This phase II trial studies the effect of isatuximab, carfilzomib, and pomalidomide in treating patients with multiple myeloma that has come back (relapsed) or does not respond to treatment (refractory). Isatuximab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as pomalidomide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving isatuximab, carfilzomib, and pomalidomide may help treat patients with multiple myeloma.
PRIMARY OBJECTIVE: I. To assess the rate of response following treatment with isatuximab combined with carfilzomib and pomalidomide (isatuximab \[Isa\] carfilzomib \[Car\] pomalidomide \[Pom\]). SECONDARY OBJECTIVES: I. To evaluate the safety profile of the IsaCarPom combination. II. To assess duration of disease response following treatment with the IsaCarPom regimen. III. To assess depth of IsaCarPom treatment as it relates to timing of subsequent therapies. IV. To assess progression-free survival associated with IsaCarPom. V. To assess overall survival associated with IsaCarPom. EXPLORATORY OBJECTIVE: I. To molecularly assess the depth of IsaCarPom treatment by measuring minimal residual disease (MRD). OUTLINE: Patients receive isatuximab intravenously (IV) over 30-60 minutes on days 1, 8, 15, and 22 of cycle 1, and days 1 and 15 of subsequent cycles, carfilzomib IV over 10 to 30 minutes on days 1, 8, 15, and pomalidomide orally (PO) once daily (QD) on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 12 weeks for up to 24 months.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
5
OHSU Knight Cancer Institute
Portland, Oregon, United States
Overall response rate (ORR)
Defined as the proportion of participants who achieve a response \>= partial response (PR) (i.e., PR, very good partial response, complete response, or stringent complete response) according to International Myeloma Working Group criteria. ORR will be measured from start of study treatment (i.e., cycle 1 day 1) to the earliest of the following events: end of cycle 4, start of new anti-myeloma therapy, documented disease progression, or death. Will be evaluated using the response-evaluable analysis set. A point estimate and exact 95% confidence interval will be provided.
Time frame: Up to end of cycle 4 (each cycles is 28 days), disease progression, start of new anti-myeloma therapy, or death (whichever occurs first)
Incidence of grade > 2 toxicities
Evaluated per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0. Descriptive statistics will be used to summarize all on-study adverse events (AEs), grade 3-4 AEs, treatment-related AEs, grade 3-4 treatment-related AEs, SAEs, treatment-related severe (S)AEs, and AEs leading to study therapy discontinuation. Grade 3-4 laboratory abnormalities will be summarized using worst grade NCI CTCAE v5.0 criteria.
Time frame: Up to 30 days after discontinuing study treatment
Duration of response (DOR)
Defined for participants with a confirmed response (\>= PR) as the time between first documentation of response and disease progression according to IMWG criteria or death due to disease, whichever occurs first. Will be analyzed using the response-evaluable analysis set. Since non-progression, non-multiple myeloma (MM)-related death is a competing risk when assessing DOR, this endpoint will be estimated by cumulative incidence functions (one for progression or MM-related death, one for non-progression death) and modeled with Fine-Gray sub-distribution hazard regression.
Time frame: From initial disease response (>= PR) until disease progression, disease-related death, death from other cause (competing risk), or end of follow-up (censored), whichever occurs first, assessed up to 24 months
Time to next treatment
Will be estimated by the Kaplan-Meier method and modeled with Cox regression.
Time frame: From start of study regimen until start of new anti-myeloma therapy, death from any cause before new therapy, or end of follow-up (censored), whichever occurs first, assessed up to 24 months
Progression-free survival
Will be analyzed using the response-evaluable analysis set. Will be estimated by the Kaplan-Meier method and modeled with Cox regression.
Time frame: From start of study treatment until disease progression, death, or end of follow-up (censored), whichever occurs first, assessed up to 24 months
Overall survival
Will be estimated by the Kaplan-Meier method and modeled with Cox regression.
Time frame: From start of study treatment until death or last known alive (censored), assessed up to 24 months
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