Genetically Engineered Lymphocyte Therapy After Peripheral Blood Stem Cell Transplant in Treating Patients With High-Risk, Intermediate-Grade, B-cell Non-Hodgkin Lymphoma

PRIMARY OBJECTIVES: I. To assess the safety of cellular immunotherapy utilizing ex vivo
expanded autologous central memory T cell (TCM)-enriched cluster of differentiation (CD)8+ T
cells genetically-modified to express a CD19-specific chimeric antigen receptor (CAR) in
conjunction with a standard myeloablative autologous hematopoietic stem cell transplantation
(aHSCT) for research participants 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 participants receiving TCM-enriched CD8+ T cells
genetically-modified to express a CD19-specific CAR for which the transferred cells are
detected in the circulation 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 participants
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 filgrastim
and/or plerixafor. Some patients may also receive rituximab intravenously (IV) within 4 weeks
of transplant. 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 transplant.

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

Inclusion Criteria:

- City of Hope (COH) pathology review confirms that research participant's diagnostic
material is consistent with history of intermediate grade B-cell NHL (e.g., diffuse
B-cell lymphoma, mantle cell lymphoma, transformed follicular lymphoma)

- History of relapse after achieving first remission with primary therapy, or failure to
achieve remission with primary therapy - Life expectancy > 16 weeks

- Karnofsky performance scale (KPS) >= 70%

- Negative serum pregnancy test for women of childbearing potential

- Research participant has an indication to be considered for autologous stem cell
transplantation

Exclusion Criteria:

- Fails to understand the basic elements of the protocol and/or the risks/benefits of
participating in this phase I/II study; evidence of understanding includes passing the
Protocol Comprehensive Screening given by the Research Subject Advocate (RSA); a legal
guardian may substitute for the research participant

- Any standard contraindications to myeloablative HSCT per standard of care practices at
COH

- Dependence on corticosteroids

- Currently enrolled in another investigational therapy protocol

- Human immunodeficiency virus (HIV) seropositive based on testing performed within 4
weeks of enrollment

- History of allogeneic HSCT or prior autologous HSCT

- Active autoimmune disease requiring systemic immunosuppressive therapy

- Research participant(s) who are to receive radioimmunotherapy (Zevalin-based)

- based conditioning regimens

- Research participant(s) with known active hepatitis B or C infection