Despite recent therapeutic advances, multiple myeloma (MM) remains an incurable disease. Although survival has improved, there are nevertheless diminishing durations of response to each subsequent line of therapy. This highlights the need for further therapeutic innovation. BCMA-targeting CAR-T cells show impressive response rates; however, their median duration of response is disappointing. The investigators propose that CS1(SLAMF7)-targeting CAR-T cells will fill a gap in the MM armamentarium. CS1 is an attractive target in MM because it is expressed in most patients. Elotuzumab (Empliciti®), an approved anti-CS1 antibody, has proven the clinical efficacy of this target. CAR-T cells are an ideal modality to target CS1, given that two approved treatments, ide-cel (idecabtagene vicleucel, AbecmaTM) and cilta-cel (ciltacabtagene autoleucel, Carvykti™), have proven the potential for cellular immunotherapy in MM. The investigators are testing the safety and preliminary anti-myeloma efficacy of WS-CART-CS1, a CAR-T cell therapy targeting CS1.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
25
-Subject will be hospitalized for 7 days
* Cyclophosphamide 500 mg/m\^2 IV on Days -5, -4, and -3 * Fludarabine 30 mg/m\^2 IV on Days -5, -4, and -3
Washington University School of Medicine
St Louis, Missouri, United States
RECRUITINGPart A: Frequency and severity of treatment-emergent adverse events
* Graded by CTCAE v 5.0. * Adverse events will be tracked at the time of leukapheresis through 28 days post leukapheresis, to capture any AEs related to leukapheresis only. * Adverse events will then be collected beginning with lymphodepletion chemotherapy and continue through Day 100 post WS-CART-CS1 infusion or until initiation of another anticancer therapy, whichever occurs first. * After Day 100, only targeted AEs will be reported through 24 months after WS-CART-CS1 infusion or until disease progression or relapse, whichever occurs first. Targeted AEs include and are limited to secondary malignancies, CRS, ICANS, prolonged cytopenia (defined as Grade 3 neutropenia or thrombocytopenia lasting more than 28 days after WS-CART-CS1 infusion), and SAEs or SUSARs that are not attributable to progressive disease or extraneous causes.
Time frame: From leukapheresis through 24 months after WS-CART-CS1 infusion (approximately 24 months and 1 week)
Part A: Frequency of dose-limiting toxicities (DLTs)
DLTs are defined in the protocol.
Time frame: From WS-CART-CS1 infusion through 28 days
Part B: Frequency and severity of treatment-emergent adverse events
* Graded by CTCAE v 5.0. * Adverse events will be tracked at the time of leukapheresis through 28 days post leukapheresis, to capture any AEs related to leukapheresis only. * Adverse events will then be collected beginning with lymphodepletion chemotherapy and continue through Day 100 post WS-CART-CS1 infusion or until initiation of another anticancer therapy, whichever occurs first. * After Day 100, only targeted AEs will be reported through 24 months after WS-CART-CS1 infusion or until disease progression or relapse, whichever occurs first. Targeted AEs include and are limited to secondary malignancies, CRS, ICANS, prolonged cytopenia (defined as Grade 3 neutropenia or thrombocytopenia lasting more than 28 days after WS-CART-CS1 infusion), and SAEs or SUSARs that are not attributable to progressive disease or extraneous causes.
Time frame: From leukaphereis through 24 months after WS-CART-CS1 infusion (approximately 24 months and 1 week)
Part A MTD and Part B: Disease-specific objective response rate (ORR)
-Defined as stringent complete response (sCR), plus complete response (CR), plus very good partial response (VGPR), plus partial response (PR), plus minimal response (MR) in MM within 3 months of infusion using the International Myeloma Working Group (IMWG) response criteria in MM.
Time frame: Within 3 months of WS-CART-CS1 infusion
Part A MTD and Part B: Minimal residual disease (MRD) negativity in the marrow
-Based on next-generation flow (NGF), next-generation sequencing (NGS), or both
Time frame: Week 12
Part A MTD and Part B: Duration of response (DoR)
-DoR for subjects who respond to treatment is measured from the time measurement criteria are met for response (whichever is first recorded) until the first date that relapse or progression is objectively documented.
Time frame: -From response 24 months after WS-CART-CS1 infusion (estimated to be 24 months)
Part A MTD and Part B: Progression-free survival (PFS)
-PFS is measured from Day 0 to time of relapse, progression or death, whichever occurs first.
Time frame: From WS-CART-CS1 infusion through completion of follow-up (estimated to be 15 years)
Part A MTD and Part B: Overall survival (OS)
-OS is defined as the time from start of treatment (Day 0) to time of death.
Time frame: From WS-CART-CS1 infusion through completion of follow-up (estimated to be 15 years)
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