A Study Comparing Daratumumab, Lenalidomide, and Dexamethasone With Lenalidomide and Dexamethasone in Relapsed or Refractory Multiple Myeloma
Sponsor
Janssen Research & Development, LLC (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT02076009
Collaborator
(none)
570
146
2
123.3
3.9
0
Study Details
Study Description
Brief Summary
The purpose of this study is to compare the effectiveness of daratumumab when combined with lenalidomide and dexamethasone (DRd) to that of lenalidomide and dexamethasone (Rd), in terms of progression-free survival in participants with relapsed or refractory multiple myeloma.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Detailed Description
This is a randomized (participants will be assigned by chance to study treatments), open-label (all participants and study personnel will know the identity of the study treatments), active-controlled (none of the study treatments are placebo), parallel-group (both treatment arms will run at the same time), multicenter study. In this study, daratumumab, lenalidomide, and low-dose dexamethasone (DRd) will be compared with lenalidomide and low dose dexamethasone (Rd) in participants with relapsed or refractory multiple myeloma. Participants will be randomized in a 1:1 ratio to receive either DRd or Rd. The study will include a Screening Phase, a Treatment Phase (involving treatment cycles of approximately 28 days in length), and a Follow-up Phase. The Treatment Phase will extend from the administration of the first dose of study medication until disease progression or unacceptable toxicity. Participants will also discontinue study treatment if: they become pregnant; have their dose held for more than 28 days (or if 3 consecutive planned doses of daratumumab are missed for reasons other than toxicity); or for safety reasons (for example, adverse event). The Follow-up Phase will begin at the end of treatment and will continue until death, loss to follow-up, consent withdrawal for study participation, or the final overall survival (OS) analysis, whichever occurs first. Eligible participants from Rd group who have had sponsor confirmed disease progression will be offered the option for treatment with daratumumab monotherapy (of 28 days cycle). The primary endpoint will be progression-free survival (PFS). Analysis of the primary endpoint was performed at a pre-specified point determined by PFS events with a clinical cutoff of March 7, 2016 when 169 events of death or progression had occurred. The end of study is anticipated at approximately 6 years after the last participant is randomized. Blood and urine samples will be obtained at time points during the study, together with bone marrow aspirates/biopsies and skeletal surveys. Participant safety will be assessed throughout the study.
Study Design
Study Type:
Interventional
Actual Enrollment
:
570 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase 3 Study Comparing Daratumumab, Lenalidomide, and Dexamethasone (DRd) vs Lenalidomide and Dexamethasone (Rd) in Subjects With Relapsed or Refractory Multiple Myeloma
Actual Study Start Date
:
May 23, 2014
Actual Primary Completion Date
:
Mar 7, 2016
Anticipated Study Completion Date
:
Aug 30, 2024
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Daratumumab + lenalidomide + dexamethasone During each 28-day treatment cycle, participants will receive daratumumab, lenalidomide, and dexamethasone. |
Drug: Daratumumab
Daratumumab 16mg/kg will be administered as an intravenous (IV) infusion (into the vein) as per the following schedule: once a week during treatment cycles 1 and 2; every 2 weeks during treatment cycles 3 to 6; and every 4 weeks for cycles 7 and onwards. Following amendment 8, participants receiving daratumumab IV have the option to switch to daratumumab subcutaneous (SC) 1800 mg/dose until documented progression, unacceptable toxicity, or the end of study on Day 1 of any cycle, at the discretion of the investigator.
Drug: Lenalidomide
Lenalidomide will be administered at a dose of 25 mg orally (by mouth) on Days 1 through 21 of each treatment cycle.
Drug: Dexamethasone
Dexamethasone (or equivalent in accordance with local standards) will be administered as a total dose of 40 mg weekly (or 20 mg weekly for participants > 75 years old or with a body mass index < 18.5).
|
| Active Comparator: Lenalidomide + dexamethasone During each 28-day treatment cycle, participants will receive lenalidomide and dexamethasone. |
Drug: Lenalidomide
Lenalidomide will be administered at a dose of 25 mg orally (by mouth) on Days 1 through 21 of each treatment cycle.
Drug: Dexamethasone
Dexamethasone (or equivalent in accordance with local standards) will be administered as a total dose of 40 mg weekly (or 20 mg weekly for participants > 75 years old or with a body mass index < 18.5).
|
Outcome Measures
Primary Outcome Measures
- Progression-free Survival (PFS) [From randomization to either disease progression or death whichever occurs first until 21 months]
PFS was defined as duration from date of randomization to either progressive disease (PD)/death, whichever occurred first. PD was defined as meeting any one of following criteria: Increase of greater than equal to (>=)25 percent (%) in level of serum M-protein from lowest response value and absolute increase must be >=0.5 gram per deciliter (g/dL); Increase of >=25% in 24-hour urinary light chain excretion (urine M-protein) from lowest response value and absolute increase must be >=200 mg/24hours; Only in participants without measurable serum and urine M-protein levels: increase of >=25% in difference between involved and uninvolved FLC levels from lowest response value and absolute increase must be >10 mg/dL; Definite increase in size of existing bone lesions or soft tissue plasmacytomas; Definite development of new bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to PC proliferative disorder.
Secondary Outcome Measures
- Time to Disease Progression (TTP) [From randomization to disease progression until 21 months]
TTP was defined as time from date of randomization to date of first documented evidence of progressive disease (PD). PD was defined as meeting any one of following criteria: Increase of >=25% in level of serum M-protein from lowest response value and absolute increase must be >=0.5 g/dL; Increase of >=25% in 24-hour urinary light chain excretion (urine M-protein) from lowest response value and absolute increase must be >=200 mg/24hours; Only in participants without measurable serum and urine M-protein levels: increase of >=25% in difference between involved and uninvolved free light chain (FLC) levels from lowest response value and absolute increase must be >10 milligram per deciliter (mg/dL); Definite increase in size of existing bone lesions or soft tissue plasmacytomas; Definite development of new bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to Plasma Cell (PC) proliferative disorder.
- Percentage of Participants Who Achieved Very Good Partial Response (VGPR) or Better [From randomization to disease progression (approximately up to 21 months)]
VGPR or better is defined as the percentage of participants who achieved VGPR, complete response (CR) and stringent complete response (sCR) according to the International Myeloma Working Group criteria (IMWG). IMWG criteria for 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, if the serum and urine M-protein are not measurable, a decrease of >90% in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria. In addition to the above criteria, if present at baseline, a >=50% reduction in the size of soft tissue plasmacytomas is also required; CR: Negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas, and <5% PCs in bone marrow; sCR: CR and normal FLC ratio, absence of clonal PCs by immunohistochemistry, immunofluorescence or 2- to 4 color flow cytometry.
- Percentage of Participants With Negative Minimal Residual Disease (MRD) [From randomization to the date of first documented evidence of PD until 21 months]
Minimal residual disease was assessed for all participants who achieved a complete response (CR) or stringent complete response (sCR). The MRD negativity rate was defined as the percentage of participants who had negative MRD assessment at any time point after the first dose of study drugs by evaluation of bone marrow aspirates or whole blood at 10^- 4 threshold.
- Overall Response Rate [From randomization to disease progression (approximately up to 21 months)]
Overall response rate was defined as the percentage of participants who achieved a partial response (PR) or better according to the International Myeloma Working Group (IMWG) criteria, during or after study treatment. IMWG criteria for PR: >=50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by >=90% or to <200 mg/24 hours, if the serum and urine M-protein are not measurable, a decrease of >=50% in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria, in addition to the above criteria, if present at baseline, a >=50% reduction in the size of soft tissue plasmacytomas is also required.
- Overall Survival (OS) [Up to approximately 21 months after the last participant is randomized]
Overall survival was measured from the date of randomization to the date of the participant's death.
- Time to Response [From randomization up to first documented CR or PR until 21 months]
Time to response was defined as the time between the date of randomization and the first efficacy evaluation that the participant met all criteria for partial response (PR) or better.
