Multiple Myeloma
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DRUGCarfilzomib 20 mg/m^2
Carfilzomib 20 mg/m\^2 will be administered intravenously (IV).
DRUGCarfilzomib 70 mg/m^2
Carfilzomib 70 mg/m\^2 will be administered IV.
Dexamethasone 40 mg will be administered as IV infusion or orally.
DRUGDara-SC 1800 mg
Dara-SC 1800 mg will be administered by SC injection.
Dexamethasone 20 mg will be administered as IV infusion or orally.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Evidence of a response (partial response or better based on investigator's determination of response by International Myeloma Working Group \[IMWG\] criteria) to daratumumab-containing therapy with response duration of at least 4 months * Participants must have progressed from or be refractory to their last line of treatment. Relapsed or refractory disease as defined as: a) Relapsed disease is defined as an initial response to previous treatment, followed by confirmed progressive disease (PD) by IMWG criteria greater than (\>) 60 days after cessation of treatment. b) Refractory disease is defined as less than (\<) 25 percent (%) reduction in M-protein or confirmed PD by IMWG criteria during previous treatment or \>60 days after cessation of treatment * Received 1 to 3 prior line(s) of treatment of which one contained daratumumab, and completed daratumumab at least 3 months prior to randomization. A single line of therapy may consist of 1 or more agents, and may include induction, hematopoietic stem cell transplantation, and maintenance therapy. Radiotherapy, bisphosphonate, or a single short course of corticosteroids (no more than the equivalent of dexamethasone 40 milligram per day \[mg/day\] for 4 days) would not be considered prior lines of therapy * Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1, or 2 * Women of childbearing potential must have a negative urine or serum pregnancy test at screening within 14 days prior to randomization
Exclusion criteria
* Previous treatment with daratumumab within the last 3 months prior to randomization * Discontinuation of daratumumab due to a daratumumab-related adverse event (AE) * History of malignancy (other than multiple myeloma) unless all treatment of that malignancy was completed at least 2 years before consent and the patient has no evidence of disease. Further exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or breast, or other non-invasive lesion, that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence within 3 years * Allergies, hypersensitivity, or intolerance to daratumumab, hyaluronidase, monoclonal antibodies (mAbs), human proteins, or their excipients, or known sensitivity to mammalian-derived products. Known history of allergy to Captisol (a cyclodextrin derivative used to solubilize carfilzomib) * Participant is: a) Known to be seropositive for human immunodeficiency virus (HIV) with one or more of the following: not receiving highly active antiretroviral therapy (ART), had a change in ART within 6 months of the start of screening, receiving ART that may interfere with study treatment, cluster of differentiation (CD)4 count \<350 (unit: cells per cubic millimeter of blood) at screening, acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection within 6 months of start of screening, and not agreeing to start ART and be on ART \>4 weeks plus having HIV viral load \<400 copies/milliliters (mL) at end of 4-week period (to ensure ART is tolerated and HIV controlled. b) Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen \[HBsAg\]). Participants with resolved infection (example: participants who are HBsAg negative but positive for antibodies to hepatitis B core antigen \[anti-HBc\] and/or antibodies to hepatitis B surface antigen \[anti-HBs\]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) levels. Those who are PCR positive will be excluded. c) Known to be seropositive for hepatitis C (except in the setting of a sustained virologic response \[SVR\], defined as aviremia at least 12 weeks after completion of antiviral therapy)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Very Good Partial Response (VGPR) or Better Response | Up to 3 years and 4 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Complete Response (CR) or Better | Up to 3 years and 7 months | 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. |
| Progression Free Survival (PFS) | Up to 3 years and 7 months | 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. |
| Overall Survival (OS) | Up to 3 years and 7 months | OS was defined as the time from the date of randomization to the date of the participant's death due to any cause. |
| Percentage of Participants With Negative Minimal Residual Disease (MRD) | Up to 3 years and 7 months | 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. |
| Overall Response Rate (ORR) | Up to 3 years and 7 months | 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. |
| Serum Concentrations of Daratumumab | 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) | Serum concentrations of daratumumab were assessed. This outcome measure was planned to be analyzed for specified arm only. |
| Number of Participants With Anti-recombinant Human Hyaluronidase (rHuPH20) Antibodies | Up to end of study; up to 30.3 months | 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. |
| Number of Participants With Anti-Daratumumab Antibodies | Up to end of study; up to 30.3 months | 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 to Next Treatment | Up to 3 years and 7 months | Time to next treatment was defined as the time from randomization to the start of the next-line treatment. |
