RecruitingPhase 1NCT06815029

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

A Phase 1 Trial to Evaluate the Safety of IL13Rα2-Targeting Chimeric Antigen Receptor (CAR) T Cells With CRISPR Knockout of TGFβR2 in Patients With Recurrent or Progressive High-Grade Glioma (HGG)


Sponsor

City of Hope Medical Center

Enrollment

27 participants

Start Date

Jun 17, 2025

Study Type

INTERVENTIONAL

Conditions

Summary

This phase I trial tests the safety, side effects and best dose of TGFβR2KO/IL13Rα2 chimeric antigen receptor (CAR) T-cells given within the skull (intracranial) in treating patients with glioblastoma or IDH-mutant grade 3 or 4 astrocytoma that has come back after a period of improvement (recurrent) or that is growing, spreading, or getting worse (progressive). CAR T-cell therapy is a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack tumor cells. T cells are taken from a patient's blood. When the cells are taken from the patient's own blood, it is known as autologous. Then the gene for special receptors that bind to a certain proteins on the patient's tumor cells are added to the T cells in the laboratory. The special receptors are called CAR. Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain tumors. Giving TGFβR2KO/IL13Rα2 CAR T cells may be safe, tolerable, and/or effective in treating patients with recurrent or progressive glioblastoma or grade 3 or 4 IDH-mutant astrocytoma.


Eligibility

Min Age: 18 Years

Plain Language Summary

Simplified for easier understanding

This study is testing a new type of engineered immune cell treatment (CAR T-cell therapy) for people with recurrent or worsening glioblastoma or a related brain tumor. These specially modified immune cells are designed to recognize and attack a protein on brain cancer cells. The cells are delivered directly into the brain through a small implanted device, aiming to fight the tumor from the inside. **You may be eligible if...** - You are 18 or older with a diagnosis of recurrent glioblastoma or grade 3–4 IDH-mutant astrocytoma (a type of brain tumor) - Your tumor has returned or continued to grow despite previous treatment - You are in reasonably good physical condition (Karnofsky score of 70% or higher) - You are able to give informed consent **You may NOT be eligible if...** - Your tumor does not express the target protein (GPC-3 or IL13Rα2) - You have serious organ failure or uncontrolled infection - You have had an organ transplant - You are pregnant Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

PROCEDUREBiospecimen Collection

Undergo CSF and blood sample collection

BIOLOGICALChimeric Antigen Receptor T-Cell Therapy

Given autologous TGF-betaR2KO/IL13R-alpha2-CAR T cells intracranially

PROCEDUREEchocardiography

Undergo echocardiography

OTHERFludeoxyglucose F-18

Undergo FDG-PET

PROCEDUREIntracranial Catheter Placement

Undergo placement of Rickham catheter

PROCEDURELeukapheresis

Undergo leukapheresis

PROCEDUREMagnetic Resonance Imaging

Undergo MRI

PROCEDUREPositron Emission Tomography

Undergo FDG-PET

PROCEDUREResection

Undergo surgical resection


Locations(1)

City of Hope Medical Center

Duarte, California, United States

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NCT06815029


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