This phase II trial studies the effects of iberdomide when given alone or in combination with dexamethasone in treating intermediate or high-risk smoldering multiple myeloma patients. Immunotherapy with iberdomide may induce changes in body's immune system and may interfere with the ability of cancer cells to grow and spread. Dexamethasone is a synthetic steroid (similar to steroid hormones produced naturally in the adrenal gland), and is used with other drugs in the treatment of some types of cancer. Giving iberdomide with dexamethasone my improve time to progression to symptomatic myeloma with improved tolerability.
PRIMARY OBJECTIVE: I. To determine the overall response rate (ORR) of iberdomide hydrochloride (iberdomide) and iberdomide with dexamethasone in intermediate- and high-risk smoldering multiple myeloma (SMM). SECONDARY OBJECTIVES: I. To determine the 1- and 2- year progression free survival rates of patients receiving iberdomide with and without dexamethasone in intermediate-risk and high-risk smoldering myeloma. II. To determine the time to progression, and overall survival of patients with intermediate- and high-risk smoldering myeloma receiving iberdomide with and without dexamethasone. III. To study the risk of adverse hematologic and non-hematologic events observed in patients receiving iberdomide with and without dexamethasone for treatment of intermediate- and high-risk smoldering myeloma. IV. To evaluate stem cell mobilization failure and early stem cell mobilization feasibility. TERTIARY/EXPLORATORY OBJECTIVES: I. To assess the effects of iberdomide on cereblon targets Aiolos and Ikaros in natural killer (NK)- and T- cells. II. To measure the effect of iberdomide with and without dexamethasone on T-cell and NK-cell counts and activation. III. To determine the prognostic impact of high-risk cytogenetic abnormalities on clinical outcomes. IV. To assess minimal residual disease (MRD) on bone marrow samples in subjects who achieved a complete response (CR) or better and evaluate the correlation between MRD status and clinical outcome measures. V. To assess the association between anti-tumor activity and immune cells in tumor and blood. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: Patients receive iberdomide hydrochloride orally (PO) once daily (QD) on days 1-21 and dexamethasone PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive iberdomide hydrochloride PO QD on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive iberdomide hydrochloride PO 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 for 4 weeks and then every 6 months thereafter.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
68
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, United States
RECRUITINGOverall response rate
Assessed per International Myeloma Working Group response criteria (to be done with serum and urine immunologic studies monthly; bone marrow biopsy and repeat imaging at either complete response or progressive disease).
Time frame: Up to 3 years
Progression-free survival
Will be estimated with the Kaplan-Meier method with 95% confidence interval (CI) for the two randomized arms separately and combined. Cox proportional hazards models will be further used to compare the two randomized arm with hazard ratio and its 95% CI reported.
Time frame: From start of protocol therapy to disease progression or death from any cause, whichever comes first, assessed at 1 and 2 years
Time to progression
Will be estimated with the Kaplan-Meier method with 95% CI for the two randomized arms separately and combined. Cox proportional hazards models will be further used to compare the two randomized arm with hazard ratio and its 95% CI reported.
Time frame: From start of protocol therapy to disease progression, assessed at 1 and 2 years
Overall survival
Will be estimated with the Kaplan-Meier method with 95% CI for the two randomized arms separately and combined. Cox proportional hazards models will be further used to compare the two randomized arm with hazard ratio and its 95% CI reported.
Time frame: From start of protocol therapy to death, censoring patients who are alive at last follow-up, assessed at 1 and 2 years
Rate of grade 3-4 adverse events
Adverse event data will be described and graded per the National Cancer Institute Common Terminology Criteria for Adverse Events guidelines. Grade 3-4 adverse events will be estimated as frequency and percentage, and then compared between the two patient groups using Chi-Square test.
Time frame: Up to 30 days after the last day of study participation
Successful stem cell mobilization
Defined as collection of 3.5 x 10\^6 CD34 cells per kilogram weight.
Time frame: Up to 3 years
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