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)
City of Hope Medical Center
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.
Description
PRIMARY OBJECTIVE: I. Assess the safety and determine the maximum tolerated dose (MTD) of intracranial (IC) administration of TGFβR2KO/IL13Rα2-CAR T cell therapy. SECONDARY OBJECTIVES: I. In participants who receive at least 50% of the assigned cell dose for each of the four cycles and at least 70% of the total cumulative dose for all cycles (1-4): Ia. Estimate overall response rates (ORR) and complete response (CR) rate at 3, 6, 9-months; and Ib. Estimate overall survival (OS) at 9-months. II. Determine feasibility of IC administered TGFβR2KO/IL13Rα2-CAR T cell therapy as assessed by leuk…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Documented informed consent of the participant and/or legally authorized representative * Note: For research participants who do not speak English, a short form consent may be used with a City of Hope (COH) certified interpreter/translator to proceed with screening and leukapheresis, while the request for a translated main consent is processed. However, the research participant is allowed to proceed with surgery/Rickham placement and CAR T cell infusion only after the translated main consent form is signed * Agreement to allow the use of archival tissue from diagnosti…
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
- Procedure
Location
- City of Hope Medical CenterDuarte, California