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

NCT07544992 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 25805NCI-2026-02448P30CA033572
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Recurrent Astrocytoma, IDH-Mutant, Grade 4; Recurrent Glioblastoma, IDH-Wildtype

Outcome Measures

Primary Outcomes (2)

• 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.

  Up to 15 years

• 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.

  Up to 5 years

Secondary Outcomes (4)

• Disease response

  Up to 15 years

• Time to progression

  From surgery/biopsy to last contact or relapse/progression date, assessed up to 15 years

• Overall survival (OS)

  From surgery/biopsy to last contact or death (from any cause), assessed up to 15 years

• EGFR/IL13Rα2 pool-CAR T cell product feasibility - leukapheresis and manufacturing processes

  Up to 5 years

Study Arms (1)

Treatment (EGFR/IL13Rα2 pool-CAR T cell therapy)

EXPERIMENTAL

Patients undergo leukapheresis followed by surgical resection, biopsy, and ICT and/or ICV catheter placement 1-3 weeks prior to cycle 1, day 0. Patients then receive EGFR/IL13Rα2 pool-CAR T cells via ICT and/or ICV catheter over 5 minutes on day 1 of each cycle. Cycles repeat every 7 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients may receive additional cycles of EGFR/IL13Rα2 pool-CAR T cells per PI and patient discretion and/or undergo additional leukapheresis as needed on study. Patients also undergo ECHO during screening, as well as FDG-PET, MRI, and blood, TCF, and CSF sample collection throughout the study.

Biological: Autologous Anti-EGFR/Anti-IL13Ralpha2 CAR T-cells; Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Echocardiography Test; Procedure: FDG-Positron Emission Tomography; Procedure: Intracranial Catheter Placement; Procedure: Leukapheresis; Procedure: Magnetic Resonance Imaging; Procedure: Resection

Interventions

Autologous Anti-EGFR/Anti-IL13Ralpha2 CAR T-cells BIOLOGICAL

Given via ICT and/or ICV catheter

Also known as: Autologous Anti-EGFR/Anti-IL13Ra2 CAR T-cells, Autologous Anti-EGFR/IL13Ra2 CAR T Cells, Autologous Anti-EGFR/IL13Ra2 CAR-T Cells, CART-EGFR-IL13Ra2 Cells

Treatment (EGFR/IL13Rα2 pool-CAR T cell therapy)

Biopsy Procedure PROCEDURE

Undergo biopsy

Also known as: Biopsy, BIOPSY_TYPE, Bx

Treatment (EGFR/IL13Rα2 pool-CAR T cell therapy)

Biospecimen Collection PROCEDURE

Undergo blood, TCF, and CSF sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (EGFR/IL13Rα2 pool-CAR T cell therapy)

Echocardiography Test PROCEDURE

Undergo ECHO

Also known as: EC, Echocardiography

Treatment (EGFR/IL13Rα2 pool-CAR T cell therapy)

FDG-Positron Emission Tomography PROCEDURE

Undergo FDG-PET

Also known as: FDG, FDG-PET, FDG-PET Imaging

Treatment (EGFR/IL13Rα2 pool-CAR T cell therapy)

Intracranial Catheter Placement PROCEDURE

Undergo ICT and/or ICV catheter placement

Treatment (EGFR/IL13Rα2 pool-CAR T cell therapy)

Leukapheresis PROCEDURE

Undergo leukapheresis

Also known as: Leukocyte Adsorptive Apheresis, Leukocytopheresis, Therapeutic Leukopheresis, White Blood Cell Reduction Apheresis

Treatment (EGFR/IL13Rα2 pool-CAR T cell therapy)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Treatment (EGFR/IL13Rα2 pool-CAR T cell therapy)

Resection PROCEDURE

Undergo surgical resection

Also known as: Surgical Resection

Treatment (EGFR/IL13Rα2 pool-CAR T cell therapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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).

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

MeSH Terms

Conditions

Astrocytoma; Glioblastoma

Interventions

Biopsy; Specimen Handling; Leukapheresis; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Cytapheresis; Biological Therapy; Therapeutics; Blood Component Removal; Leukocyte Reduction Procedures; Cell Separation; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Behnam Badie

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 16, 2026
• First Posted: April 22, 2026
• Study Start (Estimated): December 24, 2026
• Primary Completion (Estimated): November 4, 2031
• Study Completion (Estimated): November 4, 2031
• Last Updated: May 6, 2026

Record last verified: 2026-05

Locations

US (1)