Using CAR T cells after chemotherapy to treat recurrent brain tumors in children
Official title: Phase I Study of Cellular Immunotherapy Using Memory Enriched T Cells Lentivirally Transduced to Express an IL13Rα2-Targeting, Hinge-Optimized, 41BB-Costimulatory Chimeric Receptor and a Truncated CD19 for Children With Recurrent/Refractory Malignant Brain Tumors
Run by City of Hope Medical Center · NCT04510051 · Data updated 2026-11-12
This study is testing a new treatment for children with recurring brain tumors by combining chemotherapy with special immune cells to see if it helps them live longer and feel better.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Ages | 4 Years to 25 Years |
| Sex | All |
| Enrollment | 18 (estimated) |
| Sponsor | City of Hope Medical Center Academic / other |
| Drugs / interventions | bevacizumab, CAR T, chemotherapy, radiation, immunotherapy, cyclophosphamide, fludarabine, chimeric antigen receptor |
| Locations | 3 sites (Duarte, California and 2 other locations) |
| Status | Recruiting |
| Started | December 11, 2020 |
| Main results expected | February 24, 2027 |
| Study ends | February 24, 2027 |
| Registry record updated | October 15, 2026 |
| Trial ID | NCT04510051 on ClinicalTrials.gov |
Is this trial a fit for you?
✓Likely a good fit
Ideal candidates are children with IL13Rα2 positive recurrent or refractory brain tumors who have previously undergone conventional therapy.
✕Probably not a fit
Patients without IL13Rα2 positive tumors or those who have not progressed after initial treatment may not benefit from this study.
A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.
What this trial studies
This phase I trial evaluates the safety and feasibility of combining lymphodepleting chemotherapy with cellular immunotherapy for children with IL13Rα2 positive recurrent or refractory brain tumors. Participants will receive chemotherapy drugs, cyclophosphamide and fludarabine, followed by the administration of IL13Rα2-specific CAR T cells delivered intraventricularly. The study aims to assess the persistence of CAR T cells, cytokine levels, and overall survival rates, while also evaluating tumor burden through circulating tumor DNA. The trial will provide insights into the effectiveness of this innovative treatment approach for pediatric brain tumors.
Why it matters
Potential benefit: If successful, this treatment could significantly improve outcomes for children with difficult-to-treat brain tumors.
How similar studies have gone: Other studies using CAR T cell therapy for various cancers have shown promising results, indicating potential for success in this novel application.
Who can join: the full rules
Show full inclusion / exclusion criteria
Inclusion Criteria: * Documented informed consent of the participant and/or legally authorized representative. * Assent, when appropriate, will be obtained per institutional guidelines * Agreement to allow the use of archival tissue from diagnostic tumor biopsies * Karnofsky Performance Status (KPS) \>= 60% except for loss of mobility due to disease involvement; e.g., confinement to a wheelchair due to spinal cord compression * Life expectancy \> 4 weeks * Participant has a prior histologically-confirmed malignant brain neoplasm and has progressed after prior conventional therapy * Radiographic evidence of progression/recurrence of the measurable disease more than 12 weeks after the end of the initial conventional therapy (including initial radiation therapy) * City of Hope (COH) clinical pathology confirms IL13Ralpha2+ tumor expression by immunohistochemistry (IHC) at the initial tumor presentation or recurrent disease (H-score \>= 50) * If the participant has a shunt, it must be programmable and the participant must be able to tolerate the shunt being switched off for at least 2 consecutive days * Platelets \>= 50,000/mm\^3 (performed within 6 weeks of signing the main informed consent) * Total bilirubin =\< 2 X upper limit of normal (ULN) (unless has Gilbert's disease) (performed within 6 weeks of signing the main informed consent) * Aspartate transaminase (AST) =\< 2 x ULN (performed within 6 weeks of signing the main informed consent) * Alanine transferase (ALT) =\< 2 x ULN (performed within 6 weeks of signing the main informed consent) * Creatinine clearance of \>= 75mL/min/1.73m\^2 (performed within 6 weeks of signing the main informed consent) * Seronegative for human immunodeficiency virus (HIV) antigen (Ag)/antibody (Ab) combo, hepatitis C virus (HCV)\* and active HBV (surface antigen negative) (performed within 6 weeks of signing the main informed consent) * If positive, hepatitis C ribonucleic acid (RNA) quantitation must be performed * Women of childbearing potential (WOCBP): Negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required (to be performed within 6 weeks of signing the main informed consent) * Agreement by females and males of childbearing potential\* to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 6 months after the last dose of protocol therapy. * Childbearing potential defined as not being surgically sterilized (males and females) or have not been free, once initiated, from menses for \> 1 year (females only) * ELIGIBILITY TO PROCEED WITH PERIPHERAL BLOOD MONONUCLEAR COLLECTION (PBMC) COLLECTION * Research participant must not require more than 0.1mg/kg/day total dose (0.03mg/kg/dose three times per day, max of 6mg/day) of Dexamethasone on the day of peripheral blood mononuclear cell (PBMC) collection * Research participant must have appropriate venous access * At least 2 weeks must have elapsed since the research participant received his/her last dose of prior targeted agents, chemotherapy or radiation * Note: If a research participant weighs less than 50kgs, the study team should