for medulloblastoma (either with craniospinal radiation or high dose chemotherapy and autologous stem cell rescue. If other therapy utilized, must be discussed with study chairs prior to participation). Participants for Phase 1 and Phase 2 cohort 1 may have received further chemotherapy and\u002For radiation therapy beyond standard upfront therapy prior to trial enrollment. Participants within the Phase 2 cohort 1 must have experienced at least one, and at most, two relapses prior to study enrollment.\n5. Age 1-25 years old.\n6. Performance Score: Karnofsky ≥ 50 for participants \\> 16 years of age and Lansky ≥ 50 for participants ≤16 years of age (See Appendix A). 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.\n7. For those participants currently treated with levothyroxine (Synthroid) they must have stable dosing for a minimum of 3 months prior to enrollment.\n8. Organ Function Requirements\n\n   1. Peripheral absolute neutrophil count (ANC) ≥ 1000\u002Fcubic millimeters (mm3)\n   2. Platelet count ≥ 75,000\u002Fmicroliter (uL) (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).\n   3. A serum creatinine \\\u003C 1.5 institutional\u002Freference range upper Limit normal (ULN) based on age and gender\n   4. Total bilirubin ≤ 3 x upper limit of normal (ULN); in presence of Gilbert's syndrome, total bilirubin ≤ 6 x ULN or direct bilirubin ≤ 3 x ULN\n\n      * Alanine aminotransferase (ALT) ≤ 5 x upper limit of normal (ULN)\n      * Aspartate aminotransferase (AST) ≤ 5 x ULN. 3.3.7.4 Adequate Neurologic Function Defined as:\n      * Participants with seizure disorder may be enrolled if well controlled. Participants on non-enzyme inducing anticonvulsants may be excluded pending interaction(s) with study drug. 3.3.7.5 Adequate Cardiac Function Defined as:\n      * Normal left ventricular systolic function on baseline transthoracic echocardiogram (TTE)\n      * Normal left ventricular systolic function is defined as left ventricular ejection fraction (LVEF) \\>55% or shortening fraction (SF) \\>28%.\n\n   AND\n   * No clinically significant arrhythmia on baseline ECG (sinus arrhythmia, sinus tachycardia, sinus bradycardia, early repolarization and 1st degree atrioventricular block when partial response (PR) interval \\\u003C 300 millisecond (ms) are not considered clinically significant arrhythmias).\n   * In addition, the following ECG findings are not considered clinically significant in the setting of a normal echocardiogram:\n   * Left axis deviation\n   * Left atrial enlargement\n   * Right atrial enlargement\n   * Possible left ventricular hypertrophy\n   * Possible right ventricular hypertrophy\n   * Non-specific T wave abnormality 3.3.7.6 For the Phase 1 cohort, normal adrenal axis function is required. For those participants in the Phase 2 cohort, must have controlled adrenal insufficiency \\>3 months (no change in steroid replacement or stress dose plan for at least 3 months).\n   * Normal adrenal axis function as defined as:\n   * Morning (AM) cortisol \\>11mcg\u002Fdeciliter (dL)\n   * If AM cortisol is \\\u003C11 microgram (mcg)\u002FdL, cosyntropin stimulation test with rise to \\>18\n9. Endocrine conditions: Participants with diabetes insipidus, diabetes melitus, or being treated with levothyroxine, must have stable dosing and control for minimum of 3 months prior to enrollment\n10. For Cohort 1 only: participants must have recovered from any surgical procedure before enrolling on this study (see below for examples of major, intermediate, and minor surgical procedures):\n\n    1. Participants with a major surgical procedure within 28 days prior to enrollment should be excluded.\n    2. Participants with an intermediate surgical procedure within 14 days prior to enrollment should be excluded.\n    3. For minor surgical procedures (including Broviac line or infusaport placement), participants should not receive the first planned dose of bevacizumab until the wound is healed and at least 7 days have elapsed.\n    4. There should be no anticipation of need for major surgical procedures during the course of the study.\n11. The effects of L-T3 with chemotherapy on the developing human fetus are unknown. For this reason and because chemotherapy agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and 4 months after completion of L-T3 and chemotherapy administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.\n12. Participants must be enroll on PNOC COMP if PNOC COMP is open to accrual at the enrolling institution.