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

Summary

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.

Eligibility

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
* 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

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

Conditions7

Locations1 site

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