Clinical Trial Results:
A Phase 2 Study of Daratumumab Subcutaneous (Dara-SC) Administration in Combination with Carfilzomib and Dexamethasone (DKd) Compared with Carfilzomib and Dexamethasone (Kd) in Participants with Multiple Myeloma who have been Previously Treated with Daratumumab to Evaluate Daratumumab Retreatment
Summary
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EudraCT number |
2018-004185-34 |
Trial protocol |
BE DE DK NL FR ES PL GR IT |
Global end of trial date |
10 Jan 2023
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Results information
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Results version number |
v1(current) |
This version publication date |
28 Oct 2023
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First version publication date |
28 Oct 2023
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
54767414MMY2065
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03871829 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Janssen Research & Development, LLC
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Sponsor organisation address |
Antwerpseweg 15-17, Beerse, Belgium, B-2340
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Public contact |
Clinical Registry Group, Janssen Research & Development, LLC, ClinicalTrialsEU@its.jnj.com
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Scientific contact |
Clinical Registry Group, Janssen Research & Development, LLC, ClinicalTrialsEU@its.jnj.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
10 Jan 2023
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
10 Jan 2023
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
The main objective of this trial was 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 subjects with relapsed refractory multiple myeloma who were previously exposed to daratumumab to evaluate daratumumab retreatment.
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Protection of trial subjects |
This study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with Good Clinical Practice and applicable regulatory requirements.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
19 Jul 2019
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Belgium: 3
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Country: Number of subjects enrolled |
Brazil: 15
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Country: Number of subjects enrolled |
Canada: 2
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Country: Number of subjects enrolled |
Germany: 2
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Country: Number of subjects enrolled |
Denmark: 3
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Country: Number of subjects enrolled |
Spain: 11
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Country: Number of subjects enrolled |
France: 7
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Country: Number of subjects enrolled |
Greece: 12
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Country: Number of subjects enrolled |
Italy: 15
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Country: Number of subjects enrolled |
Netherlands: 2
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Country: Number of subjects enrolled |
Poland: 3
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Country: Number of subjects enrolled |
Russian Federation: 10
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Country: Number of subjects enrolled |
United States: 3
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Worldwide total number of subjects |
88
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EEA total number of subjects |
58
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
31
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From 65 to 84 years |
54
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85 years and over |
3
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Recruitment
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Recruitment details |
- | ||||||||||||||||||||||||
Pre-assignment
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Screening details |
A total of 88 subjects were enrolled and treated, and none had completed the study. | ||||||||||||||||||||||||
Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Arm A: Carfilzomib+Dexamethasone (Kd) | ||||||||||||||||||||||||
Arm description |
Subjects received carfilzomib 20 milligram per metre 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. Subjects 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. Subjects 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 cycles were of 28 days. | ||||||||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||||||||
Investigational medicinal product name |
Dexamethasone
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Infusion
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Routes of administration |
Intravenous use, Oral use
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Dosage and administration details |
Subjects received dexamethasone 20 mg on Cycle 1 Days 1 and 2. Subjects received 40 mg on Days 1, 8, 15 and 22 for Cycles 2-9, then on Days 1, 8, 15 from Cycle 10 onwards.
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Investigational medicinal product name |
Carfilzomib
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Subjects received carfilzomib 20 mg/m^2 on Cycle 1 Day 1 and 70 mg/m^2 on Cycle 1 Days 8 and 15, and thereafter on Days 1, 8, 15 from Cycle 2 onwards.
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Arm title
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Arm B: Dara-SC in combination with Kd (DKd) | ||||||||||||||||||||||||
Arm description |
Subjects received daratumumab 1800 mg by SC injection (Dara-SC) on Days 1, 8, 15, 22 of Cycles 1 and 2, Days 1 and 15 of Cycle 3-6, and on Day 1 from Cycle 7 onwards. Subjects 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. Subjects 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. Subjects 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 cycles were of 28 days. | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
Daratumumab
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Subjects received daratumumab 1800 mg on Days 1, 8, 15, 22 for Cycle 1 and 2, Days 1 and 15 for Cycle 3-6, Day 1 from Cycle 7 onwards.
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Investigational medicinal product name |
Dexamethasone
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Infusion
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Routes of administration |
Intravenous use, Oral use
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Dosage and administration details |
Subjects received dexamethasone 20 mg on Cycle 1 Days 1 and 2 and 40 mg IV or orally on Days 8, 15, 22 for Cycle 1. Subjects received dexamethasone 40 mg IV or orally on days 1, 8, 15 and 22 for cycles 2-9, then on Days 1, 8, 15 from Cycle 10 onwards.
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Investigational medicinal product name |
Carfilzomib
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Subjects received carfilzomib 20 mg/m^2 on Cycle 1 Day 1 and 70 mg/m^2 on Cycle 1 Days 8 and 15 and Days 1, 8 and 15 from Cycle 2 onwards.