\n13. A legal parent\u002Fguardian or participant must be able to understand, and willing to sign, a written informed consent and assent document, as appropriate.\n\nExclusion Criteria:\n\n1. For Cohort 1 only: participants who have previously been treated with BIT in combination. Treatment with individual bevacizumab, irinotecan or TMZ is not an exclusion criteria.\n2. Participants who have had myelosuppressive chemotherapy within 3 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. (Participants receiving chemotherapy directly into the CSF at doses not expected to be myelosuppressive may have received therapy up to 7 days prior to enrollment).\n3. Participants must be at least 7 days since the completion of therapy with a biologic or small molecule agent or non-myelosuppressive chemotherapy agent. For any agent with known adverse events that can occur beyond 7 days after administration, the period prior to enrollment must be beyond the time during which adverse events are known to occur. Such participants should also be discussed with study chairs.\n4. Radiation: For participants on the Phase 1 and Phase 2 Cohort 1, the tumor designated as \"measurable\" for protocol purposes must not have received radiation within 6 weeks prior to study entry and focal radiation to areas of symptomatic metastatic disease must not be given within 14 days of study entry. If a new lesion occurs outside the radiation field, the participant is eligible to enroll at any time point from completion of radiation. For Cohort 2 participants, there is no required washout for radiation therapy.\n5. Participants who are receiving any other investigational agents.\n6. History of allergic reactions attributed to compounds of similar chemical or biologic composition to L-T3 or other agents used in study.\n7. Participants receiving any medications or substances that are strong inhibitors or strong inducers of CYP450 enzymes are ineligible. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently updated list such as http:\u002F\u002Fmedicine.iupui.edu\u002Fclinpharm\u002Fddis\u002Ftable.aspx; medical reference texts such as the Physicians' Desk Reference may also provide this information. As part of the enrollment\u002Finformed consent procedures, the participant and\u002For legal parent or guardian will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the participant is considering.\n8. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection.\n9. Women of childbearing potential must not be pregnant or breast-feeding.\n10. Human immunodeficiency virus- (HIV) positive participants will be ineligible if HIV therapy regimen has not been stable for at least 4 weeks or there is intent to change the regimen within 8 weeks following enrollment, or if they are severely immunocompromised.\n11. Diagnosis of Graves' Disease or other pre-existing hyperthyroid disease.\n12. Participants with severe protein calorie malnutrition that in the opinion of the investigator may not tolerate protocol therapy.\n13. Participants with previous or active clinical cardiovascular disease, including the history of heart failure, myocardial infarction, cardiomyopathy, or ventricular systolic dysfunction on TTE (LVEF \\\u003C55% or SF \\\u003C28%), clinically significant arrhythmia (including atrial fibrillation, atrial flutter, frequent ventricular ectopy), clinically significant peripheral vascular disease.\n14. Participants with uncontrolled systemic hypertension (systolic blood pressure \\> 95th percentile for age and height if participant is ≤ 17 years old)\n15. Participants with uncontrolled diabetes mellitus (HbA1c \\>8%) or uncontrolled diabetes insipidus","25 Years",{"count":95,"type":21},69,[24,97],"PHASE2","This is a Phase 1\u002FPhase 2 study assessing liothyronine (L-T3) immunotherapy and in combination with standard chemotherapy (bevacizumab, irinotecan and temozolomide (BIT)) in children and young adults with medulloblastoma that is relapsed or progressive after standard upfront therapy.",[100,27,101],"Medulloblastoma","Medulloblastoma Recurrent","NOT_YET_RECRUITING","2026-05-28",{"date":105,"type":40},"2026-06-01",{"date":107,"type":21},"2026-07-30",{"date":109,"type":21},"2031-03-31",{"name":111,"class":47},"Sabine