Trial Information

Phase I/II Study of Cellular Immunotherapy Using Central Memory-Enriched CD8+ T Cells Lentivirally Transduced to Express A CD19-Specific Chimeric Immunoreceptor Following Peripheral Blood Stem Cell Transplantation for Patients With High-Risk Intermediate Grade B-Lineage Non-Hodgkin Lymphoma

PRIMARY OBJECTIVES: I. To assess the safety of cellular immunotherapy utilizing ex vivo
expanded autologous TCM-enriched CD8+ T cells genetically-modified to express a
CD19-specific chimeric antigen receptor (CAR) in conjunction with a standard myeloablative
autologous hematopoietic stem cell transplantation (HSCT) for research participant(s) with
high-risk intermediate grade B-lineage non-Hodgkin lymphomas who have relapsed after primary
therapy, or who did not achieve complete remission with primary therapy. (Phase I) II. To
determine the maximum tolerated dose (MTD) on dose limiting toxicities (DLTs) and to
describe the full toxicity profile. (Phase I) III. To determine the rate of research
participant(s) receiving TCM-enriched CD8+ T cells genetically-modified to express a
CD19-specific CAR for which the transferred cells are detected in the circulation for at
least 28 days(+/- 3 days)by woodchuck hepatitis virus post-transcriptional regulatory
element (WPRE) quantitative (Q)-polymerase chain reaction (PCR). (Phase II) SECONDARY
OBJECTIVES: I. To determine the tempo, magnitude, and duration of engraftment of the
transferred T cell product as it relates to the number of cells infused. (Phase II) II. To
study the impact of this therapeutic intervention on the development of CD19+ B-cell
precursors in the bone marrow as a surrogate for the in vivo effector function of
transferred CD19-specific T cells. (Phase II) III. To describe the progression-free and
overall survival of treated research participant(s) on this protocol. (Phase II)

OUTLINE: This is a phase I, dose-escalation study of genetically engineered lymphocyte
therapy followed by a phase II study. Patients receive standard salvage chemotherapy per
standard practice and undergo standard mobilization for stem cell collection with G-CSF
and/or plerixafor. Some patients may also receive rituximab intravenously (IV) within 4
weeks of transplantation. Patients receive standard myeloablative conditioning followed by
autologous PBSCT. Patients then undergo infusion of ex vivo expanded autologous TCM-enriched
CD8+ T cells expressing CD19-specific CAR on day 2 or 3 after transplantation.

After completion of study treatment, patients are followed up periodically for at least 15
years.