- Duration of Response (DOR) [From randomization to the date of first documented evidence of PD until 21 months]
DOR was defined for participants with confirmed response (PR or better) as time between first documentation of response and disease progression/death due to PD, whichever occurs first. PD was defined as meeting any one of following criteria: Increase of >=25% in level of serum M-protein from lowest response value and absolute increase must be >=0.5g/dL; Increase of >=25% in 24-hour urinary light chain excretion (urine M-protein) from lowest response value and absolute increase must be >=200mg/24hours; Only in participants without measurable serum and urine M-protein levels: increase of >=25% in difference between involved and uninvolved FLC levels from lowest response value and absolute increase must be >10mg/dL; Definite increase in size of existing bone lesions/soft tissue plasmacytomas; Definite development of new bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum calcium >11.5mg/dL) that can be attributed solely to PC proliferative disorder.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Must have documented multiple myeloma and measurable disease
-
Must have received at least 1 prior line of therapy for multiple myeloma and achieved a response (partial response or better) to at least one prior regimen
-
Must have documented evidence of progressive disease as defined by the International Myeloma Working Group criteria on or after their last regimen
-
Must have an Eastern Cooperative Oncology Group Performance Status score of 0, 1, or 2
-
If a participant has received subsequent anticancer therapy (salvage therapy), the participant must have a "wash-out period" defined as 2 weeks or 5 pharmacokinetic half-lives of the treatment, whichever is longer, before the planned start date of daratumumab monotherapy. The only exception is the emergency use of a short course of corticosteroids (equivalent of dexamethasone 40 milligram per day for a maximum of 4 days) before Daratumumab monotherapy
Exclusion Criteria:
-
Has received any of the following therapies: daratumumab or other anti-CD38 therapies
-
Has received anti-myeloma treatment within 2 weeks or 5 pharmacokinetic half-lives of the treatment
-
Disease shows evidence of refractoriness or intolerance to lenalidomide or if previously treated with a lenalidomide-containing regimen the participant is excluded if he or she discontinued due to any adverse event related to prior lenalidomide treatment
-
Has received autologous stem cell transplantation within 12 weeks before the date of randomization, or previously received an allogenic stem cell transplant (regardless of timing), or planning to undergo a stem cell transplant prior to progression of disease
-
History of malignancy (other than multiple myeloma) within 5 years before the first dose of daratumumab monotherapy (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or breast, or other non-invasive lesion, that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence within 5 years)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Little Rock | Arkansas | United States | ||
| 2 | Gainesville | Florida | United States | ||
| 3 | West Palm Beach | Florida | United States | ||
| 4 | Atlanta | Georgia | United States | ||
| 5 | Chicago | Illinois | United States | ||
| 6 | Iowa City | Iowa | United States | ||
| 7 | Louisville | Kentucky | United States | ||
| 8 | Baton Rouge | Louisiana | United States | ||
| 9 | New Orleans | Louisiana | United States | ||
| 10 | Bethesda | Maryland | United States | ||
| 11 | Columbia | Maryland | United States | ||
| 12 | Boston | Massachusetts | United States | ||
| 13 | Rochester | Minnesota | United States | ||
| 14 | Omaha | Nebraska | United States | ||
| 15 | New Brunswick | New Jersey | United States | ||
| 16 | New York | New York | United States | ||
| 17 | Charlotte | North Carolina | United States | ||
| 18 | Eugene | Oregon | United States | ||
| 19 | Spartanburg | South Carolina | United States | ||
| 20 | Austin | Texas | United States | ||
| 21 | Dallas | Texas | United States | ||
| 22 | Houston | Texas | United States | ||
| 23 | Fairfax | Virginia | United States | ||
| 24 | Camperdown | Australia | |||
| 25 | Geelong | Australia | |||
| 26 | Heidelberg | Australia | |||
| 27 | Malvern | Australia | |||
| 28 | South Brisbane | Australia | |||
| 29 | Southport | Australia | |||
| 30 | Anderlecht | Belgium | |||
| 31 | Antwerpen | Belgium | |||
| 32 | Edegem | Belgium | |||
| 33 | Gent | Belgium | |||
| 34 | Kortrijk | Belgium | |||
| 35 | Leuven | Belgium | |||
| 36 | Liege | Belgium | |||
| 37 | Calgary | Alberta | Canada | ||
| 38 | Edmonton | Alberta | Canada | ||
| 39 | Vancouver | British Columbia | Canada | ||
| 40 | Halifax | Nova Scotia | Canada | ||
| 41 | Hamilton | Ontario | Canada | ||
| 42 | London | Ontario | Canada | ||
| 43 | Montreal | Quebec | Canada | ||
| 44 | Quebec City | Quebec | Canada | ||
| 45 | Surrey N/a | Canada | |||
| 46 | Toronto N/a | Canada | |||
| 47 | Copenhagen | Denmark | |||
| 48 | Odense | Denmark | |||
| 49 | Vejle | Denmark | |||
| 50 | Argenteuil | France | |||
| 51 | Caen | France | |||
| 52 | Lille | France | |||
| 53 | Limoges | France | |||
| 54 | Nantes Cedex 1 | France | |||
| 55 | Paris | France | |||
| 56 | Pessac | France | |||
| 57 | Pierre Benite | France | |||
| 58 | Rennes | France | |||
| 59 | Toulouse Cedex 9 | France | |||
| 60 | Tours Cedex 9 | France | |||
| 61 | Vandoeuvre les Nancy | France | |||
| 62 | Berlin | Germany | |||
| 63 | Bonn | Germany | |||
| 64 | Hamburg | Germany | |||
| 65 | Hamm | Germany | |||
| 66 | Heidelberg | Germany | |||
| 67 | Jena | Germany | |||
| 68 | Karlsruhe | Germany | |||
| 69 | Koblenz | Germany | |||
| 70 | Köln | Germany | |||
| 71 | Saarbrücken | Germany | |||
| 72 | Villingen-Schwenningen | Germany | |||
| 73 | Athens Attica | Greece | |||
| 74 | Haifa | Israel | |||
| 75 | Jerusalem | Israel | |||
| 76 | Nahariya | Israel | |||
| 77 | Netanya | Israel | |||
| 78 | Petah Tikva | Israel | |||
| 79 | Ramat Gan | Israel | |||
| 80 | Tel Aviv | Israel | |||
| 81 | Hitachi | Japan | |||
| 82 | Kanazawa | Japan | |||
| 83 | Kobe | Japan | |||
| 84 | Kurume | Japan | |||
| 85 | Matsuyama | Japan | |||
| 86 | Nagoya | Japan | |||
| 87 | Narita | Japan | |||
| 88 | Ohgaki | Japan | |||
| 89 | Okayama | Japan | |||
| 90 | Osaka | Japan | |||
| 91 | Sendai-City | Japan | |||
| 92 | Shibukawa | Japan | |||
| 93 | Shibuya | Japan | |||
| 94 | Tachikawa | Japan | |||
| 95 | Tokyo | Japan | |||
| 96 | Gyeonggi-do | Korea, Republic of | |||
| 97 | Incheon | Korea, Republic of | |||
| 98 | Seoul | Korea, Republic of | |||
| 99 | Amsterdam | Netherlands | |||