Mueller, MD, PhD",{"id":113,"slug":114,"hasResults":11,"nctId":115,"briefTitle":116,"officialTitle":117,"acronym":118,"eligibilityCriteria":119,"healthyVolunteers":11,"sex":16,"minAge":120,"maxAge":121,"enrollmentInfo":122,"targetDuration":4,"studyType":22,"phases":124,"briefSummary":126,"conditions":127,"keywords":129,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":134,"lastUpdatePostDateStruct":135,"startDateStruct":137,"completionDateStruct":139,"leadSponsor":141,"locationsCount":143},"100456989","phase-3-effect-of-metformin-on-behaviour-and-the-brain-in-children-treated-for-a-brain-tumour-100456989","NCT05230758","Effect of Metformin on Behaviour and the Brain in Children Treated for a Brain Tumour","Phase III Randomized Double-blind Placebo-controlled Trial of Metformin for Cognitive Recovery and White Matter Growth in Paediatric Patients With a Brain Tumour","Met Med Can","Inclusion Criteria:\n\nIn order to be eligible to participate in this study, an individual must meet all of the following criteria:\n\n1. No less than 3 weeks after completion of:\n\n   * Primary therapy for:\n\n     1. medulloblastoma\n\n        OR\n     2. ependymoma\n\n        OR\n     3. craniopharyngioma\n\n        OR\n     4. germ cell tumours\n\n        OR\n   * Primary therapy for any other brain tumour treated with cranial radiation - at the discretion of the Study PI\n\n   OR\n   * Cranial radiation for relapsed ependymoma\n2. Age 7 years to 21 years and 11 months at the time of enrollment\n3. Either declare English (or French in accepting sites) as their native language or have had at least two years of schooling in English (or French in accepting sites) at the time of consent\n4. Able to swallow tablets either whole, crushed or via a feeding tube and be willing to adhere to the study intervention regimen\n5. Meet criteria for normal organ function requirements as described below:\n\n   1. Normal renal function defined as: Estimated glomerular filtration rate (eGFR) \\> 75ml\u002Fmin\u002F1.73m²\n\n      * eGFR is calculated using the Schwartz formula: eGFR (mL\u002Fmin\u002F1.73m²) = (0.41 × height in cm) \u002F creatinine in mg\u002FdL\n   2. Normal liver function defined as:\n\n      * Serum glutamic-oxaloacetic transaminase (SGOT) (AST) ≤2.5 x institutional upper limit of normal (ULN) for age and gender\n      * Serum glutamic pyruvic transaminase (SGPT) (ALT) ≤2.5 x institutional ULN for age and gender\n      * Total bilirubin \\\u003C1.5x institutional ULN for age and gender (patients with documented Gilbert's Disease may be enrolled with Sponsor approval and total bilirubin ≤2.0 x institutional ULN)\n6. Informed consent (and assent, where applicable) will be obtained from the participants and\u002For their legal guardian(s) by study team members delegated to consent for this study\n\nExclusion Criteria:\n\nParticipants who meet any of the following criteria will not be eligible to take part in the trial:\n\n1. Standard score of less than 60 for full scale IQ on the Wechsler Abbreviated Scale of Intelligence, Second Edition (WASI-II) (or other Wechsler Scale of Intelligence for English speaking participants) or pro-rated IQ score on the Wechsler Intelligence Scale for Children, Fifth Edition (WISC-V) or Wechsler Adult Intelligence Scale (WAIS-IV) for French speaking participants at Screening visit\n2. Have a known hypersensitivity to metformin hydrochloride\n3. Have unstable and\u002For insulin-dependent (Type 1) diabetes\n4. Have a history of hypoglycemia after 2 years of age\n5. Have been diagnosed with acute or chronic metabolic acidosis and\u002For lactic acidosis or if bicarbonate (Total CO2) is less than 22 mmol\u002FL at the Screening visit\n6. Have a history of renal disease or renal dysfunction pre-existing to the diagnosis of Medulloblastoma\n7. Have a history of congestive heart failure requiring pharmacologic treatment (including the use of diuretics) within two years prior to study entry\n8. Currently taking part in a cognitive rehabilitation intervention study\n9. Treatment or planned treatment involving diuretics\n10. Current or planned treatment with cationic drugs excreted by the kidneys (e.g. amiloride, cimetidine, digoxin, morphine, nifedipine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, and vancomycin)\n11. Current or planned treatment with concomitant medications with potential unacceptable interaction with metformin including, lamotrigine, beta blockers, angiotensin-converting enzyme (ACE) inhibitors, glycopyrrolate, and carbonic anhydrase inhibitors, or at the discretion of the Site PI or delegate for medications with potential interactions such as sertraline, lansoprazole and omeprazole.