This phase II trial studies the effect of isatuximab, carfilzomib, pomalidomide, and dexamethasone 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 proteins needed for cell growth. Pomalidomide may help shrink or slow the growth of multiple myeloma. Anti-inflammatory drugs, such as dexamethasone lower the body's immune response and are used with other drugs in the treatment of some types of cancer. Giving isatuximab, carfilzomib, pomalidomide, and dexamethasone may kill more cancer cells.
OUTLINE: INDUCTION: Patients receive isatuximab intravenously (IV) on days 1, 8, 15, and 22 of cycle 1 and days 1 and 15 of subsequent cycles carfilzomib IV over 30 minutes on days 1, 8, and 15, pomalidomide orally (PO) once daily (QD) on days 1-21, and dexamethasone PO or IV on days 1,8, 15, and 22. Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive isatuximab IV days 1 and 15, carfilzomib IV over 30 minutes on days 1 and 15, pomalidomide PO QD on days 1-21, and dexamethasone PO or IV on days 1, 8, 15, and 22. Cycles repeat every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity. All patients undergo bone marrow aspirate and biopsy during screening, skeletal x-ray, computed tomography (CT), positron emission tomography (PET)-CT, or magnetic resonance imaging (MRI), bone marrow and blood sample collection throughout the study. After completion of study treatment, patients are followed up at 30 days, then for up to 5 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Given IV
Given PO or IV
Given IV
Given PO
Undergo bone marrow biopsy
Undergo bone marrow aspiration
Undergo skeletal x-ray
Undergo CT
Undergo PET-CT
Undergo MRI
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States
Overall response rate
Responses will be based on the International Myeloma Working Group criteria for response in multiple myeloma.
Time frame: Up to 5 years post treatment
Progression-free survival (PFS)
PFS will be calculated using assessments by investigators. Kaplan-Meier methodology will be used to estimate event-free curves and corresponding quartiles (including the median).
Time frame: From first study drug administration to the first occurrence of disease progression or death from any cause, assessed up to 5 years
Overall survival
Kaplan-Meier methodology will be used to estimate the event-free curves.
Time frame: From the first study drug administration to death from any cause, assessed up to 5 years
Duration of response
Time frame: Up to 5 years post treatment
Time to progression
Time frame: Up to 5 years post treatment
Incidence of adverse events
Will be measured by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
Time frame: Up to 30 days post treatment
Rates of minimal residual disease negativity
Measured by next-generation sequencing of immunoglobulin genes in the bone marrow.
Time frame: Up to 5 years post treatment
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