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. Giving anti-GARP CAR T cell therapy may be safe, tolerable, and/or effective in treating patients with recurrent grade III or IV gliomas.
Patients are ≥ 18 years old
Capacity to understand and willingness to provide written informed consent
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
Patients with a history of malignancy that has been treated with curative intent at least 2 years prior to screening and with no evidence of relapse, if no concurrent anti-cancer therapy (except hormonal therapy) is being given
Patients with a history of malignancy with a negligible risk of metastasis or death (e.g., 5-year OS rate > 90%) such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or stage I uterine cancer
Patients who have prostate cancer with no evidence of metastatic disease and are not on active therapy, except anti-androgen therapy
History of autoimmune disease, or other diseases require long-term administration of high-dose steroids [> 10 mgs/day] or immunosuppressive therapies
Single group
Anti-GARP Chimeric Antigen Receptor-T Cells
Biological/VaccineGiven intracavitary
Biospecimen Collection
Procedure/SurgeryUndergo collection of CSF and blood samples
Chest Radiography
Procedure/SurgeryUndergo chest x-ray
Echocardiography Test
Procedure/SurgeryUndergo ECHO
Magnetic Resonance Imaging
Procedure/SurgeryUndergo MRI
Multigated Acquisition Scan
Procedure/SurgeryUndergo MUGA
Pheresis
Procedure/SurgeryUndergo apheresis
Surgical Procedure
Procedure/SurgeryUndergo surgery and placement of CSF reservoir
Dose limiting toxicities
The rate, frequency and severity will be defined using Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5. Will be summarized by descriptive statistics. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns.
Incidence of adverse events
The rate, frequency and severity will be defined using CTCAE v 5. Will be summarized by descriptive statistics. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns.
Cytokine levels and immunophenotype in cerebrospinal fluid (CSF)
Duration of anti-glycoprotein-A repetitions predominant (GARP) chimeric antigen receptor (CAR) T cell persistence and phenotype in CSF
Objective response rate (ORR)
ORR will be calculated and exact binomial 95% confidence interval (CI) will be provided.
Click on the lead sponsor to view all of their trials.