\n12. Pernicious anemia (according to results of the Screening visit blood draw)\n13. Current use of metformin hydrochloride\n14. Any condition or diagnosis, that could in the opinion of the Site PI or delegate interfere with the participant's ability to comply with study instructions, might confound the interpretation of the study results, or put the participant at risk\n15. Are receiving palliative care","7 Years","21 Years",{"count":123,"type":21},140,[125],"PHASE3","The efficacy of treatment with metformin for promoting cognitive recovery and brain growth in children\u002Fadolescents treated for a brain tumour will be investigated in a multi-site Phase III randomized double-blind placebo-controlled parallel arm superiority trial. Specifically, in children\u002Fadolescents aged 7 years to 21 years and 11 months who have completed treatment for a brain tumour, is oral administration of metformin for 16 weeks associated with greater improvement of cognitive function and brain growth compared to placebo administered for 16 weeks?",[27,128],"Cognitive Impairment",[130,131,132,133],"Metformin","Paediatric brain tumour","Memory","Cognitive late effects","2026-04-27",{"date":136,"type":40},"2026-05-01",{"date":138,"type":40},"2022-07-01",{"date":140,"type":21},"2027-11-30",{"name":142,"class":47},"Donald Mabbott",20,{"id":145,"slug":146,"hasResults":11,"nctId":147,"briefTitle":148,"officialTitle":149,"acronym":150,"eligibilityCriteria":151,"healthyVolunteers":11,"sex":16,"minAge":152,"maxAge":153,"enrollmentInfo":154,"targetDuration":4,"studyType":22,"phases":156,"briefSummary":158,"conditions":159,"keywords":162,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":166,"lastUpdatePostDateStruct":167,"startDateStruct":169,"completionDateStruct":171,"leadSponsor":173,"locationsCount":175},"100443691","individualized-treatment-plan-in-children-and-young-adults-with-relapsed-medulloblastoma-and-ependymoma-100443691","NCT05057702","Individualized Treatment Plan in Children and Young Adults With Relapsed Medulloblastoma and Ependymoma","A Pilot Feasibility and Efficacy (Phase 2) Trial of Real Time Drug Screening and Genomic Testing to Determine an Individualized Treatment Plan in Children and Young Adults With Relapsed Medulloblastoma and Ependymoma","PNOC027","Inclusion Criteria:\n\n1. Participants must have recurrent medulloblastoma or recurrent ependymoma previously histologically confirmed. Participants must be experiencing their first or second relapse to be eligible.\n2. Participants must have surgically accessible disease.\n3. Prior Therapy:\n\n   1. The participant must have received at least one prior therapy at the time of initial diagnosis.\n   2. Relapsed medulloblastoma or relapsed ependymoma are eligible.\n   3. Participants must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study and would be eligible for surgical resection per institutional guidelines\n\n      * Participants must have received last chemotherapy or biologic agent at least 7 days prior to registration.\n      * Monoclonal antibody treatment: \\> 21 days prior to registration.\n      * Bevacizumab participants must have received last dose \\> 21 days prior to study registration\n4. Participant must be a candidate for surgical resection or biopsy with anticipated ability to obtain the minimum tissue requirements for study.\n5. Radiation - Participants must have:\n\n   1. Had their last fraction of local irradiation to primary tumor \\>= 12 weeks prior to registration.\n   2. Had their last fraction of craniospinal irradiation or total body irradiation \\>= 12 weeks prior to registration\n   3. At least 14 days after local palliative radiation (small-port)\n6. Age \\>=12 months to \\\u003C= 39 years of age.\n7. 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.\n8. Corticosteroids: Participants who are receiving dexamethasone or equivalent must be on a stable or decreasing dose for at least 1 week prior to registration.\n9. Organ Function Requirements (within 7 days prior to study registration)\n\n   1. Adequate Bone Marrow Function Defined as:\n\n      * Peripheral absolute neutrophil count (ANC) \\>= 750\u002Fmm\\^3\n      * Platelet count \\>= 75,000\u002Fmm\\^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).\n      * Hemoglobin \\>= 8 g\u002Fdl.