Locoregional Administration of Genetically Engineered Cells (EGFR/IL13Rα2 Pool-CAR T Cells) for the Treatment of Recurrent or Progressive High-Grade Gliomas

Criteria the registry did not label

• Main Inclusion Criteria
• 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.
  • Main Exclusion Criteria
• 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.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent.
• Clinically significant uncontrolled illness.
• Active autoimmune disease requiring systemic immunosuppressive therapy
• Active infection requiring IV antibiotics (for example, minor scalp infection is not exclusion).
• Known history of immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection.
• Other active malignancy.
• Females only: Pregnant or breastfeeding.
• Any other condition that would, in the Investigator's judgment, contraindicate the subject's participation in the clinical study due to safety concerns with clinical study procedures.
• Prospective participants who, in the opinion of the Investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics).