A Phase 1 Trial to Evaluate the Safety of EGFR/IL13Rα2 Pool-CAR T Cells in Patients With Recurrent or Progressive High-Grade Glioma (HGG)
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.
• Documented informed consent of the participant and/or legally authorized representative.
• 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.
• Participant has a prior histologically confirmed diagnosis of a glioblastoma (IDH-wildtype) or grade 4 IDH-mutant astrocytoma, or has a prior histologically confirmed diagnosis of a grade 2 or 3 astrocytoma and now has radiographic progression consistent with grade 4 IDH-mutant astrocytoma.
• Relapsed disease: radiographic evidence of recurrence/progression of measurable disease after standard therapy (such as temozolomide with or without Optune device), and ≥ 12 weeks after completion of front-line radiation therapy.
• COH Clinical Pathology assessment at the initial tumor presentation or recurrent disease (reference Appendix B):
‣ IL13Rα2+ expression by IHC \> 20, and
⁃ EGFR gene-altered by NGS or FISH analysis
• No known contraindications to leukapheresis, steroids, imaging studies, or tocilizumab.
• WBC \> 2000 /dl (or ANC ≥ 1,000/mm3)
• Platelets ≥ 75,000/mm3
• Hemoglobin \> 9g/dL
• Total bilirubin ≤ 1.5x ULN
• AST ≤ 2.5x ULN
• ALT ≤ 2.5x ULN
• Serum creatinine ≤1.6 mg/dL
• O2 saturation ≥ 95% on room air.
• Seronegative for HIV Ag/Ab combo, HCV, and active HBV
• Women of childbearing potential (WOCBP): negative urine or serum pregnancy test.
• Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 3 months after the last dose of CAR T cells.