The primary objective of this study is to determine whether treatment with daratumumab administered subcutaneously (SC) prolongs progression-free survival (PFS) compared with active monitoring in participants with high-risk smoldering multiple myeloma (SMM).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
390
Participants will receive daratumumab SC injection (daratumumab 1800 mg + rHuPH20 \[2000 U/mL\]) once weekly for Cycles 1 and 2 (Days 1, 8, 15, and 22 of each week), every 2 weeks for Cycle 3 to Cycle 6 (Days 1 and 15), and thereafter every 4 weeks (Day 1) until 39 cycles or up to 36 months or until confirmed disease progression, unacceptable toxicity or withdrawal from the study treatment, study termination or study completion. Each cycle is 28 days in duration.
Progression-Free Survival (PFS) as Assessed by the Independent Review Committee (IRC)
PFS was defined as the duration from the date of randomization to either progressive to multiple myeloma (MM), according to the International Myeloma Working Group (IMWG) diagnostic criteria for MM, or death due to any cause, whichever occurred first. Per IMWG criteria, active MM by SLiM-CRAB defined as: greater than or equal to (\>=) 60 percent (%) bone marrow plasma cells (BMPCs), free light chain (FLC) involved/uninvolved ratio \>=100, greater than (\>)1 focal bone lesions on magnetic resonance imaging (MRI), calcium elevation, renal insufficiency by creatinine clearance, anemia, or bone disease due to lytic bone lesions. Kaplan-Meier estimate was used.
Time frame: From randomization (Day -5) up to 77 months
Time to Biochemical or Diagnostic (SLiM-CRAB) Progression Per Computerized Algorithm Analyses
Time frame: From randomization (Day -5) up to 8 years
Overall Response Rate (ORR)
Time frame: From randomization (Day -5) up to 8 years
Complete Response (CR) Rate
Time frame: From randomization (Day -5) up to 8 years
Time to First-Line Treatment for Multiple Myeloma
Time frame: From randomization (Day -5) up to 8 years
Progression-Free Survival on First-Line Treatment for Multiple Myeloma (PFS2)
Time frame: From randomization (Day -5) up to 8 years
Best Response on First-line Therapy for Multiple Myeloma
Time frame: From randomization (Day -5) up to 8 years
Overall Survival (OS)
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Arizona Oncology Associates, PC - HAL
Phoenix, Arizona, United States
Innovative Clinical Research Inc
Whittier, California, United States
Miami Cancer Institute
Miami, Florida, United States
Emory University
Atlanta, Georgia, United States
University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States
East Jefferson General Hospital
Metairie, Louisiana, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States
Mayo Clinic
Rochester, Minnesota, United States
Washington University
St Louis, Missouri, United States
...and 153 more locations
Time frame: From randomization (Day -5) up to 8 years
Percentage of Participants Who Progressed to Multiple Myeloma With Adverse Prognostic Features
Time frame: From randomization (Day -5) up to 8 years
Maximum Observed Serum Concentration (Cmax) of Daratumumab
Time frame: Cycles 1 and 3 : Day 1 predose, and Day 4 postdose; Cycles 5, 7, 12, and 24: Day 1 predose; end of the treatment (EOT, 37.11 months); and 8 weeks after the last daratumumab dose (up to 38.11 months). Each Cycle was 28 days
Minimum Observed Serum Concentration (Cmin) of Daratumumab
Time frame: Cycles 1 and 3 : Day 1 predose, and Day 4 postdose; Cycles 5, 7, 12, and 24: Day 1 predose; EOT( 37.11 months); and 8 weeks after the last daratumumab dose (up to 38.11 months). Each Cycle was 28 days
Number of Participants With Anti-daratumumab Antibodies
Time frame: Cycles 1 and 3 : Day 1 predose, and Day 4 postdose; Cycles 5, 7, 12, and 24: Day 1 predose; EOT (37.11 months); and 8 weeks after the last daratumumab dose (up to 38.11 months). Each Cycle was 28 days
Number of Participants With Anti-Recombinant Human Hyaluronidase (rHuPH20) Antibodies
Time frame: Cycles 1, 3, 5, 7, 12, and 24 : Predose on Day 1; EOT (37.11 months); and 8 weeks after the last daratumumab dose (up to 38.11 months). Each Cycle was 28 days
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score
Time frame: From Baseline (Day -35) up to 8 years
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Future Perspective Scale
Time frame: From Baseline (Day -35) up to 8 years
Change From Baseline in European Quality (EuroQoL) 5-Dimension 5-Level Health Status (EQ-5D-5L) Questionnaire Score
Time frame: From Baseline (Day -35) up to 8 years
Duration of Response
Time frame: From randomization (Day -5) up to 8 years
Time to Response
Time frame: From randomization (Day -5) up to 8 years