ELOQUENT - 2: Phase III Study of Lenalidomide and Dexamethasone With or Without Elotuzumab to Treat Relapsed or Refractory Multiple Myeloma

Sponsor
Bristol-Myers Squibb (Industry)
Overall Status
Completed
CT.gov ID
NCT01239797
Collaborator
AbbVie (Industry)
646
216
2
118
3
0

Study Details

Study Description

Brief Summary

The purpose of the study is to determine whether the addition of Elotuzumab to Lenalidomide/low-dose Dexamethasone will increase the progression free survival (PFS).

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
646 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase 3, Randomized, Open Label Trial of Lenalidomide/Dexamethasone With or Without Elotuzumab in Relapsed or Refractory Multiple Myeloma (MM)
Actual Study Start Date :
Jun 20, 2011
Actual Primary Completion Date :
Sep 2, 2014
Actual Study Completion Date :
Apr 21, 2021

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Lenalidomide + Dexamethasone

Drug: Lenalidomide
Capsules, Oral, 25 mg, once daily, on Days 1-21, Repeat every 28 days until subject meets criteria for discontinuation of study drug
Other Names:
  • Revlimid®
  • Drug: Dexamethasone
    Tablets, Oral, 40 mg, weekly, on Days 1, 8, 15, 22, Repeat every 28 days until subject meets criteria for discontinuation of study drug
    Other Names:
  • Decadron®
  • Dexamethasone Intensol®
  • Dexpak®
  • Taperpak®
  • Experimental: Lenalidomide + Dexamethasone +Elotuzumab

    Drug: Lenalidomide
    Capsules, Oral, 25 mg, once daily, on Days 1-21, Repeat every 28 days until subject meets criteria for discontinuation of study drug
    Other Names:
  • Revlimid®
  • Drug: Dexamethasone (Oral)
    On weeks without Elotuzumab dosing: Tablets, Oral, 40mg, Repeat every 28 days until subject meets criteria for discontinuation of study drug. On weeks with Elotuzumab dosing: Tablets, Oral, 28 mg, Repeat every 28 days until subject meets criteria for discontinuation of study drug
    Other Names:
  • Decadron®
  • Dexamethasone Intensol®
  • Dexpak®
  • Taperpak®
  • Drug: Dexamethasone (IV)
    On weeks without Elotuzumab dosing: Not Applicable (N/A) On weeks with Elotuzumab dosing: Solution, Intravenous (IV), 8 mg, weekly, Repeat every 28 days until subject meets criteria for discontinuation of study drug
    Other Names:
  • Decadron®
  • Dexamethasone Intensol®
  • Dexpak®
  • Taperpak®
  • Biological: Elotuzumab (BMS-901608; HuLuc63)
    Solution, IV, 10 mg/kg, weekly, on Days 1, 8, 15, 22 (cycles 1&2); Days 1 and 15 (cycles 3 and beyond), Repeat every 28 days until subject meets criteria for discontinuation of study drug

    Outcome Measures

    Primary Outcome Measures

    1. Median Progression Free Survival (PFS) [From randomization up to 326 events (up to approximately 38 months)]

      Primary definition of Progression-free survival (PFS) defined as the time from randomization to the date of first documented tumor progression or death due to any cause. Participants were censored at the last adequate assessment prior to the start of any subsequent systemic-therapy or at the last adequate assessment prior to 2 missing assessments (> 10 weeks). Participants who died more than 10 weeks after the randomization date and had no on-treatment assessment were censored at the randomization date. Clinical deterioration was not considered progression. The primary analysis of PFS was based on the primary definition using the Independent Review Committee (IRC) tumor assessment using the European Group for Blood and Bone Marrow Transplant (EBMT) criteria. Tumor assessments were made every 4 weeks (±1 week) relative to the first dose of study medication.

