NCT05702853

Metabolically Fit CD19 CAR T-cell Therapy With CD34 Selection in Patients With CD19+ Relapsed/Refractory NHL, CLL/SLL

A Phase 1b Dose Escalation Study of Metabolically Fit CD19 Chimeric Antigen Receptor (CAR) T Cells With CD34 Selection Markers in Adult Patients With Relapsed or Refractory CD19 B-Cell Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 27 (estimated)
• Sponsor: Medical University of South Carolina · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a single-center, nonrandomized, open-label dose-escalation study followed by dose-expansion of CD19- CD34t metabolically programmed CAR T-cell therapy in adult patients with relapsed or refractory CD19 B-cell non-Hodgkin lymphoma (NHL) or chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).

Detailed description

Although CD19 CAR T-cell therapy is a dynamic scientific and clinical breakthrough for CD19+ NHL, issues still remain in terms of relapse, toxicity, and availability. This trial will incorporate a CD34 tag (CD34t) into the CAR T-cell construct, thus allowing a more purified CAR T-cell product via CD34 selection. This purification step will hopefully lead to an improvement in safety/toxicity. Furthermore, the issue of CD19 CAR T-cell relapse has been linked to a lack of CAR T-cell fitness. With the knowledge that Th1 T-cell subsets have improved effector function and Th17 T-cell subsets have improved persistence, the investigators plan to expose the collected T-cells to priming conditions that lead to a metabolically enhanced CAR-T cell product akin to a Th1/17 hybrid cell. The investigators hypothesize that these metabolically programmed CD19 CAR-T cells will yield a high- quality product with enhanced persistence and anti-tumor efficacy when purified based on CD34t expression.

Conditions

• B-cell Non Hodgkin Lymphoma
• Chronic Lymphocytic Leukemia

Interventions

Type	Name	Description
DRUG	Cyclophosphamide injection	500 mg/m2 IV over 30-60 minutes +/- 10 minutes before Fludarabine Days -5, -4, - 3
DRUG	Fludarabine Injection	30 mg/m2 IV over 30-60 minutes +/- 10 minutes after cyclo- phosphamide infusion Days -5, 4, -3
BIOLOGICAL	CD19-CD34t metabolically programmed CAR transduced T-cells	Cells are to be infused intravenously (IV) over 30 minutes or less via nonfiltered tubing either by gravity or a peristaltic pump, gently agitating the bag during infusion to prevent cell clumping

Timeline

• Start date: 2023-11-06
• Primary completion: 2026-11-06
• Completion: 2026-12-30
• First posted: 2023-01-27
• Last updated: 2026-03-27

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study