Anti-GARP Chimeric Antigen Receptor T Cell Therapy for the Treatment of Recurrent Grade III or IV Gliomas

Inclusion criteria

• 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
• Patient has unifocal disease in one hemisphere and is supratentorial. Lesion and edema can not be located in eloquent locations (e.g., brainstem, pre-/post-central gyrus, visual cortex) or within 2 gyri of motor strip.
• 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
• Prior to apheresis and treatment 1 a 2- week washout should be observed
• Subjects must not have received bevacizumab therapy and are not planned to start such therapy
• Karnofsky performance score (KPS) ≥ 60
• Subject is a surgical candidate for surgery for malignant glioma with the intent of resecting \>80-90% of the tumor as the ideal treatment option
• 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
• Life expectancy of greater than 12 weeks
• PI clinical judgement of patients who will likely complete the trial and are able to maintain stable neurologic symptoms during intervention period

Exclusion criteria

• Patients who have a history of malignancy other than the glioma under investigation in this study, except patients with the following malignancies/treatment characteristics, who are eligible at the investigator's discretion:
• 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
• Research participants who received steroids must have either received their last dose of steroids 7 days or more prior to apheresis or have dosage tapered to \< 2mg/kg/day
• Patients being treated concurrently (within 14 days prior to study enrollment) with any other investigational agent
• Examples of other investigational agents that would be exclusionary include supportive care agents
• Patients receiving anti-cancer agents such as chemotherapy (e.g., temozolomide) must stop treatment 14 days prior to undergoing apheresis and remain off therapy throughout the duration of CAR T therapeutic intervention
• Patients with active fungal, bacterial, viral, or other infection that requires intravenous antimicrobials
• Prophylactic antimicrobials are allowed
• Patients with active invasive fungal infection should be excluded even if the treatment is oral antimicrobials
• History of allergy to study products/diluents/emulsions
• Recent history (within last 3 months) of uncontrolled seizures