    2. Objective Response Rate (ORR) [From randomization up to approximately 38 months]

      Objective response rate (ORR) defined as the percentage of participants with a best response on-study of partial response (PR) or better (stringent CR [sCR], complete response [CR], very good partial response [VGPR], and partial response [PR]) based on the Independent Review Committee (IRC) assessment of best response using the European Group for Blood and Bone Marrow Transplant (EBMT) assessment criteria. Participants were censored at the last adequate assessment prior to the start of any subsequent systemic-therapy or at the last adequate assessment prior to 2 missing assessments (> 10 weeks). Participants who died more than 10 weeks after the randomization date and had no on-treatment assessment were censored at the randomization date. Clinical deterioration was not considered progression. Assessments were made every 4 weeks.

    Secondary Outcome Measures

    1. Median Overall Survival (OS) [Randomization to the date of death from any cause (up to approximately 9 years)]

      Overall survival is defined as the time from randomization to the date of death from any cause. If a subject has not died, their survival time will be censored at the date of last contact ("last known alive date"). A subject will be censored at the date of randomization if they were randomized but had no follow-up. (Based on Kaplan Meier estimates)

    2. Change From Baseline of Mean Score Pain Severity (BPI-SF) [From baseline up to approximately 38 months]

      The change from baseline of the mean score of pain severity at the end of treatment using the Brief Pain Inventory-Short Form (BPI-SF). The BPI-SF is a self administered questionnaire developed to assess the severity of pain (the sensory dimension) as well as the degree to which pain interferes with function (the reactive dimension). The BPI-SF uses 0 ("No pain", "No interference") to 10 ("Pain as bad as you can imagine", "Highest imaginable interference") numeric rating scale.

    3. Change From Baseline of Mean Score Pain Interference (BPI-SF) [From baseline up to approximately 38 months]

      The change from baseline of the mean score of pain interference at the end of treatment using the Brief Pain Inventory-Short Form (BPI-SF). The BPI-SF is a self administered questionnaire developed to assess the severity of pain (the sensory dimension) as well as the degree to which pain interferes with function (the reactive dimension). The BPI-SF uses 0 ("No pain", "No interference") to 10 ("Pain as bad as you can imagine", "Highest imaginable interference") numeric rating scale.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com.

    Inclusion Criteria:
    • Documented progression from most recent line of therapy

    • 1-3 prior lines of therapy

    • Measurable disease

    • Life expectancy ≥3 months

    • Prior treatment with Lenalidomide permitted if:

    1. Best response achieved was ≥Partial Response (PR)

    2. Patient was not refractory

    3. Patient did not discontinue due to a Grade ≥3 related adverse event

    4. Subject did not receive more than 9 cycles of Lenalidomide and had at least 9 months between the last dose of Lenalidomide and progression

    Exclusion Criteria:
    • Subjects with non-secretory or oligo-secretory or serum free light-chain only myeloma

    • Active plasma cell leukemia

    • Known Human immunodeficiency virus (HIV) infection or active hepatitis A, B, or C

