NCT02772198

T-cells Expressing Anti-CD19 CAR in Pediatric and Young Adults With B-cell Malignancies

A Phase 1 / 2 Single Arm Study of T-cells Expressing Anti-CD19 Chimeric Antigen Receptor in Pediatric and Young Adult Patients With B-cell Malignancies

• Status: Unknown
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 300 (estimated)
• Sponsor: Sheba Medical Center · Other Government
• Sex: All
• Age: 1 Year – 50 Years
• Healthy volunteers: Not accepted

Summary

This phase 1 / 2 study will evaluate the response of B-cell malignancies expressing CD19 to autologous T cells transduced with a second generation anti-CD19 chimeric antigen receptor in children and young adults.

Detailed description

Autologous T cells transduced with chimeric antigen receptors (CAR) that recognize the CD19 antigen (CD19-CAR T cells) have been used in multiple clinical trials at several institutions worldwide. We established an in-house manufacturing process for CD19-CAR T cells with a CD28 (cluster of differentiation 28) costimulatory domain. Primary Objectives: 1. To study the safety of administration of CAR T cell at the Sheba Medical Center 2. To determine the feasibility and efficacy of administering anti-CD19-CAR T cells in children and young adults with B cell malignancies. Secondary Objectives 1. To study in vivo and in vitro behavior of CAR T cell in patients, including persistence, expansion, cytotoxic potential and exhaustion. 2. To study the cytokine milieu in CAR treated patients. Eligibility Patients 1-50 years of age, with a CD19-expressing B-cell malignancy that has recurred after, or not responded to, one or more standard chemotherapy-containing regimens. Design Peripheral blood mononuclear cells (PBMCs)will be obtained by leukapheresis. Anti-CD19 CAR T cells will be manufactured from fresh autologous PBMCs. PBMC will be cultured in the presence of anti-CD3 (cluster of differentiation 3) antibody and interleukin-2 followed by retroviral vector supernatant containing the anti-CD19 CAR. Total culture time is between 7-10 days. Patients will receive lymphodepleting chemotherapy composed of cyclophosphamide and fludarabine prior to cell infusion, and on day 0 will receive one million CAR T cells per kilogram. Patients will be monitored for toxicity including cytokine release syndrome, hematologic toxicities and B-cell aplasia; for response of their underlying malignancy; and for CAR-T cell persistence in the blood, marrow and cerebral spinal fluid (CSF).

Conditions

• Acute Lymphoblastic Leukemia, B-precursor
• Non-Hodgkin Lymphoma, B-cell

Interventions

Type	Name	Description
BIOLOGICAL	CD19 CAR T cells	Autologous T cells activated and transduced with a chimeric antigen receptor targeting CD19

Timeline

• Start date: 2016-11-01
• Primary completion: 2022-07-01
• Completion: 2022-11-01
• First posted: 2016-05-13
• Last updated: 2020-11-03

Locations

1 site across 1 country: Israel