Memory-enriched CAR-T Cells Immunotherapy for B Cell Lymphoma — MeCAR  

Recurrent Mantle Cell Lymphoma Clinical Trial

Official title: A Two-Arm, Single-Center, Open-Label Pilot Study of IL-2 Programmed or IL-7/IL-15 Programmed Anti-CD19:TCRz:CD28 T-cells in Patient With CD19-Positive Lymphoma That is Resistant or Refractory to Chemotherapy

Status Recruiting

Clinical Trial Summary

The goal of this clinical trial is to study how approaches for manufacturing chimeric antigen receptor (CAR)-modified T (CAR-T) cells affect their in vivo persistence and therapeutic efficacy against B lymphoma. Recently, cancer immunotherapy, treatments aiming to arm patients with immunity specifically against cancer cells, has emerged as a promising therapeutic strategy. Among the many emerging immunotherapeutic approaches, clinical trials utilizing CARs against B cell malignancies have demonstrated remarkable potential. CARs combine the variable region of an antibody with T-cell signaling moieties to confer T-cell activation with the targeting specificity of an antibody. Thus, CARs are not MHC-restricted so they are not vulnerable to MHC down regulation by tumors. However, defined by the activation and contraction program of their mother cells, the persistency and function of CAR-T cells are also restricted by the protocol of manufacturing. Previous clinical studies largely utilized interleukin-2 (IL-2) for the ex vivo expansion of CAR-T cells, which preferentially generate CAR-T cells with characteristics of terminally differentiated effector cells. Our preliminary data indicated that two common gamma chain cytokines, IL-7 and IL-15, can help to selectively expand CAR-T cells with various memory phenotypes. CAR-T Cells prepared under this condition resulted in improved therapeutic efficacy in preclinical animal models. This clinical investigation is to test a hypothesis whether IL-7/IL-15-programmed anti-CD19 CAR-T cells persist longer in lymphoma patients after infusion and whether the persistency of CAR-T cells can lead to improved anti-lymphoma efficacy.

Clinical Trial Description

Primary Objectives

1. To determine the safety and feasibility of CD19.CAR-T cells manufactured through IL-7/IL-15-mediated expansion or IL-2-mediated expansion

2. To determine in vivo dynamics and persistency of IL-7/IL-15 programmed CD19.CAR-T cells.

3. To determine the efficacy of IL-7/IL-15 programmed CD19.CAR-T cells in treating patients with CD19-positive lymphoma

Secondary Objectives

1. To determine whether the IL-7/IL-15 programmed CD19.CAR-T cells are superior to the IL-2 programmed cells as measured by their in vivo persistence post infusion

2. To determine whether the IL-7/IL-15 programmed CD19.CAR-T cells are superior to the IL-2 programmed cells as measured by their efficacy in lymphoma therapy

3. To assess the dynamics of intratumoral infiltration of CD19.CAR-T cells.

4. To correlate the subsets and differentiation of CD19.CAR-T cells to observed anti-tumor efficacy ;

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Follicular
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Mantle-Cell
• Lymphoma, Non-Hodgkin
• Recurrent Adult Diffuse Large Cell Lymphoma
• Recurrent Follicular Lymphoma
• Recurrent Mantle Cell Lymphoma
• Stage III Adult Diffuse Large Cell Lymphoma
• Stage III Follicular Lymphoma
• Stage III Mantle Cell Lymphoma
• Stage IV Adult Diffuse Large Cell Lymphoma
• Stage IV Follicular Lymphoma
• Stage IV Mantle Cell Lymphoma

• NCT number: NCT02652910
• Study type: Interventional
• Source: Xinqiao Hospital of Chongqing
• Contact: Qingzhu Jia, M.D.
• Phone: +(86)-152-2333-4184
• Email: jiaqingzhu0801@outlook.com
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: December 2015
• Completion date: December 2019