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Northwest Alabama Cancer Center, Pc Muscle Shoals Alabama United States 35661
    2 Acrc/Arizona Clinical Research Center, Inc. Tucson Arizona United States 85715
    3 Local Institution Berkeley California United States 94704
    4 Local Institution Burbank California United States 91505
    5 Compassionate Cancer Res Grp Corona California United States 92879
    6 Local Institution Corona California United States 92879
    7 San Diego Pacific Oncology& Hematology Associates, Inc Encinitas California United States 92024
    8 Local Institution Greenbrae California United States 94904
    9 Ucla-Division Of Hematology/Oncology Los Angeles California United States 90095
    10 Medical Oncology Care Associates Orange California United States 92868
    11 Sharp Clinical Oncology Research San Diego California United States 92123
    12 Local Institution Vallejo California United States 94589
    13 Local Institution Boca Raton Florida United States 33486
    14 Cancer Care Centers Of Florida Brooksville Florida United States 34613
    15 Mount Sinai Comprehensive Cancer Center Miami Beach Florida United States 33140
    16 Local Institution New Port Richey Florida United States 34652
    17 Cancer Institute Of Florida Orlando Florida United States 32804
    18 Local Institution Titusville Florida United States 32796
    19 Florida Cancer Specialists West Palm Beach Florida United States 33401
    20 Winship Cancer Institute. Atlanta Georgia United States 30322
    21 Georgia Health Science University Augusta Georgia United States 30912
    22 Orchard Healthcare Research Inc. Skokie Illinois United States 60077
    23 Local Institution Indianapolis Indiana United States 46260
    24 Local Institution Mishawaka Indiana United States 46545
    25 Local Institution Iowa City Iowa United States 52242
    26 Local Institution Lexington Kentucky United States 40503
    27 Local Institution Louisville Kentucky United States 40207
    28 Pikeville Medical Center Pikeville Kentucky United States 41501
    29 Cancer Center Of Acadiana At Lafayette General Lafayette Louisiana United States 70503
    30 Local Institution Shreveport Louisiana United States 71101
    31 Local Institution Shreveport Louisiana United States 71103
    32 Willis Knighton Cancer Center Shreveport Louisiana United States 71103
    33 Dana Farber Cancer Inst Boston Massachusetts United States 02215
    34 Dana-Farber Cancer Institute Boston Massachusetts United States 02215
    35 Henry Ford Health System Detroit Michigan United States 48202
    36 Capitol Comprehensive Cancer Care Center Jefferson City Missouri United States 65101
    37 Washington University School Of Medicine Saint Louis Missouri United States 63110
    38 Local Institution Springfield Missouri United States 65807
    39 Local Institution Las Vegas Nevada United States 89106
    40 NYU Clinical Cancer Center New York New York United States 10016
    41 Local Institution New York New York United States 10019
    42 Weill Cornell Medical College New York New York United States 10065
    43 Local Institution Stony Brook New York United States 11794-8151
    44 Levine Cancer Institute Charlotte North Carolina United States 28204
    45 Gaston Hematology & Oncology Gastonia North Carolina United States 28054
    46 Local Institution Bismarck North Dakota United States 58501
    47 University Of Oklahoma Health Sciences Center Oklahoma City Oklahoma United States 73104
    48 Local Institution Tulsa Oklahoma United States 74136
    49 Local Institution Bethlehem Pennsylvania United States 18015
    50 Western Pennsylvania Hospital Pittsburgh Pennsylvania United States 15224
    51 Local Institution Charleston South Carolina United States 29414
    52 Local Institution Greenville South Carolina United States 29615
    53 Local Institution Knoxville Tennessee United States 37909
    54 The West Clinic Memphis Tennessee United States 38120
    55 Cancer Specialists Of South Texas, Pa Corpus Christi Texas United States 78412
    56 Ut Southwestern Medical Center Dallas Texas United States 75390-8565
    57 University Of Texas Md Anderson Cancer Ctr Houston Texas United States 77030
    58 Northwest Cancer Center Houston Texas United States 77090
    59 Hematology-Oncology Associates Of Fredricksburg, Inc Fredericksburg Virginia United States 22408
    60 Va Puget Sound Health Care System Seattle Washington United States 98108
    61 Gundersen Clinic, Ltd La Crosse Wisconsin United States 54601
    62 University Of Wisconsin Hospital And Clinics Madison Wisconsin United States 53792
    63 Medical College of Wisconsin Milwaukee Wisconsin United States 53226
    64 Local Institution Albury New South Wales Australia 2640
    65 Local Institution Canberra New South Wales Australia 2605
    66 Local Institution South Brisbane Queensland Australia 4101
    67 Local Institution Adelaide South Australia Australia 5000
    68 Local Institution Malvern Victoria Australia 3144
    69 Local Institution Melbourne Victoria Australia 3004
    70 Local Institution Nedlands Western Australia Australia 6009
    71 Local Institution Murdoch Australia 6150
    72 Local Institution Rankweil Austria 6830
    73 Local Institution Steyr Austria 4400
    74 Local Institution Wels Austria 4600
    75 Local Institution Wien Austria 1220
    76 Local Institution Antwerpen Belgium 2060
    77 Local Institution Brussels Belgium 1000
    78 Local Institution Brussels Belgium 1020
    79 Local Institution Brussels Belgium 1090
    80 Local Institution Brussles Belgium 1200
    81 Local Institution Edegem-antwerp Belgium 2650
    82 Local Institution Liege Belgium 4000
    83 Local Institution Yvoir Belgium 5530
    84 Local Institution Calgary Alberta Canada T2N 4N2
    85 Local Institution Edmonton Alberta Canada T6G 1Z2
    86 Local Institution Halifax Nova Scotia Canada B3H 2Y9
    87 Local Institution London Ontario Canada N6A 4G5
    88 Local Institution Toronto Ontario Canada M5G 2M9
    89 Local Institution Montreal Quebec Canada H4J 1C5
    90 Local Institution Saskatoon Saskatchewan Canada S7N 4H4
    91 Local Institution Barrie Canada L4M 6M2
    92 Local Institution Montreal Canada H4A 3J1
    93 Local Institution Brno Czechia 625 00
    94 Local Institution Hradec Kralove Czechia 500 05
    95 Local Institution Praha 10 Czechia 100 34
    96 Local Institution Praha 2 Czechia 128 08
    97 Local Institution Copenhagen Denmark 2100
    98 Local Institution Odense C Denmark 5000
    99 Local Institution Vejle Denmark 7100
    100 Local Institution Blois France 41016
    101 Local Institution Bordeaux France 33076
    102 Local Institution Caen France 14000
    103 Local Institution Clamart Cedex France 92140
    104 Local Institution La Roche Sur Yon France 85925
    105 Local Institution La Tronche France 38700
    106 Local Institution Lille France 59037
    107 Local Institution Limoges France 87042
    108 Local Institution Nantes France 44093
    109 Local Institution Paris 12 France 75012
    110 Local Institution Pierre Benita France 69495
    111 Local Institution Toulouse France 31059
    112 Local Institution Tours Cedex France 37044
    113 Local Institution Vandoeuvre France 54511
    114 Local Institution Aschaffenburg Germany 63739
    115 Local Institution Berlin Germany 12200
    116 Local Institution Berlin Germany 13125
    117 Local Institution Chemnitz Germany 09113
    118 Local Institution Dresden Germany 01307
    119 Local Institution Hamburg Germany 20246
    120 Local Institution Hamburg Germany 22763
    121 Local Institution Hamburg Germany 66421
    122 Local Institution Hamm Germany 59071
    123 Local Institution Heidelberg Germany 69120
    124 Local Institution Jena Germany 07747
    125 Local Institution Kiel Germany 24105
    126 Local Institution Koln Germany 50937
    127 Local Institution Marburg Germany 35037
    128 Local Institution Munchen Germany 81377
    129 Local Institution Munchen Germany 81675
    130 Local Institution Munster Germany 48149
    131 Local Institution Ravensburg Germany 88212
    132 Local Institution Tuebingen Germany 72076
    133 Local Institution Ulm Germany 89081
    134 Local Institution Wurzburg Germany 97080
    135 Local Institution Athens Greece 11528
