Study Comparing Daratumumab, Lenalidomide, Bortezomib, and Dexamethasone (D-RVd) Versus Lenalidomide, Bortezomib, and Dexamethasone (RVd) in Subjects With Newly Diagnosed Multiple Myeloma
Study Details
Study Description
Brief Summary
The purpose of this study is to determine if the addition of daratumumab to lenalidomide-bortezomib-dexamethasone (RVd) will increase the proportion of participants achieving stringent complete response (sCR), as defined by the International Myeloma Working Group (IMWG) criteria, by the time of completion of post autologous stem cell transplantation (ASCT) consolidation treatment, compared with RVd alone.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 2 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Daratumumab+Lenalidomide+Bortezomib+Dexamethasone (D-RVd) Participants will receive lenalidomide, bortezomib, dexamethasone and daratumumab. |
Drug: Lenalidomide
Cycles 1 through 6: lenalidomide 25 (milligram) mg orally on Days 1 through 14 and each cycle is of 21-days followed by maintenance treatment with lenalidomide 10 mg on days 1-21 throughout each 28-day cycle on Cycles 7 through 9. Beginning at Cycle 10, the lenalidomide dose will be increased to 15 mg unless there is a tolerability concern.
Drug: Bortezomib
Bortezomib 1.3 mg/m^2 subcutaneously on Days 1, 4, 8, and 11 during Cycles 1-6.
Drug: Dexamethasone
Dexamethasone 40 mg orally every week (20 mg on Days 1, 2, 8, 9, 15, and 16).
Drug: Daratumumab
Daratumumab intravenously at a dose of 16 milligram per kilogram (mg/kg) weekly during induction treatment (Days 1, 8, and 15 of Cycles 1 through 4), and every 3 weeks during consolidation treatment (Day 1 of Cycles 5 and 6), followed by maintenance treatment with daratumumab every 4 or 8 weeks.
|
Experimental: Lenalidomide+Bortezomib+Dexamethasone (RVd) Participants will receive lenalidomide, bortezomib and dexamethasone. |
Drug: Lenalidomide
Cycles 1 through 6: lenalidomide 25 (milligram) mg orally on Days 1 through 14 and each cycle is of 21-days followed by maintenance treatment with lenalidomide 10 mg on days 1-21 throughout each 28-day cycle on Cycles 7 through 9. Beginning at Cycle 10, the lenalidomide dose will be increased to 15 mg unless there is a tolerability concern.
Drug: Bortezomib
Bortezomib 1.3 mg/m^2 subcutaneously on Days 1, 4, 8, and 11 during Cycles 1-6.
Drug: Dexamethasone
Dexamethasone 40 mg orally every week (20 mg on Days 1, 2, 8, 9, 15, and 16).
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants With Stringent Complete Response (sCR) [From randomization to post-ASCT consolidation (after Cycle 6) before maintenance treatment (up to 10 months)]
Percentage of participants who have achieved sCR as determined by the validated computer algorithm according to the International Myeloma Working Group (IMWG) criteria, by the end of post-autologous stem cell transplantation (post-ASCT) consolidation treatment were reported. Complete response (CR) is defined as negative immunofixation on the serum and urine, and disappearance of any soft tissue plasmacytomas, and less than (<) 5 percent (%) PCs in bone marrow. sCR is defined as in addition to CR a normal FLC ratio, and absence of clonal PCs by immunohistochemistry or immunofluorescence or 2 to 4-color flow cytometry.
Secondary Outcome Measures
- Percentage of Participants With Overall Complete Response (CR) [From randomization to end of following: induction treatment, ASCT, post-ASCT consolidation (after Cycle 6) and during maintenance treatment (up to 24 months)]
Overall CR rate is defined as the percentage of participants who achieve CR, according to the IMWG criteria. CR is negative immunofixation on the serum and urine, and disappearance of any soft tissue plasmacytomas, and < 5% PCs in bone marrow.
- Percentage of Participants With Overall Stringent Complete Response (sCR) [From randomization to end of following: induction treatment, ASCT, post-ASCT consolidation (after Cycle 6) and during maintenance treatment (up to 24 months)]
Overall sCR rate is defined as the percentage of participants who achieved sCR, according to the IMWG criteria. CR is defined as negative immunofixation on the serum and urine, and disappearance of any soft tissue plasmacytomas, and < 5 % PCs in bone marrow. sCR is defined as in addition to CR a normal FLC ratio, and absence of clonal PCs by immunohistochemistry or immunofluorescence or 2 to 4-color flow cytometry.
- Percentage of Participants With Overall Response Rate (ORR) [From randomization to end of following: induction treatment, ASCT, post-ASCT consolidation (after Cycle 6) and during maintenance treatment (up to 24 months)]
ORR -percentage of participants who achieved partial response (PR) or better (PR, Very Good Partial Response [VGPR], CR or sCR) based on computerized algorithm as per IMWG criteria. PR -greater than or equal to (>=) 50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by >=90% or to <200 mg//24 hours. If serum and urine M-protein are not measurable, a decrease of >=50% in the difference between involved and uninvolved FLC levels is required. A >=50% reduction in the size of soft tissue plasmacytomas is also required; VGPR-serum and urine M-component detectable by immunofixation but not on electrophoresis, or >= 90% reduction in serum M-protein plus urine M-protein <100 mg/24 hours; CR-negative immunofixation on the serum and urine, and disappearance of any soft tissue plasmacytomas, and <5% PCs in bone marrow. sCR- in addition to CR a normal FLC ratio, and absence of clonal PCs by immunohistochemistry or immunofluorescence or 2 to 4-color flow cytometry.
- Percentage of Participants Who Achieved Very Good Partial Response (VGPR) or Better [From randomization to end of following: induction treatment, ASCT, post-ASCT consolidation (after Cycle 6) and during maintenance treatment (up to 24 months)]
VGPR or better rate is defined as the percentage of participants who achieved VGPR or better, according to the IMWG criteria. VGPR is defined as serum and urine M-component detectable by immunofixation but not on electrophoresis, or >= 90% reduction in serum M-protein plus urine M-protein <100 mg/24 hours.
- Percentage of Participants With Negative Minimal Residual Disease (MRD) [From randomization to end of following: induction treatment, post-ASCT consolidation (after Cycle 6) (up to 4.5 months)]
Minimal residual disease negative rate is defined as the percentage of participants who achieve MRD negative status by the respective time point. Minimal residual disease was evaluated in participants who achieved CR or sCR (including participants with VGPR or better and suspected daratumumab interference) using next-generation sequencing which utilizes multiple myeloma cell DNA from bone marrow aspirates at a threshold of less than (<) 10^5.
- Duration of Complete Response [From randomization to the date of first documented evidence of progressive disease or relapse from CR (up to 2 years and 5 months)]
Duration of CR is the duration from the date of initial documentation of a CR response, according to the IMWG criteria, to the date of first documented evidence of progressive disease (PR), or relapse from CR. PD is defined as an increase of 25 % from the lowest response value in one of the following: serum and urine M-component (absolute increase must be greater than or equal to [>=] 0.5 gram per deciliter [g/dL] and >=200 milligram [mg]/24 hours respectively); Only in participants without measurable serum and urine M-protein levels the difference between involved and uninvolved FLC levels (absolute increase must be > 10 mg/dL); Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to Plasma cell (PC) proliferative disorder.
- Duration of Stringent Complete Response (sCR) [From randomization to the date of first documented evidence of progressive disease or relapse from sCR (up to 2 years and 5 months)]
Duration of sCR is the duration from the date of initial documentation of a sCR response, according to the IMWG criteria, to the date of first documented evidence of progressive disease, or relapse from sCR. PD is defined as an increase of 25 % from the lowest response value in one of the following: serum and urine M component (absolute increase must be >= 0.5 g/dL and >=200 mg/24 hours respectively); Only in participants without measurable serum and urine M-protein levels the difference between involved and uninvolved FLC levels (absolute increase must be > 10 mg/dL); Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to PC proliferative disorder.
- Time to Stringent Complete Response (sCR) [From randomization to the date of initial documentation of sCR (up to 2 years and 5 months)]
Time to sCR is the duration from the date of randomization to the date of initial documentation of sCR, which was confirmed by a repeated measurement as required by the IMWG criteria.
- Time to Complete Response or Better [From randomization to the date of initial documentation of CR (Up to 2 years and 5 months)]
Time to CR or better is the duration from the date of randomization to the date of initial documentation of CR or better, which was confirmed by a repeated measurement as required by the IMWG criteria.
- Time to Very Good Partial Response (VGPR) or Better [From randomization to the date of initial documentation of VGPR or better (up to 2 years and 5 months)]
Time to VGPR or better is the duration from the date of randomization to the date of initial documentation of VGPR or better, which was confirmed by a repeated measurement as required by the IMWG criteria.
- Time to Partial Response (PR) or Better [From randomization to the date of initial documentation of PR or better (up to 2 years and 5 months)]
Time to PR or better is the duration from the date of randomization to the date of initial documentation of PR or better, which was confirmed by a repeated measurement as required by the IMWG criteria.
- Progression-free Survival (PFS) [Up to 24 months]
PFS is defined as the duration from the date of randomization to the date of first documented evidence of progressive disease or death, whichever comes first. PD is defined as an increase of 25 % from the lowest response value in one of the following: serum and urine M-component (absolute increase must be >= 0.5 g/dL and >=200 mg/24 hours respectively); Only in participants without measurable serum and urine M-protein levels the difference between involved and uninvolved FLC levels (absolute increase must be > 10 mg/dL); Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to PC proliferative disorder.
- Overall Survival (OS) [From randomization to the date of initial documentation of participant's death (up to 2 years and 5 months)]
OS is measured from the date of randomization to the date of the participant's death.
- Time to Progression (TTP) [From randomization to the date of first documented evidence of progressive disease (up to 2 years and 5 months)]
TTP is defined as the duration from the date of randomization to the date of first documented evidence of progressive disease according to the IMWG criteria.
- Duration of Response [From the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive (up to 2 years and 5 months)]
Duration of response is defined as the duration from the date of initial documentation of a response (PR or better) according to the IMWG criteria to the date of first documented evidence of progressive disease according to the IMWG criteria. PD is defined as an increase of 25 % from the lowest response value in one of the following: serum and urine M-component (absolute increase must be >= 0.5 g/dL and >=200 mg/24 hours respectively); Only in participants without measurable serum and urine M-protein levels the difference between involved and uninvolved FLC levels (absolute increase must be > 10 mg/dL); Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to PC proliferative disorder.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Considered by the investigator to be eligible for high-dose chemotherapy (HDT) and autologous stem cell transplantation (ASCT) according to the institution's criteria based on age, medical history, cardiac and pulmonary status, overall health and condition, co-morbid condition(s), physical examination, and laboratory studies
-
Has not had prior systemic therapy for multiple myeloma. An emergency course of steroids (defined as no greater than 40 milligram [mg] of dexamethasone, or equivalent per day for a maximum of 4 days (that is, a total of 160 mg) is permitted. In addition, radiation therapy is permitted prior to study entry, during screening, and during Cycles 1-2 of study treatment as needed for lytic bone disease
-
Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
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Woman of childbearing potential must have 2 negative highly sensitive serum (beta-human chorionic gonadotropin [b-hCG]) during screening, the first one within 10 to 14 days prior to the first dose of any component of study treatment and the second within 24 hours prior to the first dose of any component of study treatment
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A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study (including during dose interruptions), and for 4 weeks following discontinuation of lenalidomide, and if receiving daratumumab, for 3 months after the last dose
Exclusion Criteria:
-
Diagnosed or treated for malignancy other than multiple myeloma, except: a) Malignancy treated with curative intent and with no known active disease present for more than equal to (>= )3 years before randomization; b) Adequately treated non-melanoma skin cancer, lentigo maligna or in situ malignancies (including but not limited to, cervical, breast) with no evidence of disease
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Exhibiting clinical signs of or has a known history of meningeal or central nervous system involvement by multiple myeloma
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Known chronic obstructive pulmonary disease with a forced expiratory volume in 1 second (FEV1) less than (<)50 percent (%) of predicted normal
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Known moderate or severe persistent asthma within the past 2 years or currently has uncontrolled asthma of any classification
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Known to be seropositive for human immunodeficiency virus, known to have hepatitis B surface antigen positivity, or known to have a history of hepatitis C. Participants who completed treatment for hepatitis C at least 6 months prior to screening and have no detectable circulating hepatitis C virus (HCV) at screening, may participate in the study. Such participants will be required to undergo regular assessment for HCV reactivation during their participation in the study. Participants who test positive for HCV at any time during these assessments will be withdrawn from the study
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Birmingham | Alabama | United States | ||
2 | Duarte | California | United States | ||
3 | La Jolla | California | United States | ||
4 | Los Angeles | California | United States | ||
5 | San Francisco | California | United States | ||
6 | Aurora | Colorado | United States | ||
7 | Washington | District of Columbia | United States | ||
8 | Orlando | Florida | United States | ||
9 | Tampa | Florida | United States | ||
10 | Atlanta | Georgia | United States | ||
11 | Chicago | Illinois | United States | ||
12 | Westwood | Kansas | United States | ||
13 | New Orleans | Louisiana | United States | ||
14 | Baltimore | Maryland | United States | ||
15 | Boston | Massachusetts | United States | ||
16 | Worcester | Massachusetts | United States | ||
17 | Detroit | Michigan | United States | ||
18 | Saint Louis | Missouri | United States | ||
19 | Omaha | Nebraska | United States | ||
20 | Buffalo | New York | United States | ||
21 | New York | New York | United States | ||
22 | Chapel Hill | North Carolina | United States | ||
23 | Charlotte | North Carolina | United States | ||
24 | Durham | North Carolina | United States | ||
25 | Winston-Salem | North Carolina | United States | ||
26 | Columbus | Ohio | United States | ||
27 | Portland | Oregon | United States | ||
28 | Abington | Pennsylvania | United States | ||
29 | Philadelphia | Pennsylvania | United States | ||
30 | Nashville | Tennessee | United States | ||
31 | Dallas | Texas | United States | ||
32 | Houston | Texas | United States | ||
33 | Salt Lake City | Utah | United States | ||
34 | Seattle | Washington | United States | ||
35 | Spokane | Washington | United States | ||
36 | Milwaukee | Wisconsin | United States |
Sponsors and Collaborators
- Janssen Research & Development, LLC
Investigators
- Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC
Study Documents (Full-Text)
More Information
Publications
None provided.- CR108195
- 54767414MMY2004
Study Results
Participant Flow
Recruitment Details | 223 participants were enrolled/randomized (16 in safety run-in,104 to D-RVd and 103 to RVd group). At clinical cut-off, among 207 (D-RVd [104]+RVd [103]) randomized, 201 received treatment (D-RVd: 100 and RVd: 101). 1 participant randomized to D-RVd group received RVd treatment and was randomized twice (resulting a total of 224 participants). |
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Pre-assignment Detail | Participant was screen-failure and was randomized to D-RVd first; after re-screening was randomized to RVd group.The participant was counted in D-RVd for ITT analysis and RVd for safety analysis. So, safety analysis set included 99 participants in D-RVd and 102 in RVd group who received at least 1 dose of study treatment. |
Arm/Group Title | Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) | Randomized: Daratumumab+RVd (D-RVd) | Safety Run-in: D-RVD |
---|---|---|---|
Arm/Group Description | Induction and Consolidation Phase (12-week induction phase followed by autologous stem cell mobilization, high-dose chemotherapy [HDT] and autologous stem cell transplantation [ASCT]; 6-week consolidation phase)- participants received lenalidomide 25 milligram (mg) orally on Days 1 to 14 of Cycles 1 through 6), bortezomib 1.3 milligram per meter square (mg/m^2) subcutaneously (SC) on Days 1, 4, 8, and 11 and dexamethasone 40 mg orally weekly (20 mg on Days 1, 2, 8, 9, 15 and 16); Maintenance phase (up to 104 week [until disease progression/up to maximum of 2 years])- participants received lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, lenalidomide dose was increased to 15 mg, unless there was tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. | Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 milligram per kilogram (mg/kg) intravenously (IV) weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. | Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 (mg/kg) IV weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. |
Period Title: Overall Study | |||
STARTED | 103 | 104 | 16 |
Safety | 102 | 99 | 16 |
COMPLETED | 0 | 0 | 0 |
NOT COMPLETED | 103 | 104 | 16 |
Baseline Characteristics
Arm/Group Title | Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) | Randomized: Daratumumab+RVd (D-RVd) | Safety Run-in: D-RVD | Total |
---|---|---|---|---|
Arm/Group Description | Induction and Consolidation Phase (12-week induction phase followed by autologous stem cell mobilization, high-dose chemotherapy [HDT] and autologous stem cell transplantation [ASCT]; 6-week consolidation phase)- participants received lenalidomide 25 milligram (mg) orally on Days 1 to 14 of Cycles 1 through 6), bortezomib 1.3 milligram per meter square (mg/m^2) subcutaneously (SC) on Days 1, 4, 8, and 11 and dexamethasone 40 mg orally weekly (20 mg on Days 1, 2, 8, 9, 15 and 16); Maintenance phase (up to 104 week [until disease progression/up to maximum of 2 years])- participants received lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, lenalidomide dose was increased to 15 mg, unless there was tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. | Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 milligram per kilogram (mg/kg) intravenously (IV) weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. | Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 (mg/kg) IV weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. | Total of all reporting groups |
Overall Participants | 102 | 99 | 16 | 217 |
Age (years) [Mean (Standard Deviation) ] | ||||
Mean (Standard Deviation) [years] |
59
(7.25)
|
57.1
(9.96)
|
59.8
(5.96)
|
58.2
(8.55)
|
Sex: Female, Male (Count of Participants) | ||||
Female |
44
43.1%
|
43
43.4%
|
8
50%
|
95
43.8%
|
Male |
58
56.9%
|
56
56.6%
|
8
50%
|
122
56.2%
|
Race/Ethnicity, Customized (Count of Participants) | ||||
Asian |
2
2%
|
0
0%
|
1
6.3%
|
3
1.4%
|
Black or African American |
18
17.6%
|
14
14.1%
|
4
25%
|
36
16.6%
|
More than one race |
1
1%
|
0
0%
|
0
0%
|
1
0.5%
|
Other |
1
1%
|
1
1%
|
0
0%
|
2
0.9%
|
Unknown or Not Reported |
6
5.9%
|
1
1%
|
0
0%
|
7
3.2%
|
White |
74
72.5%
|
83
83.8%
|
11
68.8%
|
168
77.4%
|
Region of Enrollment (Count of Participants) | ||||
