This phase I trial studies the side effects and best dose of EGFR/IL13Rα2 pool-chimeric antigen receptor (CAR) T cells when given through a thin, flexible tube into the brain (locoregional administration) in treating patients with high-grade gliomas that have come back after a period of improvement (recurrent) or that are growing, spreading, or getting worse (progressive). EGFR/IL13Rα2 pool-CAR T cells are a type of CAR T cell therapy. 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. Then the gene for a special receptor that binds to a certain protein on the patient's tumor cells is added to the T cells in the laboratory. The special receptor is called a CAR. Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers.
Agreement to allow the use of archival tissue from diagnostic tumor biopsies. If unavailable, exceptions may be granted with Study PI approval.
Age 18 years and older.
KPS ≥ 70%, ECOG ≤ 2 (Appendix A).
Life expectancy ≥ 4 weeks.
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.
Participant has received any live vaccine within 30 days prior to enrollment.
Uncontrolled seizure activity and/or clinically evident progressive encephalopathy.
Single group
Autologous Anti-EGFR/Anti-IL13Ralpha2 CAR T-cells
Biological/VaccineGiven via ICT and/or ICV catheter
Biopsy Procedure
Procedure/SurgeryUndergo biopsy
Biospecimen Collection
Procedure/SurgeryUndergo blood, TCF, and CSF sample collection
Echocardiography Test
Procedure/SurgeryUndergo ECHO
FDG-Positron Emission Tomography
Procedure/SurgeryUndergo FDG-PET
Intracranial Catheter Placement
Procedure/SurgeryUndergo ICT and/or ICV catheter placement
Leukapheresis
Procedure/SurgeryUndergo leukapheresis
Magnetic Resonance Imaging
Procedure/SurgeryUndergo MRI
Resection
Procedure/SurgeryUndergo surgical resection
Incidence of adverse events
Toxicity will be assessed using the Common Terminology Criteria for Adverse Events version 5.0, Cytokine Release Syndrome/Neurotoxicity grading by the American Society for Transplantation and Cellular Therapy Consensus Criteria, Immune Effector Cell-Associated Hemophagocytic Lymphohistiocytosis-Like Syndrome grading system, and Tumor Inflammation-Associated Neurotoxicity grading system.
Maximum tolerated dose (MTD)
The MTD will be determined based on dose limiting toxicities (DLTs), toxicities observed in later cycles (5+), and the activity data. Rate and associated 90% Clopper and Pearson binomial confidence limits (90% confidence intervals \[CI\]) will be estimated for participants experiencing DLTs at the MTD schedule. Tables will be created to summarize all toxicities and side effects by dose, time post treatment, organ, severity, attributions, and arm.
Disease response
Assessed using the Response Assessment in Neuro-Oncology Criteria with the need for bevacizumab as an additional indicator of progression. Will be estimated in study participants who received the full schedule of 4 cycles of autologous anti-EGFR/anti-IL13Ralpha2 CAR T-cell (EGFR/IL13Rα2 pool-CAR T cell) therapy.
Time to progression
Time to progression is defined as time from surgery/biopsy to last contact or relapse/progression date.
Overall survival (OS)
In study participants who received the full schedule of 4 cycles of EGFR/IL13Rα2 pool-CAR T cell therapy, will estimate the rates (90% CI) of OS at 9 months. Kaplan Meier methods will be used to estimate median OS and graph the results.
EGFR/IL13Rα2 pool-CAR T cell product feasibility - leukapheresis and manufacturing processes
We will determine feasibility of locoregionally administered EGFR/IL13Rα2 pool-CAR T cell therapy as assessed by leukapheresis and manufacturing processes, including ability to meet the EGFR/IL13Rα2 pool-CAR T cell dose and product release requirements.
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City of Hope Medical Center
Lead sponsor
National Cancer Institute (NCI)
Collaborator
