Recurrent Mantle Cell Lymphoma Clinical Trial
Official title:
Phase I Study to Evaluate Cellular Immunotherapy Using Memory-Enriched T Cells Lentivirally Transduced to Express a CD19-Specific, Hinge-Optimized, CD28-Costimulatory Chimeric Receptor and a Truncated EGFR Following Lymphodepleting Chemotherapy in Adult Patients With CD19+ B-Cell Lymphoproliferative Neoplasms
This phase I trial studies the side effects and best dose of cellular immunotherapy following chemotherapy in treating patients with non-Hodgkin lymphomas, chronic lymphocytic leukemia, or B-cell prolymphocytic leukemia that has come back. Placing a modified gene into white blood cells may help the body build an immune response to kill cancer cells.
PRIMARY OBJECTIVES: I. To assess the safety of adoptive therapy using ex vivo expanded autologous memory T cells (central memory T cells [Tcm] or naive and memory T-cells [Tn/mem]) that are enriched and genetically modified to express a cluster of differentiation (CD)19-specific, hinged optimized, CD28-costimulatory chimeric antigen receptor (CAR) as well as a truncated human epidermal growth factor receptor (EGFR) (CD19R[EQ]28zeta/truncated EGFR [EGFRt]+ Tcm or CD19R[EQ]28zeta/EGFRt+ Tn/mem) shortly following lymphodepletion for adults with recurrent/progressive/residual CD19 + B-cell lymphoproliferative neoplasms (non-Hodgkin lymphoma [NHL], chronic lymphocytic leukemia [CLL]/prolymphocytic leukemia [PLL]) and who are not eligible for or decline City of Hope (COH) Institutional Review Board (IRB) Protocol Number (No.) 13277. II. To determine the recommended Phase II dose (RP2D) in the two Tn/mem strata (NHL; CLL/PLL). SECONDARY OBJECTIVE: I. To study antitumor activity of CD19R(EQ)CD28zeta/EGFRt+Tcm or CD19R[EQ]28zeta/EGFRt+ Tn/mem (e.g., detection of CAR+ T cells, B cells, and tumor burden). OUTLINE: This is a dose-escalation study of autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing enriched T cells (T-cell infusion). Participants are assigned to 1 of 2 groups based on disease status. GROUP I (NON-HODGKIN LYMPHOMA [NHL]): LYMPHODEPLETING REGIMEN: Patients receive a chemotherapy regimen based on disease type and extent of disease comprising of cyclophosphamide, bendamustine hydrochloride, fludarabine phosphate, etoposide. CELLULAR IMMUNOTHERAPY: Beginning 3-10 days later after lymphodepletion, patients receive autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/mem-enriched T-lymphocytes IV over 10-15 minutes on day 0. Patients with relapsed, residual or progressive disease may receive an optional second infusion of autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/mem-enriched T-lymphocytes >= 28 days post T cell infusion. GROUP II (CHRONIC LYMPHOCYTIC LEUKEMIA [CLL] AND/OR PROLYMPHOCYTIC LEUKEMIA [PLL]): LYMPHODEPLETING REGIMEN: Patients receive a chemotherapy regimen based on disease type and extent of disease comprising of cyclophosphamide, bendamustine hydrochloride, fludarabine phosphate, etoposide. CELLULAR IMMUNOTHERAPY: Beginning 3-10 days later after lymphodepletion, patients receive autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/mem-enriched T-lymphocytes IV over 10-15 minutes on day 0. Patients with relapsed, residual or progressive disease may receive an optional second infusion of autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/mem-enriched T-lymphocytes >= 28 days post T cell infusion. After completion of study treatment, patients are followed up at every 2 days for 14 days, weekly for 1 month, monthly for 1 year, and then yearly for at least 15 years. ;
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