This phase III trial compares three-drug induction regimens followed by double-or single-drug maintenance therapy for the treatment of newly diagnosed multiple myeloma in patients who are not receiving a stem cell transplant and are considered frail or intermediate-fit based on age, comorbidities, and functional status. Treatment for multiple myeloma includes initial treatment (induction) which is the first treatment a patient receives for cancer followed by ongoing treatment (maintenance) which is given after initial treatment to help keep the cancer from coming back. There are three combinations of four different drugs being studied. Bortezomib is one of the drugs that may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Lenalidomide works by helping bone marrow to produce normal blood cells and killing cancer cells. 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. Daratumumab and hyaluronidase-fihj is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Patients receive 1 of 3 combinations of these drugs for treatment to determine which combination of study drugs works better to shrink and control multiple myeloma.
Participants must have documented multiple myeloma satisfying standard International Myeloma Working Group (IMWG) diagnostic criteria within 28 days prior to registration
Immunoglobulin (Ig) G myeloma (serum monoclonal paraprotein [M-protein] level >= 0.5 gram/deciliter [g/dL] or urine M-protein level >= 200 milligram[mg]/24 hours[hrs]); OR
IgA, IgM, IgD, or IgE multiple myeloma (serum M-protein level >= 0.2 g/dL or urine M-protein level >= 200 mg/24 hrs); OR
Light chain multiple myeloma (serum immunoglobulin free light chain >= 10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio)
An emergency use of a short course of corticosteroids (equivalent of dexamethasone 160 mg) any time before registration, or
Up to one complete cycle of a non-daratumumab and hyaluronidase-fihj containing anti-myeloma regimen (1 cycle = 21 or 28 days depending on the regimen being used), or
Localized palliative radiation therapy for multiple myeloma, as long as the radiation therapy is completed at least 3 days prior to starting the systemic treatment as per the study protocol.
Participants must not have evidence of grade 4 peripheral neuropathy prior to study registration
Parallel
Bortezomib
DrugGiven SC
Daratumumab and Hyaluronidase-fihj
DrugGiven SC
Dexamethasone
DrugGiven PO
Lenalidomide
DrugGiven PO
Quality-of-Life Assessment
Other interventionAncillary studies
Questionnaire Administration
Other interventionAncillary studies
Progression free survival (PFS) of Arm 1 versus (vs.) Arm 2
Analysis of each of the dual primary endpoints will be performed using a stratified log-rank test for comparison between arms. The analyses will be stratified according to frailty score (frail vs. intermediate fit), presence of one or more high-risk abnormalities by fluorescence in situ hybridization (iFISH) (yes vs. no), and prior therapy (yes vs. no). All eligible participants will be considered in analyses of the dual primary endpoints, according to their assigned arm at randomization.
Overall survival (OS) of Arm 1 vs. Arm 3
Analysis of each of the dual primary endpoints will be performed using a stratified log-rank test for comparison between arms. The analyses will be stratified according to frailty score (frail vs. intermediate fit), presence of one or more high-risk abnormalities by iFISH (yes vs. no), and prior therapy (yes vs. no). All eligible participants will be considered in analyses of the dual primary endpoints, according to their assigned arm at randomization.
PFS
Analysis of PFS and OS endpoints will be performed using a stratified log-rank test for comparison between arms, with stratification according to frailty score (frail vs. intermediate fit) presence of one or more high-risk abnormalities by iFISH (yes vs. no) and prior therapy (yes vs. no).
OS
Analysis of PFS and OS endpoints will be performed using a stratified log-rank test for comparison between arms, with stratification according to frailty score (frail vs. intermediate fit) presence of one or more high-risk abnormalities by iFISH (yes vs. no) and prior therapy (yes vs. no).
Overall response rate (ORR)
ORR is defined as the percentage of participants achieving a best response of partial response (PR) or better while on study. ORR will be reported with a binomial confidence interval. Time to response will be analyzed using the cumulative incidence competing risks method.
Time to complete response (CR)
All eligible participants will be considered in analyses of the secondary endpoints, according to their assigned arm at randomization, and with participants who go off-study prior to response assessment considered as non-responders for the analysis of response rate and as censored at the time of removal from study for the analysis of time to response. Time to response will be analyzed using the cumulative incidence competing risks method.
Click on the lead sponsor to view all of their trials.
SWOG Cancer Research Network
Lead sponsor
National Cancer Institute (NCI)
Collaborator
