A Phase 1 Multicenter, Open Label Trial Evaluating the Safety and Efficacy of DuoCAR20.19.22-D95 in Adult Patients With Relapsed or Refractory B-cell Malignancies
University of Kansas Medical Center
Summary
This multicenter phase 1 trial with "3 + 3" dose escalation design seeks to examine the feasibility and safety of the administration of autologous T cells that have been modified through the introduction of chimeric antigen receptors targeting the B cell surface antigens CD19/20/22 following administration of a chemotherapy lymphodepletion regimen in adults with relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) or Non-Hodgkin's lymphoma (NHL). The overall goals of this study are to estimate maximum tolerated dose (MTD) level, establish the overall safety profile and evaluate initial efficacy of administering duo-CAR-T cell treatment in this patient population.
Description
Dose Escalation Cohort (Phase 1) This will have 3 enrollment groups: Group A: Participants with B-ALL (CAR pre-treated or CAR naïve), Group B: Participants with B-NHL (CAR pre-treated), Group C: Participants with B-NHL (CAR naïve) The trial will begin with a phase I dose escalation evaluation in each of the three enrollment groups. Participants will be treated either at dose level 1 and dose level -1 or at dose level 1 and dose level 2 of CAR T cells. This phase will determine the MTD and /or RP2D for the subsequent Phase 2 study. The trial duration for an individual participant is 15 years…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: 1. Ability of participant to understand this study, and participant willingness to sign a written informed consent 2. Women of childbearing potential must have a negative serum pregnancy test 48 hours prior to the start of preparatory regimen 3. Patients must have histologically confirmed aggressive B-Cell NHL or ALL as stated below: A. Patients with relapsed or refractory B-Cell ALL i. Demonstration of one or more antigens of interest (CD19, CD20, CD22) in most recent disease evaluation prior to study entry and within 30 days of study entry. ii. Patients with rela…
Interventions
- DrugDuoCAR20.19.22-D95
Patient derived autologous T cells, lentiviral transduced to generate, using the Miltenyi CliniMACS Prodigy® closed transduction system, a Duo-CAR-T cells targeting cell surface antigens CD19/20/22.
- DrugFludarabine (Conditional therapy)
Lymphodepletion chemotherapy
- DrugCyclophosphamide (Conditional therapy)
Lymphodepletion chemotherapy
Location
- University of Kansas Cancer CenterWestwood, Kansas