UNITED STATES |
102
100%
|
99
100%
|
16
100%
|
217
100%
|
Outcome Measures
Title | Percentage of Participants With Stringent Complete Response (sCR) |
---|---|
Description | Percentage of participants who have achieved sCR as determined by the validated computer algorithm according to the International Myeloma Working Group (IMWG) criteria, by the end of post-autologous stem cell transplantation (post-ASCT) consolidation treatment were reported. Complete response (CR) is defined as negative immunofixation on the serum and urine, and disappearance of any soft tissue plasmacytomas, and less than (<) 5 percent (%) PCs in bone marrow. sCR is defined as in addition to CR a normal FLC ratio, and absence of clonal PCs by immunohistochemistry or immunofluorescence or 2 to 4-color flow cytometry. |
Time Frame | From randomization to post-ASCT consolidation (after Cycle 6) before maintenance treatment (up to 10 months) |
Outcome Measure Data
Analysis Population Description |
---|
Response-evaluable analysis set included all participants who had a confirmed diagnosis of multiple myeloma and measurable disease at baseline or screening visit, received at least 1 dose of study treatment and had at least 1 post baseline disease assessment. The outcome measure was planned to be reported for randomized participants only. |
Arm/Group Title | Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) | Randomized: Daratumumab+RVd (D-RVd) |
---|---|---|
Arm/Group Description | Induction and Consolidation Phase (12-week induction phase followed by autologous stem cell mobilization, high-dose chemotherapy [HDT] and autologous stem cell transplantation [ASCT]; 6-week consolidation phase)- participants received lenalidomide 25 milligram (mg) orally on Days 1 to 14 of Cycles 1 through 6), bortezomib 1.3 milligram per meter square (mg/m^2) subcutaneously (SC) on Days 1, 4, 8, and 11 and dexamethasone 40 mg orally weekly (20 mg on Days 1, 2, 8, 9, 15 and 16); Maintenance phase (up to 104 week [until disease progression/up to maximum of 2 years])- participants received lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, lenalidomide dose was increased to 15 mg, unless there was tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. | Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 milligram per kilogram (mg/kg) intravenously (IV) weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. |
Measure Participants | 97 | 99 |
Number (95% Confidence Interval) [Percentage of participants] |
32.0
31.4%
|
42.4
42.8%
|
Title | Percentage of Participants With Overall Complete Response (CR) |
---|---|
Description | Overall CR rate is defined as the percentage of participants who achieve CR, according to the IMWG criteria. CR is negative immunofixation on the serum and urine, and disappearance of any soft tissue plasmacytomas, and < 5% PCs in bone marrow. |
Time Frame | From randomization to end of following: induction treatment, ASCT, post-ASCT consolidation (after Cycle 6) and during maintenance treatment (up to 24 months) |
Outcome Measure Data
Analysis Population Description |
---|
Response-evaluable analysis set included all participants who had a confirmed diagnosis of multiple myeloma and measurable disease at baseline or screening visit, received at least 1 dose of study treatment and had at least 1 post baseline disease assessment. |
Arm/Group Title | Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) | Randomized: Daratumumab+RVd (D-RVd) | Safety Run-in: D-RVd |
---|---|---|---|
Arm/Group Description | Induction and Consolidation Phase (12-week induction phase followed by autologous stem cell mobilization, high-dose chemotherapy [HDT] and autologous stem cell transplantation [ASCT]; 6-week consolidation phase)- participants received lenalidomide 25 milligram (mg) orally on Days 1 to 14 of Cycles 1 through 6), bortezomib 1.3 milligram per meter square (mg/m^2) subcutaneously (SC) on Days 1, 4, 8, and 11 and dexamethasone 40 mg orally weekly (20 mg on Days 1, 2, 8, 9, 15 and 16); Maintenance phase (up to 104 week [until disease progression/up to maximum of 2 years])- participants received lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, lenalidomide dose was increased to 15 mg, unless there was tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. | Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 milligram per kilogram (mg/kg) intravenously (IV) weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. | Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 (mg/kg) IV weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. |
Measure Participants | 97 | 99 | 16 |
At the end of induction prior to ASCT |
6.2
6.1%
|
7.1
7.2%
|
12.5
78.1%
|
At the end of ASCT prior to consolidation |
5.2
5.1%
|
6.1
6.2%
|
12.5
78.1%
|
At the end of post-ASCT consolidation |
10.3
10.1%
|
9.1
9.2%
|
12.5
78.1%
|
During maintenance phase |
10.3
10.1%
|
13.1
13.2%
|
0
0%
|
Title | Percentage of Participants With Overall Stringent Complete Response (sCR) |
---|---|
Description | Overall sCR rate is defined as the percentage of participants who achieved sCR, according to the IMWG criteria. CR is defined as negative immunofixation on the serum and urine, and disappearance of any soft tissue plasmacytomas, and < 5 % PCs in bone marrow. sCR is defined as in addition to CR a normal FLC ratio, and absence of clonal PCs by immunohistochemistry or immunofluorescence or 2 to 4-color flow cytometry. |
Time Frame | From randomization to end of following: induction treatment, ASCT, post-ASCT consolidation (after Cycle 6) and during maintenance treatment (up to 24 months) |
Outcome Measure Data
Analysis Population Description |
---|
Response-evaluable analysis set included all participants who had a confirmed diagnosis of multiple myeloma and measurable disease at baseline or screening visit, received at least 1 dose of study treatment and had at least 1 post baseline disease assessment. |
Arm/Group Title | Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) | Randomized: Daratumumab+RVd (D-RVd) | Safety Run-in: D-RVd |
---|---|---|---|
Arm/Group Description | Induction and Consolidation Phase (12-week induction phase followed by autologous stem cell mobilization, high-dose chemotherapy [HDT] and autologous stem cell transplantation [ASCT]; 6-week consolidation phase)- participants received lenalidomide 25 milligram (mg) orally on Days 1 to 14 of Cycles 1 through 6), bortezomib 1.3 milligram per meter square (mg/m^2) subcutaneously (SC) on Days 1, 4, 8, and 11 and dexamethasone 40 mg orally weekly (20 mg on Days 1, 2, 8, 9, 15 and 16); Maintenance phase (up to 104 week [until disease progression/up to maximum of 2 years])- participants received lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, lenalidomide dose was increased to 15 mg, unless there was tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. | Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 milligram per kilogram (mg/kg) intravenously (IV) weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. | Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 (mg/kg) IV weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. |
Measure Participants | 97 | 99 | 16 |
At the end of induction prior to ASCT |
7.2
7.1%
|
12.1
12.2%
|
0
0%
|
At the end of ASCT prior to consolidation |
14.4
14.1%
|
21.2
21.4%
|
43.8
273.8%
|
At the end of post-ASCT consolidation |
32.0
31.4%
|
42.4
42.8%
|
56.3
351.9%
|
During maintenance phase |
37.1
36.4%
|
49.5
50%
|
93.8
586.3%
|
Title | Percentage of Participants With Overall Response Rate (ORR) |
---|---|
Description | ORR -percentage of participants who achieved partial response (PR) or better (PR, Very Good Partial Response [VGPR], CR or sCR) based on computerized algorithm as per IMWG criteria. PR -greater than or equal to (>=) 50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by >=90% or to <200 mg//24 hours. If serum and urine M-protein are not measurable, a decrease of >=50% in the difference between involved and uninvolved FLC levels is required. A >=50% reduction in the size of soft tissue plasmacytomas is also required; VGPR-serum and urine M-component detectable by immunofixation but not on electrophoresis, or >= 90% reduction in serum M-protein plus urine M-protein <100 mg/24 hours; CR-negative immunofixation on the serum and urine, and disappearance of any soft tissue plasmacytomas, and <5% PCs in bone marrow. sCR- in addition to CR a normal FLC ratio, and absence of clonal PCs by immunohistochemistry or immunofluorescence or 2 to 4-color flow cytometry. |
Time Frame | From randomization to end of following: induction treatment, ASCT, post-ASCT consolidation (after Cycle 6) and during maintenance treatment (up to 24 months) |
Outcome Measure Data
Analysis Population Description |
---|
Response-evaluable analysis set included all participants who had a confirmed diagnosis of multiple myeloma and measurable disease at baseline or screening visit, received at least 1 dose of study treatment and had at least 1 post baseline disease assessment. |
Arm/Group Title | Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) | Randomized: Daratumumab+RVd (D-RVd) | Safety Run-in: D-RVd |
---|---|---|---|
Arm/Group Description | Induction and Consolidation Phase (12-week induction phase followed by autologous stem cell mobilization, high-dose chemotherapy [HDT] and autologous stem cell transplantation [ASCT]; 6-week consolidation phase)- participants received lenalidomide 25 milligram (mg) orally on Days 1 to 14 of Cycles 1 through 6), bortezomib 1.3 milligram per meter square (mg/m^2) subcutaneously (SC) on Days 1, 4, 8, and 11 and dexamethasone 40 mg orally weekly (20 mg on Days 1, 2, 8, 9, 15 and 16); Maintenance phase (up to 104 week [until disease progression/up to maximum of 2 years])- participants received lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, lenalidomide dose was increased to 15 mg, unless there was tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. | Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 milligram per kilogram (mg/kg) intravenously (IV) weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. | Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 (mg/kg) IV weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. |
