This phase I trial studies the side effects and best dose of epidermal growth factor receptor variant III (EGFRvIII)-specific chimeric antigen receptor (CAR)-transduced autologous T lymphocytes (EGFRvIII CAR T cells) in treating patients with newly diagnosed glioblastoma or gliosarcoma. EGFRvIII CAR T cells may help activate the immune system and help the body fight off tumor cells in the brain.
Additional locations may be listed on ClinicalTrials.gov for NCT02664363.
See trial information on ClinicalTrials.gov for a list of participating sites.
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose (MTD) of a single intravenous (IV) infusion of EGFRvIII CAR T cells in patients with newly-diagnosed World Health Organization (WHO) grade IV malignant glioma.
SECONDARY OBJECTIVES:
I. To determine the dose limiting toxicities (DLT) of a single IV infusion EGFRvIII CAR T cells in patients with newly-diagnosed WHO grade IV malignant glioma.
TERTIARY OBJECTIVES:
I. To determine if EGFRvIII CARs transferred into patients with WHO grade IV malignant glioma expand.
II. To determine if EGFRvIII CARs persist and remain functional in the periphery.
III. To assess whether EGFRvIII CARs traffic to tumor site.
IV. To describe the survival experience of patients treated with EGFRvIII CAR T cells.
V. To describe the progression-free survival experience of newly-diagnosed, EGFRvIII-expressing WHO grade IV malignant glioma patients treated with EGFRvIII CAR T cells.
OUTLINE: This is a dose escalation study of EGFRvIII-specific CAR-transduced autologous T lymphocytes.
Patients undergo leukapheresis. Within 5 weeks of leukapheresis, patients undergo radiation therapy 5 days per week and receive concurrent temozolomide orally (PO) daily for 6 weeks. Following radiation therapy and concurrent temozolomide, patients receive temozolomide PO daily on days 1-21. Beginning 48 hours after last dose of temozolomide, patients also receive EGFRvIII-specific CAR-transduced autologous T lymphocytes IV over 30 minutes. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Beginning 1 month after infusion of EGFRvIII-specific CAR-transduced autologous T lymphocytes, patients receive temozolomide PO daily on days 1-5. Treatment repeats every 28 days for up to 9 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 1, 5, 10, and 28 days, at 3, 6, and 12 months, and then annually thereafter.
Lead OrganizationDuke University Medical Center
Principal InvestigatorDavid Michael Ashley
