Study Comparing Daratumumab, Lenalidomide, and Dexamethasone With Lenalidomide and Dexamethasone in Participants With Previously Untreated Multiple Myeloma

Sponsor
Janssen Research & Development, LLC (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT02252172
Collaborator
(none)
737
Enrollment
212
Locations
2
Arms
131.5
Anticipated Duration (Months)
3.5
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the efficacy of daratumumab in combination with lenalidomide and dexamethasone to that of lenalidomide and dexamethasone in terms of progression-free survival (PFS) in participants with newly diagnosed multiple myeloma (a blood cancer of plasma cells) who are not candidates for high dose chemotherapy (treatment of disease, usually cancer, by chemical agents) and autologous stem cell transplant (ASCT).

Condition or DiseaseIntervention/TreatmentPhase
Phase 3

Detailed Description

This is a Phase 3, randomized (study drug assigned by chance), open-label (participants and researchers are aware about the treatment, participants are receiving), active-controlled (study in which the experimental treatment or procedure is compared to a standard treatment or procedure), parallel-group (each group of participants will be treated at the same time), and multicenter (when more than one hospital or medical school team work on a medical research study) study in participants with newly diagnosed multiple myeloma and who are not candidates for high dose chemotherapy and ASCT. All the eligible participants will be randomly assigned to receive either lenalidomide and dexamethasone (Rd) (Arm A) or daratumumab in combination with lenalidomide and dexamethasone (DRd) (Arm B). Daratumumab (16 milligram per kilogram [mg/kg]) will be administered weekly for first 8 weeks (Cycles 1 to 2) of treatment and then every other week for 16 weeks (Cycles 3 to 6), then every 4 weeks (from Cycle 7 and beyond) until progression of disease or unacceptable toxicity. Lenalidomide will be administered at a dose of 25 mg orally on Days 1 through 21 of each 28-day cycle, and dexamethasone will be administered at a dose of 40 mg once a week for both treatment arms. Participants in both treatment arms will continue lenalidomide and dexamethasone until disease progression or unacceptable toxicity. All participants randomized to Treatment Arm B (DRd) in this study initially received daratumumab IV formulation; however, following implementation of protocol amendment 8, participants still receiving treatment with daratumumab IV will have the option to switch to daratumumab SC on Day 1 of any cycle, at the discretion of the investigator. Daratumumab subcutaneous (SC) will be administered by SC injection at a fixed dose of 1800 mg once every 4 weeks until documented progression, unacceptable toxicity, or study completion. Participants in Arm A who have sponsor-confirmed disease progression may have the option to receive daratumumab provided by the sponsor (in any subsequent line of therapy) in the Follow-up phase. The study consists of 3 phases: Screening Phase (within 21 days prior to the first dose administration on Day 1), Treatment Phase (Day 1 up to discontinuation of all study treatment), and Follow-up Phase (from discontinuation of all study treatment up to death, lost to follow up, consent withdrawal, or study end, whichever occurs first). The maximum duration of study will be 7 years after last participant is randomized. Efficacy will primarily be evaluated by PFS. Participants' safety will be monitored throughout the study.

Study Design

Study Type:
Interventional
Actual Enrollment :
737 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 3 Study Comparing Daratumumab, Lenalidomide, and Dexamethasone (DRd) vs Lenalidomide and Dexamethasone (Rd) in Subjects With Previously Untreated Multiple Myeloma Who Are Ineligible for High Dose Therapy
Actual Study Start Date :
Feb 16, 2015
Actual Primary Completion Date :
Sep 24, 2018
Anticipated Study Completion Date :
Jan 31, 2026

Arms and Interventions

ArmIntervention/Treatment
Active Comparator: Lenalidomide and Dexamethasone (Rd)

Participants will receive Lenalidomide 25 mg capsule orally on Day 1 through Day 21 of each 28-day cycle, Dexamethasone 40 mg orally or intravenously once a week. Study treatment continues until disease progression, unacceptable toxicity, or end of study (maximum up to 7 years after last subject is randomized) whichever comes first.

Drug: Daratumumab IV
Daratumumab will be administered at a dose of 16 milligram per kilogram (mg/kg) by intravenous (IV) infusion, once a week for 8 weeks, then once every other week for 16 weeks, thereafter once every 4 weeks until documented progression of disease, unacceptable toxicity, or end of study (maximum up to 7 years).
Other Names:
  • JNJ-54767414
  • Drug: Lenalidomide
    Lenalidomide 25 mg capsule orally on Day 1 through Day 21 of each 28-day cycle.

    Drug: Dexamethasone
    Dexamethasone 40 mg orally or intravenously once in a week.

    Active Comparator: Daratumumab + Lenalidomide + Dexamethasone (DRd)

    Participants will receive Daratumumab 16 milligram per kilogram (mg/kg) by intravenous infusion, once a week for 8 weeks, then once every other week for 16 weeks, thereafter once every 4 weeks, Lenalidomide 25 mg capsule orally on Day 1 through Day 21 of each 28-day cycle, Dexamethasone 40 mg orally or intravenously once a week. Following implementation of protocol amendment 8, participants still receiving treatment with daratumumab IV will have the option to switch to daratumumab SC on Day 1 of any cycle, at the discretion of the investigator. Daratumumab subcutaneous (SC) will be administered by SC injection at a fixed dose of 1800 mg once every 4 weeks until documented progression, unacceptable toxicity, or study completion. Study treatment continues until disease progression, unacceptable toxicity, or end of study (maximum up to 7 years after last subject is randomized) whichever comes first.

    Drug: Lenalidomide
    Lenalidomide 25 mg capsule orally on Day 1 through Day 21 of each 28-day cycle.

    Drug: Dexamethasone
    Dexamethasone 40 mg orally or intravenously once in a week.

    Drug: Daratumumab SC
    Daratumumab SC will be administered by SC injection at a fixed dose of 1800 mg once every 4 weeks until documented progression, unacceptable toxicity, or study end. Following implementation of protocol amendment 8, participants still receiving treatment with daratumumab IV will have the option to switch to daratumumab SC on Day 1 of any cycle, at the discretion of the investigator.
    Other Names:
  • JNJ-54767414
  • Outcome Measures

    Primary Outcome Measures

    1. Primary: Progression-free Survival (PFS) [From randomization to disease progression, death, subsequent anti-myeloma therapy, withdrawal of consent to study participation or clinical cut-off (CCO) whichever occurs first (up to 3.5 years)]

      PFS is defined as time from date of randomization to either progressive disease (PD) or death, whichever occurs first based on computerized algorithm as per International Myeloma Working Group (IMWG) criteria. PD is defined as an increase of 25 percent (%) from the lowest response value in one of the following: serum and urine M-component (absolute increase must be greater than or equal to [>=] 0.5 gram per deciliter [g/dL] and >=200 milligram [mg]/24 hours respectively); Only in participants without measurable serum and urine M-protein levels the difference between involved and uninvolved free light chain (FLC) levels (absolute increase must be greater than [>]10 mg/dL); Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to Plasma cell (PC) proliferative disorder.

    Secondary Outcome Measures

    1. Percentage of Participants With Complete Response (CR) or Better [From randomization to disease progression, death, subsequent anti-myeloma therapy, withdrawal of consent to study participation or CCO whichever occurs first (up to 7.8 years)]

      CR or better is defined as percentage of participants with a CR or better (CR or stringent complete response [sCR]) based on computerized algorithm as per IMWG criteria. CR is defined as negative immunofixation on the serum and urine, and disappearance of any soft tissue plasmacytomas, and less than (<) 5 percent (%) PCs in bone marrow. In participants with only measurable disease by serum FLC levels a normal serum FLC ratio is required. sCR is defined as in addition to CR a normal FLC ratio, and absence of clonal PCs by immunohistochemistry or immunofluorescence or 2 to 4-color flow cytometry.

    2. Percentage of Participants With Very Good Partial Response (VGPR) or Better [From randomization to disease progression, death, subsequent anti-myeloma therapy, withdrawal of consent to study participation or CCO whichever occurs first (up to 7.8 years)]

      VGPR or better is defined as the percentage of participants with a response of VGPR or better (VGPR, CR or sCR) based on computerized algorithm as per IMWG criteria. VGPR is defined as serum and urine M-component detectable by immunofixation but not on electrophoresis or >=90% reduction in serum M-protein plus urine M-protein <100 mg/24 hours. In participants with only measurable disease by serum FLC levels a >90% decrease in the difference between involved and uninvolved FLC levels is required.

    3. Percentage of Participants With Negative Minimal Residual Disease (MRD) [From randomization to disease progression, death, subsequent anti-myeloma therapy, withdrawal of consent to study participation or CCO whichever occurs first (up to 7.8 years)]

      MRD negativity rate is defined as the percentage of participants who had negative MRD (detection of less than 1 malignant cell among 100,000 normal cells) assessment at any timepoint after the date of randomization by evaluation of bone marrow aspirates. MRD was assessed in participants who achieved CR or better.

    4. Overall Response Rate (ORR) [From randomization to disease progression, death, subsequent anti-myeloma therapy, withdrawal of consent to study participation or CCO whichever occurs first (up to 7.8 years)]

      ORR is defined as the percentage of participants who achieved partial response (PR) or better (PR, VGPR, CR or sCR) based on computerized algorithm as per IMWG criteria. PR is defined as >=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. A >=50% reduction in the size of soft tissue plasmacytomas is also required.

    5. Overall Survival (OS) [From randomization to death, withdrawal of consent to study participation or CCO whichever occurs first (up to 7.8 years)]

      OS was measured from the date of randomization to the date of the death.

    6. Time to Disease Progression (TTP) [From randomization to disease progression, death, subsequent anti-myeloma therapy, withdrawal of consent to study participation or CCO whichever occurs first (up to 7.8 years)]

      TTP is defined as the time from the date of randomization to the date of PD based on computerized algorithm as per IMWG criteria, or death due to PD.

    7. Time to Response [From randomization to first response (PR or better) (up to 7.8 years)]

      Time to response is defined as the time from the date of randomization to the first efficacy evaluation that met criteria for PR or better based on computerized algorithm as per IMWG criteria. 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; If serum and urine M-protein are not measurable, and serum free light assay is also not measurable, >=50% reduction in bone marrow PCs is required. A >=50% reduction in the size of soft tissue plasmacytomas is also required.

    8. Duration of Response (DoR) [From first response (PR of better) to disease progression, death, subsequent anti-myeloma therapy, withdrawal of consent to study participation or CCO whichever occurs first (up to 7.8 years)]

      DoR is defined as the time from the date of initial response (PR or better) to the date of PD, based on computerized algorithm as per IMWG criteria.

    9. Time to Subsequent Anti-myeloma Treatment [From randomization to start of first subsequent anti-myeloma treatment, death, withdrawal of consent to study participation or CCO whichever is first (up to 7.8 years)]

      Time to subsequent anti-myeloma treatment is defined as the time from randomization to the start of first line of subsequent anti-myeloma treatment or death, whichever occurs first.

    10. Progression-free Survival on Next Line of Therapy (PFS2) [From randomization to disease progression on first line of subsequent anti-myeloma therapy, death, withdrawal of consent to study participation or CCO whichever occurs first (up to 7.8 years)]

      PFS2 is defined as the time from randomization to progression on the first line of subsequent anti-myeloma therapy or death, whichever occurs first. Disease progression on first line of subsequent anti-myeloma treatment was based on investigator judgment. Participants that were censored for PFS1 were also censored for PFS2.

    11. Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30 Global Health Status Score to Day 1 of Cycle 3, 6, 9 and 12 [Baseline and Day 1 of Cycle 3, 6, 9 and 12 (each Cycle of 28 days)]

      EORTC QLQ-C30 is 30 items self-reporting questionnaire, with 1 week recall period, resulting in 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 Global Health Status (GHS) scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single symptom items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Questionnaire includes 28 items with 4-point Likert type responses from "1-not at all" to "4-very much" to assess functioning and symptoms; 2 items with 7-point Likert scales (1= poor and 7= excellent) for global health and overall health related QoL. Scores are transformed to 0 to 100 scale, with higher scores representing better GHS, better functioning, and more symptoms. Negative change from baseline values shows deterioration in quality of life or functioning and reduction in symptom and positive values indicate improvement and worsening of symptoms.

    12. Change From Baseline in EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) to Day 1 of Cycle 3, 6, 9 and 12 [Baseline and Day 1 of Cycle 3, 6, 9 and 12 (each Cycle of 28 days)]

      EQ-5D-5L is a standardized, participant-rated questionnaire to assess health-related quality of life. The EQ-5D-5L includes 2 components: the EQ-5D-5L health state profile (descriptive system) and the EQ-5D-5L Visual Analog Scale. The Visual Analogue Scale is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state.

    13. Change From Baseline in EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Utility Score to Day 1 of Cycle 3, 6, 9 and 12 [Baseline and Day 1 of Cycle 3, 6, 9 and 12 (each Cycle of 28 days)]

      EQ-5D-5L is standardized, participant-reported questionnaire to assess health-related quality of life. EQ-5D-5L includes 2 components: EQ-5D-5L health state profile (descriptive system) and EQ-5D-5L VAS. EQ-5D-5L descriptive system provides a profile of participant's health state 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response options (no problems, slight problems, moderate problems, severe problems and extreme problems) that reflect increasing levels of difficulty. The participant was asked to indicate his/her current health state by selecting the most appropriate level in each of the 5 dimensions. Responses to the 5-dimension scores were combined and converted into single preference-weighted health utility index score 0 (0.0- worst health state) to 1 (1.0- better health state) representing the general health status of individual (but allows for values less than 0 by United kingdom [UK] scoring algorithm).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Participant must have documented multiple myeloma satisfying the CRAB (calcium elevation, renal insufficiency, anemia and bone abnormalities) criteria, monoclonal plasma cells in the bone marrow greater than or equal to (>=) 10 percent (%) or presence of a biopsy proven plasmacytoma and measurable disease as defined by any of the following: (a) immunoglobulin (Ig) G myeloma (serum monoclonal paraprotein [M-protein] level >=1.0 gram/deciliter [g/dL] or urine M-protein level >=200 milligram[mg]/24 hours[hrs]; or (b) IgA, IgM, IgD, or IgE multiple myeloma (serum M-protein level >=0.5 g/dL or urine M-protein level >=200 mg/24 hrs); or (c) light chain multiple myeloma without measurable disease in serum or urine (serum immunoglobulin free light chain >=10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio)

    • Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2

    • Participants who are newly diagnosed and not considered for high-dose chemotherapy due to: being age >=65 years; or participants less than (<) 65 years with presence of important comorbid condition(s) likely to have a negative impact on tolerability of high dose chemotherapy with stem cell transplantation. Sponsor review and approval of participants below 65 years of age is required before randomization

    • Women of childbearing potential must commit to either abstain continuously from sexual intercourse or to use 2 methods of reliable birth control simultaneously as deemed appropriate by the Investigator. Contraception must begin 4 weeks prior to dosing and must continue for 3 months after the last dose of daratumumab

    • Man, who is sexually active with a woman of child-bearing potential must agree to use a latex or synthetic condom, even if he had a successful vasectomy, must agree to use an adequate contraception method as deemed appropriate by the Investigator, and must also agree to not donate sperm during the study and for 4 weeks after last dose of lenalidomide and 4 months after last dose of daratumumab

    Exclusion Criteria:
    • Participant has a diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance (presence of serum M-protein <3 g/dL; absence of lytic bone lesions, anemia, hypercalcemia, and renal insufficiency related to the M-protein), or smoldering multiple myeloma (asymptomatic multiple myeloma with absence of related organ or tissue impairment end organ damage)

    • Participant has a diagnosis of Waldenström's disease, or other conditions in which IgM M protein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions

    • Participant has a history of malignancy (other than multiple myeloma) within 5 years before the date of randomization (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy 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)

    • Participant has prior or current systemic therapy or SCT for multiple myeloma, with the exception of an emergency use of a short course (equivalent of dexamethasone 40 mg/day for 4 days) of corticosteroids before treatment

    • Participant has had radiation therapy within 14 days of randomization

    • Participant has known chronic obstructive pulmonary disease (COPD) (defined as a forced expiratory volume in 1 second [FEV1] <50% of predicted normal), persistent asthma, or a history of asthma within the last 2 years (controlled intermittent asthma or controlled mild persistent asthma is allowed)

    • Participants with known or suspected COPD must have a FEV1 test during Screening

    • Participant is known to be seropositive for human immunodeficiency virus (HIV) or hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg] or antibodies to hepatitis B surface and core antigens [anti-HBs and anti-HBc, respectively]) or hepatitis C (anti-HCV antibody positive or HCV-ribonucleic acid [RNA] quantitation positive)

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1BirminghamAlabamaUnited States
    2MobileAlabamaUnited States
    3GlendaleArizonaUnited States
    4BerkeleyCaliforniaUnited States
    5Beverly HillsCaliforniaUnited States
    6El CajonCaliforniaUnited States
    7GreenbraeCaliforniaUnited States
    8Los AngelesCaliforniaUnited States
    9OceansideCaliforniaUnited States
    10San DiegoCaliforniaUnited States
    11West HillsCaliforniaUnited States
    12WhittierCaliforniaUnited States
    13DenverColoradoUnited States
    14Fort CollinsColoradoUnited States
    15Glenwood SpringsColoradoUnited States
    16New HavenConnecticutUnited States
    17NorwalkConnecticutUnited States
    18WashingtonDistrict of ColumbiaUnited States
    19Boca RatonFloridaUnited States
    20Boynton BeachFloridaUnited States
    21Fort LauderdaleFloridaUnited States
    22Fort MyersFloridaUnited States
    23HollywoodFloridaUnited States
    24JacksonvilleFloridaUnited States
    25Lake CityFloridaUnited States
    26Saint PetersburgFloridaUnited States
    27WestonFloridaUnited States
    28AtlantaGeorgiaUnited States
    29AugustaGeorgiaUnited States
    30MaconGeorgiaUnited States
    31MariettaGeorgiaUnited States
    32ChicagoIllinoisUnited States
    33NilesIllinoisUnited States
    34Fort WayneIndianaUnited States
    35Iowa CityIowaUnited States
    36LouisvilleKentuckyUnited States
    37LafayetteLouisianaUnited States
    38MarreroLouisianaUnited States
    39ShreveportLouisianaUnited States
    40AnnapolisMarylandUnited States
    41BaltimoreMarylandUnited States
    42FrederickMarylandUnited States
    43BostonMassachusettsUnited States
    44DetroitMichiganUnited States
    45DuluthMinnesotaUnited States
    46RochesterMinnesotaUnited States
    47Kansas CityMissouriUnited States
    48Saint LouisMissouriUnited States
    49OmahaNebraskaUnited States
    50HooksettNew HampshireUnited States
    51BrickNew JerseyUnited States
    52HackensackNew JerseyUnited States
    53LivingstonNew JerseyUnited States
    54PlainfieldNew JerseyUnited States
    55SomervilleNew JerseyUnited States
    56SummitNew JerseyUnited States
    57MineolaNew YorkUnited States
    58New YorkNew YorkUnited States
    59RochesterNew YorkUnited States
    60AsheboroNorth CarolinaUnited States
    61CharlotteNorth CarolinaUnited States
    62PinehurstNorth CarolinaUnited States
    63Winston-SalemNorth CarolinaUnited States
    64CantonOhioUnited States
    65ClevelandOhioUnited States
    66ColumbusOhioUnited States
    67BendOregonUnited States
    68BethlehemPennsylvaniaUnited States
    69PittsburghPennsylvaniaUnited States
    70SpartanburgSouth CarolinaUnited States
    71Sioux FallsSouth DakotaUnited States
    72ChattanoogaTennesseeUnited States
    73NashvilleTennesseeUnited States
    74ArlingtonTexasUnited States
    75EdinburgTexasUnited States
    76Fort Sam HoustonTexasUnited States
    77Fort WorthTexasUnited States
    78HoustonTexasUnited States
    79PlanoTexasUnited States
    80San AntonioTexasUnited States
    81OgdenUtahUnited States
    82SeattleWashingtonUnited States
    83SpokaneWashingtonUnited States
    84TacomaWashingtonUnited States
    85Box HillAustralia
    86FitzroyAustralia
    87FootscrayAustralia
    88KogarahAustralia
    89Kurralta ParkAustralia
    90NedlandsAustralia
    91New South WalesAustralia
    92WoodvilleAustralia
    93Woolloongabba N/aAustralia
    94InnsbruckAustria
    95LinzAustria
    96SalzburgAustria
    97Wien N/aAustria
    98Wien WienAustria
    99BruggeBelgium
    100BrusselsBelgium
    101BrusselBelgium
    102Haine-saint-paul, LA LouviereBelgium
    103LeuvenBelgium
    104LiegeBelgium
    105CalgaryAlbertaCanada
    106TorontoOntarioCanada
    107MontrealQuebecCanada
    108MontréalQuebecCanada
    109Greenfield ParkCanada
    110N/a N/aCanada
    111Nova ScotiaCanada
    112QuebecCanada
    113Aarhus CDenmark
    114OdenseDenmark
    115VejleDenmark
    116Amiens N/a PicardieFrance
    117AngersFrance
    118Bayonne CedexFrance
    119BretagneFrance
    120CaenFrance
    121Cergy PontoiseFrance
    122Chalons Sur SaoneFrance
    123Clermont-FerrandFrance
    124CreteilFrance
    125DijonFrance
    126Dunkerque Cedex 1France
    127Grenoble Cedex 9France
    128La Roche sur Yon Cedex 9France
    129Le Chesnay CedexFrance
    130Le MansFrance
    131Lille CedexFrance
    132LilleFrance
    133LimogesFrance
    134Lyon, Pierre-BeniteFrance
    135Marseille Cedex 9France
    136Metz-TessyFrance
    137MontivilliersFrance
    138MontpellierFrance
    139MulhouseFrance
    140NantesFrance
    141Nice N/aFrance
    142Paris Cedex 12France
    143Paris, 75France
    144ParisFrance
    145PERIGUEUX cedexFrance
    146PerpignanFrance
    147PessacFrance
    148PoitiersFrance
    149ReimsFrance
    150RennesFrance
    151Rouen CedexFrance
    152Saint Brieuc Cedex 1France
    153Saint Priest en JarezFrance
    154St Malo CedexFrance
    155St Quentin CedexFrance
    156StrasbourgFrance
    157Toulouse Cedex 9France
    158TOURS Cedex 9France
    159Vandoeuvre Les NancyFrance
    160AschaffenburgGermany
    161Bad BerkaGermany
    162BonnGermany
    163BraunschweigGermany
    164DresdenGermany
    165EssenGermany
    166FrankfurtGermany
    167HannoverGermany
    168HeidelbergGermany
    169HessenGermany
    170KielGermany
    171KoblenzGermany
    172MainzGermany
    173MannheimGermany
    174RostockGermany
    175SchwerinGermany
    176StuttgartGermany
    177TuebingenGermany
    178UlmGermany
    179Villingen-SchwenningenGermany
    180DublinIreland
    181GalwayIreland
    182HaderaIsrael
    183HaifaIsrael
    184JerusalemIsrael
    185NahariyaIsrael
    186Petah TikvaIsrael
    187Tel-AvivIsrael
    188HilversumNetherlands
    189HoofddorpNetherlands
    190RotterdamNetherlands
    191TilburgNetherlands
    192FalunSweden
    193GöteborgSweden
    194HalmstadSweden
    195HelsingborgSweden
    196HuddingeSweden
    197LuleaSweden
    198LundSweden
    199StockholmSweden
    200ÖrebroSweden
    201AberdeenUnited Kingdom
    202CanterburyUnited Kingdom
    203DundeeUnited Kingdom
    204LeedsUnited Kingdom
    205LondonUnited Kingdom
    206ManchesterUnited Kingdom
    207NottinghamUnited Kingdom
    208OxfordUnited Kingdom
    209Plymouth, DevonUnited Kingdom
    210SouthamptonUnited Kingdom
    211TruroUnited Kingdom
    212WolverhamptonUnited 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)

    More Information

    Publications

    None provided.
    Responsible Party:
    Janssen Research & Development, LLC
    ClinicalTrials.gov Identifier:
    NCT02252172
    Other Study ID Numbers:
    • CR104762
    • 54767414MMY3008
    • 2014-002273-11
    First Posted:
    Sep 30, 2014
    Last Update Posted:
    Nov 5, 2021
    Last Verified:
    Nov 1, 2021
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Janssen Research & Development, LLC
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group TitleLenalidomide + Dexamethasone (Rd)Daratumumab + Lenalidomide + Dexamethasone (DRd)
    Arm/Group DescriptionParticipants received Lenalidomide 25 milligrams (mg) capsule orally daily on Day 1 through Day 21 of each 28-day cycle, Dexamethasone 40 mg orally or intravenously (IV) once a week (QW) until disease progression or unacceptable toxicity.Participants received Daratumumab 16 milligrams per kilograms (mg/kg) IV QW for the first 8 weeks (cycles 1-2) and then every 2 weeks (Q2W) for 16 weeks (Cycle 3-6), then every 4 weeks (Q4W) (from Cycle 7 and beyond) (each cycle of 28 days), Lenalidomide 25 mg capsule orally daily on Day 1 through Day 21 of each 28-day cycle, Dexamethasone 40 mg orally or IV QW until disease progression or unacceptable toxicity.
    Period Title: Overall Study
    STARTED369368
    Treated365364
    COMPLETED9069
    NOT COMPLETED279299

    Baseline Characteristics

    Arm/Group TitleLenalidomide + Dexamethasone (Rd)Daratumumab + Lenalidomide + Dexamethasone (DRd)Total
    Arm/Group DescriptionParticipants received Lenalidomide 25 milligrams (mg) capsule orally daily on Day 1 through Day 21 of each 28-day cycle, Dexamethasone 40 mg orally or intravenously (IV) once a week (QW) until disease progression or unacceptable toxicity.Participants received Daratumumab 16 milligrams per kilograms (mg/kg) IV QW for the first 8 weeks (cycles 1-2) and then every 2 weeks (Q2W) for 16 weeks (Cycle 3-6), then every 4 weeks (Q4W) (from Cycle 7 and beyond) (each cycle of 28 days), Lenalidomide 25 mg capsule orally daily on Day 1 through Day 21 of each 28-day cycle, Dexamethasone 40 mg orally or IV QW until disease progression or unacceptable toxicity.Total of all reporting groups
    Overall Participants369368737
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    74.2
    (5.66)
    74.0
    (5.44)
    74.1
    (5.55)
    Sex: Female, Male (Count of Participants)
    Female
    174
    47.2%
    179
    48.6%
    353
    47.9%
    Male
    195
    52.8%
    189
    51.4%
    384
    52.1%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    12
    3.3%
    11
    3%
    23
    3.1%
    Not Hispanic or Latino
    352
    95.4%
    347
    94.3%
    699
    94.8%
    Unknown or Not Reported
    5
    1.4%
    10
    2.7%
    15
    2%
    Race/Ethnicity, Customized (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    2
    0.5%
    3
    0.8%
    5
    0.7%
    Native Hawaiian or Other Pacific Islander
    1
    0.3%
    0
    0%
    1
    0.1%
    Black or African American
    16
    4.3%
    12
    3.3%
    28
    3.8%
    White
    339
    91.9%
    336
    91.3%
    675
    91.6%
    Other
    6
    1.6%
    6
    1.6%
    12
    1.6%
    Unknown or Not Reported
    5
    1.4%
    11
    3%
    16
    2.2%
    Region of Enrollment (Count of Participants)
    AUSTRALIA
    18
    4.9%
    17
    4.6%
    35
    4.7%
    AUSTRIA
    11
    3%
    3
    0.8%
    14
    1.9%
    BELGIUM
    5
    1.4%
    2
    0.5%
    7
    0.9%
    CANADA
    28
    7.6%
    24
    6.5%
    52
    7.1%
    DENMARK
    6
    1.6%
    10
    2.7%
    16
    2.2%
    FRANCE
    155
    42%
    157
    42.7%
    312
    42.3%
    GERMANY
    16
    4.3%
    19
    5.2%
    35
    4.7%
    IRELAND
    3
    0.8%
    4
    1.1%
    7
    0.9%
    ISRAEL
    3
    0.8%
    5
    1.4%
    8
    1.1%
    ITALY
    3
    0.8%
    3
    0.8%
    6
    0.8%
    NETHERLANDS
    1
    0.3%
    4
    1.1%
    5
    0.7%
    SWEDEN
    12
    3.3%
    10
    2.7%
    22
    3%
    UNITED KINGDOM
    34
    9.2%
    33
    9%
    67
    9.1%
    UNITED STATES
    74
    20.1%
    77
    20.9%
    151
    20.5%
    Stage of Disease (ISS) (Count of Participants)
    Stage I
    103
    27.9%
    98
    26.6%
    201
    27.3%
    Stage II
    156
    42.3%
    163
    44.3%
    319
    43.3%
    Stage III
    110
    29.8%
    107
    29.1%
    217
    29.4%
    Time from Multiple Myeloma (MM) diagnosis (months) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [months]
    1.3
    (1.4)
    1.4
    (1.5)
    1.3
    (1.5)

    Outcome Measures

    1. Primary Outcome
    TitlePrimary: Progression-free Survival (PFS)
    DescriptionPFS is defined as time from date of randomization to either progressive disease (PD) or death, whichever occurs first based on computerized algorithm as per International Myeloma Working Group (IMWG) criteria. PD is defined as an increase of 25 percent (%) from the lowest response value in one of the following: serum and urine M-component (absolute increase must be greater than or equal to [>=] 0.5 gram per deciliter [g/dL] and >=200 milligram [mg]/24 hours respectively); Only in participants without measurable serum and urine M-protein levels the difference between involved and uninvolved free light chain (FLC) levels (absolute increase must be greater than [>]10 mg/dL); Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to Plasma cell (PC) proliferative disorder.
    Time FrameFrom randomization to disease progression, death, subsequent anti-myeloma therapy, withdrawal of consent to study participation or clinical cut-off (CCO) whichever occurs first (up to 3.5 years)

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat (ITT) population included all randomized participants.
    Arm/Group TitleLenalidomide + Dexamethasone (Rd)Daratumumab + Lenalidomide + Dexamethasone (DRd)
    Arm/Group DescriptionParticipants received Lenalidomide 25 milligrams (mg) capsule orally daily on Day 1 through Day 21 of each 28-day cycle, Dexamethasone 40 mg orally or intravenously (IV) once a week (QW) until disease progression or unacceptable toxicity.Participants received Daratumumab 16 milligrams per kilograms (mg/kg) IV QW for the first 8 weeks (cycles 1-2) and then every 2 weeks (Q2W) for 16 weeks (Cycle 3-6), then every 4 weeks (Q4W) (from Cycle 7 and beyond) (each cycle of 28 days), Lenalidomide 25 mg capsule orally daily on Day 1 through Day 21 of each 28-day cycle, Dexamethasone 40 mg orally or IV QW until disease progression or unacceptable toxicity.
    Measure Participants369368
    Median (95% Confidence Interval) [Months]
    31.87
    NA
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Lenalidomide + Dexamethasone (Rd), Daratumumab + Lenalidomide + Dexamethasone (DRd)
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesisp-Value<0.0001
    Comments
    MethodLog Rank
    Comments
    Method of EstimationEstimation ParameterHazard Ratio (HR)
    Estimated Value0.56
    Confidence Interval (2-Sided) 95%
    0.43 to 0.73
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    TitlePercentage of Participants With Complete Response (CR) or Better
    DescriptionCR or better is defined as percentage of participants with a CR or better (CR or stringent complete response [sCR]) based on computerized algorithm as per IMWG criteria. CR is defined as negative immunofixation on the serum and urine, and disappearance of any soft tissue plasmacytomas, and less than (<) 5 percent (%) PCs in bone marrow. In participants with only measurable disease by serum FLC levels a normal serum FLC ratio is required. sCR is defined as in addition to CR a normal FLC ratio, and absence of clonal PCs by immunohistochemistry or immunofluorescence or 2 to 4-color flow cytometry.
    Time FrameFrom randomization to disease progression, death, subsequent anti-myeloma therapy, withdrawal of consent to study participation or CCO whichever occurs first (up to 7.8 years)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    3. Secondary Outcome
    TitlePercentage of Participants With Very Good Partial Response (VGPR) or Better
    DescriptionVGPR or better is defined as the percentage of participants with a response of VGPR or better (VGPR, CR or sCR) based on computerized algorithm as per IMWG criteria. VGPR is defined as serum and urine M-component detectable by immunofixation but not on electrophoresis or >=90% reduction in serum M-protein plus urine M-protein <100 mg/24 hours. In participants with only measurable disease by serum FLC levels a >90% decrease in the difference between involved and uninvolved FLC levels is required.
    Time FrameFrom randomization to disease progression, death, subsequent anti-myeloma therapy, withdrawal of consent to study participation or CCO whichever occurs first (up to 7.8 years)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    4. Secondary Outcome
    TitlePercentage of Participants With Negative Minimal Residual Disease (MRD)
    DescriptionMRD negativity rate is defined as the percentage of participants who had negative MRD (detection of less than 1 malignant cell among 100,000 normal cells) assessment at any timepoint after the date of randomization by evaluation of bone marrow aspirates. MRD was assessed in participants who achieved CR or better.
    Time FrameFrom randomization to disease progression, death, subsequent anti-myeloma therapy, withdrawal of consent to study participation or CCO whichever occurs first (up to 7.8 years)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    5. Secondary Outcome
    TitleOverall Response Rate (ORR)
    DescriptionORR is defined as the percentage of participants who achieved partial response (PR) or better (PR, VGPR, CR or sCR) based on computerized algorithm as per IMWG criteria. PR is defined as >=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. A >=50% reduction in the size of soft tissue plasmacytomas is also required.
    Time FrameFrom randomization to disease progression, death, subsequent anti-myeloma therapy, withdrawal of consent to study participation or CCO whichever occurs first (up to 7.8 years)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    6. Secondary Outcome
    TitleOverall Survival (OS)
    DescriptionOS was measured from the date of randomization to the date of the death.
    Time FrameFrom randomization to death, withdrawal of consent to study participation or CCO whichever occurs first (up to 7.8 years)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    7. Secondary Outcome
    TitleTime to Disease Progression (TTP)
    DescriptionTTP is defined as the time from the date of randomization to the date of PD based on computerized algorithm as per IMWG criteria, or death due to PD.
    Time FrameFrom randomization to disease progression, death, subsequent anti-myeloma therapy, withdrawal of consent to study participation or CCO whichever occurs first (up to 7.8 years)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    8. Secondary Outcome
    TitleTime to Response
    DescriptionTime to response is defined as the time from the date of randomization to the first efficacy evaluation that met criteria for PR or better based on computerized algorithm as per IMWG criteria. 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; If serum and urine M-protein are not measurable, and serum free light assay is also not measurable, >=50% reduction in bone marrow PCs is required. A >=50% reduction in the size of soft tissue plasmacytomas is also required.
    Time FrameFrom randomization to first response (PR or better) (up to 7.8 years)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    9. Secondary Outcome
    TitleDuration of Response (DoR)
    DescriptionDoR is defined as the time from the date of initial response (PR or better) to the date of PD, based on computerized algorithm as per IMWG criteria.
    Time FrameFrom first response (PR of better) to disease progression, death, subsequent anti-myeloma therapy, withdrawal of consent to study participation or CCO whichever occurs first (up to 7.8 years)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    10. Secondary Outcome
    TitleTime to Subsequent Anti-myeloma Treatment
    DescriptionTime to subsequent anti-myeloma treatment is defined as the time from randomization to the start of first line of subsequent anti-myeloma treatment or death, whichever occurs first.
    Time FrameFrom randomization to start of first subsequent anti-myeloma treatment, death, withdrawal of consent to study participation or CCO whichever is first (up to 7.8 years)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    11. Secondary Outcome
    TitleProgression-free Survival on Next Line of Therapy (PFS2)
    DescriptionPFS2 is defined as the time from randomization to progression on the first line of subsequent anti-myeloma therapy or death, whichever occurs first. Disease progression on first line of subsequent anti-myeloma treatment was based on investigator judgment. Participants that were censored for PFS1 were also censored for PFS2.
    Time FrameFrom randomization to disease progression on first line of subsequent anti-myeloma therapy, death, withdrawal of consent to study participation or CCO whichever occurs first (up to 7.8 years)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    12. Secondary Outcome
    TitleChange From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30 Global Health Status Score to Day 1 of Cycle 3, 6, 9 and 12
    DescriptionEORTC QLQ-C30 is 30 items self-reporting questionnaire, with 1 week recall period, resulting in 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 Global Health Status (GHS) scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single symptom items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Questionnaire includes 28 items with 4-point Likert type responses from "1-not at all" to "4-very much" to assess functioning and symptoms; 2 items with 7-point Likert scales (1= poor and 7= excellent) for global health and overall health related QoL. Scores are transformed to 0 to 100 scale, with higher scores representing better GHS, better functioning, and more symptoms. Negative change from baseline values shows deterioration in quality of life or functioning and reduction in symptom and positive values indicate improvement and worsening of symptoms.
    Time FrameBaseline and Day 1 of Cycle 3, 6, 9 and 12 (each Cycle of 28 days)

    Outcome Measure Data

    Analysis Population Description
    ITT population included all randomized participants. Here 'N' (overall number of participants analyzed) signifies number of participants who were evaluable in this outcome measure. Here 'n' (number analyzed) signifies number of participants analyzed at specified timepoints.
    Arm/Group TitleLenalidomide + Dexamethasone (Rd)Daratumumab + Lenalidomide + Dexamethasone (DRd)
    Arm/Group DescriptionParticipants received Lenalidomide 25 milligrams (mg) capsule orally daily on Day 1 through Day 21 of each 28-day cycle, Dexamethasone 40 mg orally or intravenously (IV) once a week (QW) until disease progression or unacceptable toxicity.Participants received Daratumumab 16 milligrams per kilograms (mg/kg) IV QW for the first 8 weeks (cycles 1-2) and then every 2 weeks (Q2W) for 16 weeks (Cycle 3-6), then every 4 weeks (Q4W) (from Cycle 7 and beyond) (each cycle of 28 days), Lenalidomide 25 mg capsule orally daily on Day 1 through Day 21 of each 28-day cycle, Dexamethasone 40 mg orally or IV QW until disease progression or unacceptable toxicity.
    Measure Participants348354
    Global health status score: Cycle 3 Day 1
    1.5
    4.5
    Global health status score: Cycle 6 Day 1
    5.6
    6.4
    Global health status score: Cycle 9 Day 1
    7
    8.2
    Global health status score: Cycle 12 Day 1
    5.4
    8.4
    13. Secondary Outcome
    TitleChange From Baseline in EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) to Day 1 of Cycle 3, 6, 9 and 12
    DescriptionEQ-5D-5L is a standardized, participant-rated questionnaire to assess health-related quality of life. The EQ-5D-5L includes 2 components: the EQ-5D-5L health state profile (descriptive system) and the EQ-5D-5L Visual Analog Scale. The Visual Analogue Scale is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state.
    Time FrameBaseline and Day 1 of Cycle 3, 6, 9 and 12 (each Cycle of 28 days)

    Outcome Measure Data

    Analysis Population Description
    ITT population included all randomized participants. Here 'N' (overall number of participants analyzed) signifies number of participants who were evaluable in this outcome measure. Here 'n' signifies number of participants analyzed at specified timepoints.
    Arm/Group TitleLenalidomide + Dexamethasone (Rd)Daratumumab + Lenalidomide + Dexamethasone (DRd)
    Arm/Group DescriptionParticipants received Lenalidomide 25 milligrams (mg) capsule orally daily on Day 1 through Day 21 of each 28-day cycle, Dexamethasone 40 mg orally or intravenously (IV) once a week (QW) until disease progression or unacceptable toxicity.Participants received Daratumumab 16 milligrams per kilograms (mg/kg) IV QW for the first 8 weeks (cycles 1-2) and then every 2 weeks (Q2W) for 16 weeks (Cycle 3-6), then every 4 weeks (Q4W) (from Cycle 7 and beyond) (each cycle of 28 days), Lenalidomide 25 mg capsule orally daily on Day 1 through Day 21 of each 28-day cycle, Dexamethasone 40 mg orally or IV QW until disease progression or unacceptable toxicity.
    Measure Participants346349
    Change at Cycle 3 Day 1
    2.5
    4.9
    Change at Cycle 6 Day 1
    5.7
    8
    Change at Cycle 9 Day 1
    7.7
    10.2
    Change at Cycle 12 Day 1
    4.9
    10.1
    14. Secondary Outcome
    TitleChange From Baseline in EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Utility Score to Day 1 of Cycle 3, 6, 9 and 12
    DescriptionEQ-5D-5L is standardized, participant-reported questionnaire to assess health-related quality of life. EQ-5D-5L includes 2 components: EQ-5D-5L health state profile (descriptive system) and EQ-5D-5L VAS. EQ-5D-5L descriptive system provides a profile of participant's health state 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response options (no problems, slight problems, moderate problems, severe problems and extreme problems) that reflect increasing levels of difficulty. The participant was asked to indicate his/her current health state by selecting the most appropriate level in each of the 5 dimensions. Responses to the 5-dimension scores were combined and converted into single preference-weighted health utility index score 0 (0.0- worst health state) to 1 (1.0- better health state) representing the general health status of individual (but allows for values less than 0 by United kingdom [UK] scoring algorithm).
    Time FrameBaseline and Day 1 of Cycle 3, 6, 9 and 12 (each Cycle of 28 days)

    Outcome Measure Data

    Analysis Population Description
    ITT population included all randomized participants. Here 'N' (overall number of participants analyzed) signifies number of participants who were evaluable in this outcome measure. Here 'n' signifies number of participants analyzed at specified timepoints.
    Arm/Group TitleLenalidomide + Dexamethasone (Rd)Daratumumab + Lenalidomide + Dexamethasone (DRd)
    Arm/Group DescriptionParticipants received Lenalidomide 25 milligrams (mg) capsule orally daily on Day 1 through Day 21 of each 28-day cycle, Dexamethasone 40 mg orally or intravenously (IV) once a week (QW) until disease progression or unacceptable toxicity.Participants received Daratumumab 16 milligrams per kilograms (mg/kg) IV QW for the first 8 weeks (cycles 1-2) and then every 2 weeks (Q2W) for 16 weeks (Cycle 3-6), then every 4 weeks (Q4W) (from Cycle 7 and beyond) (each cycle of 28 days), Lenalidomide 25 mg capsule orally daily on Day 1 through Day 21 of each 28-day cycle, Dexamethasone 40 mg orally or IV QW until disease progression or unacceptable toxicity.
    Measure Participants346349
    Change at Cycle 3 Day 1
    0.08
    0.107
    Change at Cycle 6 Day 1
    0.116
    0.136
    Change at Cycle 9 Day 1
    0.124
    0.124
    Change at Cycle 12 Day 1
    0.113
    0.141

    Adverse Events

    Time FrameUp to 3.5 years
    Adverse Event Reporting Description Safety population was defined as participants who have received at least 1 administration of any study treatment (partial or complete).
    Arm/Group TitleLenalidomide + Dexamethasone (Rd)Daratumumab + Lenalidomide + Dexamethasone (DRd)
    Arm/Group DescriptionParticipants received Lenalidomide 25 milligrams (mg) capsule orally daily on Day 1 through Day 21 of each 28-day cycle, Dexamethasone 40 mg orally or intravenously (IV) once a week (QW) until disease progression or unacceptable toxicity.Participants received Daratumumab 16 milligrams per kilograms (mg/kg) IV QW for the first 8 weeks (cycles 1-2) and then every 2 weeks (Q2W) for 16 weeks (Cycle 3-6), then every 4 weeks (Q4W) (from Cycle 7 and beyond) (each cycle of 28 days), Lenalidomide 25 mg capsule orally daily on Day 1 through Day 21 of each 28-day cycle, Dexamethasone 40 mg orally or IV QW until disease progression or unacceptable toxicity.
    All Cause Mortality
    Lenalidomide + Dexamethasone (Rd)Daratumumab + Lenalidomide + Dexamethasone (DRd)
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total76/365 (20.8%) 62/364 (17%)
    Serious Adverse Events
    Lenalidomide + Dexamethasone (Rd)Daratumumab + Lenalidomide + Dexamethasone (DRd)
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total229/365 (62.7%) 229/364 (62.9%)
    Blood and lymphatic system disorders
    Anaemia12/365 (3.3%) 6/364 (1.6%)
    Anaemia Macrocytic1/365 (0.3%) 0/364 (0%)
    Disseminated Intravascular Coagulation1/365 (0.3%) 0/364 (0%)
    Febrile Neutropenia9/365 (2.5%) 9/364 (2.5%)
    Heparin-Induced Thrombocytopenia1/365 (0.3%) 0/364 (0%)
    Leukopenia0/365 (0%) 1/364 (0.3%)
    Neutropenia2/365 (0.5%) 3/364 (0.8%)
    Thrombocytopenia2/365 (0.5%) 0/364 (0%)
    Cardiac disorders
    Acute Coronary Syndrome5/365 (1.4%) 0/364 (0%)
    Acute Myocardial Infarction1/365 (0.3%) 3/364 (0.8%)
    Angina Pectoris0/365 (0%) 2/364 (0.5%)
    Arrhythmia1/365 (0.3%) 0/364 (0%)
    Arteriosclerosis Coronary Artery0/365 (0%) 1/364 (0.3%)
    Atrial Fibrillation12/365 (3.3%) 8/364 (2.2%)
    Atrial Flutter2/365 (0.5%) 2/364 (0.5%)
    Atrial Tachycardia1/365 (0.3%) 0/364 (0%)
    Atrioventricular Block0/365 (0%) 1/364 (0.3%)
    Atrioventricular Block Complete1/365 (0.3%) 0/364 (0%)
    Bradycardia1/365 (0.3%) 0/364 (0%)
    Cardiac Amyloidosis1/365 (0.3%) 0/364 (0%)
    Cardiac Arrest3/365 (0.8%) 2/364 (0.5%)
    Cardiac Failure9/365 (2.5%) 5/364 (1.4%)
    Cardiac Failure Acute0/365 (0%) 1/364 (0.3%)
    Cardiac Failure Chronic1/365 (0.3%) 0/364 (0%)
    Cardiac Failure Congestive5/365 (1.4%) 2/364 (0.5%)
    Cardio-Respiratory Arrest0/365 (0%) 1/364 (0.3%)
    Cardiogenic Shock1/365 (0.3%) 0/364 (0%)
    Coronary Artery Disease1/365 (0.3%) 2/364 (0.5%)
    Coronary Artery Stenosis0/365 (0%) 1/364 (0.3%)
    Hypertensive Heart Disease0/365 (0%) 1/364 (0.3%)
    Myocardial Infarction5/365 (1.4%) 1/364 (0.3%)
    Myocardial Ischaemia1/365 (0.3%) 2/364 (0.5%)
    Myocarditis1/365 (0.3%) 0/364 (0%)
    Pericardial Effusion0/365 (0%) 1/364 (0.3%)
    Stress Cardiomyopathy0/365 (0%) 1/364 (0.3%)
    Ventricular Tachycardia1/365 (0.3%) 1/364 (0.3%)
    Congenital, familial and genetic disorders
    Corneal Dystrophy0/365 (0%) 1/364 (0.3%)
    Ear and labyrinth disorders
    Deafness Bilateral0/365 (0%) 1/364 (0.3%)
    Vertigo2/365 (0.5%) 2/364 (0.5%)
    Endocrine disorders
    Adrenal Insufficiency0/365 (0%) 1/364 (0.3%)
    Hypothyroidism1/365 (0.3%) 0/364 (0%)
    Eye disorders
    Blepharitis0/365 (0%) 1/364 (0.3%)
    Cataract5/365 (1.4%) 2/364 (0.5%)
    Retinal Artery Occlusion0/365 (0%) 1/364 (0.3%)
    Retinal Detachment1/365 (0.3%) 0/364 (0%)
    Retinal Vein Thrombosis1/365 (0.3%) 0/364 (0%)
    Gastrointestinal disorders
    Abdominal Pain2/365 (0.5%) 4/364 (1.1%)
    Abdominal Pain Upper0/365 (0%) 1/364 (0.3%)
    Ascites0/365 (0%) 2/364 (0.5%)
    Colitis3/365 (0.8%) 1/364 (0.3%)
    Colitis Ischaemic0/365 (0%) 3/364 (0.8%)
    Constipation1/365 (0.3%) 3/364 (0.8%)
    Diarrhoea6/365 (1.6%) 9/364 (2.5%)
    Diarrhoea Haemorrhagic1/365 (0.3%) 0/364 (0%)
    Diverticular Perforation2/365 (0.5%) 4/364 (1.1%)
    Diverticulum1/365 (0.3%) 0/364 (0%)
    Diverticulum Intestinal Haemorrhagic1/365 (0.3%) 0/364 (0%)
    Dyspepsia1/365 (0.3%) 1/364 (0.3%)
    Dysphagia0/365 (0%) 1/364 (0.3%)
    Enterovesical Fistula1/365 (0.3%) 0/364 (0%)
    Faecaloma2/365 (0.5%) 0/364 (0%)
    Gastric Haemorrhage1/365 (0.3%) 0/364 (0%)
    Gastric Ulcer1/365 (0.3%) 0/364 (0%)
    Gastrointestinal Haemorrhage2/365 (0.5%) 2/364 (0.5%)
    Inguinal Hernia1/365 (0.3%) 3/364 (0.8%)
    Inguinal Hernia Strangulated1/365 (0.3%) 0/364 (0%)
    Intestinal Ischaemia0/365 (0%) 1/364 (0.3%)
    Intestinal Obstruction0/365 (0%) 2/364 (0.5%)
    Large Intestinal Obstruction1/365 (0.3%) 0/364 (0%)
    Large Intestine Perforation1/365 (0.3%) 1/364 (0.3%)
    Melaena2/365 (0.5%) 0/364 (0%)
    Nausea2/365 (0.5%) 4/364 (1.1%)
    Oesophageal Achalasia0/365 (0%) 1/364 (0.3%)
    Oesophagitis1/365 (0.3%) 0/364 (0%)
    Pancreatitis1/365 (0.3%) 1/364 (0.3%)
    Pancreatitis Acute1/365 (0.3%) 3/364 (0.8%)
    Pneumoperitoneum1/365 (0.3%) 0/364 (0%)
    Rectal Haemorrhage2/365 (0.5%) 0/364 (0%)
    Small Intestinal Obstruction0/365 (0%) 1/364 (0.3%)
    Subileus1/365 (0.3%) 0/364 (0%)
    Upper Gastrointestinal Haemorrhage0/365 (0%) 1/364 (0.3%)
    Vomiting3/365 (0.8%) 4/364 (1.1%)
    General disorders
    Asthenia7/365 (1.9%) 3/364 (0.8%)
    Chest Discomfort1/365 (0.3%) 0/364 (0%)
    Chest Pain2/365 (0.5%) 0/364 (0%)
    Chills0/365 (0%) 1/364 (0.3%)
    Extravasation0/365 (0%) 1/364 (0.3%)
    Fatigue0/365 (0%) 4/364 (1.1%)
    General Physical Health Deterioration10/365 (2.7%) 2/364 (0.5%)
    Granuloma0/365 (0%) 1/364 (0.3%)
    Malaise1/365 (0.3%) 0/364 (0%)
    Multiple Organ Dysfunction Syndrome1/365 (0.3%) 2/364 (0.5%)
    Non-Cardiac Chest Pain3/365 (0.8%) 3/364 (0.8%)
    Oedema Peripheral0/365 (0%) 1/364 (0.3%)
    Pain1/365 (0.3%) 0/364 (0%)
    Peripheral Swelling0/365 (0%) 1/364 (0.3%)
    Pyrexia11/365 (3%) 16/364 (4.4%)
    Sudden Cardiac Death1/365 (0.3%) 0/364 (0%)
    Sudden Death0/365 (0%) 1/364 (0.3%)
    Systemic Inflammatory Response Syndrome1/365 (0.3%) 0/364 (0%)
    Hepatobiliary disorders
    Acute Hepatic Failure1/365 (0.3%) 0/364 (0%)
    Bile Duct Stone0/365 (0%) 1/364 (0.3%)
    Cholecystitis1/365 (0.3%) 0/364 (0%)
    Cholecystitis Acute0/365 (0%) 4/364 (1.1%)
    Cholestasis1/365 (0.3%) 0/364 (0%)
    Hepatic Failure1/365 (0.3%) 0/364 (0%)
    Hepatocellular Injury1/365 (0.3%) 0/364 (0%)
    Hyperbilirubinaemia1/365 (0.3%) 0/364 (0%)
    Infections and infestations
    Abdominal Sepsis1/365 (0.3%) 0/364 (0%)
    Anal Abscess1/365 (0.3%) 0/364 (0%)
    Appendicitis Perforated1/365 (0.3%) 0/364 (0%)
    Arthritis Bacterial1/365 (0.3%) 0/364 (0%)
    Arthritis Infective0/365 (0%) 1/364 (0.3%)
    Bacteraemia1/365 (0.3%) 1/364 (0.3%)
    Bacterial Diarrhoea0/365 (0%) 1/364 (0.3%)
    Bronchiolitis1/365 (0.3%) 1/364 (0.3%)
    Bronchitis5/365 (1.4%) 12/364 (3.3%)
    Campylobacter Infection1/365 (0.3%) 0/364 (0%)
    Cellulitis4/365 (1.1%) 2/364 (0.5%)
    Clostridium Difficile Colitis1/365 (0.3%) 3/364 (0.8%)
    Colonic Abscess0/365 (0%) 1/364 (0.3%)
    Corona Virus Infection0/365 (0%) 1/364 (0.3%)
    Cystitis0/365 (0%) 1/364 (0.3%)
    Device Related Infection0/365 (0%) 3/364 (0.8%)
    Diverticulitis3/365 (0.8%) 6/364 (1.6%)
    Endocarditis0/365 (0%) 1/364 (0.3%)
    Endocarditis Staphylococcal1/365 (0.3%) 0/364 (0%)
    Erysipelas3/365 (0.8%) 3/364 (0.8%)
    Escherichia Pyelonephritis1/365 (0.3%) 0/364 (0%)
    Escherichia Sepsis2/365 (0.5%) 0/364 (0%)
    Escherichia Urinary Tract Infection0/365 (0%) 2/364 (0.5%)
    Gastroenteritis0/365 (0%) 1/364 (0.3%)
    Gastrointestinal Viral Infection1/365 (0.3%) 0/364 (0%)
    Groin Abscess2/365 (0.5%) 0/364 (0%)
    Haematoma Infection0/365 (0%) 1/364 (0.3%)
    Infected Cyst1/365 (0.3%) 0/364 (0%)
    Infection0/365 (0%) 1/364 (0.3%)
    Influenza6/365 (1.6%) 11/364 (3%)
    Klebsiella Bacteraemia1/365 (0.3%) 1/364 (0.3%)
    Klebsiella Infection0/365 (0%) 1/364 (0.3%)
    Laryngitis1/365 (0.3%) 0/364 (0%)
    Lower Respiratory Tract Infection11/365 (3%) 10/364 (2.7%)
    Lower Respiratory Tract Infection Bacterial2/365 (0.5%) 0/364 (0%)
    Lower Respiratory Tract Infection Viral1/365 (0.3%) 0/364 (0%)
    Lung Infection1/365 (0.3%) 7/364 (1.9%)
    Metapneumovirus Infection1/365 (0.3%) 1/364 (0.3%)
    Myocarditis Infectious0/365 (0%) 1/364 (0.3%)
    Neutropenic Infection1/365 (0.3%) 0/364 (0%)
    Neutropenic Sepsis0/365 (0%) 1/364 (0.3%)
    Nocardiosis0/365 (0%) 1/364 (0.3%)
    Oesophageal Candidiasis0/365 (0%) 1/364 (0.3%)
    Osteomyelitis2/365 (0.5%) 0/364 (0%)
    Otitis Externa1/365 (0.3%) 0/364 (0%)
    Peritonitis1/365 (0.3%) 0/364 (0%)
    Pharyngitis0/365 (0%) 1/364 (0.3%)
    Pleural Infection0/365 (0%) 1/364 (0.3%)
    Pneumocystis Jirovecii Infection0/365 (0%) 1/364 (0.3%)
    Pneumocystis Jirovecii Pneumonia0/365 (0%) 1/364 (0.3%)
    Pneumonia27/365 (7.4%) 48/364 (13.2%)
    Pulmonary Mycosis0/365 (0%) 1/364 (0.3%)
    Pyelonephritis0/365 (0%) 2/364 (0.5%)
    Respiratory Syncytial Virus Bronchiolitis1/365 (0.3%) 0/364 (0%)
    Respiratory Syncytial Virus Infection2/365 (0.5%) 1/364 (0.3%)
    Respiratory Tract Infection0/365 (0%) 1/364 (0.3%)
    Salmonellosis0/365 (0%) 1/364 (0.3%)
    Sepsis7/365 (1.9%) 9/364 (2.5%)
    Sepsis Syndrome0/365 (0%) 1/364 (0.3%)
    Septic Arthritis Staphylococcal0/365 (0%) 1/364 (0.3%)
    Septic Embolus0/365 (0%) 1/364 (0.3%)
    Septic Shock3/365 (0.8%) 4/364 (1.1%)
    Skin Infection0/365 (0%) 1/364 (0.3%)
    Soft Tissue Infection1/365 (0.3%) 0/364 (0%)
    Spinal Cord Infection1/365 (0.3%) 0/364 (0%)
    Staphylococcal Sepsis1/365 (0.3%) 0/364 (0%)
    Subcutaneous Abscess0/365 (0%) 1/364 (0.3%)
    Upper Respiratory Tract Infection4/365 (1.1%) 5/364 (1.4%)
    Ureteritis0/365 (0%) 1/364 (0.3%)
    Urinary Tract Infection5/365 (1.4%) 8/364 (2.2%)
    Urinary Tract Infection Bacterial0/365 (0%) 1/364 (0.3%)
    Urosepsis1/365 (0.3%) 1/364 (0.3%)
    Varicella Zoster Virus Infection1/365 (0.3%) 0/364 (0%)
    Vascular Stent Infection0/365 (0%) 1/364 (0.3%)
    Vestibular Neuronitis0/365 (0%) 1/364 (0.3%)
    Viral Upper Respiratory Tract Infection0/365 (0%) 2/364 (0.5%)
    Injury, poisoning and procedural complications
    Accident0/365 (0%) 1/364 (0.3%)
    Accidental Overdose1/365 (0.3%) 0/364 (0%)
    Acetabulum Fracture0/365 (0%) 1/364 (0.3%)
    Clavicle Fracture0/365 (0%) 1/364 (0.3%)
    Concussion0/365 (0%) 1/364 (0.3%)
    Craniocerebral Injury0/365 (0%) 1/364 (0.3%)
    Face Injury0/365 (0%) 1/364 (0.3%)
    Facial Bones Fracture0/365 (0%) 1/364 (0.3%)
    Fall1/365 (0.3%) 2/364 (0.5%)
    Femoral Neck Fracture2/365 (0.5%) 1/364 (0.3%)
    Femur Fracture3/365 (0.8%) 4/364 (1.1%)
    Foot Fracture1/365 (0.3%) 0/364 (0%)
    Fracture1/365 (0.3%) 1/364 (0.3%)
    Head Injury1/365 (0.3%) 0/364 (0%)
    Hip Fracture1/365 (0.3%) 4/364 (1.1%)
    Humerus Fracture0/365 (0%) 2/364 (0.5%)
    Limb Injury1/365 (0.3%) 0/364 (0%)
    Open Fracture1/365 (0.3%) 0/364 (0%)
    Pelvic Fracture1/365 (0.3%) 1/364 (0.3%)
    Periorbital Haemorrhage0/365 (0%) 1/364 (0.3%)
    Postoperative Fever1/365 (0.3%) 0/364 (0%)
    Pubis Fracture1/365 (0.3%) 0/364 (0%)
    Rib Fracture1/365 (0.3%) 3/364 (0.8%)
    Spinal Compression Fracture2/365 (0.5%) 6/364 (1.6%)
    Spinal Fracture1/365 (0.3%) 0/364 (0%)
    Sternal Fracture1/365 (0.3%) 0/364 (0%)
    Subdural Haematoma0/365 (0%) 1/364 (0.3%)
    Tendon Rupture0/365 (0%) 1/364 (0.3%)
    Upper Limb Fracture0/365 (0%) 2/364 (0.5%)
    Investigations
    Blood Creatinine Increased2/365 (0.5%) 0/364 (0%)
    C-Reactive Protein Increased1/365 (0.3%) 1/364 (0.3%)
    International Normalised Ratio Increased1/365 (0.3%) 0/364 (0%)
    Lipase Increased0/365 (0%) 1/364 (0.3%)
    Occult Blood Positive1/365 (0.3%) 0/364 (0%)
    Oxygen Saturation Decreased0/365 (0%) 1/364 (0.3%)
    Transaminases Increased1/365 (0.3%) 0/364 (0%)
    Troponin I Increased1/365 (0.3%) 0/364 (0%)
    Metabolism and nutrition disorders
    Decreased Appetite1/365 (0.3%) 2/364 (0.5%)
    Dehydration1/365 (0.3%) 6/364 (1.6%)
    Diabetes Mellitus Inadequate Control1/365 (0.3%) 1/364 (0.3%)
    Failure to Thrive1/365 (0.3%) 0/364 (0%)
    Gout2/365 (0.5%) 1/364 (0.3%)
    Hypercalcaemia3/365 (0.8%) 1/364 (0.3%)
    Hyperglycaemia1/365 (0.3%) 2/364 (0.5%)
    Hyperkalaemia2/365 (0.5%) 2/364 (0.5%)
    Hypocalcaemia3/365 (0.8%) 1/364 (0.3%)
    Hypokalaemia5/365 (1.4%) 3/364 (0.8%)
    Hypomagnesaemia1/365 (0.3%) 0/364 (0%)
    Hyponatraemia3/365 (0.8%) 2/364 (0.5%)
    Hypovolaemia1/365 (0.3%) 0/364 (0%)
    Type 1 Diabetes Mellitus0/365 (0%) 1/364 (0.3%)
    Musculoskeletal and connective tissue disorders
    Arthralgia2/365 (0.5%) 2/364 (0.5%)
    Arthritis0/365 (0%) 2/364 (0.5%)
    Back Pain8/365 (2.2%) 12/364 (3.3%)
    Bone Lesion2/365 (0.5%) 0/364 (0%)
    Bone Pain4/365 (1.1%) 4/364 (1.1%)
    Bursitis1/365 (0.3%) 0/364 (0%)
    Chondrocalcinosis1/365 (0.3%) 0/364 (0%)
    Chondrocalcinosis Pyrophosphate1/365 (0.3%) 1/364 (0.3%)
    Crystal Arthropathy1/365 (0.3%) 0/364 (0%)
    Intervertebral Disc Compression0/365 (0%) 1/364 (0.3%)
    Intervertebral Disc Protrusion0/365 (0%) 1/364 (0.3%)
    Jaw Fistula1/365 (0.3%) 0/364 (0%)
    Lumbar Spinal Stenosis0/365 (0%) 1/364 (0.3%)
    Muscle Spasms0/365 (0%) 2/364 (0.5%)
    Muscular Weakness2/365 (0.5%) 4/364 (1.1%)
    Musculoskeletal Chest Pain2/365 (0.5%) 0/364 (0%)
    Musculoskeletal Pain1/365 (0.3%) 3/364 (0.8%)
    Neck Pain1/365 (0.3%) 0/364 (0%)
    Osteoarthritis2/365 (0.5%) 1/364 (0.3%)
    Osteolysis1/365 (0.3%) 1/364 (0.3%)
    Osteonecrosis0/365 (0%) 2/364 (0.5%)
    Osteonecrosis of Jaw2/365 (0.5%) 1/364 (0.3%)
    Osteoporosis0/365 (0%) 1/364 (0.3%)
    Pain in Extremity0/365 (0%) 1/364 (0.3%)
    Pathological Fracture1/365 (0.3%) 0/364 (0%)
    Primary Sequestrum1/365 (0.3%) 0/364 (0%)
    Spinal Pain4/365 (1.1%) 2/364 (0.5%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma Gastric1/365 (0.3%) 1/364 (0.3%)
    Adrenal Adenoma1/365 (0.3%) 0/364 (0%)
    Basal Cell Carcinoma1/365 (0.3%) 2/364 (0.5%)
    Breast Cancer1/365 (0.3%) 0/364 (0%)
    Cancer Pain1/365 (0.3%) 0/364 (0%)
    Colorectal Adenocarcinoma0/365 (0%) 1/364 (0.3%)
    Diffuse Large B-Cell Lymphoma1/365 (0.3%) 1/364 (0.3%)
    Gastrointestinal Neoplasm1/365 (0.3%) 0/364 (0%)
    Gastrointestinal Stromal Tumour0/365 (0%) 1/364 (0.3%)
    Invasive Lobular Breast Carcinoma0/365 (0%) 1/364 (0.3%)
    Keratoacanthoma1/365 (0.3%) 0/364 (0%)
    Leiomyosarcoma1/365 (0.3%) 0/364 (0%)
    Lung Neoplasm Malignant1/365 (0.3%) 0/364 (0%)
    Mantle Cell Lymphoma0/365 (0%) 1/364 (0.3%)
    Meningioma0/365 (0%) 1/364 (0.3%)
    Neuroendocrine Carcinoma of the Skin1/365 (0.3%) 0/364 (0%)
    Porocarcinoma0/365 (0%) 1/364 (0.3%)
    Prostate Cancer1/365 (0.3%) 1/364 (0.3%)
    Prostatic Adenoma1/365 (0.3%) 0/364 (0%)
    Small Cell Lung Cancer1/365 (0.3%) 0/364 (0%)
    Squamous Cell Carcinoma of Skin2/365 (0.5%) 1/364 (0.3%)
    Transitional Cell Carcinoma1/365 (0.3%) 0/364 (0%)
    Nervous system disorders
    Brain Stem Infarction1/365 (0.3%) 0/364 (0%)
    Cerebral Infarction1/365 (0.3%) 1/364 (0.3%)
    Cerebrovascular Accident5/365 (1.4%) 5/364 (1.4%)
    Cognitive Disorder0/365 (0%) 1/364 (0.3%)
    Dementia Alzheimer's Type1/365 (0.3%) 0/364 (0%)
    Dizziness1/365 (0.3%) 3/364 (0.8%)
    Epilepsy0/365 (0%) 1/364 (0.3%)
    Focal Dyscognitive Seizures0/365 (0%) 1/364 (0.3%)
    Generalised Tonic-Clonic Seizure1/365 (0.3%) 0/364 (0%)
    Haemorrhage Intracranial1/365 (0.3%) 1/364 (0.3%)
    Haemorrhagic Stroke0/365 (0%) 1/364 (0.3%)
    Headache0/365 (0%) 1/364 (0.3%)
    Hepatic Encephalopathy0/365 (0%) 1/364 (0.3%)
    Hyperaesthesia1/365 (0.3%) 0/364 (0%)
    Hypoaesthesia0/365 (0%) 1/364 (0.3%)
    Ischaemic Stroke3/365 (0.8%) 1/364 (0.3%)
    Nervous System Disorder0/365 (0%) 1/364 (0.3%)
    Neuralgia1/365 (0.3%) 1/364 (0.3%)
    Orthostatic Intolerance0/365 (0%) 1/364 (0.3%)
    Peripheral Motor Neuropathy0/365 (0%) 1/364 (0.3%)
    Post Herpetic Neuralgia0/365 (0%) 1/364 (0.3%)
    Presyncope2/365 (0.5%) 0/364 (0%)
    Sciatica2/365 (0.5%) 2/364 (0.5%)
    Seizure2/365 (0.5%) 3/364 (0.8%)
    Spinal Cord Compression1/365 (0.3%) 1/364 (0.3%)
    Syncope3/365 (0.8%) 4/364 (1.1%)
    Transient Ischaemic Attack3/365 (0.8%) 0/364 (0%)
    Vith Nerve Paralysis1/365 (0.3%) 0/364 (0%)
    Product Issues
    Device Dislocation1/365 (0.3%) 0/364 (0%)
    Psychiatric disorders
    Confusional State2/365 (0.5%) 3/364 (0.8%)
    Depression1/365 (0.3%) 1/364 (0.3%)
    Eating Disorder1/365 (0.3%) 0/364 (0%)
    Major Depression1/365 (0.3%) 0/364 (0%)
    Mental Status Changes2/365 (0.5%) 1/364 (0.3%)
    Personality Change1/365 (0.3%) 0/364 (0%)
    Psychotic Disorder0/365 (0%) 1/364 (0.3%)
    Renal and urinary disorders
    Acute Kidney Injury14/365 (3.8%) 11/364 (3%)
    Bladder Stenosis0/365 (0%) 1/364 (0.3%)
    Chronic Kidney Disease1/365 (0.3%) 2/364 (0.5%)
    Dysuria0/365 (0%) 1/364 (0.3%)
    Haematuria1/365 (0.3%) 1/364 (0.3%)
    Renal Disorder0/365 (0%) 1/364 (0.3%)
    Renal Failure5/365 (1.4%) 4/364 (1.1%)
    Renal Impairment2/365 (0.5%) 0/364 (0%)
    Urethral Caruncle0/365 (0%) 1/364 (0.3%)
    Urinary Retention3/365 (0.8%) 2/364 (0.5%)
    Reproductive system and breast disorders
    Benign Prostatic Hyperplasia0/365 (0%) 1/364 (0.3%)
    Genital Prolapse1/365 (0.3%) 1/364 (0.3%)
    Pelvic Pain1/365 (0.3%) 0/364 (0%)
    Vaginal Haemorrhage0/365 (0%) 1/364 (0.3%)
    Respiratory, thoracic and mediastinal disorders
    Acute Pulmonary Oedema1/365 (0.3%) 3/364 (0.8%)
    Asthma1/365 (0.3%) 3/364 (0.8%)
    Bronchiectasis1/365 (0.3%) 0/364 (0%)
    Bronchopneumopathy0/365 (0%) 1/364 (0.3%)
    Bronchospasm0/365 (0%) 1/364 (0.3%)
    Chronic Obstructive Pulmonary Disease3/365 (0.8%) 1/364 (0.3%)
    Dyspnoea4/365 (1.1%) 6/364 (1.6%)
    Epistaxis0/365 (0%) 1/364 (0.3%)
    Haemoptysis1/365 (0.3%) 0/364 (0%)
    Hiccups1/365 (0.3%) 0/364 (0%)
    Hypoxia2/365 (0.5%) 4/364 (1.1%)
    Lung Disorder1/365 (0.3%) 0/364 (0%)
    Pleural Effusion1/365 (0.3%) 1/364 (0.3%)
    Pleurisy0/365 (0%) 1/364 (0.3%)
    Pleuritic Pain2/365 (0.5%) 0/364 (0%)
    Pneumonitis1/365 (0.3%) 0/364 (0%)
    Pulmonary Embolism14/365 (3.8%) 11/364 (3%)
    Pulmonary Thrombosis0/365 (0%) 1/364 (0.3%)
    Respiratory Distress0/365 (0%) 1/364 (0.3%)
    Respiratory Failure1/365 (0.3%) 0/364 (0%)
    Skin and subcutaneous tissue disorders
    Acute Febrile Neutrophilic Dermatosis1/365 (0.3%) 0/364 (0%)
    Dermatitis Exfoliative1/365 (0.3%) 0/364 (0%)
    Drug Reaction with Eosinophilia and Systemic Symptoms4/365 (1.1%) 0/364 (0%)
    Ecchymosis1/365 (0.3%) 0/364 (0%)
    Purpura1/365 (0.3%) 1/364 (0.3%)
    Rash1/365 (0.3%) 0/364 (0%)
    Rash Generalised5/365 (1.4%) 0/364 (0%)
    Rash Maculo-Papular0/365 (0%) 1/364 (0.3%)
    Skin Ulcer1/365 (0.3%) 0/364 (0%)
    Stevens-Johnson Syndrome1/365 (0.3%) 0/364 (0%)
    Vascular disorders
    Air Embolism0/365 (0%) 1/364 (0.3%)
    Aortic Aneurysm0/365 (0%) 1/364 (0.3%)
    Aortic Aneurysm Rupture1/365 (0.3%) 0/364 (0%)
    Arteritis1/365 (0.3%) 0/364 (0%)
    Deep Vein Thrombosis8/365 (2.2%) 5/364 (1.4%)
    Embolism1/365 (0.3%) 2/364 (0.5%)
    Haematoma3/365 (0.8%) 1/364 (0.3%)
    Haemorrhage0/365 (0%) 1/364 (0.3%)
    Hypertension0/365 (0%) 3/364 (0.8%)
    Hypotension1/365 (0.3%) 2/364 (0.5%)
    Orthostatic Hypotension1/365 (0.3%) 0/364 (0%)
    Peripheral Arterial Occlusive Disease1/365 (0.3%) 0/364 (0%)
    Peripheral Artery Stenosis0/365 (0%) 1/364 (0.3%)
    Peripheral Ischaemia0/365 (0%) 2/364 (0.5%)
    Phlebitis2/365 (0.5%) 1/364 (0.3%)
    Superior Vena Cava Occlusion0/365 (0%) 1/364 (0.3%)
    Venous Thrombosis2/365 (0.5%) 0/364 (0%)
    Other (Not Including Serious) Adverse Events
    Lenalidomide + Dexamethasone (Rd)Daratumumab + Lenalidomide + Dexamethasone (DRd)
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total355/365 (97.3%) 362/364 (99.5%)
    Blood and lymphatic system disorders
    Anaemia136/365 (37.3%) 126/364 (34.6%)
    Leukopenia34/365 (9.3%) 68/364 (18.7%)
    Lymphopenia45/365 (12.3%) 66/364 (18.1%)
    Neutropenia154/365 (42.2%) 207/364 (56.9%)
    Thrombocytopenia68/365 (18.6%) 68/364 (18.7%)
    Cardiac disorders
    Atrial Fibrillation29/365 (7.9%) 19/364 (5.2%)
    Eye disorders
    Cataract55/365 (15.1%) 52/364 (14.3%)
    Vision Blurred16/365 (4.4%) 26/364 (7.1%)
    Gastrointestinal disorders
    Abdominal Pain33/365 (9%) 40/364 (11%)
    Abdominal Pain Upper28/365 (7.7%) 33/364 (9.1%)
    Constipation129/365 (35.3%) 148/364 (40.7%)
    Diarrhoea166/365 (45.5%) 204/364 (56%)
    Dry Mouth19/365 (5.2%) 12/364 (3.3%)
    Dyspepsia27/365 (7.4%) 26/364 (7.1%)
    Nausea83/365 (22.7%) 115/364 (31.6%)
    Stomatitis13/365 (3.6%) 22/364 (6%)
    Vomiting43/365 (11.8%) 60/364 (16.5%)
    General disorders
    Asthenia85/365 (23.3%) 116/364 (31.9%)
    Chills6/365 (1.6%) 45/364 (12.4%)
    Fatigue104/365 (28.5%) 145/364 (39.8%)
    Oedema Peripheral107/365 (29.3%) 140/364 (38.5%)
    Peripheral Swelling19/365 (5.2%) 10/364 (2.7%)
    Pyrexia58/365 (15.9%) 70/364 (19.2%)
    Infections and infestations
    Bronchitis73/365 (20%) 100/364 (27.5%)
    Influenza15/365 (4.1%) 23/364 (6.3%)
    Nasopharyngitis11/365 (3%) 26/364 (7.1%)
    Oral Candidiasis19/365 (5.2%) 15/364 (4.1%)
    Pneumonia25/365 (6.8%) 41/364 (11.3%)
    Rhinitis21/365 (5.8%) 29/364 (8%)
    Sinusitis14/365 (3.8%) 20/364 (5.5%)
    Upper Respiratory Tract Infection50/365 (13.7%) 81/364 (22.3%)
    Urinary Tract Infection34/365 (9.3%) 60/364 (16.5%)
    Viral Upper Respiratory Tract Infection46/365 (12.6%) 55/364 (15.1%)
    Injury, poisoning and procedural complications
    Contusion22/365 (6%) 27/364 (7.4%)
    Investigations
    Blood Creatinine Increased13/365 (3.6%) 24/364 (6.6%)
    Weight Decreased63/365 (17.3%) 101/364 (27.7%)
    Weight Increased6/365 (1.6%) 25/364 (6.9%)
    Metabolism and nutrition disorders
    Decreased Appetite54/365 (14.8%) 78/364 (21.4%)
    Dehydration16/365 (4.4%) 19/364 (5.2%)
    Hyperglycaemia28/365 (7.7%) 50/364 (13.7%)
    Hypocalcaemia31/365 (8.5%) 49/364 (13.5%)
    Hypokalaemia60/365 (16.4%) 72/364 (19.8%)
    Hypomagnesaemia29/365 (7.9%) 18/364 (4.9%)
    Hyponatraemia11/365 (3%) 19/364 (5.2%)
    Hypophosphataemia7/365 (1.9%) 19/364 (5.2%)
    Musculoskeletal and connective tissue disorders
    Arthralgia63/365 (17.3%) 69/364 (19%)
    Back Pain93/365 (25.5%) 114/364 (31.3%)
    Bone Pain33/365 (9%) 34/364 (9.3%)
    Muscle Spasms79/365 (21.6%) 106/364 (29.1%)
    Muscular Weakness22/365 (6%) 30/364 (8.2%)
    Musculoskeletal Chest Pain41/365 (11.2%) 27/364 (7.4%)
    Musculoskeletal Pain40/365 (11%) 49/364 (13.5%)
    Myalgia25/365 (6.8%) 25/364 (6.9%)
    Neck Pain26/365 (7.1%) 21/364 (5.8%)
    Pain in Extremity50/365 (13.7%) 59/364 (16.2%)
    Nervous system disorders
    Dizziness57/365 (15.6%) 69/364 (19%)
    Dysgeusia35/365 (9.6%) 40/364 (11%)
    Headache39/365 (10.7%) 68/364 (18.7%)
    Paraesthesia30/365 (8.2%) 58/364 (15.9%)
    Peripheral Sensory Neuropathy54/365 (14.8%) 87/364 (23.9%)
    Tremor51/365 (14%) 57/364 (15.7%)
    Psychiatric disorders
    Anxiety34/365 (9.3%) 32/364 (8.8%)
    Confusional State19/365 (5.2%) 22/364 (6%)
    Depression32/365 (8.8%) 29/364 (8%)
    Insomnia107/365 (29.3%) 109/364 (29.9%)
    Renal and urinary disorders
    Acute Kidney Injury15/365 (4.1%) 23/364 (6.3%)
    Chronic Kidney Disease18/365 (4.9%) 21/364 (5.8%)
    Renal Impairment27/365 (7.4%) 26/364 (7.1%)
    Respiratory, thoracic and mediastinal disorders
    Cough59/365 (16.2%) 100/364 (27.5%)
    Dysphonia18/365 (4.9%) 27/364 (7.4%)
    Dyspnoea56/365 (15.3%) 97/364 (26.6%)
    Dyspnoea Exertional21/365 (5.8%) 23/364 (6.3%)
    Epistaxis20/365 (5.5%) 17/364 (4.7%)
    Oropharyngeal Pain9/365 (2.5%) 24/364 (6.6%)
    Rhinorrhoea11/365 (3%) 25/364 (6.9%)
    Skin and subcutaneous tissue disorders
    Dry Skin14/365 (3.8%) 25/364 (6.9%)
    Erythema18/365 (4.9%) 23/364 (6.3%)
    Hyperhidrosis5/365 (1.4%) 19/364 (5.2%)
    Pruritus29/365 (7.9%) 32/364 (8.8%)
    Rash43/365 (11.8%) 57/364 (15.7%)
    Rash Generalised23/365 (6.3%) 16/364 (4.4%)
    Rash Maculo-Papular9/365 (2.5%) 20/364 (5.5%)
    Vascular disorders
    Deep Vein Thrombosis27/365 (7.4%) 26/364 (7.1%)
    Hypertension26/365 (7.1%) 46/364 (12.6%)
    Hypotension32/365 (8.8%) 34/364 (9.3%)

    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
    OrganizationJanssen Research & Development, LLC
    Phone844-434-4210
    EmailClinicalTrialDisclosure@its.jnj.com
    Responsible Party:
    Janssen Research & Development, LLC
    ClinicalTrials.gov Identifier:
    NCT02252172
    Other Study ID Numbers:
    • CR104762
    • 54767414MMY3008
    • 2014-002273-11
    First Posted:
    Sep 30, 2014
    Last Update Posted:
    Nov 5, 2021
    Last Verified:
    Nov 1, 2021