Measure Participants | 97 | 99 | 16 |
At the end of induction prior to ASCT |
91.8
90%
|
98.0
99%
|
100
625%
|
At the end of ASCT prior to consolidation |
91.8
90%
|
99.0
100%
|
100
625%
|
At the end of post-ASCT consolidation |
91.8
90%
|
99.0
100%
|
100
625%
|
During maintenance phase |
91.8
90%
|
99.0
100%
|
100
625%
|
Title | Percentage of Participants Who Achieved Very Good Partial Response (VGPR) or Better |
---|---|
Description | VGPR or better rate is defined as the percentage of participants who achieved VGPR or better, according to the IMWG criteria. VGPR is defined as serum and urine M-component detectable by immunofixation but not on electrophoresis, or >= 90% reduction in serum M-protein plus urine M-protein <100 mg/24 hours. |
Time Frame | From randomization to end of following: induction treatment, ASCT, post-ASCT consolidation (after Cycle 6) and during maintenance treatment (up to 24 months) |
Outcome Measure Data
Analysis Population Description |
---|
Population analyzed included response evaluable analysis set who achieved response (PR or better). |
Arm/Group Title | Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) | Randomized: Daratumumab+RVd (D-RVd) | Safety Run-in: D-RVd |
---|---|---|---|
Arm/Group Description | Induction and Consolidation Phase (12-week induction phase followed by autologous stem cell mobilization, high-dose chemotherapy [HDT] and autologous stem cell transplantation [ASCT]; 6-week consolidation phase)- participants received lenalidomide 25 milligram (mg) orally on Days 1 to 14 of Cycles 1 through 6), bortezomib 1.3 milligram per meter square (mg/m^2) subcutaneously (SC) on Days 1, 4, 8, and 11 and dexamethasone 40 mg orally weekly (20 mg on Days 1, 2, 8, 9, 15 and 16); Maintenance phase (up to 104 week [until disease progression/up to maximum of 2 years])- participants received lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, lenalidomide dose was increased to 15 mg, unless there was tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. | Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 milligram per kilogram (mg/kg) intravenously (IV) weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. | Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 (mg/kg) IV weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. |
Measure Participants | 97 | 99 | 16 |
At the end of induction prior to ASCT |
56.7
55.6%
|
71.7
72.4%
|
68.8
430%
|
At the end of ASCT prior to consolidation |
66.0
64.7%
|
86.9
87.8%
|
100
625%
|
At the end of post-ASCT consolidation |
73.2
71.8%
|
90.9
91.8%
|
100
625%
|
During maintenance phase |
74.2
72.7%
|
91.9
92.8%
|
100
625%
|
Title | Percentage of Participants With Negative Minimal Residual Disease (MRD) |
---|---|
Description | Minimal residual disease negative rate is defined as the percentage of participants who achieve MRD negative status by the respective time point. Minimal residual disease was evaluated in participants who achieved CR or sCR (including participants with VGPR or better and suspected daratumumab interference) using next-generation sequencing which utilizes multiple myeloma cell DNA from bone marrow aspirates at a threshold of less than (<) 10^5. |
Time Frame | From randomization to end of following: induction treatment, post-ASCT consolidation (after Cycle 6) (up to 4.5 months) |
Outcome Measure Data
Analysis Population Description |
---|
Intent to treat (ITT) analysis set which included all randomized participants. |
Arm/Group Title | Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) | Randomized: Daratumumab+RVd (D-RVd) | Safety Run-in: D-RVd |
---|---|---|---|
Arm/Group Description | Induction and Consolidation Phase (12-week induction phase followed by autologous stem cell mobilization, high-dose chemotherapy [HDT] and autologous stem cell transplantation [ASCT]; 6-week consolidation phase)- participants received lenalidomide 25 milligram (mg) orally on Days 1 to 14 of Cycles 1 through 6), bortezomib 1.3 milligram per meter square (mg/m^2) subcutaneously (SC) on Days 1, 4, 8, and 11 and dexamethasone 40 mg orally weekly (20 mg on Days 1, 2, 8, 9, 15 and 16); Maintenance phase (up to 104 week [until disease progression/up to maximum of 2 years])- participants received lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, lenalidomide dose was increased to 15 mg, unless there was tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. | Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 milligram per kilogram (mg/kg) intravenously (IV) weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. | Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 (mg/kg) IV weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. |
Measure Participants | 103 | 104 | 16 |
MRD from randomization to prior to ASCT (10^5) |
5.8
5.7%
|
19.2
19.4%
|
18.8
117.5%
|
Post ASCT consolidation (10^5) |
14.6
14.3%
|
44.2
44.6%
|
50.0
312.5%
|
Title | Duration of Complete Response |
---|---|
Description | Duration of CR is the duration from the date of initial documentation of a CR response, according to the IMWG criteria, to the date of first documented evidence of progressive disease (PR), or relapse from CR. PD is defined as an increase of 25 % from the lowest response value in one of the following: serum and urine M-component (absolute increase must be greater than or equal to [>=] 0.5 gram per deciliter [g/dL] and >=200 milligram [mg]/24 hours respectively); Only in participants without measurable serum and urine M-protein levels the difference between involved and uninvolved FLC levels (absolute increase must be > 10 mg/dL); Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to Plasma cell (PC) proliferative disorder. |
Time Frame | From randomization to the date of first documented evidence of progressive disease or relapse from CR (up to 2 years and 5 months) |
Outcome Measure Data
Analysis Population Description |
---|
Population analyzed included response evaluable analysis set who achieved response (PR or better). |
Arm/Group Title | Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) | Randomized: Daratumumab+RVd (D-RVd) | Safety Run-in: D-RVd |
---|---|---|---|
Arm/Group Description | Induction and Consolidation Phase (12-week induction phase followed by autologous stem cell mobilization, high-dose chemotherapy [HDT] and autologous stem cell transplantation [ASCT]; 6-week consolidation phase)- participants received lenalidomide 25 milligram (mg) orally on Days 1 to 14 of Cycles 1 through 6), bortezomib 1.3 milligram per meter square (mg/m^2) subcutaneously (SC) on Days 1, 4, 8, and 11 and dexamethasone 40 mg orally weekly (20 mg on Days 1, 2, 8, 9, 15 and 16); Maintenance phase (up to 104 week [until disease progression/up to maximum of 2 years])- participants received lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, lenalidomide dose was increased to 15 mg, unless there was tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. | Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 milligram per kilogram (mg/kg) intravenously (IV) weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. | Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 (mg/kg) IV weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. |
Measure Participants | 89 | 98 | 16 |
Median (95% Confidence Interval) [Months] |
NA
|
NA
|
NA
|
Title | Duration of Stringent Complete Response (sCR) |
---|---|
Description | Duration of sCR is the duration from the date of initial documentation of a sCR response, according to the IMWG criteria, to the date of first documented evidence of progressive disease, or relapse from sCR. PD is defined as an increase of 25 % from the lowest response value in one of the following: serum and urine M component (absolute increase must be >= 0.5 g/dL and >=200 mg/24 hours respectively); Only in participants without measurable serum and urine M-protein levels the difference between involved and uninvolved FLC levels (absolute increase must be > 10 mg/dL); Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to PC proliferative disorder. |
Time Frame | From randomization to the date of first documented evidence of progressive disease or relapse from sCR (up to 2 years and 5 months) |
Outcome Measure Data
Analysis Population Description |
---|
Population analyzed included response evaluable analysis set who achieved response PR or better. |
Arm/Group Title | Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) | Randomized: Daratumumab+RVd (D-RVd) | Safety Run-in: D-RVd |
---|---|---|---|
Arm/Group Description | Induction and Consolidation Phase (12-week induction phase followed by autologous stem cell mobilization, high-dose chemotherapy [HDT] and autologous stem cell transplantation [ASCT]; 6-week consolidation phase)- participants received lenalidomide 25 milligram (mg) orally on Days 1 to 14 of Cycles 1 through 6), bortezomib 1.3 milligram per meter square (mg/m^2) subcutaneously (SC) on Days 1, 4, 8, and 11 and dexamethasone 40 mg orally weekly (20 mg on Days 1, 2, 8, 9, 15 and 16); Maintenance phase (up to 104 week [until disease progression/up to maximum of 2 years])- participants received lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, lenalidomide dose was increased to 15 mg, unless there was tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. | Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 milligram per kilogram (mg/kg) intravenously (IV) weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. | Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 (mg/kg) IV weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. |
Measure Participants | 89 | 98 | 16 |
Median (95% Confidence Interval) [Months] |
NA
|
NA
|
NA
|
Title | Time to Stringent Complete Response (sCR) |
---|---|
Description | Time to sCR is the duration from the date of randomization to the date of initial documentation of sCR, which was confirmed by a repeated measurement as required by the IMWG criteria. |
