This feasibility trial studies the efficacy of administering iberdomide (CC-220) as a priming agent prior to leukapheresis in patients with relapsed/refractory multiple myeloma (RRMM) who are already planned for standard-of-care CAR-T therapy. Giving iberdomide before CAR-T may improve T cell fitness which may improve CAR-T expansion kinetics and response after infusion.
In this feasibility study, patients with RRMM planned for standard of care CAR-T will be approached for consent for enrollment. Participating patients will receive one 28-day cycle of iberdomide at a dose of 1.0 mg daily, using a dosing schedule of 1.0 mg once daily for 21 days followed by 7 days off. After completion of the 28-day cycle, patients will proceed with leukapheresis on day 29 of therapy, with allowance for up to a 14-day delay in leukapheresis if needed. Blood samples will be collected on day 1 (prior to iberdomide exposure) and on the day of leukapheresis to compare T cell profiling before and after iberdomide priming. After leukapheresis, patients will proceed with standard of care management, including bridging therapy if indicated, until CAR-T infusion. After infusion, blood samples will be collected daily during initial hospitalization, then weekly for 1 month, and then monthly for up to 1 year. Blood samples will be evaluated for maximal CAR-T and ALC expansion and CAR-T persistence. Patients will be monitored per standard of care protocols for clinical efficacy and toxicity after CAR-T therapy for up to 1 year.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
22
1.0mg iberdomide capsules administered orally, daily on days 1-21 of a 28-day cycle
A procedure in which blood is collected and white blood cells (including T cells) are separated and collected. The remaining blood components are returned to the participant. The collected T cells will be used to manufacture the CAR-T cell therapy.
Participants will receive an intravenous infusion of standard-of-care CAR-T therapy manufactured from the participant's previously collected cells
Icahn School of Medicine at Mount Sinai
New York, New York, United States
Proportion of patients with T cell effector memory (TEM) expansion following iberdomide priming.
Proportion of patients with T cell effector memory (TEM) expansion following iberdomide priming, defined as an absolute increase of \>10 percentage points or a relative increase of \>50% in TEM cells.
Time frame: On the day of leukapheresis, after completing iberdomide therapy on Day 29
Change in Proportion of T cell subsets from baseline after iberdomide priming
Proportion of T cell subsets (including terminally differentiated effector, exhausted, and activated T cells) present for each participant in the feasibility evaluable (FE) population at leukapheresis (Priming D29 after iberdomide) to baseline (Priming-D1).
Time frame: On the day of leukapheresis, after completing iberdomide therapy on Day 29
Cmax with iberdomide priming prior to leukapheresis
Cmax is the highest measured concentration of iberdomide. Cmax will be assessed in the CAR-T evaluable (CARTE) population
Time frame: After CAR-T infusion at Day 14, Day 28, Month 3, Month 6, Month 12
Tmax with iberdomide priming prior to leukapheresis,
Time to reach Cmax. Tmax will be assessed in CAR-T (CARTE) population
Time frame: After CAR-T infusion at Day 14, Day 28, Month 3, Month 6, Month 12
AUC0-14 with iberdomide priming prior to leukapheresis
Total Exposure over time. AUC0-14 will be assessed in the CAR-T evaluable (CARTE) population.
Time frame: After CAR-T infusion at Day 14, Day 28, Month 3, Month 6, Month 12
CAR-T persistence with iberdomide priming prior to leukapheresis,
CAR-T persistence will track therapy effectiveness over time. CAR-T persistence will be assessed in the CAR-T evaluable (CARTE) population.
Time frame: After CAR-T infusion at Day 14, Day 28, Month 3, Month 6, Month 12
ALCmax with iberdomide priming prior to leukapheresis
Absolute Lymphocyte Count (ALC) is a key blood test measuring the exact number of lymphocytes. ALCmax measures the maximum count overtime. ALCmax will be assessed in the CAR-T evaluable (CARTE) population.
Time frame: After CAR-T infusion at Day 14, Day 28, Month 3, Month 6, Month 12
Time to ALCmax with iberdomide priming prior to leukapheresis
Time to reach absolute lymphocyte count maximum (ALCmax) in the CAR-T evaluable (CARTE) population.
Time frame: After CAR-T infusion at Day 14, Day 28, Month 3, Month 6, Month 12
Absolute lymphocyte count (ALC) expansion kinetics as a proxy for CAR-T expansion
Time frame: After CAR-T infusion at Day 14, Day 28, Month 3, Month 6, Month 12
Overall response rate
Overall response rate (ORR), defined as the proportion of patients that achieve at least a partial response according to IMWG criteria
Time frame: After CAR-T at Day 100 (~Month 3) and Month 12
Measurable residual disease
Rate of measurable residual disease (MRD)-negativity and MRD-negative complete response (CR) as defined by IMWG response criteria
Time frame: After CAR-T at Day 100 (~Month 3) and Month 12. Long-term follow-up for up to 5 years.
Progression-free survival
Progression-free survival (PFS), defined as the time from CAR-T infusion until progression by IMWG response criteria or death
Time frame: After CAR-T at Day 100 (~Month 3) and Month 12. Long-term follow-up for up to 5 years.
Overall survival
Overall survival (OS), defined as the time from CAR-T infusion until death
Time frame: After CAR-T at Day 100 (~Month 3) and Month 12. Long-term follow-up for up to 5 years.
Duration of response
Duration of response (DOR), defined as time from first observed response after CAR-T until progression by IMWG criteria
Time frame: After CAR-T at Day 100 (~Month 3) and Month 12. Long-term follow-up for up to 5 years.
Time to next treatment
Time to next treatment (TTNT), defined as the time from CAR-T infusion until initiation of the next line of myeloma-directed therapy for subsequent relapsed disease
Time frame: After CAR-T at Day 100 (~Month 3) and Month 12. Long-term follow-up for up to 5 years.
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