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

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.

Conditions

• 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

Interventions

DRUG

CD19.CAR-T cells

Retroviral vector-transduced autologous T cells to express CD19-specific CARs

Sponsors & Collaborators

• Xuzhou Medical University

  collaborator OTHER

• Hrain Biotechnology Co., Ltd.

  collaborator INDUSTRY

• Shanghai Changzheng Hospital

  collaborator OTHER

• Xinqiao Hospital of Chongqing

  lead OTHER

Principal Investigators

• Bo Zhu, M.D., Ph.D. · Department of Cancer of Xinqiao Hospital

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

70 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2015-12-31

Primary Completion

2019-06-30

Completion

2019-12-31

Countries

• China

Study Locations