Time Frame | From randomization to the date of initial documentation of sCR (up to 2 years and 5 months) |
Outcome Measure Data
Analysis Population Description |
---|
Response-evaluable analysis set included all participants who had a confirmed diagnosis of multiple myeloma and measurable disease at baseline or screening visit, received at least 1 dose of study treatment and had at least 1 post baseline disease assessment. |
Arm/Group Title | Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) | Randomized: Daratumumab+RVd (D-RVd) | Safety Run-in: D-RVd |
---|---|---|---|
Arm/Group Description | Induction and Consolidation Phase (12-week induction phase followed by autologous stem cell mobilization, high-dose chemotherapy [HDT] and autologous stem cell transplantation [ASCT]; 6-week consolidation phase)- participants received lenalidomide 25 milligram (mg) orally on Days 1 to 14 of Cycles 1 through 6), bortezomib 1.3 milligram per meter square (mg/m^2) subcutaneously (SC) on Days 1, 4, 8, and 11 and dexamethasone 40 mg orally weekly (20 mg on Days 1, 2, 8, 9, 15 and 16); Maintenance phase (up to 104 week [until disease progression/up to maximum of 2 years])- participants received lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, lenalidomide dose was increased to 15 mg, unless there was tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. | Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 milligram per kilogram (mg/kg) intravenously (IV) weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. | Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 (mg/kg) IV weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. |
Measure Participants | 97 | 99 | 16 |
Median (95% Confidence Interval) [Months] |
11.9
|
10.3
|
8.2
|
Title | Time to Complete Response or Better |
---|---|
Description | Time to CR or better is the duration from the date of randomization to the date of initial documentation of CR or better, which was confirmed by a repeated measurement as required by the IMWG criteria. |
Time Frame | From randomization to the date of initial documentation of CR (Up to 2 years and 5 months) |
Outcome Measure Data
Analysis Population Description |
---|
Response-evaluable analysis set included all participants who had a confirmed diagnosis of multiple myeloma and measurable disease at baseline or screening visit, received at least 1 dose of study treatment and had at least 1 post baseline disease assessment. |
Arm/Group Title | Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) | Randomized: Daratumumab+RVd (D-RVd) | Safety Run-in: D-RVd |
---|---|---|---|
Arm/Group Description | Induction and Consolidation Phase (12-week induction phase followed by autologous stem cell mobilization, high-dose chemotherapy [HDT] and autologous stem cell transplantation [ASCT]; 6-week consolidation phase)- participants received lenalidomide 25 milligram (mg) orally on Days 1 to 14 of Cycles 1 through 6), bortezomib 1.3 milligram per meter square (mg/m^2) subcutaneously (SC) on Days 1, 4, 8, and 11 and dexamethasone 40 mg orally weekly (20 mg on Days 1, 2, 8, 9, 15 and 16); Maintenance phase (up to 104 week [until disease progression/up to maximum of 2 years])- participants received lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, lenalidomide dose was increased to 15 mg, unless there was tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. | Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 milligram per kilogram (mg/kg) intravenously (IV) weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. | Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 (mg/kg) IV weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. |
Measure Participants | 97 | 99 | 16 |
Median (95% Confidence Interval) [Months] |
9.2
|
9.1
|
7.3
|
Title | Time to Very Good Partial Response (VGPR) or Better |
---|---|
Description | Time to VGPR or better is the duration from the date of randomization to the date of initial documentation of VGPR or better, which was confirmed by a repeated measurement as required by the IMWG criteria. |
Time Frame | From randomization to the date of initial documentation of VGPR or better (up to 2 years and 5 months) |
Outcome Measure Data
Analysis Population Description |
---|
Response-evaluable analysis set included all participants who had a confirmed diagnosis of multiple myeloma and measurable disease at baseline or screening visit, received at least 1 dose of study treatment and had at least 1 post baseline disease assessment. |
Arm/Group Title | Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) | Randomized: Daratumumab+RVd (D-RVd) | Safety Run-in: D-RVd |
---|---|---|---|
Arm/Group Description | Induction and Consolidation Phase (12-week induction phase followed by autologous stem cell mobilization, high-dose chemotherapy [HDT] and autologous stem cell transplantation [ASCT]; 6-week consolidation phase)- participants received lenalidomide 25 milligram (mg) orally on Days 1 to 14 of Cycles 1 through 6), bortezomib 1.3 milligram per meter square (mg/m^2) subcutaneously (SC) on Days 1, 4, 8, and 11 and dexamethasone 40 mg orally weekly (20 mg on Days 1, 2, 8, 9, 15 and 16); Maintenance phase (up to 104 week [until disease progression/up to maximum of 2 years])- participants received lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, lenalidomide dose was increased to 15 mg, unless there was tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. | Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 milligram per kilogram (mg/kg) intravenously (IV) weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. | Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 (mg/kg) IV weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. |
Measure Participants | 97 | 99 | 16 |
Median (95% Confidence Interval) [Months] |
3.0
|
2.2
|
2.1
|
Title | Time to Partial Response (PR) or Better |
---|---|
Description | Time to PR or better is the duration from the date of randomization to the date of initial documentation of PR or better, which was confirmed by a repeated measurement as required by the IMWG criteria. |
Time Frame | From randomization to the date of initial documentation of PR or better (up to 2 years and 5 months) |
Outcome Measure Data
Analysis Population Description |
---|
Response-evaluable analysis set included all participants who had a confirmed diagnosis of multiple myeloma and measurable disease at baseline or screening visit, received at least 1 dose of study treatment and had at least 1 post baseline disease assessment. |
Arm/Group Title | Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) | Randomized: Daratumumab+RVd (D-RVd) | Safety Run-in: D-RVd |
---|---|---|---|
Arm/Group Description | Induction and Consolidation Phase (12-week induction phase followed by autologous stem cell mobilization, high-dose chemotherapy [HDT] and autologous stem cell transplantation [ASCT]; 6-week consolidation phase)- participants received lenalidomide 25 milligram (mg) orally on Days 1 to 14 of Cycles 1 through 6), bortezomib 1.3 milligram per meter square (mg/m^2) subcutaneously (SC) on Days 1, 4, 8, and 11 and dexamethasone 40 mg orally weekly (20 mg on Days 1, 2, 8, 9, 15 and 16); Maintenance phase (up to 104 week [until disease progression/up to maximum of 2 years])- participants received lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, lenalidomide dose was increased to 15 mg, unless there was tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. | Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 milligram per kilogram (mg/kg) intravenously (IV) weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. | Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 (mg/kg) IV weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. |
Measure Participants | 97 | 99 | 16 |
Median (95% Confidence Interval) [Months] |
0.8
|
0.8
|
0.8
|
Title | Progression-free Survival (PFS) |
---|---|
Description | PFS is defined as the duration from the date of randomization to the date of first documented evidence of progressive disease or death, whichever comes first. PD is defined as an increase of 25 % from the lowest response value in one of the following: serum and urine M-component (absolute increase must be >= 0.5 g/dL and >=200 mg/24 hours respectively); Only in participants without measurable serum and urine M-protein levels the difference between involved and uninvolved FLC levels (absolute increase must be > 10 mg/dL); Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to PC proliferative disorder. |
Time Frame | Up to 24 months |
Outcome Measure Data
Analysis Population Description |
---|
ITT analysis set which included all randomized participants. |
Arm/Group Title | Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) | Randomized: Daratumumab+RVd (D-RVd) | Safety Run-in: D-RVd |
---|---|---|---|
Arm/Group Description | Induction and Consolidation Phase (12-week induction phase followed by autologous stem cell mobilization, high-dose chemotherapy [HDT] and autologous stem cell transplantation [ASCT]; 6-week consolidation phase)- participants received lenalidomide 25 milligram (mg) orally on Days 1 to 14 of Cycles 1 through 6), bortezomib 1.3 milligram per meter square (mg/m^2) subcutaneously (SC) on Days 1, 4, 8, and 11 and dexamethasone 40 mg orally weekly (20 mg on Days 1, 2, 8, 9, 15 and 16); Maintenance phase (up to 104 week [until disease progression/up to maximum of 2 years])- participants received lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, lenalidomide dose was increased to 15 mg, unless there was tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. | Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 milligram per kilogram (mg/kg) intravenously (IV) weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. | Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 (mg/kg) IV weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. |
Measure Participants | 103 | 104 | 16 |
Median (95% Confidence Interval) [Months] |
