Anti-GARP Chimeric Antigen Receptor-T Cells

PRIMARY OBJECTIVE: I. To assess the safety and feasibility of a CAR T targeting GARP for glioma by defining rate, frequency, and severity of dose limiting toxicities (DLT) following intracavity administration to patients with recurrent glioma, to determine recommended phase II dose (RP2D). SECONDARY OBJECTIVES: I. To describe the adverse event profile of anti-GARP CAR T cell therapy. II.

To describe the cytokine levels and immunophenotype in cerebrospinal fluid (CSF) during and following anti-GARP CAR T cell therapy. III. To describe the duration of anti-GARP CAR T cell persistence and phenotype in CSF. IV. To describe anti-tumor activity of anti-GARP CAR T cell therapy based on objective response rate (ORR), as measured by established radiological criteria. V.

Giving anti-GARP CAR T cell therapy may be safe, tolerable, and/or effective in treating patients with recurrent grade III or IV gliomas.

This phase I trial tests the safety, side effects, and best dose of anti-glycoprotein-A repetitions predominant (GARP) chimeric antigen receptor (CAR) T cell therapy and how well it works in treating patients with grade III or IV gliomas that have come back after a period of improvement (recurrent). 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, such as GARP, 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 tumors.

Live record on ClinicalTrials.gov →

• Patients are ≥ 18 years old
• Capacity to understand and willingness to provide written informed consent
• Diagnosis or clinical suspicion of recurrent malignant glioma, including:
• History of high-grade glioma (World Health Organization \[WHO\] grade III or IV), or
• Prior, histologically-confirmed diagnosis of grade II glioma with new radiographic findings consistent with a high-grade glioma
• Imaging and/or histopathological confirmation of recurrent disease, or verification of "high risk" histology confirmed by a biopsy with measurable disease by the Radiologic Assessment in Neuro-Oncology (RANO) criteria

Inclusion criteria as written on the registry, trimmed. The full list, with exclusions, is on the live record.