The purpose of this study is to evaluate the efficacy and safety of 2 daratumumab treatment regimens in participants with multiple myeloma who have received at least 3 prior lines of therapy (including a proteasome inhibitor \[PI\] and immunomodulatory drug \[IMiD\]) or are double refractory to a PI and an IMiD.
This is an open-label (identity of assigned study drug will be known) study of daratumumab for the treatment of participants with multiple myeloma who have received at least 3 prior lines of therapy including a PI and an IMiD or whose disease is double refractory to both a PI and an IMiD. Up to approximately 150 participants are to be enrolled. The study includes screening, treatment, and follow-up phases. Participants will receive daratumumab by intravenous infusion (28-day cycles) until disease progression, unacceptable toxicity, or other protocol-defined reasons. For all study drug administrations, participants will receive pre- and post-infusion medications for the prevention of infusion related reactions. Follow-up will continue until death, loss to follow up, consent withdrawal for study participation, or study end, whichever occurs first. The study will consist of 2 sequential parts (Part 1 and Part 2). The purpose of Part 1 is to select a dose and schedule for Part 2 of the study. Assessment of tumor response and disease progression will be conducted according to IMWG response criteria. Serial pharmacokinetic blood samples and a pharmacogenomic blood sample will be collected. Safety will be monitored throughout the study. At the end of the study, participants who are benefiting from treatment with daratumumab will have the option to continue treatment.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
124
Daratumumab 16 mg/kg administered at weekly intervals (QW) for 8 weeks, then every 2 weeks (Q2W) for an additional 16 weeks, then every 4 weeks (Q4W) thereafter by intravenous infusion
Daratumumab 8 mg/kg every 4 weeks (Q4W) continuously by intravenous infusion
Administered in prophylactic doses intravenously (or equivalent in accordance with local standards) prior to and after study drug administration. Intravenous administration is preferred, but oral steroids may be substituted
650 to 1000 mg administered in prophylactic doses by mouth prior to study drug administration.
25 to 50 mg administered in prophylactic doses by mouth (or equivalent in accordance with local standards) prior to and after study drug administration.
Based on the Part 1 response rate, Group A or B treatment will be selected as the treatment regimen for participants enrolled in Part 2.
Unnamed facility
Duarte, California, United States
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Los Angeles, California, United States
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Atlanta, Georgia, United States
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Chicago, Illinois, United States
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Louisville, Kentucky, United States
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Detroit, Michigan, United States
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New Brunswick, New Jersey, United States
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New York, New York, United States
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Chapel Hill, North Carolina, United States
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Charlotte, North Carolina, United States
...and 13 more locations
Percentage of Participants With Overall Response
Overall response defined as percentage of participants who achieved stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR). Per IMWG criteria, sCR: is defined as normal free light chain (FLC) ratio, and absence of clonal plasma cells (PCs) by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry; CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \< 5 % plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or \>= 90% reduction in serum M-protein plus urine M-protein level \< 100mg/24 hours; PR: \>= 50 % reduction of serum M-protein and reduction in 24 hour urinary M-protein by \>= 90% or to \<200 mg/24 hours; if the serum and urine M-protein are not measurable, a decrease of \>=50% in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria.
Time frame: Up to 14.4 Months
Duration of Response
Duration of response was calculated from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease, as defined in IMWG criteria. Disease progression (IMWG criteria): increase of 25 percent (%) from lowest response level in Serum M-component (the absolute increase must be \>=0.5 g/dL) and/or; urine M-component (the absolute increase must be \>=200 mg/24 hours) and/or; only in participants without measurable serum and urine M-protein levels: the difference between involved and uninvolved free light chain levels (absolute increase must be \>10 milligram per deciliter (mg/dL); Development of hypercalcemia (corrected serum calcium \>11.5 mg/dL or 2.65 millimole per liter \[mmol/L\]) that can be attributed solely to the plasma cell proliferative disorder.
Time frame: Up to 14.4 Months
Overall Survival
Overall Survival (OS) was defined as the number of days from administration of the first infusion (Day 1) to date of death. Median Overall Survival was estimated by using the Kaplan-Meier method.
Time frame: Approximately up to 3 years
Percentage of Participants With Clinical Benefit
Clinical benefit rate defined as percentage of participants who achieved minimal response (MR) or better. MR: \>=25% but \<= 49% reduction of serum M-protein and reduction in urine M-protein by 50%-89%. If present at baseline 25% to 49% reduction in size of soft tissue plasmacytomas.
Time frame: Up to 14.4 Months
Time to Response
Time to response was defined as the time from the date of first dose of daratumumab to the date of initial documentation of a response (PR or better).
Time frame: Up to 14.4 Months
Progression Free Survival
Progression free survival (PFS) was defined as the time between the date of first dose of daratumumab and either disease progression or death, whichever occurs first.
Time frame: Up to 14.4 Months
Time to Disease Progression
Time to progression was defined as the number of days from the date of first dose of daratumumab to the date of first record of disease progression.
Time frame: Up to 14.4 Months
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