A Phase I, Dose-Escalation Trial of Anti-GARP Chimeric Antigen Receptor-T Cell Therapy in Patients With Recurrent High-Grade Glioma Treated at a Single Medical Center
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
• 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
• Disease in one hemisphere and is supratentorial
• If on steroids such as dexamethasone, must be on a low dose (≤ 4mg per day) at the time of treatment, and not at an ascending dosage schedule at time of enrollment/leukapheresis
• Subjects must not have received bevacizumab therapy and are not planned to start such therapy
• Karnofsky performance score (KPS) ≥ 60
• Surgical candidate for surgery for malignant glioma
• White blood cells (WBC) \> 4,000 cells/uL
• Hemoglobin (Hgb) \> 7 gm/dL
• Platelets (Plt) \> 100/dL
• Serum creatinine ≤ 1.5 x institutional upper limit of normal
• Liver function tests within 1.5 x institutional upper limit of normal
• Women of reproductive potential must have a negative pregnancy test within 7 days of study start. All patients of reproductive potential must use a physician-approved contraceptive and refrain from sperm donation for at least two weeks prior, during, and six months after final T cell infusion. Women must refrain from breastfeeding for six months after final T cell infusion
• Sufficient venous access, to be confirmed prior to apheresis