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
Enrollment
146
Locations
2
Arms
123.3
Anticipated Duration (Months)
3.9
Patients Per Site
0
Patients Per Site Per Month

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 DiseaseIntervention/TreatmentPhase
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

ArmIntervention/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

  1. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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

SiteCityStateCountryPostal Code
1Little RockArkansasUnited States
2GainesvilleFloridaUnited States
3West Palm BeachFloridaUnited States
4AtlantaGeorgiaUnited States
5ChicagoIllinoisUnited States
6Iowa CityIowaUnited States
7LouisvilleKentuckyUnited States
8Baton RougeLouisianaUnited States
9New OrleansLouisianaUnited States
10BethesdaMarylandUnited States
11ColumbiaMarylandUnited States
12BostonMassachusettsUnited States
13RochesterMinnesotaUnited States
14OmahaNebraskaUnited States
15New BrunswickNew JerseyUnited States
16New YorkNew YorkUnited States
17CharlotteNorth CarolinaUnited States
18EugeneOregonUnited States
19SpartanburgSouth CarolinaUnited States
20AustinTexasUnited States
21DallasTexasUnited States
22HoustonTexasUnited States
23FairfaxVirginiaUnited States
24CamperdownAustralia
25GeelongAustralia
26HeidelbergAustralia
27MalvernAustralia
28South BrisbaneAustralia
29SouthportAustralia
30AntwerpenBelgium
31BrusselBelgium
32EdegemBelgium
33GentBelgium
34KortrijkBelgium
35LeuvenBelgium
36LiegeBelgium
37CalgaryAlbertaCanada
38EdmontonAlbertaCanada
39VancouverBritish ColumbiaCanada
40HalifaxNova ScotiaCanada
41HamiltonOntarioCanada
42LondonOntarioCanada
43MontrealQuebecCanada
44Quebec CityQuebecCanada
45Surrey N/aCanada
46Toronto N/aCanada
47CopenhagenDenmark
48OdenseDenmark
49VejleDenmark
50ArgenteuilFrance
51CaenFrance
52LilleFrance
53LimogesFrance
54Nantes Cedex 1France
55ParisFrance
56PessacFrance
57Pierre BeniteFrance
58RennesFrance
59Toulouse Cedex 9France
60Tours Cedex 9France
61Vandoeuvre les NancyFrance
62BerlinGermany
63BonnGermany
64HamburgGermany
65HammGermany
66HeidelbergGermany
67JenaGermany
68KarlsruheGermany
69KoblenzGermany
70KölnGermany
71SaarbrückenGermany
72Villingen-SchwenningenGermany
73Athens AtticaGreece
74HaifaIsrael
75JerusalemIsrael
76NahariyaIsrael
77NetanyaIsrael
78Petah TikvaIsrael
79Ramat GanIsrael
80Tel AvivIsrael
81HitachiJapan
82KanazawaJapan
83KobeJapan
84KurumeJapan
85MatsuyamaJapan
86NagoyaJapan
87NaritaJapan
88OhgakiJapan
89OkayamaJapan
90OsakaJapan
91SendaiJapan
92ShibukawaJapan
93ShibuyaJapan
94TachikawaJapan
95TokyoJapan
96Gyeonggi-doKorea, Republic of
97IncheonKorea, Republic of
98SeoulKorea, Republic of
99AmsterdamNetherlands
100RotterdamNetherlands
101UtrechtNetherlands
102ZwolleNetherlands
103BrzozowPoland
104ChorzówPoland
105GdanskPoland
106LegnicaPoland
107LublinPoland
108PoznanPoland
109SlupskPoland
110WroclawaPoland
111DzerzhinskRussian Federation
112EkaterinburgRussian Federation
113MoscowRussian Federation
114Nizhny NovgorodRussian Federation
115PetrozavodskRussian Federation
116RyazanRussian Federation
117SamaraRussian Federation
118St-PetersburgRussian Federation
119St. PetersburgRussian Federation
120SyktyvkarRussian Federation
121BadalonaSpain
122BarcelonaSpain
123La Laguna (Santa Cruz De Tenerife)Spain
124MadridSpain
125PamplonaSpain
126SalamancaSpain
127SevillaSpain
128FalunSweden
129GöteborgSweden
130HelsingborgSweden
131HuddingeSweden
132LundSweden
133StockholmSweden
134UppsalaSweden
135ChanghuaTaiwan
136Taichung CityTaiwan
137TainanTaiwan
138TaipeiTaiwan
139TaoyuanTaiwan
140BirminghamUnited Kingdom
141LeedsUnited Kingdom
142LondonUnited Kingdom
143OxfordUnited Kingdom
144SouthamptonUnited Kingdom
145SurreyUnited Kingdom
146WolverhamptonUnited 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:
Nov 8, 2021
Last Verified:
Nov 1, 2021

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail
Arm/Group TitleLenalidomide, Low-dose Dexamethasone (Rd)Daratumumab, Lenalidomide, Dexamethasone (DRd)
Arm/Group DescriptionParticipants 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
STARTED283286
Treated281283
COMPLETED00
NOT COMPLETED283286

Baseline Characteristics

Arm/Group TitleLenalidomide, Low-dose Dexamethasone (Rd)Daratumumab, Lenalidomide, Dexamethasone (DRd)Total
Arm/Group DescriptionParticipants 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 Participants283286569
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

1. Primary Outcome
TitleProgression-free Survival (PFS)
DescriptionPFS 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 FrameFrom 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 TitleLenalidomide, Low-dose Dexamethasone (Rd)Daratumumab, Lenalidomide, Dexamethasone (DRd)
Arm/Group DescriptionParticipants 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 Participants283286
Median (95% Confidence Interval) [months]
18.43
NA
2. Secondary Outcome
TitleTime to Disease Progression (TTP)
DescriptionTTP 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 FrameFrom 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 TitleLenalidomide, Low-dose Dexamethasone (Rd)Daratumumab, Lenalidomide, Dexamethasone (DRd)
Arm/Group DescriptionParticipants 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 Participants283286
Median (95% Confidence Interval) [months]
18.43
NA
3. Secondary Outcome
TitlePercentage of Participants Who Achieved Very Good Partial Response (VGPR) or Better
DescriptionVGPR 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 FrameFrom 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 TitleLenalidomide, Low-dose Dexamethasone (Rd)Daratumumab, Lenalidomide, Dexamethasone (DRd)
Arm/Group DescriptionParticipants 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 Participants276281
Number (95% Confidence Interval) [percentage of participants]
44.2
15.6%
75.8
26.5%
4. Secondary Outcome
TitlePercentage of Participants With Negative Minimal Residual Disease (MRD)
DescriptionMinimal 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 FrameFrom 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 TitleLenalidomide, Low-dose Dexamethasone (Rd)Daratumumab, Lenalidomide, Dexamethasone (DRd)
Arm/Group DescriptionParticipants 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 Participants283286
Number [percentage of participants]
7.8
2.8%
29.0
10.1%
5. Secondary Outcome
TitleOverall Response Rate
DescriptionOverall 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 FrameFrom 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 TitleLenalidomide, Low-dose Dexamethasone (Rd)Daratumumab, Lenalidomide, Dexamethasone (DRd)
Arm/Group DescriptionParticipants 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 Participants276281
Number [percentage of participants]
76.4
27%
92.9
32.5%
6. Secondary Outcome
TitleOverall Survival (OS)
DescriptionOverall survival was measured from the date of randomization to the date of the participant's death.
Time FrameUp 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 TitleLenalidomide, Low-dose Dexamethasone (Rd)Daratumumab, Lenalidomide, Dexamethasone (DRd)
Arm/Group DescriptionParticipants 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 Participants283286
Median (95% Confidence Interval) [months]
NA
NA
7. Secondary Outcome
TitleTime to Response
DescriptionTime 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 FrameFrom 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 TitleLenalidomide, Low-dose Dexamethasone (Rd)Daratumumab, Lenalidomide, Dexamethasone (DRd)
Arm/Group DescriptionParticipants 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 Participants276281
Median (95% Confidence Interval) [months]
1.3
1.0
8. Secondary Outcome
TitleDuration of Response (DOR)
DescriptionDOR 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 FrameFrom 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 TitleLenalidomide, Low-dose Dexamethasone (Rd)Daratumumab, Lenalidomide, Dexamethasone (DRd)
Arm/Group DescriptionParticipants 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 Participants211261
Median (95% Confidence Interval) [months]
17.4
NA

Adverse Events

Time FrameUp 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 TitleLenalidomide, Low-dose Dexamethasone (Rd)Daratumumab, Lenalidomide, Dexamethasone (DRd)
Arm/Group DescriptionParticipants 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 (%)# EventsAffected / at Risk (%)# Events
Total/ (NaN) / (NaN)
Serious Adverse Events
Lenalidomide, Low-dose Dexamethasone (Rd)Daratumumab, Lenalidomide, Dexamethasone (DRd)
Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total118/281 (42%) 138/283 (48.8%)
Blood and lymphatic system disorders
Anaemia2/281 (0.7%) 2/283 (0.7%)
Bone Marrow Failure1/281 (0.4%) 0/283 (0%)
Febrile Neutropenia4/281 (1.4%) 12/283 (4.2%)
Hyperviscosity Syndrome1/281 (0.4%) 0/283 (0%)
Lymphadenopathy1/281 (0.4%) 0/283 (0%)
Neutropenia0/281 (0%) 2/283 (0.7%)
Sideroblastic Anaemia1/281 (0.4%) 0/283 (0%)
Thrombocytopenia1/281 (0.4%) 1/283 (0.4%)
Thrombotic Thrombocytopenic Purpura1/281 (0.4%) 0/283 (0%)
Cardiac disorders
Acute Coronary Syndrome0/281 (0%) 1/283 (0.4%)
Acute Myocardial Infarction3/281 (1.1%) 0/283 (0%)
Angina Pectoris0/281 (0%) 1/283 (0.4%)
Atrial Fibrillation2/281 (0.7%) 2/283 (0.7%)
Atrial Flutter0/281 (0%) 1/283 (0.4%)
Cardiac Amyloidosis0/281 (0%) 1/283 (0.4%)
Cardiac Arrest1/281 (0.4%) 0/283 (0%)
Cardiac Failure Congestive0/281 (0%) 1/283 (0.4%)
Cardiopulmonary Failure0/281 (0%) 1/283 (0.4%)
Myocardial Infarction1/281 (0.4%) 1/283 (0.4%)
Pericarditis1/281 (0.4%) 0/283 (0%)
Sinus Arrhythmia0/281 (0%) 1/283 (0.4%)
Supraventricular Tachycardia1/281 (0.4%) 0/283 (0%)
Eye disorders
Cataract0/281 (0%) 1/283 (0.4%)
Posterior Capsule Rupture0/281 (0%) 1/283 (0.4%)
Gastrointestinal disorders
Colitis1/281 (0.4%) 1/283 (0.4%)
Constipation0/281 (0%) 1/283 (0.4%)
Diarrhoea6/281 (2.1%) 5/283 (1.8%)
Diverticular Perforation0/281 (0%) 2/283 (0.7%)
Gastrointestinal Angiodysplasia Haemorrhagic0/281 (0%) 1/283 (0.4%)
Gastrointestinal Disorder0/281 (0%) 1/283 (0.4%)
Haematemesis1/281 (0.4%) 0/283 (0%)
Inguinal Hernia0/281 (0%) 1/283 (0.4%)
Intestinal Obstruction1/281 (0.4%) 0/283 (0%)
Lower Gastrointestinal Haemorrhage1/281 (0.4%) 0/283 (0%)
Nausea0/281 (0%) 2/283 (0.7%)
Oesophagitis1/281 (0.4%) 0/283 (0%)
Vomiting1/281 (0.4%) 1/283 (0.4%)
General disorders
Asthenia0/281 (0%) 1/283 (0.4%)
Chest Discomfort0/281 (0%) 1/283 (0.4%)
Fatigue1/281 (0.4%) 0/283 (0%)
Gait Disturbance0/281 (0%) 1/283 (0.4%)
General Physical Health Deterioration0/281 (0%) 2/283 (0.7%)
Generalised Oedema1/281 (0.4%) 0/283 (0%)
Multi-Organ Failure0/281 (0%) 1/283 (0.4%)
Non-Cardiac Chest Pain1/281 (0.4%) 1/283 (0.4%)
Pain2/281 (0.7%) 1/283 (0.4%)
Pyrexia4/281 (1.4%) 8/283 (2.8%)
Systemic Inflammatory Response Syndrome0/281 (0%) 1/283 (0.4%)
Hepatobiliary disorders
Bile Duct Stone1/281 (0.4%) 0/283 (0%)
Liver Disorder1/281 (0.4%) 0/283 (0%)
Infections and infestations
Acute Sinusitis0/281 (0%) 1/283 (0.4%)
Anal Abscess1/281 (0.4%) 0/283 (0%)
Appendicitis1/281 (0.4%) 2/283 (0.7%)
Bacterial Infection0/281 (0%) 1/283 (0.4%)
Bronchiolitis0/281 (0%) 1/283 (0.4%)
Bronchitis4/281 (1.4%) 5/283 (1.8%)
Bronchitis Bacterial0/281 (0%) 1/283 (0.4%)
Bronchopneumonia0/281 (0%) 2/283 (0.7%)
Candida Infection0/281 (0%) 1/283 (0.4%)
Cellulitis1/281 (0.4%) 1/283 (0.4%)
Clostridium Difficile Infection2/281 (0.7%) 0/283 (0%)
Cytomegalovirus Infection0/281 (0%) 1/283 (0.4%)
Enterocolitis Infectious1/281 (0.4%) 0/283 (0%)
Epiglottitis0/281 (0%) 1/283 (0.4%)
Erysipelas1/281 (0.4%) 0/283 (0%)
Escherichia Bacteraemia0/281 (0%) 1/283 (0.4%)
Extradural Abscess0/281 (0%) 1/283 (0.4%)
Gastroenteritis1/281 (0.4%) 1/283 (0.4%)
Gastroenteritis Viral1/281 (0.4%) 2/283 (0.7%)
Gastrointestinal Infection1/281 (0.4%) 0/283 (0%)
Gingivitis0/281 (0%) 1/283 (0.4%)
H1n1 Influenza0/281 (0%) 1/283 (0.4%)
Haemophilus Infection1/281 (0.4%) 0/283 (0%)
Infection3/281 (1.1%) 2/283 (0.7%)
Infective Spondylitis0/281 (0%) 1/283 (0.4%)
Influenza4/281 (1.4%) 8/283 (2.8%)
Keratitis Fungal1/281 (0.4%) 0/283 (0%)
Listeria Sepsis0/281 (0%) 1/283 (0.4%)
Lobar Pneumonia1/281 (0.4%) 2/283 (0.7%)
Lower Respiratory Tract Infection3/281 (1.1%) 7/283 (2.5%)
Lung Infection1/281 (0.4%) 1/283 (0.4%)
Nasal Abscess0/281 (0%) 1/283 (0.4%)
Necrotising Fasciitis1/281 (0.4%) 0/283 (0%)
Neutropenic Sepsis0/281 (0%) 1/283 (0.4%)
Oral Fungal Infection0/281 (0%) 1/283 (0.4%)
Osteomyelitis2/281 (0.7%) 0/283 (0%)
Parainfluenzae Virus Infection1/281 (0.4%) 1/283 (0.4%)
Parotitis0/281 (0%) 1/283 (0.4%)
Periorbital Cellulitis0/281 (0%) 1/283 (0.4%)
Pharyngitis1/281 (0.4%) 0/283 (0%)
Pneumonia24/281 (8.5%) 23/283 (8.1%)
Pneumonia Bacterial1/281 (0.4%) 2/283 (0.7%)
Pneumonia Haemophilus0/281 (0%) 1/283 (0.4%)
Pneumonia Influenzal0/281 (0%) 3/283 (1.1%)
Pneumonia Klebsiella0/281 (0%) 1/283 (0.4%)
Pneumonia Legionella1/281 (0.4%) 1/283 (0.4%)
Pneumonia Streptococcal0/281 (0%) 1/283 (0.4%)
Pulmonary Tuberculosis1/281 (0.4%) 0/283 (0%)
Pyelonephritis Acute1/281 (0.4%) 0/283 (0%)
Respiratory Syncytial Virus Infection0/281 (0%) 2/283 (0.7%)
Respiratory Tract Infection2/281 (0.7%) 5/283 (1.8%)
Respiratory Tract Infection Viral0/281 (0%) 1/283 (0.4%)
Salmonella Bacteraemia0/281 (0%) 1/283 (0.4%)
Sepsis5/281 (1.8%) 2/283 (0.7%)
Septic Shock1/281 (0.4%) 3/283 (1.1%)
Skin Infection0/281 (0%) 1/283 (0.4%)
Soft Tissue Infection0/281 (0%) 1/283 (0.4%)
Tonsillitis0/281 (0%) 1/283 (0.4%)
Upper Respiratory Tract Infection5/281 (1.8%) 1/283 (0.4%)
Upper Respiratory Tract Infection Bacterial0/281 (0%) 1/283 (0.4%)
Urinary Tract Infection1/281 (0.4%) 3/283 (1.1%)
Urosepsis1/281 (0.4%) 0/283 (0%)
Uterine Abscess0/281 (0%) 1/283 (0.4%)
Varicella Zoster Virus Infection1/281 (0.4%) 0/283 (0%)
Viral Infection1/281 (0.4%) 0/283 (0%)
Injury, poisoning and procedural complications
Compression Fracture0/281 (0%) 1/283 (0.4%)
Fall1/281 (0.4%) 0/283 (0%)
Femoral Neck Fracture1/281 (0.4%) 0/283 (0%)
Foot Fracture0/281 (0%) 1/283 (0.4%)
Hand Fracture0/281 (0%) 1/283 (0.4%)
Hip Fracture1/281 (0.4%) 1/283 (0.4%)
Humerus Fracture1/281 (0.4%) 0/283 (0%)
Joint Dislocation1/281 (0.4%) 0/283 (0%)
Pelvic Fracture1/281 (0.4%) 0/283 (0%)
Peroneal Nerve Injury0/281 (0%) 1/283 (0.4%)
Radius Fracture1/281 (0.4%) 0/283 (0%)
Rib Fracture0/281 (0%) 1/283 (0.4%)
Spinal Compression Fracture0/281 (0%) 1/283 (0.4%)
Subdural Haematoma1/281 (0.4%) 0/283 (0%)
Investigations
Body Temperature Increased1/281 (0.4%) 0/283 (0%)
Diagnostic Procedure1/281 (0.4%) 0/283 (0%)
International Normalised Ratio Increased0/281 (0%) 1/283 (0.4%)
Troponin Increased0/281 (0%) 1/283 (0.4%)
Metabolism and nutrition disorders
Decreased Appetite1/281 (0.4%) 0/283 (0%)
Dehydration0/281 (0%) 1/283 (0.4%)
Electrolyte Imbalance0/281 (0%) 1/283 (0.4%)
Gout1/281 (0.4%) 0/283 (0%)
Hypercalcaemia1/281 (0.4%) 2/283 (0.7%)
Hyperglycaemia0/281 (0%) 1/283 (0.4%)
Hypocalcaemia0/281 (0%) 1/283 (0.4%)
Musculoskeletal and connective tissue disorders
Back Pain5/281 (1.8%) 2/283 (0.7%)
Bone Pain0/281 (0%) 2/283 (0.7%)
Flank Pain0/281 (0%) 1/283 (0.4%)
Intervertebral Disc Protrusion0/281 (0%) 1/283 (0.4%)
Muscular Weakness1/281 (0.4%) 0/283 (0%)
Musculoskeletal Pain1/281 (0.4%) 1/283 (0.4%)
Osteonecrosis of Jaw2/281 (0.7%) 0/283 (0%)
Pain in Extremity0/281 (0%) 1/283 (0.4%)
Pathological Fracture1/281 (0.4%) 0/283 (0%)
Spinal Column Stenosis2/281 (0.7%) 0/283 (0%)
Spinal Pain1/281 (0.4%) 0/283 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute Monocytic Leukaemia0/281 (0%) 1/283 (0.4%)
Benign Anorectal Neoplasm1/281 (0.4%) 0/283 (0%)
Bladder Transitional Cell Carcinoma1/281 (0.4%) 0/283 (0%)
Bowen's Disease0/281 (0%) 1/283 (0.4%)
Epstein-Barr Virus Associated Lymphoproliferative Disorder0/281 (0%) 1/283 (0.4%)
Lung Adenocarcinoma1/281 (0.4%) 0/283 (0%)
Plasma Cell Leukaemia2/281 (0.7%) 1/283 (0.4%)
Prostate Cancer1/281 (0.4%) 0/283 (0%)
Rectal Adenocarcinoma1/281 (0.4%) 0/283 (0%)
Squamous Cell Carcinoma1/281 (0.4%) 0/283 (0%)
Nervous system disorders
Aphasia1/281 (0.4%) 0/283 (0%)
Carotid Arteriosclerosis1/281 (0.4%) 0/283 (0%)
Cerebral Haemorrhage1/281 (0.4%) 0/283 (0%)
Cerebral Infarction1/281 (0.4%) 1/283 (0.4%)
Cognitive Disorder0/281 (0%) 1/283 (0.4%)
Intercostal Neuralgia1/281 (0.4%) 0/283 (0%)
Ischaemic Stroke1/281 (0.4%) 0/283 (0%)
Loss of Consciousness1/281 (0.4%) 0/283 (0%)
Nervous System Disorder1/281 (0.4%) 0/283 (0%)
Peripheral Sensory Neuropathy1/281 (0.4%) 0/283 (0%)
Presyncope0/281 (0%) 1/283 (0.4%)
Seizure0/281 (0%) 1/283 (0.4%)
Somnolence1/281 (0.4%) 0/283 (0%)
Syncope1/281 (0.4%) 2/283 (0.7%)
Transient Ischaemic Attack1/281 (0.4%) 1/283 (0.4%)
Trigeminal Nerve Disorder0/281 (0%) 1/283 (0.4%)
Viith Nerve Paralysis1/281 (0.4%) 0/283 (0%)
Psychiatric disorders
Confusional State1/281 (0.4%) 0/283 (0%)
Depression0/281 (0%) 1/283 (0.4%)
Depressive Symptom1/281 (0.4%) 0/283 (0%)
Renal and urinary disorders
Acute Kidney Injury8/281 (2.8%) 3/283 (1.1%)
Azotaemia1/281 (0.4%) 1/283 (0.4%)
Renal Failure3/281 (1.1%) 1/283 (0.4%)
Urethral Haemorrhage0/281 (0%) 1/283 (0.4%)
Reproductive system and breast disorders
Prostatomegaly0/281 (0%) 1/283 (0.4%)
Respiratory, thoracic and mediastinal disorders
Acute Pulmonary Oedema0/281 (0%) 1/283 (0.4%)
Acute Respiratory Failure1/281 (0.4%) 0/283 (0%)
Bronchospasm1/281 (0.4%) 0/283 (0%)
Dyspnoea1/281 (0.4%) 2/283 (0.7%)
Hypoxia0/281 (0%) 1/283 (0.4%)
Interstitial Lung Disease1/281 (0.4%) 0/283 (0%)
Lung Disorder1/281 (0.4%) 0/283 (0%)
Pneumonitis0/281 (0%) 1/283 (0.4%)
Pneumothorax1/281 (0.4%) 0/283 (0%)
Pulmonary Calcification0/281 (0%) 1/283 (0.4%)
Pulmonary Embolism8/281 (2.8%) 7/283 (2.5%)
Pulmonary Oedema1/281 (0.4%) 2/283 (0.7%)
Respiratory Failure1/281 (0.4%) 2/283 (0.7%)
Skin and subcutaneous tissue disorders
Rash Generalised0/281 (0%) 1/283 (0.4%)
Rash Papular0/281 (0%) 1/283 (0.4%)
Vascular disorders
Deep Vein Thrombosis1/281 (0.4%) 0/283 (0%)
Embolism0/281 (0%) 1/283 (0.4%)
Haemorrhagic Infarction0/281 (0%) 1/283 (0.4%)
Hypertension0/281 (0%) 1/283 (0.4%)
Hypotension0/281 (0%) 1/283 (0.4%)
Orthostatic Hypotension0/281 (0%) 1/283 (0.4%)
Peripheral Artery Stenosis0/281 (0%) 1/283 (0.4%)
Phlebitis1/281 (0.4%) 0/283 (0%)
Venous Occlusion1/281 (0.4%) 0/283 (0%)
Other (Not Including Serious) Adverse Events
Lenalidomide, Low-dose Dexamethasone (Rd)Daratumumab, Lenalidomide, Dexamethasone (DRd)
Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total274/281 (97.5%) 276/283 (97.5%)
Blood and lymphatic system disorders
Anaemia98/281 (34.9%) 87/283 (30.7%)
Leukopenia17/281 (6%) 21/283 (7.4%)
Lymphopenia15/281 (5.3%) 17/283 (6%)
Neutropenia121/281 (43.1%) 168/283 (59.4%)
Thrombocytopenia77/281 (27.4%) 76/283 (26.9%)
Eye disorders
Cataract8/281 (2.8%) 18/283 (6.4%)
Vision Blurred14/281 (5%) 19/283 (6.7%)
Gastrointestinal disorders
Abdominal Pain11/281 (3.9%) 20/283 (7.1%)
Abdominal Pain Upper10/281 (3.6%) 21/283 (7.4%)
Constipation71/281 (25.3%) 82/283 (29%)
Diarrhoea65/281 (23.1%) 121/283 (42.8%)
Dyspepsia6/281 (2.1%) 18/283 (6.4%)
Nausea40/281 (14.2%) 67/283 (23.7%)
Stomatitis6/281 (2.1%) 17/283 (6%)
Vomiting14/281 (5%) 46/283 (16.3%)
General disorders
Asthenia36/281 (12.8%) 45/283 (15.9%)
Chills9/281 (3.2%) 17/283 (6%)
Fatigue78/281 (27.8%) 100/283 (35.3%)
Influenza Like Illness12/281 (4.3%) 17/283 (6%)
Oedema Peripheral37/281 (13.2%) 43/283 (15.2%)
Pyrexia30/281 (10.7%) 53/283 (18.7%)
Infections and infestations
Bronchitis31/281 (11%) 36/283 (12.7%)
Nasopharyngitis43/281 (15.3%) 68/283 (24%)
Pneumonia17/281 (6%) 20/283 (7.1%)
Respiratory Tract Infection22/281 (7.8%) 28/283 (9.9%)
Rhinitis3/281 (1.1%) 15/283 (5.3%)
Sinusitis10/281 (3.6%) 18/283 (6.4%)
Upper Respiratory Tract Infection54/281 (19.2%) 89/283 (31.4%)
Investigations
Alanine Aminotransferase Increased10/281 (3.6%) 15/283 (5.3%)
Weight Decreased9/281 (3.2%) 16/283 (5.7%)
Metabolism and nutrition disorders
Decreased Appetite28/281 (10%) 32/283 (11.3%)
Hyperglycaemia19/281 (6.8%) 25/283 (8.8%)
Hypocalcaemia11/281 (3.9%) 17/283 (6%)
Hypokalaemia22/281 (7.8%) 30/283 (10.6%)
Hypophosphataemia11/281 (3.9%) 16/283 (5.7%)
Musculoskeletal and connective tissue disorders
Arthralgia21/281 (7.5%) 24/283 (8.5%)
Back Pain45/281 (16%) 49/283 (17.3%)
Bone Pain12/281 (4.3%) 17/283 (6%)
Muscle Spasms52/281 (18.5%) 73/283 (25.8%)
Muscular Weakness21/281 (7.5%) 23/283 (8.1%)
Musculoskeletal Chest Pain17/281 (6%) 15/283 (5.3%)
Musculoskeletal Pain15/281 (5.3%) 17/283 (6%)
Myalgia9/281 (3.2%) 16/283 (5.7%)
Pain in Extremity30/281 (10.7%) 20/283 (7.1%)
Nervous system disorders
Dizziness24/281 (8.5%) 22/283 (7.8%)
Dysgeusia15/281 (5.3%) 21/283 (7.4%)
Headache19/281 (6.8%) 37/283 (13.1%)
Neuropathy Peripheral15/281 (5.3%) 12/283 (4.2%)
Peripheral Sensory Neuropathy18/281 (6.4%) 23/283 (8.1%)
Tremor24/281 (8.5%) 26/283 (9.2%)
Psychiatric disorders
Anxiety12/281 (4.3%) 18/283 (6.4%)
Depression5/281 (1.8%) 17/283 (6%)
Insomnia55/281 (19.6%) 55/283 (19.4%)
Renal and urinary disorders
Renal Impairment13/281 (4.6%) 20/283 (7.1%)
Respiratory, thoracic and mediastinal disorders
Cough35/281 (12.5%) 82/283 (29%)
Dyspnoea32/281 (11.4%) 51/283 (18%)
Skin and subcutaneous tissue disorders
Hyperhidrosis8/281 (2.8%) 20/283 (7.1%)
Pruritus29/281 (10.3%) 28/283 (9.9%)
Rash29/281 (10.3%) 35/283 (12.4%)
Vascular disorders
Hypertension7/281 (2.5%) 20/283 (7.1%)
Hypotension6/281 (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/TitleDirector, Clinical Research
OrganizationJanssen R&D US
Phone
EmailClinicalTrialDisclosure@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:
Nov 8, 2021
Last Verified:
Nov 1, 2021