provide the Donor Apheresis Center (DAC) with the participant's current weight so that institutional guidelines can be followed * ELIGIBILITY TO PROCEED WITH INDWELLING CENTRAL NERVOUS SYSTEM (CNS) CATHETER PLACEMENT * Serum creatinine \< 1.6 mg/dL * White blood cell (WBC) \>= 2,000/dL * Absolute neutrophil count (ANC) \>= 1,000 * Platelets \> 50,000/dL * International normalized ratio =\< 1.3 * Bilirubin \< 1.5 mg/dL * Alanine transferase (ALT) and aspartate transaminase (AST) \< 2 x upper limits of normal * KPS \>= 60% except for loss of mobility due to disease involvement; e.g., confinement to a wheelchair due to spinal cord compression * Second-line radiation therapy (post-leukapheresis) completed at least 4 weeks prior to surgical resection or biopsy/catheter placement * ELIGIBILITY TO PROCEED WITH LYMPHODEPLETION * Pulmonary: Research participant does not require supplemental oxygen to keep saturation greater than 95% and/or does not have presence of any radiographic abnormalities on chest x-ray that are progressive * Cardiac: Research participant does not require pressor support and/or does not have symptomatic cardiac arrhythmias * Active infection: Research participant does not have a fever exceeding 38.5 degree celsius; there is an absence of positive blood cultures for bacteria, fungus, or virus within 48-hours prior to CAR T cell infusion and/or there aren't any indications of meningitis * Hepatic: Research participant serum total bilirubin or transaminases does not exceed 2 x normal limit * Renal: Research participant serum creatinine \< 1.8 mg/dL * Neurologic: Research participant does not have uncontrolled seizure activity following surgery prior to starting lymphodepletion * ELIGIBILITY TO PROCEED WITH EACH CAR T CELL INFUSION * Research participant has a released cryopreserved T cell product * Research participant does not require supplemental oxygen to keep saturation greater than 95% and/or does not have presence of any radiographic abnormalities on chest x-ray that are progressive * Research participant does not require pressor support and/or does not have symptomatic cardiac arrhythmias * Research participant does not have a fever exceeding 38.5 degree celsius; there is an absence of positive blood cultures for bacteria, fungus, or virus within 48-hours prior to T cell infusion and/or there aren't any indications of meningitis * Research participant serum total bilirubin or transaminases does not exceed 2 x normal limit * Research participant serum creatinine \< 1.8 mg/dL * Research participant does not have uncontrolled seizure activity * Research participant platelet count must be \>= 50,000. However, if platelet level is between 25,000-49,000, then T-cell infusion may proceed after platelet transfusion is given and the post transfusion platelet count is \>= 50,000 * Research participants must not require more than 0.1mg/kg/day total dose (0.03mg/kg/dose three times per day, max of 6mg/day) of dexamethasone during CAR T cell therapy * Wash-out requirements: * At least 6 weeks since the completion of a nitrosourea-containing chemotherapy regimen; * At least 23 days since the completion of temozolomide and/or 4 weeks for any other non-nitrosourea-containing cytotoxic chemotherapy regimen. If a patient's most recent treatment was with a targeted agent only, and s/he has recovered from any toxicity of this targeted agent, then a waiting period of only 2 weeks is needed from the last dose * For bevacizumab the wash out period of at least 4 weeks is required before starting study treatment Exclusion Criteria: * Pulmonary: Research participant requires supplemental oxygen to keep saturation greater than 95% and the situation is not expected to resolve within 2 weeks * Cardiac: Research participant requires pressor support and/or has symptomatic cardiac arrhythmias * Renal: Research participant requires dialysis * Neurologic: Research participant has uncontrolled seizure activity and/or clinically evident progressive encephalopathy * Failure of research participant to understand the basic elements of the protocol and/or the risks/benefits of participating in this phase I study. A legal guardian may substitute for the research participant * Research participant with any non-malignant intercurrent illness which is either poorly controlled with currently available treatment, or which is of such severity that the study team deems it unwise to enter the research participant on protocol shall be ineligible * Research participant with any other active malignancies * Research participant being treated for severe infection or recovering from major surgery is ineligible until recovery is deemed complete by the study team * Research participant with any uncontrolled illness including ongoing or active infection. Research participant with known active hepatitis B or C infection; research participant with any signs or symptoms of active infection, positive blood cultures or radiological evidence of infections * Research participant who has confirmed HIV positivity within 4 weeks of enrollment * Females only: Pregnant or breastfeeding * Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)
Where it's running
-
City of Hope Medical Center
Duarte, California, United States Recruiting -
Children's Hospital Los Angeles
Los Angeles, California, United States Recruiting -
C.S. Mott Children's Hospital, University of Michigan
Ann Arbor, Michigan, United States Recruiting
Study contacts
- Principal investigator: Leo D Wang — City of Hope Medical Center
Similar studies
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How to take part
- Review the eligibility criteria above with your treating physician.
- Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
- Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.