Pilot Study Of Redirected Autologous T Cells Engineered To Contain an Anti-BCMA scFv Coupled To TCRζ And 4-1BB Signaling Domains in Patients With Relapsed and/or Refractory Multiple Myeloma
Overview
- Phase
- Phase 1
- Intervention
- CART-BCMA
- Conditions
- Multiple Myeloma
- Sponsor
- University of Pennsylvania
- Enrollment
- 25
- Locations
- 1
- Primary Endpoint
- Number of Adverse Events
- Status
- Completed
- Last Updated
- 10 months ago
Overview
Brief Summary
Open-label, single-center, pilot study to assess the safety and feasibility of infusion of autologous T cells expressing BCMA (B-cell maturation antigen)-specific chimeric antigen receptors with tandem TCR and 4-1BB costimulatory domains (referred to as CART-BCMA ) in adult patients with multiple myeloma (MM). CART-BCMA cells will be given as a split dose intravenous infusion over 3 days. The duration of active intervention and monitoring is approximately 2 years.
Detailed Description
At entry subjects will undergo routine laboratory and imaging assessment of their multiple myeloma. Eligible subjects will undergo steady-state apheresis to obtain large numbers of peripheral blood mononuclear cells (PBMC) for CART-BCMA manufacturing. Cryopreserved historical apheresis products collected from the patient prior to study entry are usable for CART-BCMA manufacturing if collected at an appropriately certified apheresis center and the product meets adequate mononuclear cell yields. If a historical apheresis product is not available, an apheresis procedure will be scheduled for cell procurement after study entry. The T cells will be purified from the PBMC, transduced with TCRζ/4-1BB lentiviral vector, expanded in vitro and then frozen for future administration. The number of subjects who have inadequate T cell collections, expansion or manufacturing compared to the number of subjects who have CAR T cells successfully manufactured will be recorded; feasibility of product manufacturing is not expected to be problematic in this patient population.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Cohort 1
will receive 1-5x10\^7 CART-BCMA cells given as a split dose infusion over 3 days.
Intervention: CART-BCMA
Cohort 2
Cyclophosphamide infusion prior to 1-5x10\^7 CART BCMA cells given as a split dose infusion over 3 days.
Intervention: CART-BCMA
Cohort 3
Cyclophosphamide infusion prior to 1-5x10\^8 CART BCMA cells given as a split dose infusion over 3 days.
Intervention: CART-BCMA
Outcomes
Primary Outcomes
Number of Adverse Events
Time Frame: 2 years
Study related adverse events (defined as ≥ Grade 3 signs/symptoms according to CTCAE 4.03, laboratory toxicities, and clinical events) that are "possibly", "probably", or "definitely" related to study treatment any time from the first day of study treatment until end of study visit.