\n   2. Adequate Renal Function Defined as:\n\n      * Creatinine clearance or radioisotope GFR \\>= 70 milliliter\u002Fminute (mL\u002Fmin) \u002F1.73 m\\^2 or\n      * A serum creatinine based on age\u002Fsex as follows:\n\n      Age \u002F Maximum Serum Creatinine (mg\u002FdL) Male \u002F Maximum Serum Creatinine (mg\u002FdL) Female.\n      * 1 to \\\u003C 2 years \u002F 0.6 \u002F 0.6.\n      * 2 to \\\u003C 6 years \u002F 0.8 \u002F 0.8.\n      * 6 to \\\u003C 10 years \u002F 1 \u002F 1.\n      * 10 to \\\u003C 13 years \u002F 1.2 \u002F 1.2.\n      * 13 to \\\u003C 16 years \u002F 1.5 \u002F 1.4.\n      * \\>= 16 years \u002F 1.7 \u002F 1.4.\n      * \\- The threshold creatinine values in this table were derived from the Schwartz formula for estimating Glomerular filtration rate (GFR) utilizing child length and stature data published by the Center for Disease Control (CDC) (Schwartz GJ and Gauthier B 1985).\n   3. Adequate Liver Function Defined as:\n\n      * Total Bilirubin \\\u003C= 1.5 x upper limit of normal (ULN) for age; in presence of Gilbert's syndrome, total bilirubin \\\u003C 3 x ULN or direct bilirubin \\\u003C 1.5 x ULN.\n      * Alanine aminotransferase (ALT) \\\u003C= 3x ULN.\n      * Aspartate aminotransferase (AST) \\\u003C= 3x ULN.\n10. The effects of the agents used in this study on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and 4 months after completion of therapy administration. Should a woman become pregnant or suspect pregnancy while participating in this study, the treating physician should be informed immediately.\n11. Adequate neurologic function defined as participants with seizure disorder may be enrolled if seizures are well controlled. Participants on non-enzyme inducing anticonvulsants may be excluded pending interaction(s) with study drug.\n12. Participants must enroll on the Protocol for Children and Young Adults Diagnosed with a Central Nervous System (CNS) Tumor to Assess Cognitive, Quality of Life (QOL), and Comprehensive Effects of Therapies (PNOC COMP) study if PNOC COMP is open to accrual at the enrolling institution\n13. A legal parent\u002Fguardian or participant must be able to understand, and willing to sign, a written informed consent and assent document, as appropriate.\n\nExclusion Criteria:\n\n1. Participants who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.\n2. Participants who are receiving any other investigational agents.\n3. Participants must be at least 7 days since the completion of therapy with a biologic or small molecule agent. For any agent with known adverse events that can occur beyond 7 days after administration, the period prior to enrollment must be beyond the time during which adverse events are known to occur. Such participants should also be discussed with study chairs.\n4. Participants who are currently taking any anti-cancer direct therapy. Steroids are not considered anti-cancer therapy.\n5. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection.\n6. Women of childbearing potential must not be pregnant or breast-feeding. A negative serum or urine pregnancy test is required prior to start of therapy.\n7. Participants must not receive any tumor-directed therapy after enrollment, except for surgical resection\u002F biopsy.\n\nImportant note: The eligibility criteria listed above are interpreted literally and cannot be waived.","12 Months","39 Years",{"count":155,"type":21},74,[157],"NA","The current study will use a new treatment approach based on the molecular characteristics of each participant's tumor. The study will test the feasibility in the pilot phase of performing real-time drug screening on tissue taken during surgery in patients with relapsed medulloblastoma or ependymoma and of having a specialized tumor board assign a treatment plan based on the results of this screening and genomic sequencing. The aim of this trial is to allow every child and young adult with relapsed medulloblastoma and ependymoma to receive the most effective and least toxic therapies currently available and will pave the way for improved understanding and treatment of these tumors in the future. Moreover, if successful, it could serve as a paradigm for personalized medicine programs for other types of cancer.",[100,27,101,32,160,161],"Ependymoma Malignant","Ependymoma of Brain",[163,164,165],"Individualized Treatment Plan","Genetic Screening","Screening","2026-04-13",{"date":168,"type":40},"2026-04-15",{"date":170,"type":40},"2022-02-22",{"date":172,"type":21},"2028-01-31",{"name":174,"class":47},"University of California, San