    136 Local Institution Ioannina Greece 45500
    137 Local Institution Larissa Greece 41110
    138 Local Institution Budapest Hungary 1125
    139 Local Institution Debrecen Hungary H-4032
    140 Local Institution Gyor Hungary 9024
    141 Local Institution Szeged Hungary H-6725
    142 Local Institution Dublin Ireland 7
    143 Local Institution Tullamore Ireland
    144 Local Institution Afula Israel 18101
    145 Local Institution Jerusalem Israel 91120
    146 Local Institution Petah Tikva Israel 49100
    147 Local Institution Rehovot Israel 76100
    148 Local Institution Zerifin Israel 70300
    149 Local Institution Ancona Italy 60126
    150 Local Institution Bergamo Italy 24127
    151 Local Institution Bologna Italy 40138
    152 Local Institution Firenze Italy 50134
    153 Local Institution Genova Italy 16132
    154 Local Institution Meldola Italy 47014
    155 Local Institution Milano Italy 20133
    156 Local Institution Palermo Italy 90146
    157 Local Institution Ravenna Italy 48100
    158 Local Institution Rimini Italy 47923
    159 Local Institution Roma Italy 00161
    160 Local Institution Roma Italy 00168
    161 Local Institution Torino Italy 10126
    162 Local Institution Nagoya-shi Aichi Japan 4600001
    163 Local Institution Nagoya-shi Aichi Japan 4678602
    164 Local Institution Maebashi-shi Gunma Japan 371-8511
    165 Local Institution Shibukawa-shi Gunma Japan 3770280
    166 Local Institution Sapporo-city Hokkaido Japan 0608543
    167 Local Institution Sendai-shi Miyagi Japan 980-8754
    168 Local Institution Osaka-shi Osaka Japan 5438555
    169 Local Institution Bunkyo-Ku Tokyo Japan 1138677
    170 Local Institution Koto-ku Tokyo Japan 1358550
    171 Local Institution Shibuya-ku Tokyo Japan 1508935
    172 Local Institution Shinjuuku-ku Tokyo Japan 1608582
    173 Local Institution Kamogawa Toyko Japan 296-8602
    174 Local Institution Chiba-shi Japan 260-8677
    175 Local Institution Fukuoka Japan 812-8582
    176 Local Institution Kyoto Japan 602-8566
    177 Local Institution Niigata Japan 9518566
    178 Local Institution Okayama Japan 7011192
    179 Local Institution Toyohashi-shi Japan 4418570
    180 Local Institution Bialystok Poland 15-276
    181 Local Institution Chorzow Poland 41-500
    182 Local Institution Lublin Poland 20-081
    183 Local Institution Poznan Poland 60-569
    184 Local Institution Warszawa Poland 02-106
    185 Local Institution Warszawa Poland 02-507
    186 Local Institution Warszawa Poland 02-776
    187 Local Institution Wroclaw Poland 50-367
    188 Local Institution Ponce Puerto Rico 00716
    189 Local Institution San Juan Puerto Rico 00918
    190 Local Institution Brasov Romania 500152
    191 Local Institution Brasov Romania 700106
    192 Local Institution Bucaresti Romania 030171
    193 Local Institution Bucuresti Romania 22328
    194 Local Institution Badalona-Barcelona Spain 08916
    195 Local Institution Madrid Spain 28006
    196 Local Institution Madrid Spain 28007
    197 Local Institution Murcia Spain 30008
    198 Local Institution Salamanca Spain 37007
    199 Local Institution Santiago De Comp-coruna Spain 15706
    200 Local Institution Toledo Spain 45004
    201 Local Institution Bern Switzerland 3010
    202 Local Institution Geneve 14 Switzerland 1211
    203 Local Institution Izmir Bornova Turkey 35100
    204 Local Institution Istanbul Capa Turkey 34390
    205 Local Institution Ankara Turkey 06620
    206 Local Institution Izmir Turkey 35330
    207 Local Institution Leicester United Arab Emirates LE1 5WW
    208 Local Institution London Greater London United Kingdom EC1A 7BE
    209 Local Institution Manchester Greater Manchester United Kingdom M20 4BX
    210 Local Institution Airdrie Lancashire United Kingdom ML6 OJS
    211 Local Institution Edinburgh Midlothian United Kingdom EH4 2XU
    212 Local Institution Nottingham Nottinghamshire United Kingdom NG5 1PB
    213 Local Institution Sutton Surrey United Kingdom SM2 5PT
    214 Local Institution Leeds United Kingdom LS9 7FT
    215 Local Institution London United Kingdom NW1 2PG
    216 Local Institution Newcastle Upon Tyne United Kingdom NE7 7DN