| 100 | Rotterdam | Netherlands | |||
| 101 | Utrecht | Netherlands | |||
| 102 | Zwolle | Netherlands | |||
| 103 | Brzozow | Poland | |||
| 104 | Chorzów | Poland | |||
| 105 | Gdansk | Poland | |||
| 106 | Legnica | Poland | |||
| 107 | Lublin | Poland | |||
| 108 | Poznan | Poland | |||
| 109 | Slupsk | Poland | |||
| 110 | Wroclawa | Poland | |||
| 111 | Dzerzhinsk | Russian Federation | |||
| 112 | Ekaterinburg | Russian Federation | |||
| 113 | Moscow | Russian Federation | |||
| 114 | Nizhny Novgorod | Russian Federation | |||
| 115 | Petrozavodsk | Russian Federation | |||
| 116 | Ryazan | Russian Federation | |||
| 117 | Samara | Russian Federation | |||
| 118 | St-Petersburg | Russian Federation | |||
| 119 | St. Petersburg | Russian Federation | |||
| 120 | Syktyvkar | Russian Federation | |||
| 121 | Badalona | Spain | |||
| 122 | Barcelona | Spain | |||
| 123 | La Laguna (Santa Cruz De Tenerife) | Spain | |||
| 124 | Madrid | Spain | |||
| 125 | Pamplona | Spain | |||
| 126 | Salamanca | Spain | |||
| 127 | Sevilla | Spain | |||
| 128 | Falun | Sweden | |||
| 129 | Göteborg | Sweden | |||
| 130 | Helsingborg | Sweden | |||
| 131 | Huddinge | Sweden | |||
| 132 | Lund | Sweden | |||
| 133 | Stockholm | Sweden | |||
| 134 | Uppsala | Sweden | |||
| 135 | Changhua | Taiwan | |||
| 136 | Taichung City | Taiwan | |||
| 137 | Tainan | Taiwan | |||
| 138 | Taipei | Taiwan | |||
| 139 | Taoyuan | Taiwan | |||
| 140 | Birmingham | United Kingdom | |||
| 141 | Leeds | United Kingdom | |||
| 142 | London | United Kingdom | |||
| 143 | Oxford | United Kingdom | |||
| 144 | Southampton | United Kingdom | |||
| 145 | Surrey | United Kingdom | |||
| 146 | Wolverhampton | United Kingdom |
Sponsors and Collaborators
- Janssen Research & Development, LLC
Investigators
- Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT02076009
Other Study ID Numbers:
- CR103663
- 54767414MMY3003
- 2013-005525-23
First Posted:
Mar 3, 2014
Last Update Posted:
Aug 12, 2022
Last Verified:
Aug 1, 2022
Keywords provided by Janssen Research & Development, LLC
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Lenalidomide, Low-dose Dexamethasone (Rd) | Daratumumab, Lenalidomide, Dexamethasone (DRd) |
|---|---|---|
| Arm/Group Description | Participants received lenalidomide at a dose of 25 milligram (mg) orally on Days 1 through 21 of each treatment cycle and dexamethasone as a total dose of 40 mg weekly (or 20 mg weekly for participants greater than (>) 75 years old or with a body mass index less than [<] 8.5). | Participants received daratumumab 16 milligram per kilogram (mg/kg) as an intravenous (IV) infusion once a week during treatment cycles 1 and 2 (for 8 weeks); every 2 weeks during treatment cycles 3 to 6 (for 16 weeks); once only (on Day 1) during treatment cycles 7 onwards (for every 4 weeks). Lenalidomide was administered at a dose of 25 mg orally on Days 1 through 21 of each treatment cycle and dexamethasone was administered as a total dose of 40 mg weekly (or 20 mg weekly for participants > 75 years old or with a body mass index < 8.5). |
| Period Title: Overall Study | ||
| STARTED | 283 | 286 |
| Treated | 281 | 283 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 283 | 286 |
Baseline Characteristics
| Arm/Group Title | Lenalidomide, Low-dose Dexamethasone (Rd) | Daratumumab, Lenalidomide, Dexamethasone (DRd) | Total |
|---|---|---|---|
| Arm/Group Description | Participants received lenalidomide at a dose of 25 milligram (mg) orally on Days 1 through 21 of each treatment cycle and dexamethasone as a total dose of 40 mg weekly (or 20 mg weekly for participants greater than (>) 75 years old or with a body mass index less than [<] 8.5). | Participants received daratumumab 16 milligram per kilogram (mg/kg) as an intravenous (IV) infusion once a week during treatment cycles 1 and 2 (for 8 weeks); every 2 weeks during treatment cycles 3 to 6 (for 16 weeks); once only (on Day 1) during treatment cycles 7 onwards (for every 4 weeks). Lenalidomide was administered at a dose of 25 mg orally on Days 1 through 21 of each treatment cycle and dexamethasone was administered as a total dose of 40 mg weekly (or 20 mg weekly for participants > 75 years old or with a body mass index < 8.5). | Total of all reporting groups |
| Overall Participants | 283 | 286 | 569 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
64.3
(8.84)
|
64.4
(9.03)
|
64.4
(8.93)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
119
42%
|
113
39.5%
|
232
40.8%
|
| Male |
164
58%
|
173
60.5%
|
337
59.2%
|
| Region of Enrollment (Count of Participants) | |||
| Australia |
9
3.2%
|
9
3.1%
|
18
3.2%
|
| Belgium |
10
3.5%
|
12
4.2%
|
22
3.9%
|
| Canada |
17
6%
|
17
5.9%
|
34
6%
|
| Denmark |
7
2.5%
|
10
3.5%
|
17
3%
|
| France |
36
12.7%
|
21
7.3%
|
57
10%
|
| Germany |
7
2.5%
|
11
3.8%
|
18
3.2%
|
| Greece |
8
2.8%
|
11
3.8%
|
19
3.3%
|
| Israel |
20
7.1%
|
19
6.6%
|
39
6.9%
|
| Japan |
15
5.3%
|
21
7.3%
|
36
6.3%
|
| Korea, Republic Of |
20
7.1%
|
20
7%
|
40
7%
|
| Netherlands |
3
1.1%
|
1
0.3%
|
4
0.7%
|
| Poland |
13
4.6%
|
15
5.2%
|
28
4.9%
|
| Russia |
30
10.6%
|
18
6.3%
|
48
8.4%
|
| Spain |
25
8.8%
|
26
9.1%
|
51
9%
|
| Sweden |
15
5.3%
|
16
5.6%
|
31
5.4%
|
| Taiwan, Province Of China |
9
3.2%
|
11
3.8%
|
20
3.5%
|
| United Kingdom |
24
8.5%
|
27
9.4%
|
51
9%
|
| United States |
15
5.3%
|
21
7.3%
|
36
6.3%
|
| Stage of Disease (ISS) (Count of Participants) | |||
| I |
140
49.5%
|
137
47.9%
|
277
48.7%
|
| II |
86
30.4%
|
93
32.5%
|
179
31.5%
|
| III |
57
20.1%
|
56
19.6%
|
113
19.9%
|
| No. of Prior Lines of Therapy (Count of Participants) | |||
| 1 |
146
51.6%
|
149
52.1%
|
295
51.8%
|
| 2 |
80
28.3%
|
85
29.7%
|
165
29%
|
| 3 |
38
13.4%
|
38
13.3%
|
76
13.4%
|
| >3 |
19
6.7%
|
14
4.9%
|
33
5.8%
|
Outcome Measures
| Title | Progression-free Survival (PFS) |
|---|---|
| Description | PFS was defined as duration from date of randomization to either progressive disease (PD)/death, whichever occurred first. PD was defined as meeting any one of following criteria: Increase of greater than equal to (>=)25 percent (%) in level of serum M-protein from lowest response value and absolute increase must be >=0.5 gram per deciliter (g/dL); Increase of >=25% in 24-hour urinary light chain excretion (urine M-protein) from lowest response value and absolute increase must be >=200 mg/24hours; Only in participants without measurable serum and urine M-protein levels: increase of >=25% in difference between involved and uninvolved FLC levels from lowest response value and absolute increase must be >10 mg/dL; Definite increase in size of existing bone lesions or soft tissue plasmacytomas; Definite development of new bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to PC proliferative disorder. |