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Baseline characteristics reporting groups
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Reporting group title |
Arm A: Carfilzomib+Dexamethasone (Kd)
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Reporting group description |
Subjects received carfilzomib 20 milligram per metre 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. Subjects 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. Subjects 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 cycles were of 28 days. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Arm B: Dara-SC in combination with Kd (DKd)
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Reporting group description |
Subjects received daratumumab 1800 mg by SC injection (Dara-SC) on Days 1, 8, 15, 22 of Cycles 1 and 2, Days 1 and 15 of Cycle 3-6, and on Day 1 from Cycle 7 onwards. Subjects 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. Subjects 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. Subjects 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 cycles were of 28 days. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Arm A: Carfilzomib+Dexamethasone (Kd)
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Reporting group description |
Subjects received carfilzomib 20 milligram per metre 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. Subjects 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. Subjects 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 cycles were of 28 days. | ||
Reporting group title |
Arm B: Dara-SC in combination with Kd (DKd)
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Reporting group description |
Subjects received daratumumab 1800 mg by SC injection (Dara-SC) on Days 1, 8, 15, 22 of Cycles 1 and 2, Days 1 and 15 of Cycle 3-6, and on Day 1 from Cycle 7 onwards. Subjects 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. Subjects 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. Subjects 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 cycles were of 28 days. |
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End point title |
Percentage of Subjects Achieving Very Good Partial Response (VGPR) or Better Response [1] | ||||||||||||
End point description |
VGPR or better rate was defined as the percentage of subjects achieving VGPR, complete response (CR), or stringent complete response (sCR) in accordance with the International Myeloma Working Group (IMWG) criteria, during/after the study treatment but before the start of subsequent anti-myeloma therapy. IMWG criteria: VGPR: Serum and urine M-component detected by immunofixation but not on electrophoresis, or greater than or equal to (>=)90 percent (%) reduction in serum Mprotein plus urine M-protein less than (<)100 milligram (mg)/24hours; CR: Negative immunofixation on the serum and urine, and Disappearance of any soft tissue plasmacytomas (PCs), and <5% PCs in bone marrow; sCR: CR plus normal free light chain (FLC) ratio, and Absence of clonal PCs by immunohistochemistry, immunofluorescence or 2 to 4 color flow cytometry. The response-evaluable analysis set included subjects who had confirmed diagnosis of multiple myeloma (MM) and measurable disease at baseline or screening visit.
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End point type |
Primary
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End point timeframe |
Up to 3 years and 7 months
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive statistics was done, no inferential statistical analysis was performed. |
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No statistical analyses for this end point |
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End point title |
Overall Response Rate (ORR) | ||||||||||||
End point description |
ORR was defined as the proportion of subjects who achieved partial response [PR] or better responses based on the computerized algorithm, in accordance with the IMWG criteria. IMWG criteria for PR: >=50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by >=90% or <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 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. The response-evaluable analysis set included subjects who had confirmed diagnosis of MM and measurable disease at baseline or screening visit.
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End point type |
Secondary
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End point timeframe |
Up to 3 years and 7 months
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No statistical analyses for this end point |
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End point title |
Progression Free Survival (PFS) | ||||||||||||
End point description |
PFS was defined as the duration from the date of randomisation to either progressive disease (PD) or death, whichever comes first. IMWG criteria: PD: >=25% from lowest response level in serum M-component and/or in urine M-component; only in subjects without measurable serum and urine M-protein levels: increase of >=25% in the difference between involved and uninvolved FLC 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. Intent-to-treat (ITT) analysis set included all subjects who were randomised in the study. Here, 'N' (number of subjects analysed) signifies subjects who were evaluable for this endpoint.
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End point type |
Secondary
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End point timeframe |
Up to 3 years and 7 months
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No statistical analyses for this end point |
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End point title |
Percentage of Subjects Achieving Complete Response (CR) or Better | ||||||||||||
End point description |
Percentage of subjects achieving CR or better were reported. CR or better rate was defined as the proportion of subjects 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. The response-evaluable analysis set included subjects who had confirmed diagnosis of multiple myeloma and measurable disease at baseline or screening visit.
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End point type |
Secondary
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End point timeframe |
Up to 3 years and 7 months
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No statistical analyses for this end point |
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End point title |
Overall Survival (OS) | ||||||||||||
End point description |
OS was defined as the time from the date of randomisation to the date of the subject’s death due to any cause. ITT analysis set analysis set included all subjects who were randomised in the study. Here, 'N' (number of subjects analysed) signifies subjects who were evaluable for this outcome measure. Here, 99999 signifies data was not estimable due to insufficient number of events.
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End point type |
Secondary
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End point timeframe |
Up to 3 years and 7 months
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No statistical analyses for this end point |
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End point title |
Percentage of Subjects With Negative Minimal Residual Disease (MRD) | ||||||||||||
End point description |
Percentage of subjects with negative MRD were reported. MRD negativity rate, defined as the proportion of subjects who had MRD negative status at 10^-5 by bone marrow aspirate after the date of randomisation and prior to PD or subsequent anti-myeloma therapy. MRD negativity rate, defined as the proportion of subjects who have MRD negative status at 10-5 by bone marrow aspirate after the date of randomization and prior to PD or subsequent anti-myeloma therapy. ITT analysis set analysis set included all subjects who were randomised in the study.
