Intracranial Genetically Modified Immune Cells (TGFβR2KO/IL13Rα2 CAR T-Cells) for the Treatment of Recurrent or Progressive Glioblastoma or Grade 3 or 4 IDH-Mutant Astrocytoma

NCT06815029 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 24717NCI-2025-00342P30CA033572
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial tests the safety, side effects and best dose of TGFβR2KO/IL13Rα2 chimeric antigen receptor (CAR) T-cells given within the skull (intracranial) in treating patients with glioblastoma or IDH-mutant grade 3 or 4 astrocytoma that has come back after a period of improvement (recurrent) or that is growing, spreading, or getting worse (progressive). 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. When the cells are taken from the patient's own blood, it is known as autologous. Then the gene for special receptors that bind to a certain proteins on the patient's tumor cells are added to the T cells in the laboratory. The special receptors are called CAR. Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain tumors. Giving TGFβR2KO/IL13Rα2 CAR T cells may be safe, tolerable, and/or effective in treating patients with recurrent or progressive glioblastoma or grade 3 or 4 IDH-mutant astrocytoma.

Conditions

Recurrent Astrocytoma, IDH-Mutant, Grade 3; Recurrent Astrocytoma, IDH-Mutant, Grade 4; Recurrent Glioblastoma

Outcome Measures

Primary Outcomes (4)

• Dose-limiting toxicities (DLTs)

  Will be assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. Rate and associated 90% Clopper and Pearson binomial confidence limits (90% CI) will be estimated for participants experiencing DLTs at the maximum tolerated dose schedule

  Up to 28 days

• Incidence of grade 3+ adverse events (AEs)

  Will be assessed using the CTCAE v 5.0. Tables will be created to summarize all toxicities and side effects by dose, time post treatment, organ, severity, attributions, and arm. In study participants who received the full schedule of 4 cycles.

  Up to 30 days after last dose of study drug

• Incidence of cytokine release syndrome

  Will be graded using American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Criteria. Tables will be created to summarize all toxicities and side effects by dose, time post treatment, organ, severity, attributions, and arm. In study participants who received the full schedule of 4 cycles.

  Up to 30 days after last dose of study drug

• Incidence of all other AEs

  Will be assessed using the CTCAE v 5.0. Neurotoxicity will be graded using ASTCT Consensus Criteria, Immune Effector Cell-Associated Hemophagocytic Lymphohistiocytosis-Like Syndrome grading system, and tumor inflammation-associated neurotoxicity grading system. Tables will be created to summarize all toxicities and side effects by dose, time post treatment, organ, severity, attributions, and arm.

  Up to 30 days after last dose of study drug

Secondary Outcomes (6)

• Overall response rate

  At 3, 6, and 9 months

• Complete response rate

  At 3, 6, and 9 months

• Overall survival (OS)

  From cycle 1 to last contact or death from any cause, assessed at 9 months

• Ability to meet the TGFβR2KO/IL13Rα2-CAR T cell dose requirements (product feasibility)

  Up to 1 year

• Ability to meet product release requirements (product feasibility)

  Up to 1 year

Study Arms (1)

Treatment (TGFβR2KO/IL13Rα2 CAR T-cells)

EXPERIMENTAL

Patients undergo leukapheresis and standard of care surgical resection with or without placement of Rickham catheter. Starting on day 0, patients receive autologous TGFβR2KO/IL13Rα2-CAR T cells intracranially over approximately 5 minutes QW. Cycles repeat weekly for up to 4 cycles (28 days) in the absence of disease progression or unacceptable toxicity. Patients may receive additional cycles if they continue to meet infusion criteria and have doses available for infusion. Patients also undergo CSF and blood sample collection and fludeoxyglucose F-18 (FDG)-positron emission tomography (PET) and MRI throughout the study. Additionally, patients may undergo echocardiography at screening.