| Time Frame | From randomization to either disease progression or death whichever occurs first until 21 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) analysis set included all participants who were randomly assigned to the daratumumab, lenalidomide, dexamethasone (DRd) or lenalidomide, low-dose dexamethasone (Rd) group. |
| Arm/Group Title | Lenalidomide, Low-dose Dexamethasone (Rd) | Daratumumab, Lenalidomide, Dexamethasone (DRd) |
|---|---|---|
| Arm/Group Description | Participants received lenalidomide at a dose of 25 milligram (mg) orally on Days 1 through 21 of each treatment cycle and dexamethasone as a total dose of 40 mg weekly (or 20 mg weekly for participants greater than (>) 75 years old or with a body mass index less than [<] 8.5). | Participants received daratumumab 16 milligram per kilogram (mg/kg) as an intravenous (IV) infusion once a week during treatment cycles 1 and 2 (for 8 weeks); every 2 weeks during treatment cycles 3 to 6 (for 16 weeks); once only (on Day 1) during treatment cycles 7 onwards (for every 4 weeks). Lenalidomide was administered at a dose of 25 mg orally on Days 1 through 21 of each treatment cycle and dexamethasone was administered as a total dose of 40 mg weekly (or 20 mg weekly for participants > 75 years old or with a body mass index < 8.5). |
| Measure Participants | 283 | 286 |
| Median (95% Confidence Interval) [months] |
18.43
|
NA
|
| Title | Time to Disease Progression (TTP) |
|---|---|
| Description | TTP was defined as time from date of randomization to date of first documented evidence of progressive disease (PD). PD was defined as meeting any one of following criteria: Increase of >=25% in level of serum M-protein from lowest response value and absolute increase must be >=0.5 g/dL; Increase of >=25% in 24-hour urinary light chain excretion (urine M-protein) from lowest response value and absolute increase must be >=200 mg/24hours; Only in participants without measurable serum and urine M-protein levels: increase of >=25% in difference between involved and uninvolved free light chain (FLC) levels from lowest response value and absolute increase must be >10 milligram per deciliter (mg/dL); Definite increase in size of existing bone lesions or soft tissue plasmacytomas; Definite development of new bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to Plasma Cell (PC) proliferative disorder. |
| Time Frame | From randomization to disease progression until 21 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT analysis set included all participants who were randomly assigned to the DRd or Rd group. |
| Arm/Group Title | Lenalidomide, Low-dose Dexamethasone (Rd) | Daratumumab, Lenalidomide, Dexamethasone (DRd) |
|---|---|---|
| Arm/Group Description | Participants received lenalidomide at a dose of 25 milligram (mg) orally on Days 1 through 21 of each treatment cycle and dexamethasone as a total dose of 40 mg weekly (or 20 mg weekly for participants greater than (>) 75 years old or with a body mass index less than [<] 8.5). | Participants received daratumumab 16 milligram per kilogram (mg/kg) as an intravenous (IV) infusion once a week during treatment cycles 1 and 2 (for 8 weeks); every 2 weeks during treatment cycles 3 to 6 (for 16 weeks); once only (on Day 1) during treatment cycles 7 onwards (for every 4 weeks). Lenalidomide was administered at a dose of 25 mg orally on Days 1 through 21 of each treatment cycle and dexamethasone was administered as a total dose of 40 mg weekly (or 20 mg weekly for participants > 75 years old or with a body mass index < 8.5). |
| Measure Participants | 283 | 286 |
| Median (95% Confidence Interval) [months] |
18.43
|
NA
|
| Title | Percentage of Participants Who Achieved Very Good Partial Response (VGPR) or Better |
|---|---|
| Description | VGPR or better is defined as the percentage of participants who achieved VGPR, complete response (CR) and stringent complete response (sCR) according to the International Myeloma Working Group criteria (IMWG). IMWG criteria for 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, if the serum and urine M-protein are not measurable, a decrease of >90% in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria. In addition to the above criteria, if present at baseline, a >=50% reduction in the size of soft tissue plasmacytomas is also required; CR: Negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas, and <5% PCs in bone marrow; sCR: CR and normal FLC ratio, absence of clonal PCs by immunohistochemistry, immunofluorescence or 2- to 4 color flow cytometry. |
| Time Frame | From randomization to disease progression (approximately up to 21 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Response-evaluable set included participants who have a confirmed diagnosis of multiple myeloma and measurable disease and must have received at least 1 administration of study treatment and have at least 1 post baseline disease assessment. |
| Arm/Group Title | Lenalidomide, Low-dose Dexamethasone (Rd) | Daratumumab, Lenalidomide, Dexamethasone (DRd) |
|---|---|---|
| Arm/Group Description | Participants received lenalidomide at a dose of 25 milligram (mg) orally on Days 1 through 21 of each treatment cycle and dexamethasone as a total dose of 40 mg weekly (or 20 mg weekly for participants greater than (>) 75 years old or with a body mass index less than [<] 8.5). | Participants received daratumumab 16 milligram per kilogram (mg/kg) as an intravenous (IV) infusion once a week during treatment cycles 1 and 2 (for 8 weeks); every 2 weeks during treatment cycles 3 to 6 (for 16 weeks); once only (on Day 1) during treatment cycles 7 onwards (for every 4 weeks). Lenalidomide was administered at a dose of 25 mg orally on Days 1 through 21 of each treatment cycle and dexamethasone was administered as a total dose of 40 mg weekly (or 20 mg weekly for participants > 75 years old or with a body mass index < 8.5). |
| Measure Participants | 276 | 281 |
| Number (95% Confidence Interval) [percentage of participants] |
44.2
15.6%
|
75.8
26.5%
|
| Title | Percentage of Participants With Negative Minimal Residual Disease (MRD) |
|---|---|
| Description | Minimal residual disease was assessed for all participants who achieved a complete response (CR) or stringent complete response (sCR). The MRD negativity rate was defined as the percentage of participants who had negative MRD assessment at any time point after the first dose of study drugs by evaluation of bone marrow aspirates or whole blood at 10^- 4 threshold. |
| Time Frame | From randomization to the date of first documented evidence of PD until 21 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT analysis set included all participants who were randomly assigned to the DRd or Rd group. |