    Sponsors and Collaborators

    • Bristol-Myers Squibb
    • AbbVie

    Investigators

    • Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Bristol-Myers Squibb
    ClinicalTrials.gov Identifier:
    NCT01239797
    Other Study ID Numbers:
    • CA204-004
    • 2010-020347-12
    First Posted:
    Nov 11, 2010
    Last Update Posted:
    Jun 1, 2022
    Last Verified:
    May 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail 646 participants were randomized and 635 were treated
    Arm/Group Title Lenalidomide + Dexamethasone + Elotuzumab Lenalidomide + Dexamethasone
    Arm/Group Description Lenalidomide: Capsules, Oral, 25 mg, once daily, on Days 1-21 Repeat every 28 days until participants met criteria for discontinuation of study drug Dexamethasone (Oral): On weeks without Elotuzumab dosing: Tablets, Oral, 40mg Repeat every 28 days until participants met criteria for discontinuation of study drug On weeks with Elotuzumab dosing: Tablets, Oral, 28 mg Repeat every 28 days until participants met criteria for discontinuation of study drug Dexamethasone (IV): On weeks without Elotuzumab dosing: Not Applicable (N/A) On weeks with Elotuzumab dosing: Solution, Intravenous (IV), 8 mg, weekly Repeat every 28 days until participants met criteria for discontinuation of study drug Elotuzumab (BMS-901608; HuLuc63): Solution, IV, 10 mg/kg, weekly, on Days 1, 8, 15, 22 (cycles 1&2); Days 1 and 15 (cycles 3 and beyond) Repeat every 28 days until participants met criteria for discontinuation of study drug Lenalidomide: Capsules, Oral, 25 mg, once daily, on Days 1-21 Regimen repeated every 28 days until participants met criteria for discontinuation of study drug Dexamethasone: Tablets, Oral, 40 mg, weekly, on Days 1, 8, 15, 22 Regimen repeated every 28 days until participants met criteria for discontinuation of study drug
    Period Title: Randomized Participants
    STARTED 321 325
    COMPLETED 319 316
    NOT COMPLETED 2 9
    Period Title: Randomized Participants
    STARTED 318 317
    COMPLETED 0 0
    NOT COMPLETED 318 317

    Baseline Characteristics

    Arm/Group Title Lenalidomide + Dexamethasone + Elotuzumab Lenalidomide + Dexamethasone Total
    Arm/Group Description Lenalidomide: Capsules, Oral, 25 mg, once daily, on Days 1-21 Repeat every 28 days until participants met criteria for discontinuation of study drug Dexamethasone (Oral): On weeks without Elotuzumab dosing: Tablets, Oral, 40mg Repeat every 28 days until participants met criteria for discontinuation of study drug On weeks with Elotuzumab dosing: Tablets, Oral, 28 mg Repeat every 28 days until participants met criteria for discontinuation of study drug Dexamethasone (IV): On weeks without Elotuzumab dosing: Not Applicable (N/A) On weeks with Elotuzumab dosing: Solution, Intravenous (IV), 8 mg, weekly Repeat every 28 days until participants met criteria for discontinuation of study drug Elotuzumab (BMS-901608; HuLuc63): Solution, IV, 10 mg/kg, weekly, on Days 1, 8, 15, 22 (cycles 1&2); Days 1 and 15 (cycles 3 and beyond) Repeat every 28 days until participants met criteria for discontinuation of study drug Lenalidomide: Capsules, Oral, 25 mg, once daily, on Days 1-21 Regimen repeated every 28 days until participants met criteria for discontinuation of study drug Dexamethasone: Tablets, Oral, 40 mg, weekly, on Days 1, 8, 15, 22 Regimen repeated every 28 days until participants met criteria for discontinuation of study drug Total of all reporting groups
    Overall Participants 321 325 646
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    66.2
    (9.34)
    65.3
    (10.26)
    65.7
    (9.81)
    Age, Customized (Count of Participants)
    < 65 years old
    134
    41.7%
    142
    43.7%
    276
    42.7%
    >= 65 and < 75 years old
    119
    37.1%
    122
    37.5%
    241
    37.3%
    >= 75 years old
    68
    21.2%
    61
    18.8%
    129
    20%
    Sex: Female, Male (Count of Participants)
    Female
    129
    40.2%
    132
    40.6%
    261
    40.4%
    Male
    192
    59.8%
    193
    59.4%
    385
    59.6%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    5
    1.6%
    1
    0.3%
    6
    0.9%
    Not Hispanic or Latino
    28
    8.7%
    33
    10.2%
    61
    9.4%
    Unknown or Not Reported
    288
    89.7%
    291
    89.5%
    579
    89.6%
    Race/Ethnicity, Customized (Count of Participants)
    White
    264
    82.2%
    280
    86.2%
    544
    84.2%
    Black or African American
    13
    4%
    10
    3.1%
    23
    3.6%
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    33
    10.3%
    31
    9.5%
    64
    9.9%
    Native Hawaiian or Other Pacific Islander
    1
    0.3%
    0
    0%
    1
    0.2%
    Other
    9
    2.8%
    4
    1.2%
    13
    2%
    Not Reported
    1
    0.3%
    0
    0%
    1
    0.2%