NA
|
NA
|
NA
|
Title | Overall Survival (OS) |
---|---|
Description | OS is measured from the date of randomization to the date of the participant's death. |
Time Frame | From randomization to the date of initial documentation of participant's death (up to 2 years and 5 months) |
Outcome Measure Data
Analysis Population Description |
---|
ITT analysis set which included all randomized participants. |
Arm/Group Title | Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) | Randomized: Daratumumab+RVd (D-RVd) | Safety Run-in: D-RVd |
---|---|---|---|
Arm/Group Description | Induction and Consolidation Phase (12-week induction phase followed by autologous stem cell mobilization, high-dose chemotherapy [HDT] and autologous stem cell transplantation [ASCT]; 6-week consolidation phase)- participants received lenalidomide 25 milligram (mg) orally on Days 1 to 14 of Cycles 1 through 6), bortezomib 1.3 milligram per meter square (mg/m^2) subcutaneously (SC) on Days 1, 4, 8, and 11 and dexamethasone 40 mg orally weekly (20 mg on Days 1, 2, 8, 9, 15 and 16); Maintenance phase (up to 104 week [until disease progression/up to maximum of 2 years])- participants received lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, lenalidomide dose was increased to 15 mg, unless there was tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. | Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 milligram per kilogram (mg/kg) intravenously (IV) weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. | Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 (mg/kg) IV weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. |
Measure Participants | 103 | 104 | 16 |
Median (95% Confidence Interval) [Months] |
NA
|
NA
|
NA
|
Title | Time to Progression (TTP) |
---|---|
Description | TTP is defined as the duration from the date of randomization to the date of first documented evidence of progressive disease according to the IMWG criteria. |
Time Frame | From randomization to the date of first documented evidence of progressive disease (up to 2 years and 5 months) |
Outcome Measure Data
Analysis Population Description |
---|
ITT analysis set which included all randomized participants. |
Arm/Group Title | Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) | Randomized: Daratumumab+RVd (D-RVd) | Safety Run-in: D-RVd |
---|---|---|---|
Arm/Group Description | Induction and Consolidation Phase (12-week induction phase followed by autologous stem cell mobilization, high-dose chemotherapy [HDT] and autologous stem cell transplantation [ASCT]; 6-week consolidation phase)- participants received lenalidomide 25 milligram (mg) orally on Days 1 to 14 of Cycles 1 through 6), bortezomib 1.3 milligram per meter square (mg/m^2) subcutaneously (SC) on Days 1, 4, 8, and 11 and dexamethasone 40 mg orally weekly (20 mg on Days 1, 2, 8, 9, 15 and 16); Maintenance phase (up to 104 week [until disease progression/up to maximum of 2 years])- participants received lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, lenalidomide dose was increased to 15 mg, unless there was tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. | Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 milligram per kilogram (mg/kg) intravenously (IV) weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. | Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 (mg/kg) IV weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. |
Measure Participants | 103 | 104 | 16 |
Median (95% Confidence Interval) [Months] |
NA
|
NA
|
NA
|
Title | Duration of Response |
---|---|
Description | Duration of response is defined as the duration from the date of initial documentation of a response (PR or better) according to the IMWG criteria to the date of first documented evidence of progressive disease according to the IMWG criteria. PD is defined as an increase of 25 % from the lowest response value in one of the following: serum and urine M-component (absolute increase must be >= 0.5 g/dL and >=200 mg/24 hours respectively); Only in participants without measurable serum and urine M-protein levels the difference between involved and uninvolved FLC levels (absolute increase must be > 10 mg/dL); Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to PC proliferative disorder. |
Time Frame | From the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive (up to 2 years and 5 months) |
Outcome Measure Data
Analysis Population Description |
---|
ITT analysis set which included all randomized participants. |
Arm/Group Title | Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) | Randomized: Daratumumab+RVd (D-RVd) | Safety Run-in: D-RVd |
---|---|---|---|
Arm/Group Description | Induction and Consolidation Phase (12-week induction phase followed by autologous stem cell mobilization, high-dose chemotherapy [HDT] and autologous stem cell transplantation [ASCT]; 6-week consolidation phase)- participants received lenalidomide 25 milligram (mg) orally on Days 1 to 14 of Cycles 1 through 6), bortezomib 1.3 milligram per meter square (mg/m^2) subcutaneously (SC) on Days 1, 4, 8, and 11 and dexamethasone 40 mg orally weekly (20 mg on Days 1, 2, 8, 9, 15 and 16); Maintenance phase (up to 104 week [until disease progression/up to maximum of 2 years])- participants received lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, lenalidomide dose was increased to 15 mg, unless there was tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. | Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 milligram per kilogram (mg/kg) intravenously (IV) weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. | Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 (mg/kg) IV weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. |
Measure Participants | 103 | 104 | 16 |
Median (95% Confidence Interval) [Months] |
NA
|
NA
|
NA
|
Adverse Events
Time Frame | Up to 3 years and 5 months | |||||
---|---|---|---|---|---|---|
Adverse Event Reporting Description | 4 participants in D-RVd and 2 in RVd group were randomized but did not receive any treatment. 1 participant randomized to D-RVd group received RVd treatment and was counted in D-RVd group for ITT analysis and RVd group for safety analysis. So, safety analysis set included 99 participants in D-RVd and 102 in RVd group who received at least 1 dose of study treatment. | |||||
Arm/Group Title | Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) | Randomized: Daratumumab+RVd (D-RVd) | Safety Run-in: D-RVD | |||
Arm/Group Description | Induction and Consolidation Phase (12-week induction phase followed by autologous stem cell mobilization, high-dose chemotherapy [HDT] and autologous stem cell transplantation [ASCT]; 6-week consolidation phase)- participants received lenalidomide 25 milligram (mg) orally on Days 1 to 14 of Cycles 1 through 6), bortezomib 1.3 milligram per meter square (mg/m^2) subcutaneously (SC) on Days 1, 4, 8, and 11 and dexamethasone 40 mg orally weekly (20 mg on Days 1, 2, 8, 9, 15 and 16); Maintenance phase (up to 104 week [until disease progression/up to maximum of 2 years])- participants received lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, lenalidomide dose was increased to 15 mg, unless there was tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. | Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 milligram per kilogram (mg/kg) intravenously (IV) weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. | Induction and Consolidation Phase (12 week induction phase followed by autologous stem cell mobilization, HDT and ASCT; a 6-week consolidation phase)-participants received RVd with daratumumab 16 (mg/kg) IV weekly on Days 1, 8, and 15 of Cycles 1 to 4 during induction treatment and every 3 weeks on Day 1 of Cycles 5 and 6 during consolidation treatment; Maintenance phase (up to 104-week [until disease progression/up to maximum of 2 years])- participants received daratumumab 16 mg every 4 weeks/8 weeks plus lenalidomide 10 mg orally on Days 1 to 21 throughout each 28-day cycle on Cycles 7 through 9 during maintenance treatment. Beginning at Cycle 10, the lenalidomide dose was increased to 15 mg, unless there was a tolerability concern. Long-term follow-up phase- all participants are followed for at least 1 year after last dose of study drug and to continue until death, withdrawal of consent or end of study. | |||
All Cause Mortality |
||||||
Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) | Randomized: Daratumumab+RVd (D-RVd) | Safety Run-in: D-RVD | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 3/102 (2.9%) | 2/99 (2%) | 1/16 (6.3%) | |||
Serious Adverse Events |
||||||
Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) | Randomized: Daratumumab+RVd (D-RVd) | Safety Run-in: D-RVD | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 49/102 (48%) | 35/99 (35.4%) | 10/16 (62.5%) | |||
Blood and lymphatic system disorders | ||||||
Anaemia | 2/102 (2%) | 0/99 (0%) | 0/16 (0%) | |||
Febrile Neutropenia | 0/102 (0%) | 2/99 (2%) | 2/16 (12.5%) | |||
Neutropenia | 0/102 (0%) | 1/99 (1%) | 0/16 (0%) | |||
Cardiac disorders | ||||||
Angina Pectoris | 1/102 (1%) | 0/99 (0%) | 0/16 (0%) | |||
Atrial Flutter | 1/102 (1%) | 1/99 (1%) | 0/16 (0%) | |||
Atrial Tachycardia | 1/102 (1%) | 0/99 (0%) | 0/16 (0%) | |||
Sinus Bradycardia | 0/102 (0%) | 1/99 (1%) | 0/16 (0%) | |||
Congenital, familial and genetic disorders | ||||||
Sickle Cell Anaemia | 1/102 (1%) | 0/99 (0%) | 0/16 (0%) | |||
Gastrointestinal disorders | ||||||
Abdominal Pain | 1/102 (1%) | 3/99 (3%) | 0/16 (0%) | |||
Abdominal Pain Upper | 0/102 (0%) | 0/99 (0%) | 1/16 (6.3%) | |||
Colitis | 0/102 (0%) | 1/99 (1%) | 0/16 (0%) | |||
Diarrhoea | 1/102 (1%) | 4/99 (4%) | 0/16 (0%) | |||
Haemorrhoidal Haemorrhage | 1/102 (1%) | 0/99 (0%) | 0/16 (0%) | |||
Intestinal Infarction | 0/102 (0%) | 1/99 (1%) | 0/16 (0%) | |||
Nausea | 0/102 (0%) | 2/99 (2%) | 1/16 (6.3%) | |||
Small Intestinal Obstruction | 2/102 (2%) | 0/99 (0%) | 0/16 (0%) | |||
Vomiting | 0/102 (0%) | 1/99 (1%) | 1/16 (6.3%) | |||
General disorders | ||||||
Chills | 1/102 (1%) | 0/99 (0%) | 0/16 (0%) | |||