| Arm/Group Title | Lenalidomide, Low-dose Dexamethasone (Rd) | Daratumumab, Lenalidomide, Dexamethasone (DRd) |
|---|---|---|
| Arm/Group Description | Participants received lenalidomide at a dose of 25 milligram (mg) orally on Days 1 through 21 of each treatment cycle and dexamethasone as a total dose of 40 mg weekly (or 20 mg weekly for participants greater than (>) 75 years old or with a body mass index less than [<] 8.5). | Participants received daratumumab 16 milligram per kilogram (mg/kg) as an intravenous (IV) infusion once a week during treatment cycles 1 and 2 (for 8 weeks); every 2 weeks during treatment cycles 3 to 6 (for 16 weeks); once only (on Day 1) during treatment cycles 7 onwards (for every 4 weeks). Lenalidomide was administered at a dose of 25 mg orally on Days 1 through 21 of each treatment cycle and dexamethasone was administered as a total dose of 40 mg weekly (or 20 mg weekly for participants > 75 years old or with a body mass index < 8.5). |
| Measure Participants | 283 | 286 |
| Number [percentage of participants] |
7.8
2.8%
|
29.0
10.1%
|
| Title | Overall Response Rate |
|---|---|
| Description | Overall response rate was defined as the percentage of participants who achieved a partial response (PR) or better according to the International Myeloma Working Group (IMWG) criteria, during or after study treatment. IMWG criteria for PR: >=50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by >=90% or to <200 mg/24 hours, if the serum and urine M-protein are not measurable, a decrease of >=50% in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria, in addition to the above criteria, if present at baseline, a >=50% reduction in the size of soft tissue plasmacytomas is also required. |
| Time Frame | From randomization to disease progression (approximately up to 21 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Response-evaluable set included participants who have a confirmed diagnosis of multiple myeloma and measurable disease and must have received at least 1 administration of study treatment and have at least 1 post baseline disease assessment. |
| Arm/Group Title | Lenalidomide, Low-dose Dexamethasone (Rd) | Daratumumab, Lenalidomide, Dexamethasone (DRd) |
|---|---|---|
| Arm/Group Description | Participants received lenalidomide at a dose of 25 milligram (mg) orally on Days 1 through 21 of each treatment cycle and dexamethasone as a total dose of 40 mg weekly (or 20 mg weekly for participants greater than (>) 75 years old or with a body mass index less than [<] 8.5). | Participants received daratumumab 16 milligram per kilogram (mg/kg) as an intravenous (IV) infusion once a week during treatment cycles 1 and 2 (for 8 weeks); every 2 weeks during treatment cycles 3 to 6 (for 16 weeks); once only (on Day 1) during treatment cycles 7 onwards (for every 4 weeks). Lenalidomide was administered at a dose of 25 mg orally on Days 1 through 21 of each treatment cycle and dexamethasone was administered as a total dose of 40 mg weekly (or 20 mg weekly for participants > 75 years old or with a body mass index < 8.5). |
| Measure Participants | 276 | 281 |
| Number [percentage of participants] |
76.4
27%
|
92.9
32.5%
|
| Title | Overall Survival (OS) |
|---|---|
| Description | Overall survival was measured from the date of randomization to the date of the participant's death. |
| Time Frame | Up to approximately 21 months after the last participant is randomized |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT analysis set included all participants who were randomly assigned to the DRd or Rd group. |
| Arm/Group Title | Lenalidomide, Low-dose Dexamethasone (Rd) | Daratumumab, Lenalidomide, Dexamethasone (DRd) |
|---|---|---|
| Arm/Group Description | Participants received lenalidomide at a dose of 25 milligram (mg) orally on Days 1 through 21 of each treatment cycle and dexamethasone as a total dose of 40 mg weekly (or 20 mg weekly for participants greater than (>) 75 years old or with a body mass index less than [<] 8.5). | Participants received daratumumab 16 milligram per kilogram (mg/kg) as an intravenous (IV) infusion once a week during treatment cycles 1 and 2 (for 8 weeks); every 2 weeks during treatment cycles 3 to 6 (for 16 weeks); once only (on Day 1) during treatment cycles 7 onwards (for every 4 weeks). Lenalidomide was administered at a dose of 25 mg orally on Days 1 through 21 of each treatment cycle and dexamethasone was administered as a total dose of 40 mg weekly (or 20 mg weekly for participants > 75 years old or with a body mass index < 8.5). |
| Measure Participants | 283 | 286 |
| Median (95% Confidence Interval) [months] |
NA
|
NA
|
| Title | Time to Response |
|---|---|
| Description | Time to response was defined as the time between the date of randomization and the first efficacy evaluation that the participant met all criteria for partial response (PR) or better. |
| Time Frame | From randomization up to first documented CR or PR until 21 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Response-evaluable set is defined as participants who have a confirmed diagnosis of multiple myeloma and measurable disease at baseline or screening visit. In addition, participants must have received at least 1 administration of study treatment and have at least 1 post baseline disease assessment. |
| Arm/Group Title | Lenalidomide, Low-dose Dexamethasone (Rd) | Daratumumab, Lenalidomide, Dexamethasone (DRd) |
|---|---|---|
| Arm/Group Description | Participants received lenalidomide at a dose of 25 milligram (mg) orally on Days 1 through 21 of each treatment cycle and dexamethasone as a total dose of 40 mg weekly (or 20 mg weekly for participants greater than (>) 75 years old or with a body mass index less than [<] 8.5). | Participants received daratumumab 16 milligram per kilogram (mg/kg) as an intravenous (IV) infusion once a week during treatment cycles 1 and 2 (for 8 weeks); every 2 weeks during treatment cycles 3 to 6 (for 16 weeks); once only (on Day 1) during treatment cycles 7 onwards (for every 4 weeks). Lenalidomide was administered at a dose of 25 mg orally on Days 1 through 21 of each treatment cycle and dexamethasone was administered as a total dose of 40 mg weekly (or 20 mg weekly for participants > 75 years old or with a body mass index < 8.5). |
| Measure Participants | 276 | 281 |
| Median (95% Confidence Interval) [months] |
1.3
|
1.0
|
| Title | Duration of Response (DOR) |
|---|---|