Francisco",8,{"id":177,"slug":178,"hasResults":11,"nctId":179,"briefTitle":180,"officialTitle":181,"acronym":4,"eligibilityCriteria":182,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":183,"enrollmentInfo":184,"targetDuration":4,"studyType":22,"phases":186,"briefSummary":187,"conditions":188,"keywords":198,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":200,"lastUpdatePostDateStruct":201,"startDateStruct":202,"completionDateStruct":204,"leadSponsor":206,"locationsCount":48},"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","26 Years",{"count":185,"type":21},90,[24],"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.",[189,190,191,32,27,192,193,194,195,196,197],"Central Nervous System Tumor","Diffuse Intrinsic Pontine Glioma","Diffuse Midline Glioma","Germ Cell Tumor","Atypical Teratoid\u002FRhabdoid Tumor","Primitive Neuroectodermal Tumor","Choroid Plexus Carcinoma","Pineoblastoma, Childhood","Glioma",[199],"CNS, CAR T cell, B7-H3, pediatric, young adult, brain tumor, DIPG, DMG","2026-04-07",{"date":166,"type":40},{"date":203,"type":40},"2019-12-11",{"date":205,"type":21},"2042-05",{"name":207,"class":47},"Seattle Children's Hospital",{"id":209,"slug":210,"hasResults":11,"nctId":211,"briefTitle":212,"officialTitle":213,"acronym":4,"eligibilityCriteria":214,"healthyVolunteers":11,"sex":16,"minAge":215,"maxAge":121,"enrollmentInfo":216,"targetDuration":4,"studyType":22,"phases":218,"briefSummary":219,"conditions":220,"keywords":228,"overallStatus":102,"whyStopped":4,"lastUpdateSubmitDate":232,"lastUpdatePostDateStruct":233,"startDateStruct":235,"completionDateStruct":237,"leadSponsor":239,"locationsCount":241},"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":217,"type":21},70,[24],"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)",[221,222,223,224,225,100,27,226,101,32,193,29,30,227],"Central Nervous System Neoplasms","Brain Tumor","Brain Tumor, Recurrent","Brain Tumor, Pediatric","Brain Tumor Adult","Medulloblastoma, Adult","Leptomeningeal Disease",[221,222,224,229,230,100,27,226,101,32,193,231,30,227],"Brain Tumor, Adult","Brain Tumor Recurrent","Embryonal Tumor with Multilayered Rosettes","2026-01-28",{"date":234,"type":40},"2026-02-05",{"date":236,"type":21},"2026-07",{"date":238,"type":21},"2032-08-31",{"name":240,"class":47},"Robbie Majzner",2,{"id":243,"slug":244,"hasResults":11,"nctId":245,"briefTitle":246,"officialTitle":247,"acronym":248,"eligibilityCriteria":249,"healthyVolunteers":11,"sex":16,"minAge":250,"maxAge":251,"enrollmentInfo":252,"targetDuration":4,"studyType":22,"phases":253,"briefSummary":254,"conditions":255,"keywords":256,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":260,"lastUpdatePostDateStruct":261,"startDateStruct":263,"completionDateStruct":265,"leadSponsor":267,"locationsCount":241},"100585155","medulloblastoma-online-video-based-exercise-pilot-study-100585155","NCT06898684","Medulloblastoma Online Video-based Exercise Pilot Study","Medulloblastoma Online Video-based Exercise Pilot Study (MOVE)","MOVE","Inclusion Criteria: Completed therapy for medulloblastoma, including craniospinal radiation therapy, within 36 months before study entry.\n\n\\-\n\nExclusion Criteria: Inability to walk without support. Progressive disease.\n\n\\-","3 Years","18 Years",{"count":58,"type":21},[157],"In this study, the investigators test whether it is possible to deliver an exercise intervention via video meetings to children and adolescents who have completed therapy for medulloblastoma. The exercise sessions will be individualized and offered three times weekly during 12 weeks.",[27],[257,258,259],"exercise","rehabilitation","medulloblastoma","2025-12-08",{"date":262,"type":40},"2025-12-16",{"date":264,"type":40},"2025-12-09",{"date":266,"type":21},"2027-12",{"name":268,"class":269},"Aron Onerup","OTHER_GOV",{"id":271,"slug":272,"hasResults":11,"nctId":273,"briefTitle":274,"officialTitle":274,"acronym":4,"eligibilityCriteria":275,"healthyVolunteers":11,"sex":16,"minAge":276,"maxAge":251,"enrollmentInfo":277,"targetDuration":4,"studyType":22,"phases":279,"briefSummary":280,"conditions":281,"keywords":4,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":282,"lastUpdatePostDateStruct":283,"startDateStruct":285,"completionDateStruct":287,"leadSponsor":289,"locationsCount":48},"100589866","early-phase-1-novel-molecular-targets-and-innovative-therapeutic-perspective-in-medulloblastoma-100589866","NCT06959979","Novel Molecular Targets and Innovative