Actively Recruiting

Phase 1
Age: 4Years - 25Years
All Genders
ID04510051

Phase I Study of Cellular Immunotherapy Using Memory Enriched T Cells Lentivirally Transduced to Express an IL13Ralpha2-Targeting, Hinge-Optimized, 41BB-Costimulatory Chimeric Receptor and a Truncated CD19 for Children With Recurrent/Refractory Malignant Brain Tumors

Led by City of Hope Medical Center · Updated on 2026-03-05

18

Participants Needed

3

Research Sites

N/A

Total Duration

On this page

Sponsors

C

City of Hope Medical Center

Lead Sponsor

N

National Cancer Institute (NCI)

Collaborating Sponsor

AI-Summary

What this Trial Is About

Researchers are evaluating the side effects of combining chemotherapy and cellular immunotherapy in children and young adults with IL13Ralpha2 positive brain tumors that have returned after improvement or do not respond to treatment. This phase I trial focuses on using specialized immune cells called IL13(EQ)BBzeta/CD19t+ T cells, designed to target brain tumors, alongside chemotherapy drugs cyclophosphamide and fludarabine. The goal is to study the safety and feasibility of this combination treatment in this patient group. Participants receive chemotherapy with cyclophosphamide intravenously on days -5 and -4, and fludarabine intravenously on days -5 to -2. Following chemotherapy, patients are given their own modified immune cells (IL13(EQ)BBzeta/CD19t+ T cells) by intraventricular delivery once a week for up to four cycles, each administered over five minutes. Additional cycles may be given if the patient remains eligible and doses are available. The study uses a dose-escalation design to evaluate different levels of this cellular immunotherapy. During the trial, participants are closely monitored for side effects for up to one year after their last immune cell infusion. Follow-up visits occur at 30 days, then at 3, 6, 9, and 12 months, and yearly for up to 15 years. Researchers assess immune cell persistence in the blood and cerebrospinal fluid, tumor response, survival rates, and changes in tumor DNA. Safety is the primary focus, including recording any adverse events during and after treatment.

CONDITIONS

Brief Title

CAR T Cells After Lymphodepletion for the Treatment of IL13Rα2 Positive Recurrent or Refractory Brain Tumors in Children

Who Can Participate

Age: 4Years - 25Years
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Signed informed consent and assent when appropriate
  • Agreement to use archival tumor tissue
  • Karnofsky Performance Status of 60% or higher except for loss of mobility due to disease
  • Life expectancy greater than 4 weeks
  • Histologically confirmed malignant brain tumor with progression after prior therapy
  • Radiographic evidence of tumor progression more than 12 weeks after initial therapy
  • Tumor confirmed IL13Ralpha2 positive by immunohistochemistry (H-score ≥ 50)
  • Programmable shunt if present and able to tolerate being switched off for 2 days
  • Platelets ≥ 50,000/mm³ within 6 weeks
  • Total bilirubin ≤ 2 times upper limit of normal (ULN) within 6 weeks
  • AST and ALT ≤ 2 times ULN within 6 weeks
  • Creatinine clearance ≥ 75 mL/min/1.73m² within 6 weeks
  • Negative for HIV, hepatitis C, and active hepatitis B within 6 weeks
  • Negative pregnancy test for women of childbearing potential within 6 weeks
  • Agreement to use effective birth control or abstain during and 6 months after treatment
  • No more than 0.1 mg/kg/day dexamethasone on PBMC collection day
  • Appropriate venous access
  • At least 2 weeks since last targeted therapy, chemotherapy, or radiation
  • Serum creatinine < 1.6 mg/dL before CNS catheter placement
  • WBC ≥ 2,000/dL, ANC ≥ 1,000, platelets > 50,000/dL before CNS catheter placement
  • INR ≤ 1.3 before CNS catheter placement
  • Bilirubin < 1.5 mg/dL before CNS catheter placement
  • Completed second-line radiation at least 4 weeks before surgery
  • No need for supplemental oxygen or pressor support before lymphodepletion
  • No active infections or fever > 38.5°C before CAR T cell infusion
  • Platelet count ≥ 50,000 before each CAR T cell infusion (transfusion allowed if between 25,000-49,000)
  • Washout periods observed for specific prior chemotherapies and targeted agents
Not Eligible

You will not qualify if you...

  • Need for supplemental oxygen expected to last more than 2 weeks
  • Need for pressor support or symptomatic cardiac arrhythmias
  • Requirement for dialysis
  • Uncontrolled seizures or progressive encephalopathy
  • Unable to understand study risks and procedures
  • Poorly controlled non-malignant illnesses deemed unsafe for study
  • Other active malignancies
  • Severe infection or recent major surgery without recovery
  • Uncontrolled illness or active infection including hepatitis B or C
  • Confirmed HIV positive within 4 weeks
  • Pregnant or breastfeeding females
  • Inability to comply with study procedures or logistics

AI-Screening

AI-Powered Screening

Complete this quick 3-step screening to check your eligibility

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Your Study Journey

Screening

Duration - 2 to 4 weeks

Participants are screened for eligibility to participate in the trial.

1 visit (in-person)

Run-in Period

Duration - 4 days

Participants receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine intravenously before starting cellular immunotherapy.

Daily visits for 4 days

Treatment

Duration - Up to 4 weeks or longer depending on additional cycles

Participants receive autologous IL13Ralpha2-specific CAR T cells delivered intraventricularly once a week for up to 4 cycles, with possible additional cycles if eligible.

Weekly visits for up to 4 weeks or more depending on treatment cycles

Follow-up

Duration - Up to 15 years

Participants are monitored for safety, disease progression, and CAR T cell persistence with periodic visits over several years.

Visits at 30 days, 3, 6, 9, and 12 months, then yearly

Trial Site Locations

Total: 3 locations

1

City of Hope Medical Center

Duarte, California, United States, 91010

Actively Recruiting

2

Children's Hospital Los Angeles

Los Angeles, California, United States, 90027

Actively Recruiting

3

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

Ann Arbor, Michigan, United States, 48109

Actively Recruiting

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How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

NA

Model

SINGLE_GROUP

Primary Purpose

TREATMENT

Number of Arms

1

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