Genetically Modified T-cell Infusion Following Peripheral Blood Stem Cell Transplant in Treating Patients With Recurrent or High-Risk Non-Hodgkin Lymphoma

This phase I trial studies the side effects and best dose of genetically modified T-cells following peripheral blood stem cell transplant in treating patients with recurrent or high-risk non-Hodgkin lymphoma. Giving chemotherapy before a stem cell transplant helps stop the growth of cancer cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Removing the T cells from the donor cells before transplant may stop this from happening. Giving an infusion of the donor's T cells (donor lymphocyte infusion) later may help the patient's immune system see any remaining cancer cells as not belonging in the patient's body and destroy them (called graft-versus-tumor effect)

PRIMARY OBJECTIVES: I. To assess the safety and describe the full toxicity profile of cellular immunotherapy utilizing ex vivo expanded autologous central memory T cell (Tcm)-enriched T cells that are genetically modified using a self-inactivating (SIN) lentiviral vector to express a costimulatory cluster of differentiation (CD)19-specific chimeric antigen receptors (CAR) as well as a truncated human epidermal growth factor receptor (EGFR) (CD19R:CD28 zeta/EGFR tau +Tcm) (CD19-CAR-specific/truncated EGFR lentiviral vector-transduced autologous T cells) in conjunction with a standard myeloablative autologous hematopoietic stem cell transplant (HSCT) for patients with high-risk intermediate grade B-lineage non-Hodgkin lymphoma (e.g., diffuse large B-cell lymphoma \[DLBCL\], mantle cell lymphoma \[MCL\] or transformed non-Hodgkin lymphoma \[NHL\]). II. To determine the maximum tolerated dose (MTD) based on dose limiting toxicities (DLTs). 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. II. To study the impact of this therapeutic intervention on the development of normal CD19+ B-cell precursors in the peripheral blood as a surrogate for the in vivo effector function of transferred autologous CD19R:CD28 zeta/EGFR tau +Tcm. OUTLINE: This is a dose-escalation study of CD19-CAR-specific/truncated EGFR lentiviral vector-transduced autologous T cells. Patients undergo mobilization for autologous stem cell collection with cytoreductive chemotherapy and filgrastim and/or plerixafor per current standard operating policies. Patients undergo myeloablative conditioning regimen per institutional standards beginning day -7 followed by hematopoietic stem cell transplantation on day 0. Patients receive CD19-CAR-specific/truncated EGFR lentiviral vector-transduced autologous T cells IV on day 2 or 3 (may be delayed up to day 45 if the patient is not yet eligible). Patients who experience disease progression and have not experienced DLTs at greater than or equal to 100 days post HSCT will be allowed to receive an optional second T cell infusion. After completion of study treatment, patients are followed up weekly for 1 month, monthly for 1 year, and then yearly for 15 years.