Localised Oedema | 1/102 (1%) | 0/99 (0%) | 0/16 (0%) | |||
Non-Cardiac Chest Pain | 1/102 (1%) | 0/99 (0%) | 0/16 (0%) | |||
Pyrexia | 8/102 (7.8%) | 9/99 (9.1%) | 1/16 (6.3%) | |||
Systemic Inflammatory Response Syndrome | 1/102 (1%) | 0/99 (0%) | 0/16 (0%) | |||
Immune system disorders | ||||||
Hypersensitivity | 1/102 (1%) | 0/99 (0%) | 0/16 (0%) | |||
Serum Sickness-Like Reaction | 1/102 (1%) | 0/99 (0%) | 0/16 (0%) | |||
Infections and infestations | ||||||
Aspergillus Infection | 0/102 (0%) | 1/99 (1%) | 0/16 (0%) | |||
Bacteraemia | 1/102 (1%) | 0/99 (0%) | 0/16 (0%) | |||
Bronchitis | 1/102 (1%) | 0/99 (0%) | 0/16 (0%) | |||
Escherichia Bacteraemia | 0/102 (0%) | 0/99 (0%) | 1/16 (6.3%) | |||
Gastroenteritis | 0/102 (0%) | 0/99 (0%) | 1/16 (6.3%) | |||
Gastroenteritis Escherichia Coli | 0/102 (0%) | 1/99 (1%) | 0/16 (0%) | |||
Influenza | 5/102 (4.9%) | 1/99 (1%) | 0/16 (0%) | |||
Lung Infection | 1/102 (1%) | 1/99 (1%) | 0/16 (0%) | |||
Pneumonia | 8/102 (7.8%) | 8/99 (8.1%) | 4/16 (25%) | |||
Pneumonia Bacterial | 0/102 (0%) | 1/99 (1%) | 0/16 (0%) | |||
Respiratory Syncytial Virus Bronchiolitis | 0/102 (0%) | 1/99 (1%) | 0/16 (0%) | |||
Respiratory Syncytial Virus Infection | 0/102 (0%) | 1/99 (1%) | 0/16 (0%) | |||
Sepsis | 1/102 (1%) | 3/99 (3%) | 0/16 (0%) | |||
Septic Shock | 1/102 (1%) | 0/99 (0%) | 0/16 (0%) | |||
Sinusitis | 0/102 (0%) | 0/99 (0%) | 1/16 (6.3%) | |||
Staphylococcal Infection | 1/102 (1%) | 0/99 (0%) | 0/16 (0%) | |||
Upper Respiratory Tract Infection | 1/102 (1%) | 1/99 (1%) | 0/16 (0%) | |||
Viral Infection | 0/102 (0%) | 0/99 (0%) | 1/16 (6.3%) | |||
Viral Upper Respiratory Tract Infection | 0/102 (0%) | 1/99 (1%) | 0/16 (0%) | |||
Injury, poisoning and procedural complications | ||||||
Fibula Fracture | 1/102 (1%) | 0/99 (0%) | 0/16 (0%) | |||
Hip Fracture | 1/102 (1%) | 0/99 (0%) | 0/16 (0%) | |||
Spinal Compression Fracture | 1/102 (1%) | 0/99 (0%) | 0/16 (0%) | |||
Investigations | ||||||
Blood Creatine Phosphokinase Increased | 1/102 (1%) | 0/99 (0%) | 0/16 (0%) | |||
Metabolism and nutrition disorders | ||||||
Dehydration | 3/102 (2.9%) | 1/99 (1%) | 0/16 (0%) | |||
Gout | 1/102 (1%) | 0/99 (0%) | 0/16 (0%) | |||
Hyperkalaemia | 1/102 (1%) | 0/99 (0%) | 0/16 (0%) | |||
Hypokalaemia | 0/102 (0%) | 1/99 (1%) | 0/16 (0%) | |||
Hyponatraemia | 0/102 (0%) | 1/99 (1%) | 0/16 (0%) | |||
Tumour Lysis Syndrome | 1/102 (1%) | 0/99 (0%) | 0/16 (0%) | |||
Musculoskeletal and connective tissue disorders | ||||||
Arthralgia | 1/102 (1%) | 0/99 (0%) | 0/16 (0%) | |||
Back Pain | 2/102 (2%) | 1/99 (1%) | 0/16 (0%) | |||
Bone Lesion | 0/102 (0%) | 1/99 (1%) | 0/16 (0%) | |||
Neck Pain | 1/102 (1%) | 0/99 (0%) | 0/16 (0%) | |||
Pain in Extremity | 0/102 (0%) | 1/99 (1%) | 1/16 (6.3%) | |||
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
Renal Cell Carcinoma | 0/102 (0%) | 1/99 (1%) | 0/16 (0%) | |||
Squamous Cell Carcinoma of Skin | 0/102 (0%) | 2/99 (2%) | 0/16 (0%) | |||
Nervous system disorders | ||||||
Headache | 0/102 (0%) | 2/99 (2%) | 0/16 (0%) | |||
Neuralgia | 2/102 (2%) | 0/99 (0%) | 0/16 (0%) | |||
Neuropathy Peripheral | 1/102 (1%) | 0/99 (0%) | 0/16 (0%) | |||
Peripheral Sensory Neuropathy | 2/102 (2%) | 1/99 (1%) | 0/16 (0%) | |||
Seizure | 1/102 (1%) | 1/99 (1%) | 0/16 (0%) | |||
Syncope | 0/102 (0%) | 2/99 (2%) | 0/16 (0%) | |||
Renal and urinary disorders | ||||||
Acute Kidney Injury | 4/102 (3.9%) | 2/99 (2%) | 0/16 (0%) | |||
Bladder Perforation | 0/102 (0%) | 0/99 (0%) | 1/16 (6.3%) | |||
Reproductive system and breast disorders | ||||||
Female Genital Tract Fistula | 0/102 (0%) | 0/99 (0%) | 1/16 (6.3%) | |||
Respiratory, thoracic and mediastinal disorders | ||||||
Asthma | 0/102 (0%) | 1/99 (1%) | 0/16 (0%) | |||
Dyspnoea | 4/102 (3.9%) | 0/99 (0%) | 0/16 (0%) | |||
Pneumonitis | 1/102 (1%) | 0/99 (0%) | 1/16 (6.3%) | |||
Pulmonary Embolism | 4/102 (3.9%) | 1/99 (1%) | 0/16 (0%) | |||
Pulmonary Oedema | 1/102 (1%) | 0/99 (0%) | 0/16 (0%) | |||
Skin and subcutaneous tissue disorders | ||||||
Drug Reaction with Eosinophilia and Systemic Symptoms | 2/102 (2%) | 0/99 (0%) | 0/16 (0%) | |||
Hypersensitivity Vasculitis | 1/102 (1%) | 0/99 (0%) | 0/16 (0%) | |||
Surgical and medical procedures | ||||||
Cholecystectomy | 0/102 (0%) | 0/99 (0%) | 1/16 (6.3%) | |||
Vascular disorders | ||||||
Deep Vein Thrombosis | 1/102 (1%) | 1/99 (1%) | 0/16 (0%) | |||
Hypotension | 1/102 (1%) | 1/99 (1%) | 0/16 (0%) | |||
Thrombophlebitis Superficial | 0/102 (0%) | 0/99 (0%) | 1/16 (6.3%) | |||
Other (Not Including Serious) Adverse Events |
||||||
Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) | Randomized: Daratumumab+RVd (D-RVd) | Safety Run-in: D-RVD | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 102/102 (100%) | 99/99 (100%) | 16/16 (100%) | |||
Blood and lymphatic system disorders | ||||||
Anaemia | 32/102 (31.4%) | 32/99 (32.3%) | 7/16 (43.8%) | |||
Leukopenia | 27/102 (26.5%) | 34/99 (34.3%) | 9/16 (56.3%) | |||
Lymphopenia | 29/102 (28.4%) | 30/99 (30.3%) | 13/16 (81.3%) | |||
Monocytosis | 0/102 (0%) | 1/99 (1%) | 2/16 (12.5%) | |||
Neutropenia | 32/102 (31.4%) | 47/99 (47.5%) | 12/16 (75%) | |||
Thrombocytopenia | 31/102 (30.4%) | 43/99 (43.4%) | 8/16 (50%) | |||
Cardiac disorders | ||||||
Palpitations | 1/102 (1%) | 5/99 (5.1%) | 0/16 (0%) | |||
Sinus Tachycardia | 1/102 (1%) | 2/99 (2%) | 2/16 (12.5%) | |||
Tachycardia | 3/102 (2.9%) | 3/99 (3%) | 3/16 (18.8%) | |||
Bradycardia | 0/102 (0%) | 2/99 (2%) | 0/16 (0%) | |||
Sinus Bradycardia | 1/102 (1%) | 2/99 (2%) | 0/16 (0%) | |||
Ear and labyrinth disorders | ||||||
Ear Pain | 0/102 (0%) | 2/99 (2%) | 1/16 (6.3%) | |||
Tinnitus | 4/102 (3.9%) | 5/99 (5.1%) | 1/16 (6.3%) | |||
Vertigo | 0/102 (0%) | 3/99 (3%) | 1/16 (6.3%) | |||
Ear Congestion | 1/102 (1%) | 2/99 (2%) | 0/16 (0%) | |||
Ear Discomfort | 0/102 (0%) | 2/99 (2%) | 0/16 (0%) | |||
Hypoacusis | 0/102 (0%) | 2/99 (2%) | 0/16 (0%) | |||
Endocrine disorders | ||||||
Adrenal Insufficiency | 0/102 (0%) | 1/99 (1%) | 1/16 (6.3%) | |||
Hypothyroidism | 1/102 (1%) | 0/99 (0%) | 1/16 (6.3%) | |||
Eye disorders | ||||||
Dry Eye | 2/102 (2%) | 4/99 (4%) | 0/16 (0%) | |||
Eye Irritation | 3/102 (2.9%) | 1/99 (1%) | 0/16 (0%) | |||
Lacrimation Increased | 2/102 (2%) | 4/99 (4%) | 1/16 (6.3%) | |||
Vision Blurred | 13/102 (12.7%) | 16/99 (16.2%) | 1/16 (6.3%) | |||
Cataract | 1/102 (1%) | 1/99 (1%) | 1/16 (6.3%) | |||
Visual Impairment | 2/102 (2%) | 2/99 (2%) | 0/16 (0%) | |||
Gastrointestinal disorders | ||||||
Abdominal Distension | 4/102 (3.9%) | 5/99 (5.1%) | 3/16 (18.8%) | |||
Abdominal Pain | 9/102 (8.8%) | 21/99 (21.2%) | 4/16 (25%) | |||
Abdominal Pain Upper | 2/102 (2%) | 5/99 (5.1%) | 1/16 (6.3%) | |||
Constipation | 41/102 (40.2%) | 46/99 (46.5%) | 8/16 (50%) | |||
Diarrhoea | 43/102 (42.2%) | 51/99 (51.5%) | 8/16 (50%) | |||
Dry Mouth | 4/102 (3.9%) | 7/99 (7.1%) | 1/16 (6.3%) | |||
Dyspepsia | 8/102 (7.8%) | 13/99 (13.1%) | 0/16 (0%) | |||
Flatulence | 0/102 (0%) | 3/99 (3%) | 0/16 (0%) | |||
Gastrooesophageal Reflux Disease | 2/102 (2%) | 9/99 (9.1%) | 1/16 (6.3%) | |||
Haemorrhoids | 2/102 (2%) | 2/99 (2%) | 1/16 (6.3%) | |||
Nausea | 47/102 (46.1%) | 45/99 (45.5%) | 5/16 (31.3%) | |||
Stomatitis | 4/102 (3.9%) | 2/99 (2%) | 3/16 (18.8%) | |||
Toothache | 1/102 (1%) | 4/99 (4%) | 0/16 (0%) | |||
Vomiting | 24/102 (23.5%) | 27/99 (27.3%) | 5/16 (31.3%) | |||
Abdominal Pain Lower | 2/102 (2%) | 2/99 (2%) | 0/16 (0%) | |||
Dental Caries | 0/102 (0%) | 2/99 (2%) | 0/16 (0%) | |||
Dysphagia | 0/102 (0%) | 2/99 (2%) | 0/16 (0%) | |||
Food Poisoning | 0/102 (0%) | 1/99 (1%) | 1/16 (6.3%) | |||
Haemorrhoidal Haemorrhage | 2/102 (2%) | 0/99 (0%) | 1/16 (6.3%) | |||
Oral Dysaesthesia | 0/102 (0%) | 0/99 (0%) | 1/16 (6.3%) | |||
General disorders | ||||||
Asthenia | 9/102 (8.8%) | 3/99 (3%) | 1/16 (6.3%) | |||
Chest Discomfort | 3/102 (2.9%) | 8/99 (8.1%) | 0/16 (0%) | |||
Chills | 8/102 (7.8%) | 22/99 (22.2%) | 4/16 (25%) | |||
Face Oedema | 1/102 (1%) | 3/99 (3%) | 2/16 (12.5%) | |||
Fatigue | 56/102 (54.9%) | 61/99 (61.6%) | 9/16 (56.3%) | |||
Gait Disturbance | 3/102 (2.9%) | 2/99 (2%) | 0/16 (0%) | |||
Influenza Like Illness | 5/102 (4.9%) | 12/99 (12.1%) | 0/16 (0%) | |||
Injection Site Erythema | 1/102 (1%) | 4/99 (4%) | 0/16 (0%) | |||
Injection Site Rash | 5/102 (4.9%) | 4/99 (4%) | 1/16 (6.3%) | |||
Injection Site Reaction | 4/102 (3.9%) | 3/99 (3%) | 0/16 (0%) | |||
Localised Oedema | 2/102 (2%) | 4/99 (4%) | 0/16 (0%) | |||
Malaise | 1/102 (1%) | 3/99 (3%) | 2/16 (12.5%) | |||
Non-Cardiac Chest Pain | 7/102 (6.9%) | 6/99 (6.1%) | 2/16 (12.5%) | |||
Oedema | 7/102 (6.9%) | 4/99 (4%) | 1/16 (6.3%) | |||
Oedema Peripheral | 35/102 (34.3%) | 32/99 (32.3%) | 6/16 (37.5%) | |||
Pain | 5/102 (4.9%) | 8/99 (8.1%) | 1/16 (6.3%) | |||
Peripheral Swelling | 3/102 (2.9%) | 8/99 (8.1%) | 1/16 (6.3%) | |||
Pyrexia | 20/102 (19.6%) | 33/99 (33.3%) | 6/16 (37.5%) | |||
Injection Site Pruritus | 0/102 (0%) | 0/99 (0%) | 1/16 (6.3%) | |||
Swelling | 0/102 (0%) | 1/99 (1%) | 1/16 (6.3%) | |||
Hepatobiliary disorders | ||||||
Hyperbilirubinaemia | 3/102 (2.9%) | 2/99 (2%) | 2/16 (12.5%) | |||
Cholelithiasis | 0/102 (0%) | 0/99 (0%) | 1/16 (6.3%) | |||
Immune system disorders | ||||||
Hypersensitivity | 0/102 (0%) | 2/99 (2%) | 1/16 (6.3%) | |||
Hypogammaglobulinaemia | 0/102 (0%) | 2/99 (2%) | 3/16 (18.8%) | |||
Seasonal Allergy | 2/102 (2%) | 3/99 (3%) | 0/16 (0%) | |||
Infections and infestations | ||||||
Bronchitis | 1/102 (1%) | 2/99 (2%) | 2/16 (12.5%) | |||
Cellulitis | 3/102 (2.9%) | 1/99 (1%) | 1/16 (6.3%) | |||
Ear Infection | 0/102 (0%) | 1/99 (1%) | 2/16 (12.5%) | |||
Gastroenteritis Viral | 1/102 (1%) | 1/99 (1%) | 2/16 (12.5%) | |||
Hordeolum | 3/102 (2.9%) | 4/99 (4%) | 0/16 (0%) | |||
Influenza | 4/102 (3.9%) | 4/99 (4%) | 1/16 (6.3%) | |||
Lung Infection | 1/102 (1%) | 2/99 (2%) | 1/16 (6.3%) | |||
Nasopharyngitis | 3/102 (2.9%) | 7/99 (7.1%) | 1/16 (6.3%) | |||
Otitis Media | 0/102 (0%) | 4/99 (4%) | 0/16 (0%) | |||
Parainfluenzae Virus Infection | 2/102 (2%) | 5/99 (5.1%) | 1/16 (6.3%) | |||
Pneumonia | 2/102 (2%) | 5/99 (5.1%) | 2/16 (12.5%) | |||
