This phase II trial studies how well ixazomib citrate, lenalidomide, dexamethasone, and daratumumab work in treating patients with newly diagnosed multiple myeloma. Ixazomib citrate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as lenalidomide and dexamethasone, 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. Monoclonal antibodies, such as daratumumab, may block cancer growth in different ways by targeting certain cells. Giving ixazomib citrate, lenalidomide, dexamethasone, and daratumumab may work better in treating patients with newly diagnosed multiple myeloma.
PRIMARY OBJECTIVES: I. To determine the complete response rate (CR) of the four-drug combination of ixazomib, lenalidomide, dexamethasone and daratumumab in patients with previously untreated symptomatic multiple myeloma (MM). SECONDARY OBJECTIVES: I. To determine the overall response rate (ORR), and very good partial response (VGPR) rate with the four drug combination of ixazomib, lenalidomide, dexamethasone and daratumumab, when used as initial therapy in patients with previously untreated symptomatic MM. II. To determine the progression free survival and overall survival among patients with previously untreated symptomatic MM following treatment with the four drug combination of Ixazomib, lenalidomide, dexamethasone and daratumumab followed by ixazomib and daratumumab maintenance till progression. II. To determine the toxicities associated with the four drug combination of ixazomib, lenalidomide, dexamethasone and daratumumab in patients with previously untreated symptomatic MM. TERTIARY OBJECTIVES: I. To examine the proportion of minimal residual disease (MRD) negativity following induction therapy with the four-drug combination of ixazomib, lenalidomide, dexamethasone and daratumumab. II. To assess the quality of life using patient completed Functional Assessment of Cancer Treatment (FACT)/Gynecologic Oncology Group (GOG) questionnaires. OUTLINE: INDUCTION PHASE: Patients receive ixazomib citrate orally (PO) on days 1, 8, and 15 and lenalidomide PO on days 1-21. Patients receive daratumumab intravenously (IV) over 3-7 hours on days 1, 8, 15, and 22 of courses 1 and 2, on days 1 and 15 of courses 3, 4, and 5, and on day 1 of courses 7 and beyond. Patients also receive dexamethasone PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive ixazomib citrate PO on days 1, 8, and 15 and daratumumab IV over 3-7 hours on day 1. Courses repeat every 28 days for up to 36 months from registration in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 or 6 months.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
80
Given IV
Given PO
Given PO
Correlative studies
Given PO
Ancillary studies
Mayo Clinic
Rochester, Minnesota, United States
Proportion of Patients Who Achieve a Confirmed Complete Response (CR)
Time frame: 2 years
Proportion of Patients That Experienced a Grade 3 or Higher Adverse Event.
The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables are in the adverse event section of this report. The rate of patients that suffered a grade 3 or higher adverse event are reported here.
Time frame: 2 years
Overall Response Rate (ORR)
Will be estimated by the number of patients who achieve a stringent complete response (sCR), CR, VGPR or partial response (PR) divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true success proportions will be calculated.
Time frame: 2 years
Overall Survival (OS)
The distribution of overall survival will be estimated using the method of Kaplan-Meier.
Time frame: 2 years
Progression Free Survival
The distribution of progression-free survival will be estimated using the method of Kaplan-Meier.
Time frame: 2 years
Rate of >= Very Good Partial Response (VGPR)
Will be estimated by the number of patients with a VGPR, CR, or Stringent Complete Response (sCR) divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true success proportions will be calculated.
Time frame: 2 years
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