Actively Recruiting
A Phase 1 Trial to Evaluate the Safety of IL13Rα2-Targeting CAR T Cells With CRISPR Knockout of TGFβR2 in Patients With Recurrent or Progressive High-Grade Glioma
Led by City of Hope Medical Center · Updated on 2025-06-26
27
Participants Needed
1
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 a phase 1 trial to test the safety, side effects, and best dose of genetically modified immune cells called TGFβR2KO/IL13Rα2 chimeric antigen receptor (CAR) T-cells. These cells are given directly inside the skull to treat adults with glioblastoma or grade 3 or 4 IDH-mutant astrocytoma that has returned or worsened after previous treatment. CAR T-cell therapy involves changing a patient’s own immune cells in the lab to attack tumor cells. This study aims to find safe dose levels and assess preliminary effectiveness in these brain cancers. Participants first undergo a process to collect their immune cells (leukapheresis) and may have surgery to remove tumor tissue and place a catheter for treatment delivery. Starting on day 0, they receive weekly infusions of their own modified CAR T-cells directly into the brain for up to four weeks, with additional cycles possible if safe and feasible. Throughout the study, patients have samples taken of cerebrospinal fluid and blood and undergo imaging tests like PET and MRI scans. Echocardiography may also be done at screening. During the study, researchers monitor participants for treatment side effects, immune response, and tumor changes. They measure safety by tracking dose-limiting toxicities, serious adverse events, and cytokine release syndrome during and after treatment. They also evaluate tumor response and survival at several months. Follow-up visits occur up to 15 years after treatment to observe long-term effects. This comprehensive monitoring helps understand how the CAR T-cells behave in the body and their impact on the tumor and immune environment.
CONDITIONS
Brief Title
Intracranial Genetically Modified Immune Cells (TGFβR2KO/IL13Rα2 CAR T-Cells) for the Treatment of Recurrent or Progressive Glioblastoma or Grade 3 or 4 IDH-Mutant Astrocytoma
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Provide documented informed consent or have a legally authorized representative consent
- Age 18 years or older
- Karnofsky performance status of 70% or higher and ECOG score 2 or less
- Life expectancy of at least 4 weeks
- Prior histologically confirmed diagnosis of grade 3 or 4 IDH-mutant astrocytoma or glioblastoma, or radiographic progression consistent with grade 3 or 4 IDH-mutant astrocytoma
- Radiographic evidence of recurrence or progression after standard therapy, at least 12 weeks after radiation
- Tumor expression of IL13Rα2 confirmed by immunohistochemistry with H-score of 80 or higher
- No known contraindications to leukapheresis, steroids, or tocilizumab
- White blood cell count above 2000/dl or absolute neutrophil count of 1000/mm³ or higher
- Platelet count of 75,000/mm³ or higher
- Hemoglobin of 8 g/dl or higher
- Liver enzymes and creatinine within specified normal limits
- Oxygen saturation of 95% or higher on room air
- Negative for HIV antigen/antibody, hepatitis B and C
- Women of childbearing potential must have a negative pregnancy test
- Agreement by participants of childbearing potential to use effective birth control or abstain during the study and for 3 months after
You will not qualify if you...
- Currently receiving active bevacizumab therapy
- Not recovered from toxicities of prior therapy
- Uncontrolled seizures or progressive encephalopathy
- History of allergic reactions to similar compounds
- Clinically significant uncontrolled illness
- Active autoimmune disease requiring systemic immunosuppression
- Active infection requiring intravenous antibiotics
- Known HIV, hepatitis B or C infection
- Other active malignancies that may interfere with study
- Pregnant or breastfeeding women
- Any condition or circumstance that would pose safety concerns or prevent compliance with study procedures
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Variable, prior to treatment start
Participants undergo leukapheresis, standard of care surgical resection with or without placement of Rickham catheter, and echocardiography if indicated.
1 to 2 visits depending on procedures
Duration - Up to 4 weeks or longer if additional cycles are administered
Participants receive intracranial administration of autologous TGFβR2KO/IL13Rα2-CAR T cells once weekly over approximately 5 minutes per infusion. Up to 4 weekly cycles (28 days) are given in the absence of disease progression or unacceptable toxicity. Additional cycles may be given if participants meet infusion criteria and doses are available.
Weekly visits for up to 4 weeks or longer if extended treatment
Duration - Throughout treatment duration
Participants undergo cerebrospinal fluid (CSF) and blood sample collection, MRI, and FDG-PET imaging throughout the study to assess treatment effects and safety.
Multiple visits concurrent with treatment visits
Duration - Up to 15 years
After completion of study treatment, participants are followed with visits at day 30, months 3, 6, 9, and 12, then yearly for up to 15 years to monitor safety and long-term outcomes.
1 visit at day 30, visits at months 3, 6, 9, 12, then annual visits
Trial Site Locations
Total: 1 location
1
City of Hope Medical Center
Duarte, California, United States, 91010
Actively Recruiting
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
Similar Trials
Frequently Asked Questions
Have more questions? Get in touch with our team for quick support
Not the Right Trial for You?
Explore thousands of other clinical trials that might be a better match.
Sign up to get personalized trial recommendations delivered to your inbox.
Already have an account? Log in here