Anti-CD19 Chimeric Antigen Receptor (CAR)-Transduced T Cell Therapy for Patients With B Cell Malignancies

Lymphoma Clinical Trial

Official title: Genetically Engineered T Cells Expressing an Anti-CD19 Chimeric Antigen Receptor for Treatment of Patients With B Cell Malignancies

Status Recruiting

Clinical Trial Summary

Autologous T cells engineered to express an anti-CD19 chimeric antigen receptor (CAR) with a safety switch will be infused back to patients with B cell malignancies, including lymphoma and leukemia. The patients will be monitored after infusion of anti-CD19 CAR-transduced T cells for adverse events, persistence of anti-CD19 CAR-transduced T cells and treatment efficacy.

Objectives:

To evaluate the safety and the efficacy of anti-CD19 CAR-transduced T cell therapy for patients with B cell malignancies.

Eligibility:

Patients between 1 and 85 years of age, who have relapsed or refractory CD19-expressing B-cell malignancies (leukemia or lymphoma) that have not responded to standard treatments.

Patients with a history of allogeneic stem cell transplant who meet all eligibility criteria are eligible to participate.

Patients must have adequate organ functions.

Design:

• Peripheral blood from patients will be collected for isolation of peripheral blood mononuclear cells (PBMCs), which will be transduced with a lentiviral or retroviral vector encoding anti-CD19 CAR containing a CD28 and a CD3 zeta as costimulatory domains as well as a safety switch.

• Patients will receive a lymphodepleting preconditioning regimen to prepare their immune system to accept modified T cells.

• Patients will receive an infusion of their own modified T cells. They will remain in the hospital to be monitored for adverse events until they have recovered from the treatment.

• Patients will have frequent follow-up visits to monitor the persistence of modified T cells and efficacy of the treatment.

Clinical Trial Description

Despite progress has been made to date in the treatment of patients with B cell malignancies, including leukemia and lymphoma, many patients with relapsed or refractory diseases do not respond to the standard treatments. It has been shown that anti-CD19 CAR-transduced T cells may be an effective approach to treat the relapsed or refractory diseases. The procedure involves collecting PBMCs from the patients and modifying the T cells to attack the malignant B cells. In this trial, autologous T cells engineered to express an anti-CD19 chimeric antigen receptor (CAR) containing the signaling domains of CD28 and CD3-zeta, and a safety switch will be infused back to patients with B cell malignancies, including lymphoma and leukemia. The patients will be pretreated with a lymphodepleting preconditioning regimen before the infusion of anti-CD19 CAR T cells, and will be monitored for adverse events, persistence of anti-CD19 CAR-transduced T cells and the treatment efficacy.

OBJECTIVES:

• Primary objectives

• To determine the safety and feasibility of the administration of anti-CD19 CAR transduced T cells in patients with CD19+ B-cell malignancies.

• Secondary objectives:

• To determine if the treatment regimen can result in clinical regression of B-cell malignancies in the patients as described above.

• To determine the in vivo persistency of the anti-CD19 CAR-transduced T cells. ;

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Lymphocytic Leukemia
• Chronic Lymphocytic Leukemia
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Lymphoma
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

• NCT number: NCT02456350
• Study type: Interventional
• Source: Shenzhen Second People's Hospital
• Contact: Mingjun Wang, M.D., Ph.D.
• Phone: 15814723218
• Email: mingjunw429@163.com
• Status: Recruiting
• Phase: Phase 1
• Start date: April 2015
• Completion date: December 2019