Pilot study of redirected autologous T cells engineered to contain anti-CD19 attached to TCRζ and 4-1BB signaling domains in patients with chemotherapy-resistant or -refractory CD19+ leukemia and lymphoma.

Abstract

TPS10072 Background: Outcomes remain poor for patients (pts) with relapsed or refractory (r/r) B-cell malignancies such as acute lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia (CLL). CD19 is an attractive therapeutic target because it is widely expressed on normal and malignant B cells throughout B-cell maturation but not on pluripotent stem cells or non–B-cell tissues. We have developed chimeric antigen receptor T cells to target CD19+ cells (CART-19 or CTL019). This approach involves patient-derived T cells that are genetically modified via lentiviral transduction to express a CD19 antigen recognition domain attached to intracellular signaling domains (TCRζ and 4-1BB) that mediate T-cell activation. A recent study in CLL showed that CART-19 therapy had potent activity with responses in 5/8 evaluable pts (3 CR, 2 PR). Pts achieving CR (two > 24 months and one > 5 months) remain in CR with detectable CART-19 cells (Porter et al. ASH 2012). Here we describe a study of CART-19 therapy in pediatric pts with r/r leukemia and lymphoma (NCT01626495). Methods: Pts eligible for this single-arm, open-label study are aged 1 to 24 years with r/r CD19+ B-cell malignancies, without a transplant option or having relapsed after allogeneic stem cell transplantation (ASCT). Pts will undergo leukapheresis to obtain T cells, which will be stimulated, expanded, and transduced ex vivo to express the chimeric antigen receptor. Pts may receive lymphodepleting chemotherapy prior to CART-19 infusion. Study objectives: determine the safety and feasibility of administering CART-19 therapy to pediatric pts, assess duration of in vivo survival of CART-19 cells, and measure antitumor response. There are 2 cohorts in the study: Cohort 1 includes pts who have not undergone ASCT and are not currently eligible for a transplant, and cohort 2 includes pts who relapsed after ASCT. Cells are collected from the recipient, not the donor, which allows for this approach to be used in pts s/p cord blood transplant, and which we hypothesize will reduce the risk of GVHD as a result of toleration of the T cells in the recipient. To date, 7 pts have been enrolled. Clinical trial information: NCT01626495.