| Description | DOR was defined for participants with confirmed response (PR or better) as time between first documentation of response and disease progression/death due to PD, whichever occurs first. PD was defined as meeting any one of following criteria: Increase of >=25% in level of serum M-protein from lowest response value and absolute increase must be >=0.5g/dL; Increase of >=25% in 24-hour urinary light chain excretion (urine M-protein) from lowest response value and absolute increase must be >=200mg/24hours; Only in participants without measurable serum and urine M-protein levels: increase of >=25% in difference between involved and uninvolved FLC levels from lowest response value and absolute increase must be >10mg/dL; Definite increase in size of existing bone lesions/soft tissue plasmacytomas; Definite development of new bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum calcium >11.5mg/dL) that can be attributed solely to PC proliferative disorder. |
| Time Frame | From randomization to the date of first documented evidence of PD until 21 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Response-evaluable set included participants who have a confirmed diagnosis of multiple myeloma and measurable disease and must have received at least 1 administration of study treatment and have at least 1 post baseline disease assessment. Here 'N' signifies number of participants who had PR or better response. |
| Arm/Group Title | Lenalidomide, Low-dose Dexamethasone (Rd) | Daratumumab, Lenalidomide, Dexamethasone (DRd) |
|---|---|---|
| Arm/Group Description | Participants received lenalidomide at a dose of 25 milligram (mg) orally on Days 1 through 21 of each treatment cycle and dexamethasone as a total dose of 40 mg weekly (or 20 mg weekly for participants greater than (>) 75 years old or with a body mass index less than [<] 8.5). | Participants received daratumumab 16 milligram per kilogram (mg/kg) as an intravenous (IV) infusion once a week during treatment cycles 1 and 2 (for 8 weeks); every 2 weeks during treatment cycles 3 to 6 (for 16 weeks); once only (on Day 1) during treatment cycles 7 onwards (for every 4 weeks). Lenalidomide was administered at a dose of 25 mg orally on Days 1 through 21 of each treatment cycle and dexamethasone was administered as a total dose of 40 mg weekly (or 20 mg weekly for participants > 75 years old or with a body mass index < 8.5). |
| Measure Participants | 211 | 261 |
| Median (95% Confidence Interval) [months] |
17.4
|
NA
|
Adverse Events
| Time Frame | Up to 21 months | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Safety Population included participants who were randomized and received at least 1 dose of any study treatment. | |||
| Arm/Group Title | Lenalidomide, Low-dose Dexamethasone (Rd) | Daratumumab, Lenalidomide, Dexamethasone (DRd) | ||
| Arm/Group Description | Participants received lenalidomide at a dose of 25 milligram (mg) orally on Days 1 through 21 of each treatment cycle and dexamethasone as a total dose of 40 mg weekly (or 20 mg weekly for participants greater than (>) 75 years old or with a body mass index less than [<] 8.5). | Participants received daratumumab 16 milligram per kilogram (mg/kg) as an intravenous (IV) infusion once a week during treatment cycles 1 and 2 (for 8 weeks); every 2 weeks during treatment cycles 3 to 6 (for 16 weeks); once only (on Day 1) during treatment cycles 7 onwards (for every 4 weeks). Lenalidomide was administered at a dose of 25 mg orally on Days 1 through 21 of each treatment cycle and dexamethasone was administered as a total dose of 40 mg weekly (or 20 mg weekly for participants > 75 years old or with a body mass index < 8.5). | ||
All Cause Mortality |
||||
| Lenalidomide, Low-dose Dexamethasone (Rd) | Daratumumab, Lenalidomide, Dexamethasone (DRd) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Lenalidomide, Low-dose Dexamethasone (Rd) | Daratumumab, Lenalidomide, Dexamethasone (DRd) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 118/281 (42%) | 138/283 (48.8%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 2/281 (0.7%) | 2/283 (0.7%) | ||
| Bone Marrow Failure | 1/281 (0.4%) | 0/283 (0%) | ||
| Febrile Neutropenia | 4/281 (1.4%) | 12/283 (4.2%) | ||
| Hyperviscosity Syndrome | 1/281 (0.4%) | 0/283 (0%) | ||
| Lymphadenopathy | 1/281 (0.4%) | 0/283 (0%) | ||
| Neutropenia | 0/281 (0%) | 2/283 (0.7%) | ||
| Sideroblastic Anaemia | 1/281 (0.4%) | 0/283 (0%) | ||
| Thrombocytopenia | 1/281 (0.4%) | 1/283 (0.4%) | ||
| Thrombotic Thrombocytopenic Purpura | 1/281 (0.4%) | 0/283 (0%) | ||
| Cardiac disorders | ||||
| Acute Coronary Syndrome | 0/281 (0%) | 1/283 (0.4%) | ||
| Acute Myocardial Infarction | 3/281 (1.1%) | 0/283 (0%) | ||
| Angina Pectoris | 0/281 (0%) | 1/283 (0.4%) | ||
| Atrial Fibrillation | 2/281 (0.7%) | 2/283 (0.7%) | ||
| Atrial Flutter | 0/281 (0%) | 1/283 (0.4%) | ||
| Cardiac Amyloidosis | 0/281 (0%) | 1/283 (0.4%) | ||
| Cardiac Arrest | 1/281 (0.4%) | 0/283 (0%) | ||
| Cardiac Failure Congestive | 0/281 (0%) | 1/283 (0.4%) | ||
| Cardiopulmonary Failure | 0/281 (0%) | 1/283 (0.4%) | ||
| Myocardial Infarction | 1/281 (0.4%) | 1/283 (0.4%) | ||
| Pericarditis | 1/281 (0.4%) | 0/283 (0%) | ||
| Sinus Arrhythmia | 0/281 (0%) | 1/283 (0.4%) | ||
| Supraventricular Tachycardia | 1/281 (0.4%) | 0/283 (0%) | ||
| Eye disorders | ||||
| Cataract | 0/281 (0%) | 1/283 (0.4%) | ||
| Posterior Capsule Rupture | 0/281 (0%) | 1/283 (0.4%) | ||
| Gastrointestinal disorders | ||||
| Colitis | 1/281 (0.4%) | 1/283 (0.4%) | ||
| Constipation | 0/281 (0%) | 1/283 (0.4%) | ||
| Diarrhoea | 6/281 (2.1%) | 5/283 (1.8%) | ||
| Diverticular Perforation | 0/281 (0%) | 2/283 (0.7%) | ||
| Gastrointestinal Angiodysplasia Haemorrhagic | 0/281 (0%) | 1/283 (0.4%) | ||
| Gastrointestinal Disorder | 0/281 (0%) | 1/283 (0.4%) | ||
| Haematemesis | 1/281 (0.4%) | 0/283 (0%) | ||
| Inguinal Hernia | 0/281 (0%) | 1/283 (0.4%) | ||
| Intestinal Obstruction | 1/281 (0.4%) | 0/283 (0%) | ||
| Lower Gastrointestinal Haemorrhage | 1/281 (0.4%) | 0/283 (0%) | ||
| Nausea | 0/281 (0%) | 2/283 (0.7%) | ||
| Oesophagitis | 1/281 (0.4%) | 0/283 (0%) | ||
| Vomiting | 1/281 (0.4%) | 1/283 (0.4%) | ||
| General disorders | ||||
| Asthenia | 0/281 (0%) | 1/283 (0.4%) | ||
| Chest Discomfort | 0/281 (0%) | 1/283 (0.4%) | ||
| Fatigue | 1/281 (0.4%) | 0/283 (0%) | ||
| Gait Disturbance | 0/281 (0%) | 1/283 (0.4%) | ||
| General Physical Health Deterioration | 0/281 (0%) | 2/283 (0.7%) | ||
| Generalised Oedema | 1/281 (0.4%) | 0/283 (0%) | ||
| Multi-Organ Failure | 0/281 (0%) | 1/283 (0.4%) | ||
| Non-Cardiac Chest Pain | 1/281 (0.4%) | 1/283 (0.4%) | ||
| Pain | 2/281 (0.7%) | 1/283 (0.4%) | ||
| Pyrexia | 4/281 (1.4%) | 8/283 (2.8%) | ||
| Systemic Inflammatory Response Syndrome | 0/281 (0%) | 1/283 (0.4%) | ||
| Hepatobiliary disorders | ||||
| Bile Duct Stone | 1/281 (0.4%) | 0/283 (0%) | ||
| Liver Disorder | 1/281 (0.4%) | 0/283 (0%) | ||
| Infections and infestations | ||||
| Acute Sinusitis | 0/281 (0%) | 1/283 (0.4%) | ||