Countries
Belgium, Brazil, Canada, Denmark, France, Germany, Greece, Italy, Netherlands, Poland, Russia, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm A: Carfilzomib+Dexamethasone (Kd) Participants received carfilzomib 20 milligram per meter square (mg/m\^2) intravenously (IV) on Cycle 1 Day 1 and then 70 mg/m\^2 on Cycle 1 Days 8 and 15, and thereafter on Days 1, 8, 15 from Cycle 2 onwards. Participants received dexamethasone 20 milligrams (mg) on Cycle 1 Days 1 and 2, and 40 mg IV or orally on Days 8, 15, 22 of Cycle 1. Participants then received dexamethasone 40 mg IV or orally on Days 1, 8, 15 and 22 of Cycles 2-9, then on Days 1, 8, 15 from Cycle 10 onwards, until confirmed progressive disease (PD), death, intolerable toxicity, start of a new treatment for multiple myeloma, withdrawal of consent, or end of the study, whichever occurs first. Each cycle of 28 days. | 44 |
| Arm B: Dara-SC in Combination With Kd (DKd) Participants received daratumumab 1800 mg by SC injection (Dara-SC) on Days 1, 8, 15, 22 of Cycle 1 and 2, Days 1 and 15 of Cycle 3-6, and on Day 1 from Cycle 7 onwards. Participants received carfilzomib 20 mg/m\^2 IV on Cycle 1 Day 1 and then 70 mg/m\^2 on Cycle 1 Days 8 and 15, and Days 1, 8 and 15 from Cycle 2 onwards. Participants received dexamethasone 20 mg on Cycle 1 Days 1 and 2 and 40 mg IV or orally on Days 8, 15, 22 of Cycle 1. Participants then received dexamethasone 40 mg IV or orally on Days 1, 8, 15 and 22 of Cycles 2-9, then on Days 1, 8, 15 from Cycle 10 onwards, until confirmed PD, death, intolerable toxicity, start of a new treatment for multiple myeloma, withdrawal of consent, or end of the study, whichever occurs first. Each cycle of 28 days. | 44 |
| Total | 88 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 12 | 8 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Study terminated by sponsor | 31 | 34 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Total | Arm B: Dara-SC in Combination With Kd (DKd) | Arm A: Carfilzomib+Dexamethasone (Kd) |
|---|---|---|---|
| Age, Continuous | 67 years STANDARD_DEVIATION 9.12 | 66.7 years STANDARD_DEVIATION 9.72 | 67.4 years STANDARD_DEVIATION 8.56 |
| Age, Customized 85 years and over | 3 Participants | 0 Participants | 3 Participants |
| Age, Customized Adolescents (12-17 years) | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Adults (18-64 years) | 31 Participants | 16 Participants | 15 Participants |
| Age, Customized Children (2-11 years) | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized From 65 to 84 years | 54 Participants | 28 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 20 Participants | 8 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 55 Participants | 28 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 13 Participants | 8 Participants | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 7 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) White | 75 Participants | 36 Participants | 39 Participants |
| Refractory status Anti-CD38 antibody only | 15 Participants | 7 Participants | 8 Participants |
| Refractory status Both PI and IMiD | 15 Participants | 5 Participants | 10 Participants |
| Refractory status IMiD + anti-CD38 | 25 Participants | 14 Participants | 11 Participants |
| Refractory status IMiD only | 5 Participants | 1 Participants | 4 Participants |
| Refractory status PI + IMiD + anti-CD38 | 9 Participants | 4 Participants | 5 Participants |
| Refractory status PI only | 1 Participants | 1 Participants | 0 Participants |
| Region of Enrollment BELGIUM | 3 Participants | 2 Participants | 1 Participants |
| Region of Enrollment BRAZIL | 15 Participants | 7 Participants | 8 Participants |
| Region of Enrollment CANADA | 2 Participants | 2 Participants | 0 Participants |
| Region of Enrollment DENMARK | 3 Participants | 3 Participants | 0 Participants |
| Region of Enrollment FRANCE | 7 Participants | 5 Participants | 2 Participants |
| Region of Enrollment GERMANY | 2 Participants | 2 Participants | 0 Participants |
| Region of Enrollment GREECE | 12 Participants | 5 Participants | 7 Participants |
| Region of Enrollment ITALY | 15 Participants | 5 Participants | 10 Participants |
| Region of Enrollment NETHERLANDS | 2 Participants | 1 Participants | 1 Participants |
| Region of Enrollment POLAND | 3 Participants | 1 Participants | 2 Participants |
| Region of Enrollment RUSSIAN FEDERATION | 10 Participants | 6 Participants | 4 Participants |
| Region of Enrollment SPAIN | 11 Participants | 4 Participants | 7 Participants |
| Region of Enrollment UNITED STATES | 3 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Female | 39 Participants | 18 Participants | 21 Participants |
| Sex: Female, Male Male | 49 Participants | 26 Participants | 23 Participants |
| Stage of Disease (ISS) STAGE I | 36 Participants | 24 Participants | 12 Participants |
| Stage of Disease (ISS) STAGE II | 30 Participants | 11 Participants | 19 Participants |
| Stage of Disease (ISS) STAGE III | 21 Participants | 9 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 12 / 44 | 8 / 44 |
| other Total, other adverse events | 39 / 43 | 37 / 43 |
| serious Total, serious adverse events | 20 / 43 | 12 / 43 |
Outcome results
Primary
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
Population: The response-evaluable analysis set included participants who had confirmed diagnosis of multiple myeloma and measurable disease at baseline or screening visit.