Procedure: Biospecimen Collection; Biological: Chimeric Antigen Receptor T-Cell Therapy; Procedure: Echocardiography; Other: Fludeoxyglucose F-18; Procedure: Intracranial Catheter Placement; Procedure: Leukapheresis; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Procedure: Resection

Interventions

Biospecimen Collection PROCEDURE

Undergo CSF and blood sample collection

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

Treatment (TGFβR2KO/IL13Rα2 CAR T-cells)

Chimeric Antigen Receptor T-Cell Therapy BIOLOGICAL

Given autologous TGF-betaR2KO/IL13R-alpha2-CAR T cells intracranially

Also known as: CAR T Infusion, CAR T Therapy, CAR T-cell Therapy, Chimeric Antigen Receptor T-cell Infusion

Treatment (TGFβR2KO/IL13Rα2 CAR T-cells)

Echocardiography PROCEDURE

Undergo echocardiography

Also known as: EC

Treatment (TGFβR2KO/IL13Rα2 CAR T-cells)

Fludeoxyglucose F-18 OTHER

Undergo FDG-PET

Also known as: 18FDG, FDG, Fludeoxyglucose (18F), fludeoxyglucose F 18, Fludeoxyglucose F18, Fluorine-18 2-Fluoro-2-deoxy-D-Glucose, Fluorodeoxyglucose F18

Treatment (TGFβR2KO/IL13Rα2 CAR T-cells)

Intracranial Catheter Placement PROCEDURE

Undergo placement of Rickham catheter

Treatment (TGFβR2KO/IL13Rα2 CAR T-cells)

Leukapheresis PROCEDURE

Undergo leukapheresis

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

Treatment (TGFβR2KO/IL13Rα2 CAR T-cells)

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 (TGFβR2KO/IL13Rα2 CAR T-cells)

Positron Emission Tomography PROCEDURE

Undergo FDG-PET

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging, PT

Treatment (TGFβR2KO/IL13Rα2 CAR T-cells)

Resection PROCEDURE

Undergo surgical resection

Also known as: Surgical Resection

Treatment (TGFβR2KO/IL13Rα2 CAR T-cells)

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
• Note: For research participants who do not speak English, a short form consent may be used with a City of Hope (COH) certified interpreter/translator to proceed with screening and leukapheresis, while the request for a translated main consent is processed. However, the research participant is allowed to proceed with surgery/Rickham placement and CAR T cell infusion only after the translated main consent form is signed
• Agreement to allow the use of archival tissue from diagnostic tumor biopsies. If unavailable, exceptions may be granted with study principal investigator (PI) approval
• Age: ≥ 18 years
• Karnofsky performance status (KPS) ≥ 70%, Eastern Cooperative Oncology Group (ECOG) ≤ 2
• Life expectancy ≥ 4 weeks
• If the participant has a shunt, they must be informed of the following:
• If the shunt is not programmable, the participant must be willing to have a programmable shunt placed prior to CAR T cell infusion, and
• If the shunt is programmable, in order to proceed to the treatment portion of the study, the participant must be able to tolerate their shunt being functionally closed for at least 2 hours
• Participant has a prior histologically-confirmed diagnosis of a grade 3 or 4 IDH-mutant astrocytoma or glioblastoma, or has a prior histologically-confirmed diagnosis of a grade 2 or 3 astrocytoma and now has radiographic progression consistent with grade 3 or 4 IDH-mutant astrocytoma
• Relapsed disease: radiographic evidence of recurrence/progression of measurable disease after standard therapy, and ≥ 12 weeks after completion of front-line radiation therapy
• COH clinical pathology confirms IL13Rα2+ tumor expression by immunohistochemistry (H-score ≥ 80)
• No known contraindications to leukapheresis, steroids, or tocilizumab
• White blood cell (WBC) \> 2000 /dl (or absolute neutrophil count \[ANC\] ≥ 1,000/mm\^3) (to be performed within 14 days prior to leukapheresis unless otherwise stated)
• Platelets ≥ 75,000/mm\^3 (to be performed within 14 days prior to leukapheresis unless otherwise stated)

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
• 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 human immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection
• Other active malignancy. Note: Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
• Females only: Pregnant or breastfeeding
• Any other condition that would, in the investigator's judgment, contraindicate the patient'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; Lymphoma, Follicular; Glioblastoma

Interventions

Specimen Handling; Immunotherapy, Adoptive; Fluorodeoxyglucose F18; 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; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Adoptive Transfer; Immunization, Passive; Immunization; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Deoxyglucose; Deoxy Sugars; Carbohydrates; Cytapheresis; Blood Component Removal; Leukocyte Reduction Procedures; Cell Separation; Cytological Techniques; 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: February 4, 2025
• First Posted: February 7, 2025
• Study Start: June 17, 2025
• Primary Completion (Estimated): October 11, 2030
• Study Completion (Estimated): October 11, 2030
• Last Updated: June 26, 2025

Record last verified: 2025-06

Locations

US (1)