CD19-Directed CAR-T Cell Therapy for the Treatment of Relapsed/Refractory B Cell Malignancies

Description

PRIMARY OBJECTIVE:

I. To determine the maximum tolerated dose of in-house, point of care manufactured autologous anti-CD19 CAR-expressing T-lymphocytes IC19/1563 (IC19/1563) in patient with relapsed/refractory B cell malignancies.

SECONDARY OBJECTIVES:

I. Assess the feasibility of in-house, point of care manufactured IC19/1563 cells.

II. Evaluate safety, including all grades of neurotoxicity (ICANS) and cytokine release syndrome as determined by the American Society for Transplantation and Cellular Therapy (ASTCT) criteria, by monitoring adverse events, laboratory abnormalities, vital signs, and other safety parameters.

III. Estimate the incidence of grade 3 or higher of neurotoxicity and cytokine release syndrome by grade 3 or higher neurotoxicity (ICANS) or CRS per the ASTCT criteria.

IV. Assess efficacy of a single dose of IC19/1563 cells:

IVa. Overall response rate (ORR); IVb. Duration of response (DOR); IVc. Progression-free survival (PFS); IVd. Minimal residual disease (MRD) negative bone marrow disease in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), based on one month post evaluation.

CORRELATIVE RESEARCH OBJECTIVES:

I. Characterize the in vivo cellular kinetics profile (levels, persistence, trafficking) of CAR19 transgene and CD3+CAR+ cells into blood.

II. Characterize the changes in cytokine levels over time. III. Assess hospital resource utilization and health economics.

OUTLINE: This is a dose-escalation study of IC19/1563.

Patients receive cyclophosphamide intravenously (IV) over 60 minutes and fludarabine IV over 30 minutes on days -5, -4, -3, or bendamustine IV over 10 minutes on days -4 and -3, and IC19/1563 IV on day 0. Patients also undergo bone marrow biopsy and aspiration, computed tomography/positron emission tomography (CT/PET) or CT scans, magnetic resonance imaging (MRI), and collection of blood and tumor samples throughout the trial.

After completion of study treatment, patients are followed up on days 60, every 3 months up to year 3, every 6 months from years 3-5, and then annually for up to 15.5 years.