NCT02652910

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

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: Unknown
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Sponsor: Xinqiao Hospital of Chongqing · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

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.

Detailed 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

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

Type	Name	Description
DRUG	CD19.CAR-T cells	Retroviral vector-transduced autologous T cells to express CD19-specific CARs

Timeline

• Start date: 2015-12-01
• Primary completion: 2019-06-01
• Completion: 2019-12-01
• First posted: 2016-01-12
• Last updated: 2019-02-27

Locations

1 site across 1 country: China