NCT04892277

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

Phase I Dose Escalation Trial of CD19 Directed Chimeric Antigen Receptor T Cell Therapy in the Treatment of Relapsed/Refractory B Cell Malignancies

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 25 (estimated)
• Sponsor: Mayo Clinic · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies the effects of CD-19 directed chimeric antigen receptor (CAR)-T cell therapy for the treatment of patients with B cell malignancies that have come back (recurrent) or have not responded to treatment (refractory). CD-19 CAR-T cells use some of a patient's own immune cells, called T cells, to kill cancer. T cells fight infections and, in some cases, can also kill cancer cells. Some T cells are removed from the blood, and then laboratory, researchers will put a new gene into the T cells. This gene allows the T cells to recognize and possibly treat cancer. The new modified T cells are called the IC19/1563 treatment. IC19/1563 may help treat patients with relapsed/refractory B cell malignancies.

Detailed 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.

Conditions

• Recurrent B-Cell Non-Hodgkin Lymphoma
• Recurrent Chronic Lymphocytic Leukemia
• Recurrent Small Lymphocytic Lymphoma
• Recurrent Transformed Chronic Lymphocytic Leukemia
• Refractory B-Cell Non-Hodgkin Lymphoma
• Refractory Chronic Lymphocytic Leukemia
• Refractory Small Lymphocytic Lymphoma
• Refractory Transformed Chronic Lymphocytic Leukemia

Interventions

Type	Name	Description
BIOLOGICAL	Autologous Anti-CD19 CAR-expressing T-lymphocytes IC19/1563	Given IV
DRUG	Bendamustine	Given IV
PROCEDURE	Biospecimen Collection	Undergo collection of blood and tissue samples
PROCEDURE	Bone Marrow Aspiration	Undergo bone marrow aspiration
PROCEDURE	Bone Marrow Biopsy	Undergo bone marrow biopsy
PROCEDURE	Computed Tomography	Undergo CT
DRUG	Cyclophosphamide	Given IV
DRUG	Fludarabine	Given IV
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
PROCEDURE	Positron Emission Tomography	Undergo CT/PET

Timeline

• Start date: 2022-10-03
• Primary completion: 2028-03-27
• Completion: 2040-03-27
• First posted: 2021-05-19
• Last updated: 2025-07-01

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study