    Outcome Measures

    1. Primary Outcome
    Title Median Progression Free Survival (PFS)
    Description Primary definition of Progression-free survival (PFS) defined as the time from randomization to the date of first documented tumor progression or death due to any cause. Participants were censored at the last adequate assessment prior to the start of any subsequent systemic-therapy or at the last adequate assessment prior to 2 missing assessments (> 10 weeks). Participants who died more than 10 weeks after the randomization date and had no on-treatment assessment were censored at the randomization date. Clinical deterioration was not considered progression. The primary analysis of PFS was based on the primary definition using the Independent Review Committee (IRC) tumor assessment using the European Group for Blood and Bone Marrow Transplant (EBMT) criteria. Tumor assessments were made every 4 weeks (±1 week) relative to the first dose of study medication.
    Time Frame From randomization up to 326 events (up to approximately 38 months)

    Outcome Measure Data

    Analysis Population Description
    All randomized participants
    Arm/Group Title Lenalidomide + Dexamethasone + Elotuzumab Lenalidomide + Dexamethasone
    Arm/Group Description Lenalidomide: Capsules, Oral, 25 mg, once daily, on Days 1-21 Repeat every 28 days until participants met criteria for discontinuation of study drug Dexamethasone (Oral): On weeks without Elotuzumab dosing: Tablets, Oral, 40mg Repeat every 28 days until participants met criteria for discontinuation of study drug On weeks with Elotuzumab dosing: Tablets, Oral, 28 mg Repeat every 28 days until participants met criteria for discontinuation of study drug Dexamethasone (IV): On weeks without Elotuzumab dosing: Not Applicable (N/A) On weeks with Elotuzumab dosing: Solution, Intravenous (IV), 8 mg, weekly Repeat every 28 days until participants met criteria for discontinuation of study drug Elotuzumab (BMS-901608; HuLuc63): Solution, IV, 10 mg/kg, weekly, on Days 1, 8, 15, 22 (cycles 1&2); Days 1 and 15 (cycles 3 and beyond) Repeat every 28 days until participants met criteria for discontinuation of study drug Lenalidomide: Capsules, Oral, 25 mg, once daily, on Days 1-21 Regimen repeated every 28 days until participants met criteria for discontinuation of study drug Dexamethasone: Tablets, Oral, 40 mg, weekly, on Days 1, 8, 15, 22 Regimen repeated every 28 days until participants met criteria for discontinuation of study drug
    Measure Participants 321 325
    Median (95% Confidence Interval) [Months]
    19.35
    14.85
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Lenalidomide + Dexamethasone + Elotuzumab, Lenalidomide + Dexamethasone
    Comments Hazard Ratio of Lenalidomide + Dexamethasone + Elotuzumab to Lenalidomide + Dexamethasone
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0014
    Comments
    Method Log Rank
    Comments 2-sided p-value for stratified log rank test
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.73
    Confidence Interval (2-Sided) 95%
    0.60 to 0.89
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Post-Hoc Outcome
    Title Median Progression Free Survival (PFS) - Extended Collection
    Description The time from randomization to the date of first documented tumor progression or death due to any cause. Participants were censored at the last adequate assessment prior to the start of any subsequent systemic-therapy or at the last adequate assessment prior to 2 missing assessments (> 10 weeks). Participants who died more than 10 weeks after the randomization date and had no on-treatment assessment were censored at the randomization date. Clinical deterioration was not considered progression. Tumor assessments were made every 4 weeks (±1 week) relative to the first dose of study medication based on Independent Review Committee (IRC) tumor assessment using the European Group for Blood and Bone Marrow Transplant (EBMT) criteria. Note: This outcome measure represents an updated version of the primary endpoint to include additional data collection that has occurred after the primary completion date. (Assessments were made until 06-Jul-2018)
    Time Frame From randomization up to to the date of first documented tumor progression or death (up to approximately 85 months)