| Anal Abscess | 1/281 (0.4%) | 0/283 (0%) | ||
| Appendicitis | 1/281 (0.4%) | 2/283 (0.7%) | ||
| Bacterial Infection | 0/281 (0%) | 1/283 (0.4%) | ||
| Bronchiolitis | 0/281 (0%) | 1/283 (0.4%) | ||
| Bronchitis | 4/281 (1.4%) | 5/283 (1.8%) | ||
| Bronchitis Bacterial | 0/281 (0%) | 1/283 (0.4%) | ||
| Bronchopneumonia | 0/281 (0%) | 2/283 (0.7%) | ||
| Candida Infection | 0/281 (0%) | 1/283 (0.4%) | ||
| Cellulitis | 1/281 (0.4%) | 1/283 (0.4%) | ||
| Clostridium Difficile Infection | 2/281 (0.7%) | 0/283 (0%) | ||
| Cytomegalovirus Infection | 0/281 (0%) | 1/283 (0.4%) | ||
| Enterocolitis Infectious | 1/281 (0.4%) | 0/283 (0%) | ||
| Epiglottitis | 0/281 (0%) | 1/283 (0.4%) | ||
| Erysipelas | 1/281 (0.4%) | 0/283 (0%) | ||
| Escherichia Bacteraemia | 0/281 (0%) | 1/283 (0.4%) | ||
| Extradural Abscess | 0/281 (0%) | 1/283 (0.4%) | ||
| Gastroenteritis | 1/281 (0.4%) | 1/283 (0.4%) | ||
| Gastroenteritis Viral | 1/281 (0.4%) | 2/283 (0.7%) | ||
| Gastrointestinal Infection | 1/281 (0.4%) | 0/283 (0%) | ||
| Gingivitis | 0/281 (0%) | 1/283 (0.4%) | ||
| H1n1 Influenza | 0/281 (0%) | 1/283 (0.4%) | ||
| Haemophilus Infection | 1/281 (0.4%) | 0/283 (0%) | ||
| Infection | 3/281 (1.1%) | 2/283 (0.7%) | ||
| Infective Spondylitis | 0/281 (0%) | 1/283 (0.4%) | ||
| Influenza | 4/281 (1.4%) | 8/283 (2.8%) | ||
| Keratitis Fungal | 1/281 (0.4%) | 0/283 (0%) | ||
| Listeria Sepsis | 0/281 (0%) | 1/283 (0.4%) | ||
| Lobar Pneumonia | 1/281 (0.4%) | 2/283 (0.7%) | ||
| Lower Respiratory Tract Infection | 3/281 (1.1%) | 7/283 (2.5%) | ||
| Lung Infection | 1/281 (0.4%) | 1/283 (0.4%) | ||
| Nasal Abscess | 0/281 (0%) | 1/283 (0.4%) | ||
| Necrotising Fasciitis | 1/281 (0.4%) | 0/283 (0%) | ||
| Neutropenic Sepsis | 0/281 (0%) | 1/283 (0.4%) | ||
| Oral Fungal Infection | 0/281 (0%) | 1/283 (0.4%) | ||
| Osteomyelitis | 2/281 (0.7%) | 0/283 (0%) | ||
| Parainfluenzae Virus Infection | 1/281 (0.4%) | 1/283 (0.4%) | ||
| Parotitis | 0/281 (0%) | 1/283 (0.4%) | ||
| Periorbital Cellulitis | 0/281 (0%) | 1/283 (0.4%) | ||
| Pharyngitis | 1/281 (0.4%) | 0/283 (0%) | ||
| Pneumonia | 24/281 (8.5%) | 23/283 (8.1%) | ||
| Pneumonia Bacterial | 1/281 (0.4%) | 2/283 (0.7%) | ||
| Pneumonia Haemophilus | 0/281 (0%) | 1/283 (0.4%) | ||
| Pneumonia Influenzal | 0/281 (0%) | 3/283 (1.1%) | ||
| Pneumonia Klebsiella | 0/281 (0%) | 1/283 (0.4%) | ||
| Pneumonia Legionella | 1/281 (0.4%) | 1/283 (0.4%) | ||
| Pneumonia Streptococcal | 0/281 (0%) | 1/283 (0.4%) | ||
| Pulmonary Tuberculosis | 1/281 (0.4%) | 0/283 (0%) | ||
| Pyelonephritis Acute | 1/281 (0.4%) | 0/283 (0%) | ||
| Respiratory Syncytial Virus Infection | 0/281 (0%) | 2/283 (0.7%) | ||
| Respiratory Tract Infection | 2/281 (0.7%) | 5/283 (1.8%) | ||
| Respiratory Tract Infection Viral | 0/281 (0%) | 1/283 (0.4%) | ||
| Salmonella Bacteraemia | 0/281 (0%) | 1/283 (0.4%) | ||
| Sepsis | 5/281 (1.8%) | 2/283 (0.7%) | ||
| Septic Shock | 1/281 (0.4%) | 3/283 (1.1%) | ||
| Skin Infection | 0/281 (0%) | 1/283 (0.4%) | ||
| Soft Tissue Infection | 0/281 (0%) | 1/283 (0.4%) | ||
| Tonsillitis | 0/281 (0%) | 1/283 (0.4%) | ||
| Upper Respiratory Tract Infection | 5/281 (1.8%) | 1/283 (0.4%) | ||
| Upper Respiratory Tract Infection Bacterial | 0/281 (0%) | 1/283 (0.4%) | ||
| Urinary Tract Infection | 1/281 (0.4%) | 3/283 (1.1%) | ||
| Urosepsis | 1/281 (0.4%) | 0/283 (0%) | ||
| Uterine Abscess | 0/281 (0%) | 1/283 (0.4%) | ||
| Varicella Zoster Virus Infection | 1/281 (0.4%) | 0/283 (0%) | ||
| Viral Infection | 1/281 (0.4%) | 0/283 (0%) | ||
| Injury, poisoning and procedural complications | ||||
| Compression Fracture | 0/281 (0%) | 1/283 (0.4%) | ||
| Fall | 1/281 (0.4%) | 0/283 (0%) | ||
| Femoral Neck Fracture | 1/281 (0.4%) | 0/283 (0%) | ||
| Foot Fracture | 0/281 (0%) | 1/283 (0.4%) | ||
| Hand Fracture | 0/281 (0%) | 1/283 (0.4%) | ||
| Hip Fracture | 1/281 (0.4%) | 1/283 (0.4%) | ||
| Humerus Fracture | 1/281 (0.4%) | 0/283 (0%) | ||
| Joint Dislocation | 1/281 (0.4%) | 0/283 (0%) | ||
| Pelvic Fracture | 1/281 (0.4%) | 0/283 (0%) | ||
| Peroneal Nerve Injury | 0/281 (0%) | 1/283 (0.4%) | ||
| Radius Fracture | 1/281 (0.4%) | 0/283 (0%) | ||
| Rib Fracture | 0/281 (0%) | 1/283 (0.4%) | ||
| Spinal Compression Fracture | 0/281 (0%) | 1/283 (0.4%) | ||
| Subdural Haematoma | 1/281 (0.4%) | 0/283 (0%) | ||
| Investigations | ||||
| Body Temperature Increased | 1/281 (0.4%) | 0/283 (0%) | ||
| Diagnostic Procedure | 1/281 (0.4%) | 0/283 (0%) | ||
| International Normalised Ratio Increased | 0/281 (0%) | 1/283 (0.4%) | ||
| Troponin Increased | 0/281 (0%) | 1/283 (0.4%) | ||
| Metabolism and nutrition disorders | ||||
| Decreased Appetite | 1/281 (0.4%) | 0/283 (0%) | ||
| Dehydration | 0/281 (0%) | 1/283 (0.4%) | ||
| Electrolyte Imbalance | 0/281 (0%) | 1/283 (0.4%) | ||
| Gout | 1/281 (0.4%) | 0/283 (0%) | ||
| Hypercalcaemia | 1/281 (0.4%) | 2/283 (0.7%) | ||
| Hyperglycaemia | 0/281 (0%) | 1/283 (0.4%) | ||
| Hypocalcaemia | 0/281 (0%) | 1/283 (0.4%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Back Pain | 5/281 (1.8%) | 2/283 (0.7%) | ||
| Bone Pain | 0/281 (0%) | 2/283 (0.7%) | ||
| Flank Pain | 0/281 (0%) | 1/283 (0.4%) | ||
| Intervertebral Disc Protrusion | 0/281 (0%) | 1/283 (0.4%) | ||
| Muscular Weakness | 1/281 (0.4%) | 0/283 (0%) | ||
| Musculoskeletal Pain | 1/281 (0.4%) | 1/283 (0.4%) | ||
| Osteonecrosis of Jaw | 2/281 (0.7%) | 0/283 (0%) | ||
| Pain in Extremity | 0/281 (0%) | 1/283 (0.4%) | ||
| Pathological Fracture | 1/281 (0.4%) | 0/283 (0%) | ||
| Spinal Column Stenosis | 2/281 (0.7%) | 0/283 (0%) | ||
| Spinal Pain | 1/281 (0.4%) | 0/283 (0%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Acute Monocytic Leukaemia | 0/281 (0%) | 1/283 (0.4%) | ||
| Benign Anorectal Neoplasm | 1/281 (0.4%) | 0/283 (0%) | ||
| Bladder Transitional Cell Carcinoma | 1/281 (0.4%) | 0/283 (0%) | ||
| Bowen's Disease | 0/281 (0%) | 1/283 (0.4%) | ||
| Epstein-Barr Virus Associated Lymphoproliferative Disorder | 0/281 (0%) | 1/283 (0.4%) | ||
| Lung Adenocarcinoma | 1/281 (0.4%) | 0/283 (0%) | ||
| Plasma Cell Leukaemia | 2/281 (0.7%) | 1/283 (0.4%) | ||
| Prostate Cancer | 1/281 (0.4%) | 0/283 (0%) | ||
| Rectal Adenocarcinoma | 1/281 (0.4%) | 0/283 (0%) | ||
| Squamous Cell Carcinoma | 1/281 (0.4%) | 0/283 (0%) | ||
| Nervous system disorders | ||||
| Aphasia | 1/281 (0.4%) | 0/283 (0%) | ||
| Carotid Arteriosclerosis | 1/281 (0.4%) | 0/283 (0%) | ||
| Cerebral Haemorrhage | 1/281 (0.4%) | 0/283 (0%) | ||
| Cerebral Infarction | 1/281 (0.4%) | 1/283 (0.4%) | ||
| Cognitive Disorder | 0/281 (0%) | 1/283 (0.4%) | ||
| Intercostal Neuralgia | 1/281 (0.4%) | 0/283 (0%) | ||
| Ischaemic Stroke | 1/281 (0.4%) | 0/283 (0%) | ||
| Loss of Consciousness | 1/281 (0.4%) | 0/283 (0%) | ||
| Nervous System Disorder | 1/281 (0.4%) | 0/283 (0%) | ||
| Peripheral Sensory Neuropathy | 1/281 (0.4%) | 0/283 (0%) | ||
| Presyncope | 0/281 (0%) | 1/283 (0.4%) | ||
| Seizure | 0/281 (0%) | 1/283 (0.4%) | ||
| Somnolence | 1/281 (0.4%) | 0/283 (0%) | ||
| Syncope | 1/281 (0.4%) | 2/283 (0.7%) | ||
| Transient Ischaemic Attack | 1/281 (0.4%) | 1/283 (0.4%) | ||
| Trigeminal Nerve Disorder | 0/281 (0%) | 1/283 (0.4%) | ||
| Viith Nerve Paralysis | 1/281 (0.4%) | 0/283 (0%) | ||
| Psychiatric disorders | ||||
| Confusional State | 1/281 (0.4%) | 0/283 (0%) | ||
| Depression | 0/281 (0%) | 1/283 (0.4%) | ||
| Depressive Symptom | 1/281 (0.4%) | 0/283 (0%) | ||
| Renal and urinary disorders | ||||
| Acute Kidney Injury | 8/281 (2.8%) | 3/283 (1.1%) | ||
| Azotaemia | 1/281 (0.4%) | 1/283 (0.4%) | ||
| Renal Failure | 3/281 (1.1%) | 1/283 (0.4%) | ||
| Urethral Haemorrhage | 0/281 (0%) | 1/283 (0.4%) | ||
| Reproductive system and breast disorders | ||||
| Prostatomegaly | 0/281 (0%) | 1/283 (0.4%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Acute Pulmonary Oedema | 0/281 (0%) | 1/283 (0.4%) | ||
| Acute Respiratory Failure | 1/281 (0.4%) | 0/283 (0%) | ||
| Bronchospasm | 1/281 (0.4%) | 0/283 (0%) | ||
| Dyspnoea | 1/281 (0.4%) | 2/283 (0.7%) | ||
| Hypoxia | 0/281 (0%) | 1/283 (0.4%) | ||
| Interstitial Lung Disease | 1/281 (0.4%) | 0/283 (0%) | ||
| Lung Disorder | 1/281 (0.4%) | 0/283 (0%) | ||
| Pneumonitis | 0/281 (0%) | 1/283 (0.4%) | ||
| Pneumothorax | 1/281 (0.4%) | 0/283 (0%) | ||
| Pulmonary Calcification | 0/281 (0%) | 1/283 (0.4%) | ||
| Pulmonary Embolism | 8/281 (2.8%) | 7/283 (2.5%) | ||
| Pulmonary Oedema | 1/281 (0.4%) | 2/283 (0.7%) | ||
| Respiratory Failure | 1/281 (0.4%) | 2/283 (0.7%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Rash Generalised | 0/281 (0%) | 1/283 (0.4%) | ||
| Rash Papular | 0/281 (0%) | 1/283 (0.4%) | ||
| Vascular disorders | ||||
| Deep Vein Thrombosis | 1/281 (0.4%) | 0/283 (0%) | ||
| Embolism | 0/281 (0%) | 1/283 (0.4%) | ||
| Haemorrhagic Infarction | 0/281 (0%) | 1/283 (0.4%) | ||
| Hypertension | 0/281 (0%) | 1/283 (0.4%) | ||
| Hypotension | 0/281 (0%) | 1/283 (0.4%) | ||
| Orthostatic Hypotension | 0/281 (0%) | 1/283 (0.4%) | ||
| Peripheral Artery Stenosis | 0/281 (0%) | 1/283 (0.4%) | ||
| Phlebitis | 1/281 (0.4%) | 0/283 (0%) | ||
| Venous Occlusion | 1/281 (0.4%) | 0/283 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Lenalidomide, Low-dose Dexamethasone (Rd) | Daratumumab, Lenalidomide, Dexamethasone (DRd) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 274/281 (97.5%) | 276/283 (97.5%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 98/281 (34.9%) | 87/283 (30.7%) | ||
| Leukopenia | 17/281 (6%) | 21/283 (7.4%) | ||
| Lymphopenia | 15/281 (5.3%) | 17/283 (6%) | ||
| Neutropenia | 121/281 (43.1%) | 168/283 (59.4%) | ||
| Thrombocytopenia | 77/281 (27.4%) | 76/283 (26.9%) | ||
| Eye disorders | ||||
| Cataract | 8/281 (2.8%) | 18/283 (6.4%) | ||
| Vision Blurred | 14/281 (5%) | 19/283 (6.7%) | ||
| Gastrointestinal disorders | ||||
| Abdominal Pain | 11/281 (3.9%) | 20/283 (7.1%) | ||
| Abdominal Pain Upper | 10/281 (3.6%) | 21/283 (7.4%) | ||
| Constipation | 71/281 (25.3%) | 82/283 (29%) | ||
| Diarrhoea | 65/281 (23.1%) | 121/283 (42.8%) | ||
| Dyspepsia | 6/281 (2.1%) | 18/283 (6.4%) | ||
| Nausea | 40/281 (14.2%) | 67/283 (23.7%) | ||
| Stomatitis | 6/281 (2.1%) | 17/283 (6%) | ||
| Vomiting | 14/281 (5%) | 46/283 (16.3%) | ||
| General disorders | ||||
| Asthenia | 36/281 (12.8%) | 45/283 (15.9%) | ||
| Chills | 9/281 (3.2%) | 17/283 (6%) | ||
| Fatigue | 78/281 (27.8%) | 100/283 (35.3%) | ||
| Influenza Like Illness | 12/281 (4.3%) | 17/283 (6%) | ||
| Oedema Peripheral | 37/281 (13.2%) | 43/283 (15.2%) | ||
| Pyrexia | 30/281 (10.7%) | 53/283 (18.7%) | ||
| Infections and infestations | ||||
| Bronchitis | 31/281 (11%) | 36/283 (12.7%) | ||
| Nasopharyngitis | 43/281 (15.3%) | 68/283 (24%) | ||
| Pneumonia | 17/281 (6%) | 20/283 (7.1%) | ||
| Respiratory Tract Infection | 22/281 (7.8%) | 28/283 (9.9%) | ||
| Rhinitis | 3/281 (1.1%) | 15/283 (5.3%) | ||
| Sinusitis | 10/281 (3.6%) | 18/283 (6.4%) | ||
| Upper Respiratory Tract Infection | 54/281 (19.2%) | 89/283 (31.4%) | ||
| Investigations | ||||
| Alanine Aminotransferase Increased | 10/281 (3.6%) | 15/283 (5.3%) | ||
| Weight Decreased | 9/281 (3.2%) | 16/283 (5.7%) | ||
| Metabolism and nutrition disorders | ||||
| Decreased Appetite | 28/281 (10%) | 32/283 (11.3%) | ||
| Hyperglycaemia | 19/281 (6.8%) | 25/283 (8.8%) | ||
| Hypocalcaemia | 11/281 (3.9%) | 17/283 (6%) | ||
| Hypokalaemia | 22/281 (7.8%) | 30/283 (10.6%) | ||
| Hypophosphataemia | 11/281 (3.9%) | 16/283 (5.7%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 21/281 (7.5%) | 24/283 (8.5%) | ||
| Back Pain | 45/281 (16%) | 49/283 (17.3%) | ||
| Bone Pain | 12/281 (4.3%) | 17/283 (6%) | ||
| Muscle Spasms | 52/281 (18.5%) | 73/283 (25.8%) | ||
| Muscular Weakness | 21/281 (7.5%) | 23/283 (8.1%) | ||
| Musculoskeletal Chest Pain | 17/281 (6%) | 15/283 (5.3%) | ||
| Musculoskeletal Pain | 15/281 (5.3%) | 17/283 (6%) | ||
| Myalgia | 9/281 (3.2%) | 16/283 (5.7%) | ||
| Pain in Extremity | 30/281 (10.7%) | 20/283 (7.1%) | ||
| Nervous system disorders | ||||
| Dizziness | 24/281 (8.5%) | 22/283 (7.8%) | ||
| Dysgeusia | 15/281 (5.3%) | 21/283 (7.4%) | ||
| Headache | 19/281 (6.8%) | 37/283 (13.1%) | ||
| Neuropathy Peripheral | 15/281 (5.3%) | 12/283 (4.2%) | ||
| Peripheral Sensory Neuropathy | 18/281 (6.4%) | 23/283 (8.1%) | ||
| Tremor | 24/281 (8.5%) | 26/283 (9.2%) | ||
| Psychiatric disorders | ||||
| Anxiety | 12/281 (4.3%) | 18/283 (6.4%) | ||
| Depression | 5/281 (1.8%) | 17/283 (6%) | ||
| Insomnia | 55/281 (19.6%) | 55/283 (19.4%) | ||
| Renal and urinary disorders | ||||
| Renal Impairment | 13/281 (4.6%) | 20/283 (7.1%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 35/281 (12.5%) | 82/283 (29%) | ||
| Dyspnoea | 32/281 (11.4%) | 51/283 (18%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Hyperhidrosis | 8/281 (2.8%) | 20/283 (7.1%) | ||
| Pruritus | 29/281 (10.3%) | 28/283 (9.9%) | ||
| Rash | 29/281 (10.3%) | 35/283 (12.4%) | ||
| Vascular disorders | ||||
| Hypertension | 7/281 (2.5%) | 20/283 (7.1%) | ||
| Hypotension | 6/281 (2.1%) | 19/283 (6.7%) | ||
Limitations/Caveats
[Not Specified]
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 | Director, Clinical Research |
|---|---|
| Organization | Janssen R&D US |
| Phone | |
| ClinicalTrialDisclosure@its.jnj.com |
Responsible Party:
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT02076009
Other Study ID Numbers:
- CR103663
- 54767414MMY3003
- 2013-005525-23
First Posted:
Mar 3, 2014
Last Update Posted:
Aug 12, 2022
Last Verified:
Aug 1, 2022