Recruiting

Phase 1

Chemotherapy & Cellular ImmunotherapyCAR T Cells After Lymphodepletion for the Treatment of IL13Rα2 Positive Recurrent or Refractory Brain Tumors in Children

Sponsor:

City of Hope Medical Center

Code:

NCT04510051

Conditions

Malignant Brain Neoplasm

Recurrent Malignant Brain Neoplasm

Refractory Malignant Brain Neoplasm

Eligibility Criteria

Sex: All

Age: 4 - 25

Healthy Volunteers: Not accepted

Interventions

Cyclophosphamide

Fludarabine

IL13Ralpha2-specific Hinge-optimized 41BB-co-stimulatory CAR Truncated CD19-expressing Autologous T-Lymphocytes

Study Details

Brief summary:

This phase I trial investigates the side effects of chemotherapy and cellular immunotherapy in treating children with IL13Ralpha2 positive brain tumors that have come back after a period of improvement (recurrent) or do not respond to treatment (refractory). Cellular immunotherapy (IL13(EQ)BBzeta/CD19t+ T cells) are brain-tumor specific cells that may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as as cyclophosphamide and fludarabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Many patients with brain tumor respond to treatment, but then the tumor starts to grow again. Giving chemotherapy in combination with cellular immunotherapy may kill more tumor cells and improve the outcome of treatment.

Conditions

Malignant Brain Neoplasm

Recurrent Malignant Brain Neoplasm

Refractory Malignant Brain Neoplasm

Study ID

NCT04510051

Start date

Dec 4, 2020

Status verified date

Mar, 2026

Completion date

Feb 24, 2027

Anticipated

Primary completion date

Feb 24, 2027

Anticipated

Eligibility Criteria

Sex: All

Age: 4 - 25

Healthy Volunteers: Not accepted

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)

Study Design

Enrollment

18 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Treatment (chemotherapy, IL13(EQ)BBzeta/CD19t+ T cells)

Patients receive cyclophosphamide intravenously IV on days -5 and -4, and fludarabine IV on days -5 to -2. Patients then receive autologous IL13(EQ)BBzeta/CD19t+ T cells intraventricularly over 5 minutes QW on day 0. Treatment with autologous IL13(EQ)BBzeta/CD19t+ T cells repeats every 7 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients may receive additional cycles of IL13(EQ)BBzeta/CD19t+ T cells as long as they continue to meet eligibility criteria and have doses available for infusion.

Interventions

Cyclophosphamide

Given IV

Fludarabine

Given IV

IL13Ralpha2-specific Hinge-optimized 41BB-co-stimulatory CAR Truncated CD19-expressing Autologous T-Lymphocytes

Given intraventricularly

Primary outcome measure

Incidence of adverse events [ Time Frame: Up to 1 year after the last chimeric antigen response (CAR) T cell infusion ]

Central Contacts and Locations

Locations

City of Hope Medical Center

Recruiting

Duarte, California, United States, 91010

Contacts

Leo D. Wang

833-582-4673 PediatricTrials@coh.org

Principal Investigator:

Leo D. Wang

Children's Hospital Los Angeles

Recruiting

Los Angeles, California, United States, 90027

Contacts

Tom Belle Davidson, MD

323-361-8147 tdavidson@chla.usc.edu

C.S. Mott Children's Hospital, University of Michigan

Recruiting

Ann Arbor, Michigan, United States, 48109

Contacts

Santhosh Upadhyaya, MD

734-936-4000 NeuroOncIntake@med.umich.edu

More Information

Sponsor

City of Hope Medical Center

Last update posted

Mar 5, 2026

Last verified

Mar, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-25. This information was provided to ClinicalTrials.gov by City of Hope Medical Center on 2026-03-05. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.