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
Medical University of South Carolina
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).
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 im…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: Patients eligible for study participation must meet all of the following criteria: 1. Disease Related Criteria Participants must have histologic confirmation of one of the following: 1. CD19+ aggressive non-Hodgkin lymphoma including any of the following subtypes * Diffuse Large B-cell Lymphoma, not otherwise specified * DLBCL, germinal-center B-cell type (GCB) * DLBCL, activated B-cell type (ABC) * T-cell histiocyte-rich B-cell lymphomas (THRBCL) * Primary cutaneous DLBCL, leg type * Intravascular large B cell lymphoma *…
Interventions
- DrugCyclophosphamide injection
500 mg/m2 IV over 30-60 minutes +/- 10 minutes before Fludarabine Days -5, -4, - 3
- DrugFludarabine Injection
30 mg/m2 IV over 30-60 minutes +/- 10 minutes after cyclo- phosphamide infusion Days -5, 4, -3
- BiologicalCD19-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
Location
- Hollings Cancer Center at Medical University of South CarolinaCharleston, South Carolina