Title
A Phase II Study of CART-ddBCMA for the Treatment of Patients with Relapsed or Refractory Multiple Myeloma

Description
This is a Phase II open-label study of CART-ddBCMA* in patients with relapsed or refractory multiple myeloma (MM). The study will have the following sequential phases: screening, enrollment, pre-treatment with lymphodepleting chemotherapy, treatment with CART-ddBCMA, and follow-up. If necessary, bridging therapy is allowed to control growth of MM disease while CART-ddBCMA is being manufactured.

Following a single infusion of CART-ddBCMA both safety and efficacy data will be assessed. Efficacy will be assessed monthly for the first 6 months, then quarterly up to 2 years, or upon patient relapse. The primary analysis will be conducted approximately 13 months after the final patient is dosed. This will allow approximately 12 months follow up from the time of the last observed response on study.

Long-term safety data will be collected under a separate long-term follow up study for up to 15 years per health authority guidelines.

*CART-ddBCMA drug product consists of autologous T cells that have been genetically modified ex vivo to express a D-domain Chimeric Antigen Receptor (CAR), followed by a cluster of differentiation 8 (CD8) hinge and transmembrane region that is fused to the intracellular signaling domains for 4-1BB and CD3ξ, that specifically recognizes B-cell maturation antigen (BCMA). The active substance of CART-ddBCMA is CAR+ CD3+ T cells that have undergone ex vivo T-cell activation, gene transfer by replication-deficient lentiviral vector, and expansion.

Objective
Primary:
-To determine the efficacy, as assessed by ORR, of CARTddBCMA in subjects with relapsed or refractory multiple myeloma (RRMM).
Secondary:
-To determine the efficacy, as assessed by ORR, of CART-ddBCMA in subjects with relapsed or refractory multiple myeloma (RRMM) limited to three lines of prior treatment
-To further characterize the safety of CART-ddBCMA in subjects with RRMM
-To describe depth (i.e., rate of CR/sCR, VGPR, PR) and duration of responses (DoR), progression free survival (PFS), Time to Progression (TTP), and Overall Survival (OS)
-To characterize the cell expansion kinetics of CART-ddBCMA in terms of peak quantification in peripheral blood, timing of peak expansion, relationship of peak expansion timing and quantification to efficacy and toxicity as assessed by vector copy
number (VCN)
-To characterize cell persistence of CART-ddBCMA and relationship to efficacy as assessed by vector copy number (VCN) measurability at each timepoint
-To characterize the anti-CART-ddBCMA antibody response in subjects with RRMM
-To characterize the impact of baseline tumor burden in patients with RRMM on efficacy, safety, and cell expansion
-To characterize the frequency with which minimal residual disease (MRD) becomes undetectable (i.e., MRD-negative) in subjects with RRMM after treatment with CARTddBCMA and assess the relationship of MRD-negativity to ORR, CR/sCR rate, DoR, PFS, TTP, and OS
-To characterize the impact of CART-ddBCMA in subjects with RRMM on healthrelated quality of life (HRQoL) using the EQ-5D-5L, EORTC-QLQ-C30, and EORTCQLQ- My20 quality of life assessments.

Treatment Experimental: CART-ddBCMA
Single dose of 115±10 x 10e-6 CAR+ CART-ddBCMA cells infused intravenously
Biological: CART-ddBCMA
BCMA-directed CAR T-cell therapy using a novel, synthetic binding domain, called a D-domain

Key Eligibility For full study eligibility, see this study's ClinicalTrials.gov record.

Applicable Disease Sites
Multiple Myeloma

Participating Institutions
UW Health University Hospital