Therapeutic Perspective in Medulloblastoma","Inclusion Criteria:\n\n* All patients affected by Medulloblastoma operated on at the Pediatric Neurosurgery Unit during their pediatric age will be elected to take part to the study","0 Years",{"count":278,"type":21},60,[60],"Medulloblastoma (MB), a rare yet critical pediatric brain tumor, is divided into 4 molecular subgroups (WNT, SHH, Group 3, Group 4), each with distinct genetic profiles. Despite diagnostic and therapeutic advances, neurotoxicity from standard treatments (resection, radiotherapy, chemotherapy) and the need for long-term care remain challenges. CDK4\u002F6 inhibitors (palbociclib, ribociclib, abemaciclib), approved for breast cancer, show potential in other tumors, but their efficacy in MB is unclear. Treatment resistance is a concern. This project aims to identify genetic markers of sensitivity to CDK4\u002F6 inhibitors in MB, to improve therapies and overcome resistance.",[27],"2025-04-28",{"date":284,"type":40},"2025-05-07",{"date":286,"type":40},"2024-11-25",{"date":288,"type":21},"2026-08-31",{"name":290,"class":47},"Fondazione Policlinico Universitario Agostino Gemelli IRCCS",{"id":292,"slug":293,"hasResults":11,"nctId":294,"briefTitle":295,"officialTitle":296,"acronym":4,"eligibilityCriteria":297,"healthyVolunteers":11,"sex":16,"minAge":298,"maxAge":18,"enrollmentInfo":299,"targetDuration":4,"studyType":22,"phases":301,"briefSummary":302,"conditions":303,"keywords":306,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":314,"lastUpdatePostDateStruct":315,"startDateStruct":317,"completionDateStruct":319,"leadSponsor":321,"locationsCount":48},"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)","6 Months",{"count":300,"type":21},54,[24],"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.",[224,27,304,305,191,190,225],"Embryonal Tumor","High Grade Glioma",[307,308,259,191,190,309,310,311,312,313],"Brain tumors","high grade glioma","CAR T cell","GD2-antigen","Immunotherapy","Pediatric Central Nervous System tumours","Central nervous system tumour young adults","2025-02-03",{"date":316,"type":40},"2025-02-05",{"date":318,"type":40},"2023-11-09",{"date":320,"type":21},"2038-11",{"name":322,"class":47},"Bambino Gesù Hospital and Research Institute",{"id":324,"slug":325,"hasResults":11,"nctId":326,"briefTitle":327,"officialTitle":327,"acronym":4,"eligibilityCriteria":328,"healthyVolunteers":11,"sex":16,"minAge":298,"maxAge":251,"enrollmentInfo":329,"targetDuration":4,"studyType":331,"phases":4,"briefSummary":332,"conditions":333,"keywords":334,"overallStatus":102,"whyStopped":4,"lastUpdateSubmitDate":337,"lastUpdatePostDateStruct":338,"startDateStruct":340,"completionDateStruct":342,"leadSponsor":344,"locationsCount":4},"100470521","establishment-and-clinical-application-of-risk-classification-model-based-on-molecular-typing-of-medulloblastoma-in-children-100470521","NCT05406947","Establishment and Clinical Application of Risk Classification Model Based on Molecular Typing of Medulloblastoma in Children","Inclusion Criteria:\n\n* Age 0.5-18 years (except neonates).\n* Pathologically confirmed medulloblastoma.\n* Not having received any other relevant treatment before surgery.\n* Completion of enhanced MRI of the head and spinal cord.\n* Availability of tumor samples and determination of molecular typing.\n* Postoperative KPS score ≥ 70.\n* Voluntary enrollment in the group and the ability to receive long-term follow-up.\n* The patient or the patient's family voluntarily signed the informed consent form.\n\nExclusion Criteria:\n\n* Patients who have recently received other drugs or radiation therapy.\n* Patients suffering from acute or chronic infectious diseases\n* Patients suffering from neurological or psychiatric diseases or mental disorders that cannot be easily controlled, or poor compliance.\n* Patients who cannot receive enhanced MRI scans.\n* Other conditions that the investigator believes make the patient unfit to participate in this trial.",{"count":330,"type":21},350,"OBSERVATIONAL","The purpose of this study:(1) Development of a new risk classification model for childhood medulloblastoma. (2) Evaluation and improvement of existing individualized treatment protocols.",[27],[100,197,335,336],"Medulloblastoma, Childhood, Recurrent","Neuroepithelioma","2023-02-06",{"date":339,"type":40},"2023-02-08",{"date":341,"type":21},"2023-01-30",{"date":343,"type":21},"2030-12-31",{"name":345,"class":47},"Beijing Tiantan Hospital"]