The purpose of this study is to compare the efficacy (rate of very good partial response \[VGPR\] or better as best response as defined by the International Myeloma Working Group \[IMWG\] criteria) of daratumumab subcutaneous (Dara-SC) in combination with carfilzomib and dexamethasone (Kd) with the efficacy of Kd in participants with relapsed refractory multiple myeloma who were previously exposed to daratumumab to evaluate daratumumab retreatment.
For relapsed or refractory multiple myeloma, the treatment is determined on an individual basis. Common standard of care regimens use either a proteasome inhibitor (PI) or an immunomodulatory agent (IMiD) in combination with dexamethasone with or without a monoclonal antibody (mAb) such as daratumumab. After relapse from PIs or IMiDs, patients are often retreated with drugs that have same mechanism of action to which they have been sensitive. The disease becomes refractory and all effective treatment options are exhausted. Daratumumab is a human IgG1 mAb that binds with high affinity to unique epitope on cluster of differentiation 38 (CD38) and attacks tumor cells that overexpress CD38. Study is to determine the efficacy of Dara-SC in combination with carfilzomib and dexamethasone (DKd) in adult participants with relapsed refractory MM who had 1 to 3 prior line(s) of treatment including a line containing daratumumab to evaluate daratumumab retreatment. The MM treatment is determined on an individual basis where patient's age, prior therapy, bone marrow function, co-morbidities, patient preference and time to relapse are considered. Common standard of care regimens use either PI or an IMiD in combination with dexamethasone with or without a mAb. It is a targeted immunotherapy that attacks tumor cells that overexpress CD38, a transmembrane glycoprotein, in a variety of hematological malignancies including multiple myeloma. The study will be conducted in 3 phases: Screening (28 days), Treatment, and Follow-Up. Assessments like chest X-ray, spirometry test, electrocardiogram (ECG), will be performed during Screening phase. During the Treatment Phase, participants will be randomized to receive Kd or DKd. Efficacy assessments like bone marrow examination will be performed. Follow-up will continue until the end of study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
Carfilzomib 20 mg/m\^2 will be administered intravenously (IV).
Carfilzomib 70 mg/m\^2 will be administered IV.
Dexamethasone 40 mg will be administered as IV infusion or orally.
Percentage of Participants Achieving Very Good Partial Response (VGPR) or Better Response
Percentage of participants achieving VGPR or better response were reported. VGPR or better rate was defined as the percentage of participants achieving VGPR, complete response (CR), or stringent complete response (sCR) in accordance with the International Myeloma Working Group (IMWG) criteria, during or after the study treatment but before the start of subsequent anti-myeloma therapy. IMWG criteria for VGPR: Serum and urine M-component detectable by immunofixation but not on electrophoresis, or greater than or equal to (\>=) 90 percent (%) reduction in serum M-protein plus urine M-protein less than (\<) 100 milligram (mg)/24 hours; for CR: Negative immunofixation on the serum and urine, and Disappearance of any soft tissue plasmacytomas (PCs), and \<5% PCs in bone marrow; for sCR: CR plus normal free light chain (FLC) ratio, and Absence of clonal PCs by immunohistochemistry, immunofluorescence or 2- to 4- color flow cytometry.
Time frame: Up to 3 years and 4 months
Overall Response Rate (ORR)
ORR was defined as the percentage of participants who achieved partial response (PR) or better responses based on the computerized algorithm, in accordance with the IMWG criteria, during or after the study treatment but before the start of subsequent anti-myeloma therapy. IMWG criteria for PR: greater than or equal to (\>=)50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by \>=90% or less than (\<)200 mg/24 hours; If the serum and urine M-protein were not measurable, a decrease of \>=50% in the difference between involved and uninvolved free light chain (FLC) levels was required in place of the M-protein criteria; If serum and urine M-protein were not measurable, and serum free light assay is also not measurable, \>=50% reduction in bone marrow plasma cells (PCs) was required in place of M-protein, provided baseline bone marrow plasma cell percentage was \>=30%; additionally, if present at baseline, \>=50% reduction in the size of soft tissue PCs was also required.
