Phase II Study of the Administration of T Lymphocytes Expressing the CD30 Chimeric Antigen Receptor (CAR) for Relapsed/Refractory CD30+ Peripheral T Cell Lymphoma

This multicenter, open-label phase II study will determine the efficacy and safety of autologous activated T lymphocytes (ATLs) expressing the chimeric antigen receptor specific for CD30 (ATLCAR.CD30) administered in two sequential infusions in subjects with relapsed/refractory CD30+ PTCL. Up to 20 subjects will receive 2 infusions of 2 × 108 cells/m2 of ATL product expressing the CAR.CD30. It can take time to procure the subjects cells and manufacture the ATLCAR.CD30 cells. During the time period required to manufacture the product the subjects will be able to receive standard of care bridging therapy to be determined by their primary local oncologist. Prior to receiving the first cell infusion, subjects will undergo lymphodepletion with fludarabine and bendamustine. Any subject with prior hypersensitivity reaction to bendamustine will be considered for an alternative lymphodepletion regimen. Subjects will have their disease assessed at week 8 by either CT chest, abdomen and pelvis or PET/CT. Subjects who have stable disease (SD), partial response (PR) or complete response (CR) without subsequent progressive disease and meet the eligibility criteria for a second infusion, will receive lymphodepletion followed by a second infusion. The lymphodepletion for the second infusion will consist of cyclophosphamide and fludarabine.

OUTLINE

Cell Procurement Up to 300 mL of peripheral blood (in up to 3 collections) will be obtained from subjects for cell procurement. Additionally, leukapheresis may be performed to isolate sufficient cells in subjects with a low absolute lymphocyte count or who had inadequate peripheral blood collection. The parameters for apheresis will be up to 2 blood volumes.

Bridging Chemotherapy while waiting for CAR_T cells to be prepared Subjects will be allowed to receive additional standard of care therapy (e.g., chemotherapy or radiation therapy) to stabilize their disease if the treating physician feels it is in the subject's best interests.

Lymphodepleting Chemotherapy Prior to the initial cellular product administration subjects will receive a lymphodepleting regimen of bendamustine 70 mg/m^2/day administered IV over 1 hour followed by an IV dose over 30 minutes of fludarabine 30 mg/m^2/day administered over 3 consecutive days. These agents will be administered per institutional guidelines. Prophylaxis (e.g., hydration, antiemetics, etc.) needed prior to fludarabine and bendamustine chemotherapy will be provided per institutional guidelines. Lymphodepletion will be given 2-14 days prior to the initial cell product administration. Subjects who have previously had hypersensitivity to bendamustine may receive a lymphodepletion regimen of cyclophosphamide 300 mg/m^2 IV and fludarabine 30 mg/m^2 each as a daily infusion for 3 days 2-14 days prior to the initial cell product administration.