CD30 CAR for Relapsed/Refractory CD30+ T Cell Lymphoma

Description

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. Subjects will have cells procured to manufacture the ATLCAR.CD30 cells and 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 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 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 per institutional guidelines 2-14 days prior to the initial cell product administration.

Two to 14 days prior to the second infusion, subjects will 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 per institutional guidelines. Subjects whose absolute neutrophil count and/or platelet count takes >/= 3 months (from the first day of lymphodepletion prior to the initial cellular product administration) to recover to levels required to meet eligibility for lymphodepletion (ANC >/= 1.0 x 10^9/L and platelet count >/= 50 x 10^9/L) prior to the second infusion will receive a 25% dose reduction in cyclophosphamide and fludarabine lymphodepletion for the second round of lymphodepletion.

ATLCAR.CD30 Cell Administration The cellular product consisting of ATLCAR.CD30 cells will be administered by a licensed healthcare provider (oncology nurse or physician) via intravenous injection over 5 - 10 minutes through either a peripheral or a central line. The volume of infusion will depend upon the concentration of the cells when frozen and the size of the subject. The expected volume will be 1 - 50 mL. Post lymphodepletion, subjects who meet eligibility criteria for cellular therapy will receive ATLCAR.CD30 cells within 2 - 14 days after completing the lymphodepleting chemotherapy regimen. The recommended phase 2 dose (RP2D) determined in the phase 1 study of ATLCAR.CD30 will be administered to subjects (2 108 CAR-T/m2).

If a subject only has enough ATLCAR.CD30 cells product for one infusion, they will still be able to receive one infusion of cells and will not have a 2nd lymphodepletion or infusion of cells. These subjects will be replaced for the purposes of efficacy determination.

Details