Time frame: Up to 3 years and 7 months
Percentage of Participants Achieving Complete Response (CR) or Better
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TREATMENT
Masking
NONE
Enrollment
88
Dara-SC 1800 mg will be administered by SC injection.
Dexamethasone 20 mg will be administered as IV infusion or orally.
Banner MD Anderson Cancer Center
Gilbert, Arizona, United States
Oncology Institute of Hope and Innovation
Tucson, Arizona, United States
American Institute of Research (AIR)
Whittier, California, United States
Fort Wayne Medical Oncology and Hematology, Inc.
Fort Wayne, Indiana, United States
Karmanos Cancer Institute - Wayne State University
Detroit, Michigan, United States
Mayo Clinic - Rochester
Rochester, Minnesota, United States
Washington University School Of Medicine
St Louis, Missouri, United States
Weill Medical College of Cornell University
New York, New York, United States
Cleveland Clinic Main Campus
Cleveland, Ohio, United States
Baylor Scott and White Health
Dallas, Texas, United States
...and 98 more locations
Percentage of participants achieving CR or better were reported. CR or better rate was defined as the percentage of participants achieving CR or sCR based on the computerized algorithm, according to IMWG response criteria. IMWG criteria for CR: Negative immunofixation on the serum and urine, and Disappearance of any soft tissue plasmacytomas (PCs), and \<5% PCs in bone marrow.
Time frame: Up to 3 years and 7 months
Progression Free Survival (PFS)
PFS was defined as the duration from the date of randomization to either progressive disease (PD) or death, whichever comes first. IMWG criteria for PD: \>=25% from lowest response level in serum M-component (the absolute increase must be \>=0.5 gram per deciliter \[g/dL\]) and/or in urine M-component (the absolute increase must be \>=200 mg/24 hour); only in participants without measurable serum and urine M-protein levels: increase of \>=25% in the difference between involved and uninvolved free light chain levels and the absolute increase must be \>10 mg/dL. BMPC%: the absolute % must be \>=10%; definite increase in size of existing bone lesions or soft tissue plasmacytomas; definite development of new bone lesions or soft tissue plasmacytomas; development of hypercalcemia (corrected serum calcium \>11.5 milligrams per deciliter (mg/dL) or 2.65 millimoles per liter \[mmol/L\]) that can be attributed solely to PC proliferative disorder.
Time frame: Up to 3 years and 7 months
Overall Survival (OS)
OS was defined as the time from the date of randomization to the date of the participant's death due to any cause.
Time frame: Up to 3 years and 7 months
Percentage of Participants With Negative Minimal Residual Disease (MRD)
Percentage of participants with negative MRD were reported. MRD negativity rate, defined as the percentage of participants who had MRD negative status at 10\^-5 by bone marrow aspirate after the date of randomization and prior to PD or subsequent anti-myeloma therapy.
Time frame: Up to 3 years and 7 months
Time to Next Treatment
Time to next treatment was defined as the time from randomization to the start of the next-line treatment.
Time frame: Up to 3 years and 7 months
Serum Concentrations of Daratumumab
Serum concentrations of daratumumab were assessed. This outcome measure was planned to be analyzed for specified arm only.
Time frame: Day 1 of Cycles 1, 3, and 7 (each cycle of 28 days) and Follow Up (post treatment Week 8; up to 30.3 months)
Number of Participants With Anti-recombinant Human Hyaluronidase (rHuPH20) Antibodies
The incidence of anti-rHuPH20 antibodies were summarized for all participants who received at least one dose of Dara-SC and had appropriate plasma samples for detection of antibodies to rHuPH20 (at least 1 sample after the start of the first dose of Dara-SC). This outcome measure was planned to be analyzed for specified arm only.
Time frame: Up to end of study; up to 30.3 months
Number of Participants With Anti-Daratumumab Antibodies
Number of participants who test positive for anti-daratumumab antibodies were reported. This outcome measure was planned to be analyzed for specified arm only.
Time frame: Up to end of study; up to 30.3 months