Rhinovirus Infection | 2/102 (2%) | 5/99 (5.1%) | 0/16 (0%) | |||
Sinusitis | 2/102 (2%) | 6/99 (6.1%) | 2/16 (12.5%) | |||
Tooth Infection | 1/102 (1%) | 2/99 (2%) | 1/16 (6.3%) | |||
Upper Respiratory Tract Infection | 37/102 (36.3%) | 46/99 (46.5%) | 8/16 (50%) | |||
Urinary Tract Infection | 3/102 (2.9%) | 2/99 (2%) | 1/16 (6.3%) | |||
Viral Upper Respiratory Tract Infection | 4/102 (3.9%) | 3/99 (3%) | 0/16 (0%) | |||
Acute Sinusitis | 1/102 (1%) | 2/99 (2%) | 0/16 (0%) | |||
Anal Tinea | 0/102 (0%) | 0/99 (0%) | 1/16 (6.3%) | |||
Diverticulitis | 1/102 (1%) | 1/99 (1%) | 1/16 (6.3%) | |||
Eye Infection | 1/102 (1%) | 0/99 (0%) | 1/16 (6.3%) | |||
Gastrointestinal Infection | 0/102 (0%) | 2/99 (2%) | 0/16 (0%) | |||
Herpes Zoster | 0/102 (0%) | 2/99 (2%) | 0/16 (0%) | |||
Laryngitis | 0/102 (0%) | 0/99 (0%) | 1/16 (6.3%) | |||
Metapneumovirus Infection | 0/102 (0%) | 0/99 (0%) | 1/16 (6.3%) | |||
Pneumonia Influenzal | 0/102 (0%) | 0/99 (0%) | 1/16 (6.3%) | |||
Respiratory Syncytial Virus Infection | 2/102 (2%) | 2/99 (2%) | 0/16 (0%) | |||
Skin Infection | 1/102 (1%) | 2/99 (2%) | 0/16 (0%) | |||
Staphylococcal Infection | 0/102 (0%) | 0/99 (0%) | 1/16 (6.3%) | |||
Subcutaneous Abscess | 0/102 (0%) | 2/99 (2%) | 0/16 (0%) | |||
Viral Infection | 0/102 (0%) | 1/99 (1%) | 1/16 (6.3%) | |||
Injury, poisoning and procedural complications | ||||||
Contusion | 7/102 (6.9%) | 8/99 (8.1%) | 0/16 (0%) | |||
Fall | 9/102 (8.8%) | 4/99 (4%) | 1/16 (6.3%) | |||
Infusion Related Reaction | 0/102 (0%) | 3/99 (3%) | 0/16 (0%) | |||
Procedural Pain | 0/102 (0%) | 3/99 (3%) | 0/16 (0%) | |||
Spinal Fracture | 3/102 (2.9%) | 0/99 (0%) | 0/16 (0%) | |||
Tooth Fracture | 0/102 (0%) | 3/99 (3%) | 0/16 (0%) | |||
Vascular Access Site Swelling | 0/102 (0%) | 0/99 (0%) | 1/16 (6.3%) | |||
Investigations | ||||||
Alanine Aminotransferase Increased | 15/102 (14.7%) | 13/99 (13.1%) | 1/16 (6.3%) | |||
Aspartate Aminotransferase Increased | 14/102 (13.7%) | 10/99 (10.1%) | 2/16 (12.5%) | |||
Blood Alkaline Phosphatase Increased | 9/102 (8.8%) | 8/99 (8.1%) | 1/16 (6.3%) | |||
Blood Creatinine Increased | 7/102 (6.9%) | 6/99 (6.1%) | 0/16 (0%) | |||
Weight Decreased | 4/102 (3.9%) | 9/99 (9.1%) | 0/16 (0%) | |||
Weight Increased | 2/102 (2%) | 3/99 (3%) | 0/16 (0%) | |||
Adjusted Calcium | 1/102 (1%) | 1/99 (1%) | 1/16 (6.3%) | |||
Gamma-Glutamyltransferase Increased | 0/102 (0%) | 2/99 (2%) | 0/16 (0%) | |||
Metabolism and nutrition disorders | ||||||
Decreased Appetite | 11/102 (10.8%) | 21/99 (21.2%) | 2/16 (12.5%) | |||
Dehydration | 2/102 (2%) | 3/99 (3%) | 0/16 (0%) | |||
Hypercalcaemia | 4/102 (3.9%) | 1/99 (1%) | 1/16 (6.3%) | |||
Hyperglycaemia | 20/102 (19.6%) | 9/99 (9.1%) | 2/16 (12.5%) | |||
Hyperkalaemia | 2/102 (2%) | 4/99 (4%) | 0/16 (0%) | |||
Hypermagnesaemia | 3/102 (2.9%) | 2/99 (2%) | 0/16 (0%) | |||
Hypernatraemia | 3/102 (2.9%) | 1/99 (1%) | 0/16 (0%) | |||
Hyperuricaemia | 7/102 (6.9%) | 4/99 (4%) | 0/16 (0%) | |||
Hypoalbuminaemia | 9/102 (8.8%) | 11/99 (11.1%) | 4/16 (25%) | |||
Hypocalcaemia | 14/102 (13.7%) | 13/99 (13.1%) | 8/16 (50%) | |||
Hypoglycaemia | 4/102 (3.9%) | 3/99 (3%) | 1/16 (6.3%) | |||
Hypokalaemia | 21/102 (20.6%) | 20/99 (20.2%) | 6/16 (37.5%) | |||
Hypomagnesaemia | 8/102 (7.8%) | 3/99 (3%) | 5/16 (31.3%) | |||
Hyponatraemia | 11/102 (10.8%) | 14/99 (14.1%) | 3/16 (18.8%) | |||
Hypophosphataemia | 12/102 (11.8%) | 9/99 (9.1%) | 5/16 (31.3%) | |||
Hypercholesterolaemia | 0/102 (0%) | 0/99 (0%) | 1/16 (6.3%) | |||
Hyperphosphataemia | 2/102 (2%) | 2/99 (2%) | 0/16 (0%) | |||
Musculoskeletal and connective tissue disorders | ||||||
Arthralgia | 29/102 (28.4%) | 24/99 (24.2%) | 3/16 (18.8%) | |||
Arthritis | 3/102 (2.9%) | 0/99 (0%) | 0/16 (0%) | |||
Back Pain | 27/102 (26.5%) | 32/99 (32.3%) | 5/16 (31.3%) | |||
Bone Pain | 6/102 (5.9%) | 11/99 (11.1%) | 0/16 (0%) | |||
Flank Pain | 3/102 (2.9%) | 1/99 (1%) | 0/16 (0%) | |||
Joint Swelling | 0/102 (0%) | 3/99 (3%) | 0/16 (0%) | |||
Limb Discomfort | 3/102 (2.9%) | 0/99 (0%) | 0/16 (0%) | |||
Muscle Spasms | 15/102 (14.7%) | 18/99 (18.2%) | 2/16 (12.5%) | |||
Muscular Weakness | 13/102 (12.7%) | 7/99 (7.1%) | 1/16 (6.3%) | |||
Musculoskeletal Chest Pain | 9/102 (8.8%) | 11/99 (11.1%) | 1/16 (6.3%) | |||
Musculoskeletal Pain | 6/102 (5.9%) | 5/99 (5.1%) | 3/16 (18.8%) | |||
Musculoskeletal Stiffness | 1/102 (1%) | 3/99 (3%) | 0/16 (0%) | |||
Myalgia | 17/102 (16.7%) | 20/99 (20.2%) | 2/16 (12.5%) | |||
Neck Pain | 1/102 (1%) | 5/99 (5.1%) | 0/16 (0%) | |||
Pain in Extremity | 16/102 (15.7%) | 14/99 (14.1%) | 5/16 (31.3%) | |||
Kyphosis | 0/102 (0%) | 0/99 (0%) | 1/16 (6.3%) | |||
Osteonecrosis of Jaw | 0/102 (0%) | 0/99 (0%) | 1/16 (6.3%) | |||
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
Basal Cell Carcinoma | 0/102 (0%) | 0/99 (0%) | 1/16 (6.3%) | |||
Squamous Cell Carcinoma | 0/102 (0%) | 0/99 (0%) | 1/16 (6.3%) | |||
Uterine Leiomyoma | 0/102 (0%) | 0/99 (0%) | 1/16 (6.3%) | |||
Nervous system disorders | ||||||
Cognitive Disorder | 1/102 (1%) | 3/99 (3%) | 0/16 (0%) | |||
Disturbance in Attention | 1/102 (1%) | 3/99 (3%) | 0/16 (0%) | |||
Dizziness | 22/102 (21.6%) | 17/99 (17.2%) | 2/16 (12.5%) | |||
Dizziness Postural | 1/102 (1%) | 3/99 (3%) | 0/16 (0%) | |||
Dysgeusia | 22/102 (21.6%) | 23/99 (23.2%) | 2/16 (12.5%) | |||
Headache | 19/102 (18.6%) | 25/99 (25.3%) | 1/16 (6.3%) | |||
Hypoaesthesia | 6/102 (5.9%) | 5/99 (5.1%) | 0/16 (0%) | |||
Memory Impairment | 6/102 (5.9%) | 1/99 (1%) | 0/16 (0%) | |||
Neuralgia | 9/102 (8.8%) | 10/99 (10.1%) | 1/16 (6.3%) | |||
Neuropathy Peripheral | 41/102 (40.2%) | 24/99 (24.2%) | 2/16 (12.5%) | |||
Paraesthesia | 10/102 (9.8%) | 20/99 (20.2%) | 3/16 (18.8%) | |||
Peripheral Sensory Neuropathy | 37/102 (36.3%) | 35/99 (35.4%) | 6/16 (37.5%) | |||
Presyncope | 3/102 (2.9%) | 2/99 (2%) | 0/16 (0%) | |||
Syncope | 3/102 (2.9%) | 4/99 (4%) | 0/16 (0%) | |||
Tremor | 8/102 (7.8%) | 10/99 (10.1%) | 2/16 (12.5%) | |||
Hyperaesthesia | 0/102 (0%) | 2/99 (2%) | 0/16 (0%) | |||
Peripheral Motor Neuropathy | 0/102 (0%) | 0/99 (0%) | 1/16 (6.3%) | |||
Restless Legs Syndrome | 0/102 (0%) | 2/99 (2%) | 0/16 (0%) | |||
Sinus Headache | 1/102 (1%) | 0/99 (0%) | 1/16 (6.3%) | |||
Somnolence | 1/102 (1%) | 0/99 (0%) | 1/16 (6.3%) | |||
Psychiatric disorders | ||||||
Anxiety | 12/102 (11.8%) | 12/99 (12.1%) | 3/16 (18.8%) | |||
Confusional State | 1/102 (1%) | 2/99 (2%) | 1/16 (6.3%) | |||
Depression | 5/102 (4.9%) | 6/99 (6.1%) | 1/16 (6.3%) | |||
Insomnia | 30/102 (29.4%) | 39/99 (39.4%) | 6/16 (37.5%) | |||
Agitation | 1/102 (1%) | 2/99 (2%) | 0/16 (0%) | |||
Libido Decreased | 1/102 (1%) | 0/99 (0%) | 1/16 (6.3%) | |||
Restlessness | 2/102 (2%) | 2/99 (2%) | 0/16 (0%) | |||
Renal and urinary disorders | ||||||
Dysuria | 5/102 (4.9%) | 4/99 (4%) | 0/16 (0%) | |||
Pollakiuria | 1/102 (1%) | 2/99 (2%) | 0/16 (0%) | |||
Polyuria | 0/102 (0%) | 2/99 (2%) | 0/16 (0%) | |||
Proteinuria | 1/102 (1%) | 1/99 (1%) | 1/16 (6.3%) | |||
Reproductive system and breast disorders | ||||||
Erectile Dysfunction | 2/102 (2%) | 2/99 (2%) | 1/16 (6.3%) | |||
Vulvovaginal Pruritus | 1/102 (1%) | 0/99 (0%) | 1/16 (6.3%) | |||
Respiratory, thoracic and mediastinal disorders | ||||||
Cough | 25/102 (24.5%) | 38/99 (38.4%) | 9/16 (56.3%) | |||
Dysphonia | 2/102 (2%) | 4/99 (4%) | 1/16 (6.3%) | |||
Dyspnoea | 29/102 (28.4%) | 22/99 (22.2%) | 3/16 (18.8%) | |||
Dyspnoea Exertional | 2/102 (2%) | 5/99 (5.1%) | 0/16 (0%) | |||
Epistaxis | 7/102 (6.9%) | 4/99 (4%) | 0/16 (0%) | |||
Hiccups | 3/102 (2.9%) | 2/99 (2%) | 1/16 (6.3%) | |||
Nasal Congestion | 12/102 (11.8%) | 18/99 (18.2%) | 4/16 (25%) | |||
Oropharyngeal Pain | 9/102 (8.8%) | 6/99 (6.1%) | 2/16 (12.5%) | |||
Rhinitis Allergic | 2/102 (2%) | 5/99 (5.1%) | 1/16 (6.3%) | |||
Rhinorrhoea | 1/102 (1%) | 5/99 (5.1%) | 0/16 (0%) | |||
Sinus Congestion | 3/102 (2.9%) | 4/99 (4%) | 0/16 (0%) | |||
Throat Irritation | 0/102 (0%) | 6/99 (6.1%) | 0/16 (0%) | |||
Upper-Airway Cough Syndrome | 0/102 (0%) | 3/99 (3%) | 1/16 (6.3%) | |||
Productive Cough | 2/102 (2%) | 1/99 (1%) | 1/16 (6.3%) | |||
Respiratory Alkalosis | 0/102 (0%) | 0/99 (0%) | 1/16 (6.3%) | |||
Sneezing | 0/102 (0%) | 2/99 (2%) | 0/16 (0%) | |||
Wheezing | 1/102 (1%) | 1/99 (1%) | 1/16 (6.3%) | |||
Skin and subcutaneous tissue disorders | ||||||
Alopecia | 5/102 (4.9%) | 5/99 (5.1%) | 1/16 (6.3%) | |||
Dry Skin | 9/102 (8.8%) | 9/99 (9.1%) | 0/16 (0%) | |||
Erythema | 4/102 (3.9%) | 3/99 (3%) | 0/16 (0%) | |||
Hyperhidrosis | 5/102 (4.9%) | 2/99 (2%) | 2/16 (12.5%) | |||
Night Sweats | 4/102 (3.9%) | 1/99 (1%) | 0/16 (0%) | |||
Pruritus | 10/102 (9.8%) | 13/99 (13.1%) | 1/16 (6.3%) | |||
Pruritus Generalised | 0/102 (0%) | 3/99 (3%) | 0/16 (0%) | |||
Rash | 24/102 (23.5%) | 19/99 (19.2%) | 4/16 (25%) | |||
Rash Maculo-Papular | 24/102 (23.5%) | 20/99 (20.2%) | 2/16 (12.5%) | |||
Urticaria | 3/102 (2.9%) | 5/99 (5.1%) | 0/16 (0%) | |||
Actinic Keratosis | 0/102 (0%) | 0/99 (0%) | 1/16 (6.3%) | |||
Ecchymosis | 0/102 (0%) | 0/99 (0%) | 1/16 (6.3%) | |||
Ingrowing Nail | 0/102 (0%) | 2/99 (2%) | 0/16 (0%) | |||
Rash Generalised | 2/102 (2%) | 2/99 (2%) | 0/16 (0%) | |||
Rash Pruritic | 2/102 (2%) | 2/99 (2%) | 0/16 (0%) | |||
Skin Mass | 0/102 (0%) | 2/99 (2%) | 0/16 (0%) | |||
Swelling Face | 0/102 (0%) | 0/99 (0%) | 1/16 (6.3%) | |||
Vascular disorders | ||||||
Deep Vein Thrombosis | 5/102 (4.9%) | 1/99 (1%) | 0/16 (0%) | |||
Flushing | 2/102 (2%) | 8/99 (8.1%) | 2/16 (12.5%) | |||
Hot Flush | 5/102 (4.9%) | 5/99 (5.1%) | 0/16 (0%) | |||
Hypertension | 9/102 (8.8%) | 10/99 (10.1%) | 3/16 (18.8%) | |||
Hypotension | 13/102 (12.7%) | 9/99 (9.1%) | 1/16 (6.3%) | |||
Orthostatic Hypotension | 3/102 (2.9%) | 5/99 (5.1%) | 0/16 (0%) | |||
Lymphoedema | 0/102 (0%) | 0/99 (0%) | 1/16 (6.3%) | |||
Orthostatic Hypertension | 0/102 (0%) | 0/99 (0%) | 1/16 (6.3%) |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days.
Results Point of Contact
Name/Title | Clinical Leader |
---|---|
Organization | Janssen Research & Development, LLC |
Phone | 844-434-4210 |
ClinicalTrialDisclosure@its.jnj.com |
- CR108195
- 54767414MMY2004