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End point type |
Secondary
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End point timeframe |
Up to 3 years and 7 months
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No statistical analyses for this end point |
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End point title |
Time to Next Treatment | ||||||||||||
End point description |
Time to next treatment was defined as the time from randomisation to the start of the next-line treatment. ITT analysis set analysis set included all subjects who were randomised in the study. Here, 'N' (number of subjects analysed) signifies subjects who were evaluable for this endpoint. Here, 99999 signifies data was not estimable due to insufficient number of events.
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End point type |
Secondary
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End point timeframe |
Up to 3 years and 7 months
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No statistical analyses for this end point |
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End point title |
Serum Concentrations of Daratumumab [2] | ||||||||||||||||
End point description |
Serum concentrations of daratumumab were assessed. Pharmacokinetic (PK) analysis set included all subjects 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 subjects analysed) signifies subjects who were evaluable for this endpoint and 'n' (number analysed) signifies number of subjects analysed at each specified timepoints. This outcome measure was planned to be analysed for specified arm only.
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End point type |
Secondary
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End point timeframe |
Cycle 1 Day 1, Cycle 3 Day 1, Cycle 7 Day 1 (each cycle of 28 days) and Follow Up (post treatment Week 8)
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Notes [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This outcome measure was planned to be analysed for specified arm only. |
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No statistical analyses for this end point |
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End point title |
Number of Subjects with Anti-recombinant Human Hyaluronidase (rHuPH20) Antibodies [3] | ||||||
End point description |
Number of subjects with rHuPH20 antibodies were reported. The immunogenicity analysis set for dara-SC included all randomised subjects who had appropriate samples for detection of the antibodies. This outcome measure was planned to be analysed for specified arm only.
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End point type |
Secondary
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End point timeframe |
Cycle 1 Day 1, Cycle 3 Day 1, Cycle 7 Day 1 (each cycle of 28 days) and Follow Up (post treatment Week 8)
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Notes [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This outcome measure was planned to be analysed for specified arm only. |
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No statistical analyses for this end point |
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End point title |
Number of Subjects with Anti-Daratumumab Antibodies [4] | ||||||
End point description |
Number of subjects who test positive for anti-daratumumab antibodies were reported. The immunogenicity analysis set for dara-SC included all randomised subjects who had appropriate samples for detection of the antibodies. This outcome measure was planned to be analysed for specified arm only.
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End point type |
Secondary
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End point timeframe |
Cycle 1 Day 1, Cycle 3 Day 1, Cycle 7 Day 1 (each cycle of 28 days) and Follow Up (post treatment Week 8)
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Notes [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This outcome measure was planned to be analysed for specified arm only. |
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
Up to 3 years and 7 months
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Adverse event reporting additional description |
Safety analysis set included all subjects who received at least 1 dose of study treatment.
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Assessment type |
Non-systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
24.0
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Reporting groups
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Reporting group title |
Arm B: Dara-SC in combination with Kd (DKd)
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Reporting group description |
Subjects received daratumumab subcutaneous (Dara-SC) 1800 mg by SC injection on Days 1, 8, 15, 22 for Cycle 1 and 2, Days 1 and 15 for Cycle 3-6, Day 1 from Cycle 7 onwards. Subjects received carfilzomib 20 mg/m^2 IV on Cycle 1 Day 1 and then 70 mg/m^2 on Day 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2. Subjects received dexamethasone 20 mg on Cycle 1 Days 1 and 2 and 40 mg IV or orally on Days 8, 15, 22 for Cycle 1. Subjects then received dexamethasone 40 mg on days 1, 8, 15 and 22 for 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. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Arm A: Carfilzomib+Dexamethasone (Kd)
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Reporting group description |
Subjects received carfilzomib 20 milligram per square meter (mg/m^2) intravenously (IV) on Day 1 of Cycle 1 and then 70 mg/m^2 on Days 8 and 15 of Cycle 1 and thereafter on Days 1, 8, 15 from Cycle 2 onwards. Subjects received dexamethasone 20 mg on Cycle 1 Days 1 and 2 and 40 mg IV or orally on Days 8, 15, 22 for Cycle 1. Subjects then received dexamethasone 40 mg IV or orally on Days 1, 8, 15 and 22 for 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. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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14 Oct 2019 |
The purpose of the amendment was to include the language clarifying the need for contraception for all subjects to continue for 3 months after the end of study treatment as well as the caution for women who are at high risk for thrombosis to use other means of birth control other than hormonal birth control which carries the highest risk of thrombosis. |
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13 Jun 2021 |
The purpose of this amendment was to expand eligibility. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |