CAR T-cell Therapy for Recurrent or Refractory Brain Tumors in Children
This study is looking at the safety of a new treatment for children and young adults (ages 4-25) with brain tumors that have come back or haven't responded to other treatments. The treatment involves two chemotherapy drugs, cyclophosphamide and fludarabine, followed by a special cell therapy called IL13Ralpha2-specific CAR T-lymphocytes. These CAR T-lymphocytes are designed to help your body's immune system fight the tumor. The study will track any side effects for up to one year after the CAR T-cell treatment. To join, you'll need to have a specific marker on your tumor (IL13Ralpha2 positive) and a good performance status. This study aims to see if this treatment is safe and how well it works.
- Study design
- This is an interventional study, meaning participants will receive specific treatments. It plans to enroll 18 participants, but the phase of the study is not specified.
- What's involved
- You would receive chemotherapy drugs (cyclophosphamide and fludarabine) intravenously, followed by IL13Ralpha2-specific CAR T-lymphocytes given into the brain's fluid spaces (intraventricularly).
- Compensation
- Not stated in the trial record.
- Follow-up
- Researchers will monitor for side effects for up to one year after your last CAR T-cell infusion.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT04510051
CAR T Cells After Lymphodepletion for the Treatment of IL13Rα2 Positive Recurrent or Refractory Brain Tumors in Children
Recruiting
PHASE1Ages 4–25InterventionalTreatmentCity of Hope Medical CenterInvestigator-initiated
~18 participants
Updated 2026-03-05 on ClinicalTrials.gov
What's tested:CyclophosphamideFludarabineIL13Ralpha2-specific Hinge-optimized 41BB-co-stimulatory CAR Truncated CD19-expressing Autologous T-Lymphocytes
At a glance
Recruiting sites
3 of 3 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Incidence of adverse events
Measured over Up to 1 year after the last chimeric antigen response (CAR) T cell infusion
Conditions
Where it's being run
3 sites across 2 statesCalifornia2
Michigan1
Study leadership
- Leo D Wang · PRINCIPAL_INVESTIGATOR · City of Hope Medical Center
Who to contact
Opens a ready-to-send draft in your own email app — review before sending.
Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
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
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)
What this trial measures
- Incidence of adverse eventsUp to 1 year after the last chimeric antigen response (CAR) T cell infusion
Will assess the incidence of grade 3 toxicities, dose limiting toxicities, and all other toxicities. Toxicity and adverse events will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0 and the revised cytokine release syndrome (CRS) grading system. Symptoms and toxicities will be evaluated by physical exam and blood chemistry/hematology results and adverse event reporting. Rate and associated 90% Clopper and Pearson binomial confidence limits (90% CI) will be estimated for participants experiencing dose limiting toxicities. Tables will be created to summarize all toxicities and side effects by time post treatment, organ, severity and disease subgroup.