Locoregional Administration of Genetically Engineered Cells (EGFR/IL13Rα2 Pool-CAR T Cells) for the Treatment of Recurrent or Progressive High-Grade Gliomas
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)
City of Hope Medical Center
24 participants
Dec 24, 2026
INTERVENTIONAL
Conditions
Summary
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.
Eligibility
Inclusion Criteria22
- 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 > 8g/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.
Exclusion Criteria13
- 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).
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Interventions
Given via ICT and/or ICV catheter
Undergo biopsy
Undergo blood, TCF, and CSF sample collection
Undergo ECHO
Undergo FDG-PET
Undergo ICT and/or ICV catheter placement
Undergo leukapheresis
Undergo MRI
Undergo surgical resection
Locations(1)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT07544992