NCT06815029

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

Recruiting now Phase 1 Last updated 26 June 2025

What this trial tests

Phase 1 trial testing Biospecimen Collection in Recurrent Astrocytoma, IDH-Mutant, Grade 3 in 27 participants. Currently enrolling.

Timeline

17 June 2025

Primary endpoint
11 October 2030

11 October 2030

Quick facts

Lead sponsor	City of Hope Medical Center
Phase	Phase 1
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	27
Start date	17 June 2025
Primary completion	11 October 2030
Estimated completion	11 October 2030
Sites	1 location across United States

Drugs / interventions tested

• Biospecimen Collection — full drug profile →
• Chimeric Antigen Receptor T-Cell Therapy — full drug profile →
• Echocardiography
• Fludeoxyglucose F-18 (FLUDEOXYGLUCOSE) — full drug profile →
• Intracranial Catheter Placement
• Leukapheresis — full drug profile →
• Magnetic Resonance Imaging
• Positron Emission Tomography
• Resection

Conditions studied

• Recurrent Astrocytoma, IDH-Mutant, Grade 3 — all drugs for Recurrent Astrocytoma, IDH-Mutant, Grade 3 →
• Recurrent Astrocytoma, IDH-Mutant, Grade 4 — all drugs for Recurrent Astrocytoma, IDH-Mutant, Grade 4 →
• Recurrent Glioblastoma — all drugs for Recurrent Glioblastoma →

Sponsor

City of Hope Medical Center

Who can join

18 and older, any sex, with Recurrent Astrocytoma, IDH-Mutant, Grade 3 or Recurrent Astrocytoma, IDH-Mutant, Grade 4. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Evolving therapeutic strategies in glioblastoma: traditional approaches and novel interventions.
   Shetty C, Tamatta R, Dhas N, Singh AK. · · 2025 · cited 3× · PMID 40893155 · DOI 10.1007/s13205-025-04493-1
2. Glioblastoma: From Pathophysiology to Novel Therapeutic Approaches.
   Ribeiro A, Fote G, Himstead A, Zheng M, et al · · 2025 · cited 3× · PMID 40868217 · DOI 10.3390/biomedicines13081963
3. Harnessing the potential of gene editing technology for CAR-T cell therapy of solid tumors.
   Khodabandehloo E, Rayati M, Ahmadi E, Naghdibadi M, et al · · 2025 · cited 2× · PMID 41276863 · DOI 10.1186/s41232-025-00398-x
4. Emerging insights into the immunosuppressive tumor microenvironment and its implications for glioblastoma immunotherapy.
   Nicolaou N, Andreou MS, Neophytou CM, Papageorgis P. · · 2025 · cited 2× · PMID 41208963 · DOI 10.3389/fimmu.2025.1665742
5. Highlights in IO: next-generation CAR-T therapy for glioblastoma.
   Yamaguchi J, Okada H. · · 2026 · PMID 41922085 · DOI 10.1136/jitc-2025-014670
6. Astrocytes in neuroinflammation and brain cancer.
   Sun W, Chen P, Xu XY, Zhang JQ, et al · · 2026 · PMID 41910655 · DOI 10.1186/s43556-026-00439-y
7. Endogenous immune recruitment in glioblastoma CAR T therapy: cytokine, myeloid, and chemokine circuitry.
   Liu J, Abikenari M, Annagiri S, Ha JH, et al · · 2026 · PMID 41820710 · DOI 10.1007/s11060-026-05497-4
8. Recurrent Glioblastoma and the Tumor Immune Landscape: Emerging Immunotherapeutic Strategies.
   Cao Z, Tong S, Wang Z, Ji C, et al · · 2026 · PMID 41809120 · DOI 10.2147/itt.s581012