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Arm A: Carfilzomib+Dexamethasone (Kd) | Percentage of Participants Achieving Very Good Partial Response (VGPR) or Better Response | 46.2 Percentage of participants | 90% Confidence Interval 32.3 |
| Arm B: Dara-SC in Combination With Kd (DKd) | Percentage of Participants Achieving Very Good Partial Response (VGPR) or Better Response | 48.8 Percentage of participants | 90% Confidence Interval 35.1 |
Secondary
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
Population: The immunogenicity analysis set for dara-SC included all randomized participants who had appropriate samples for detection of the antibodies.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A: Carfilzomib+Dexamethasone (Kd) | Number of Participants With Anti-Daratumumab Antibodies | 0 Participants |
Secondary
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
Population: The immunogenicity analysis set for dara-SC included all randomized participants who had appropriate samples for detection of the antibodies.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A: Carfilzomib+Dexamethasone (Kd) | Number of Participants With Anti-recombinant Human Hyaluronidase (rHuPH20) Antibodies | 1 Participants |
Secondary
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
Population: The response-evaluable analysis set included participants who had confirmed diagnosis of multiple myeloma and measurable disease at baseline or screening visit.
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Arm A: Carfilzomib+Dexamethasone (Kd) | Overall Response Rate (ORR) | 64.1 Percentage of participants | 90% Confidence Interval 49.7 |
| Arm B: Dara-SC in Combination With Kd (DKd) | Overall Response Rate (ORR) | 75.6 Percentage of participants | 90% Confidence Interval 62.1 |
Secondary
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
Population: ITT analysis set included all participants who were randomized in the study. Here, 'N' (number of participants analyzed) signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: Carfilzomib+Dexamethasone (Kd) | Overall Survival (OS) | NA months |
| Arm B: Dara-SC in Combination With Kd (DKd) | Overall Survival (OS) | NA months |
Secondary
Percentage of Participants Achieving Complete Response (CR) or Better
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
Population: The response-evaluable analysis set included participants who had confirmed diagnosis of multiple myeloma and measurable disease at baseline or screening visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A: Carfilzomib+Dexamethasone (Kd) | Percentage of Participants Achieving Complete Response (CR) or Better | 25.6 Percentage of participants |
| Arm B: Dara-SC in Combination With Kd (DKd) | Percentage of Participants Achieving Complete Response (CR) or Better | 12.2 Percentage of participants |
Secondary
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
Population: ITT analysis set included all participants who were randomized in the study.
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Arm A: Carfilzomib+Dexamethasone (Kd) | Percentage of Participants With Negative Minimal Residual Disease (MRD) | 11.4 Percentage of participants | 95% Confidence Interval 3.8 |
| Arm B: Dara-SC in Combination With Kd (DKd) | Percentage of Participants With Negative Minimal Residual Disease (MRD) | 6.8 Percentage of participants | 95% Confidence Interval 1.4 |
Secondary
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
Population: Intent-to-treat (ITT) analysis set included all participants who were randomized in the study. Here, 'N' (number of participants analyzed) signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Arm A: Carfilzomib+Dexamethasone (Kd) | Progression Free Survival (PFS) | 10.61 months | 90% Confidence Interval 4.7 |
| Arm B: Dara-SC in Combination With Kd (DKd) | Progression Free Survival (PFS) | 10.74 months | 90% Confidence Interval 7.49 |
Secondary
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)
Population: Pharmacokinetic (PK) analysis set included all participants who had received at least 1 dose of daratumumab subcutaneous (dara-SC) and had at least 1 post-dose PK sample. Here, 'N' (number of participants analysed) signifies participants who were evaluable for this outcome measure and 'n' (number analyzed) signifies number of participants analyzed at each specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm A: Carfilzomib+Dexamethasone (Kd) | Serum Concentrations of Daratumumab | Cycle 7 Day 1 | 715 microgram per milliliters (mcg/mL) | Standard Deviation 381 |
| Arm A: Carfilzomib+Dexamethasone (Kd) | Serum Concentrations of Daratumumab | Cycle 1 Day 1 | 39.1 microgram per milliliters (mcg/mL) | Standard Deviation 44.1 |
| Arm A: Carfilzomib+Dexamethasone (Kd) | Serum Concentrations of Daratumumab | Cycle 3 Day 1 | 849 microgram per milliliters (mcg/mL) | Standard Deviation 329 |
| Arm A: Carfilzomib+Dexamethasone (Kd) | Serum Concentrations of Daratumumab | Post-treatment Week 8 | 85.5 microgram per milliliters (mcg/mL) | Standard Deviation 131 |
Secondary
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
Population: ITT analysis set analysis set included all participants who were randomized in the study. Here, 'N' (number of participants analyzed) signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: Carfilzomib+Dexamethasone (Kd) | Time to Next Treatment | 20.60 months |
| Arm B: Dara-SC in Combination With Kd (DKd) | Time to Next Treatment | 20.14 months |