NCT03076437

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

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 28 (actual)
• Sponsor: Shenzhen Institute for Innovation and Translational Medicine · Academic / Other
• Sex: All
• Age: 1 Year – 80 Years
• Healthy volunteers: Not accepted

Summary

Autologous T cells engineered to express an anti-CD19 chimeric antigen receptor (CAR) 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 80 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 or 4-1BB and a CD3 zeta as costimulatory domains. 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.

Detailed 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 or 4-1BB and CD3-zeta 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.

Conditions

• Acute Lymphocytic Leukemia
• Chronic Lymphocytic Leukemia
• Lymphoma

Interventions

Type	Name	Description
COMBINATION_PRODUCT	Drugs and Anti-CD19-CAR transduced T cells	Drug: Fludarabine On days -4 through -2, Fludarabine 30mg/m2 IV will be infused over 30 minutes. Drug: Cyclophosphamide On days -4 through -2, Cyclophosphamide 300mg/m2 IV will be infused over 60 minutes followed by fludarabine. Biological: Anti-CD19-CAR transduced T cells Modified cells will be infused IV over 30 minutes (1-3 days after the last dose of fludarabine).

Timeline

• Start date: 2016-01-15
• Primary completion: 2019-05-26
• Completion: 2019-12-31
• First posted: 2017-03-10
• Last updated: 2021-03-19

Locations

1 site across 1 country: China