NCT07544992 · City of Hope Medical Center
Locoregional Administration of Genetically Engineered Cells (EGFR/IL13Rα2 Pool-CAR T Cells) for the Treatment of Recurrent or Progressive High-Grade Gliomas
What this study is about
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).
View original scientific description
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.
Interventions
BIOLOGICAL
Autologous Anti-EGFR/Anti-IL13Ralpha2 CAR T-cells
Given via ICT and/or ICV catheter
PROCEDURE
Biopsy Procedure
Undergo biopsy
PROCEDURE
Biospecimen Collection
Undergo blood, TCF, and CSF sample collection
PROCEDURE
Echocardiography Test
Undergo ECHO
PROCEDURE
FDG-Positron Emission Tomography
Undergo FDG-PET
PROCEDURE
Intracranial Catheter Placement
Undergo ICT and/or ICV catheter placement
PROCEDURE
Leukapheresis
Undergo leukapheresis
PROCEDURE
Magnetic Resonance Imaging
Undergo MRI
PROCEDURE
Resection
Undergo surgical resection
Primary outcome measures
Incidence of adverse events
Time frame: Up to 15 years
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)
Time frame: Up to 5 years
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.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
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).
Where
- Duarte, California
Collaborators
National Cancer Institute (NCI)
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Jun 12, 2026 · Source of record for eligibility and locations