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.
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 diagnostic tumor biopsies. If unavailable, exceptions may be granted with study principal investigator (PI) approval
Age: ≥ 18 years
Owing to higher frequency of wound-related complications, participants who require active bevacizumab therapy at the time of enrollment are excluded
Participant has not yet recovered from toxicities of prior therapy
Uncontrolled seizure activity and/or clinically evident progressive encephalopathy
History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
Single group
Biospecimen Collection
Procedure/SurgeryUndergo CSF and blood sample collection
Chimeric Antigen Receptor T-Cell Therapy
Biological/VaccineGiven autologous TGF-betaR2KO/IL13R-alpha2-CAR T cells intracranially
Echocardiography
Procedure/SurgeryUndergo echocardiography
Fludeoxyglucose F-18
Other interventionUndergo FDG-PET
Intracranial Catheter Placement
Procedure/SurgeryUndergo placement of Rickham catheter
Leukapheresis
Procedure/SurgeryUndergo leukapheresis
Magnetic Resonance Imaging
Procedure/SurgeryUndergo MRI
Positron Emission Tomography
Procedure/SurgeryUndergo FDG-PET
Resection
Procedure/SurgeryUndergo surgical resection
Dose-limiting toxicities (DLTs)
Will be assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. Rate and associated 90% Clopper and Pearson binomial confidence limits (90% CI) will be estimated for participants experiencing DLTs at the maximum tolerated dose schedule
Incidence of grade 3+ adverse events (AEs)
Will be assessed using the CTCAE v 5.0. Tables will be created to summarize all toxicities and side effects by dose, time post treatment, organ, severity, attributions, and arm. In study participants who received the full schedule of 4 cycles.
Incidence of cytokine release syndrome
Will be graded using American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Criteria. Tables will be created to summarize all toxicities and side effects by dose, time post treatment, organ, severity, attributions, and arm. In study participants who received the full schedule of 4 cycles.
Incidence of all other AEs
Will be assessed using the CTCAE v 5.0. Neurotoxicity will be graded using ASTCT Consensus Criteria, Immune Effector Cell-Associated Hemophagocytic Lymphohistiocytosis-Like Syndrome grading system, and tumor inflammation-associated neurotoxicity grading system. Tables will be created to summarize all toxicities and side effects by dose, time post treatment, organ, severity, attributions, and arm.
Overall response rate
Evaluated using Response Assessment in Neuro-Oncology (RANO) criteria. Will estimate the rates (90% CI) of disease response.
Complete response rate
Evaluated using RANO criteria. Will estimate the rates (90% CI) of disease response.
Overall survival (OS)
Will estimate the rates (90% CI) of OS. Kaplan Meier methods will be used to estimate median OS and graph the results.
Ability to meet the TGFβR2KO/IL13Rα2-CAR T cell dose requirements (product feasibility)
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City of Hope Medical Center
Lead sponsor
National Cancer Institute (NCI)
Collaborator