    Outcome Measure Data

    Analysis Population Description
    All randomized participants
    Arm/Group Title Lenalidomide + Dexamethasone + Elotuzumab Lenalidomide + Dexamethasone
    Arm/Group Description Lenalidomide: Capsules, Oral, 25 mg, once daily, on Days 1-21 Repeat every 28 days until participants met criteria for discontinuation of study drug Dexamethasone (Oral): On weeks without Elotuzumab dosing: Tablets, Oral, 40mg Repeat every 28 days until participants met criteria for discontinuation of study drug On weeks with Elotuzumab dosing: Tablets, Oral, 28 mg Repeat every 28 days until participants met criteria for discontinuation of study drug Dexamethasone (IV): On weeks without Elotuzumab dosing: Not Applicable (N/A) On weeks with Elotuzumab dosing: Solution, Intravenous (IV), 8 mg, weekly Repeat every 28 days until participants met criteria for discontinuation of study drug Elotuzumab (BMS-901608; HuLuc63): Solution, IV, 10 mg/kg, weekly, on Days 1, 8, 15, 22 (cycles 1&2); Days 1 and 15 (cycles 3 and beyond) Repeat every 28 days until participants met criteria for discontinuation of study drug Lenalidomide: Capsules, Oral, 25 mg, once daily, on Days 1-21 Regimen repeated every 28 days until participants met criteria for discontinuation of study drug Dexamethasone: Tablets, Oral, 40 mg, weekly, on Days 1, 8, 15, 22 Regimen repeated every 28 days until participants met criteria for discontinuation of study drug
    Measure Participants 321 325
    Median (95% Confidence Interval) [Months]
    19.42
    14.92
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Lenalidomide + Dexamethasone + Elotuzumab, Lenalidomide + Dexamethasone
    Comments Hazard Ratio of Lenalidomide + Dexamethasone + Elotuzumab to Lenalidomide + Dexamethasone
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0005
    Comments
    Method Log Rank
    Comments 2-sided p-value for stratified log rank test
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.72
    Confidence Interval (2-Sided) 95%
    0.60 to 0.87
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Primary Outcome
    Title Objective Response Rate (ORR)
    Description Objective response rate (ORR) defined as the percentage of participants with a best response on-study of partial response (PR) or better (stringent CR [sCR], complete response [CR], very good partial response [VGPR], and partial response [PR]) based on the Independent Review Committee (IRC) assessment of best response using the European Group for Blood and Bone Marrow Transplant (EBMT) assessment criteria. Participants were censored at the last adequate assessment prior to the start of any subsequent systemic-therapy or at the last adequate assessment prior to 2 missing assessments (> 10 weeks). Participants who died more than 10 weeks after the randomization date and had no on-treatment assessment were censored at the randomization date. Clinical deterioration was not considered progression. Assessments were made every 4 weeks.
    Time Frame From randomization up to approximately 38 months

    Outcome Measure Data

    Analysis Population Description
    All randomized participants
    Arm/Group Title Lenalidomide + Dexamethasone + Elotuzumab Lenalidomide + Dexamethasone
    Arm/Group Description Lenalidomide: Capsules, Oral, 25 mg, once daily, on Days 1-21 Repeat every 28 days until participants met criteria for discontinuation of study drug Dexamethasone (Oral): On weeks without Elotuzumab dosing: Tablets, Oral, 40mg Repeat every 28 days until participants met criteria for discontinuation of study drug On weeks with Elotuzumab dosing: Tablets, Oral, 28 mg Repeat every 28 days until participants met criteria for discontinuation of study drug Dexamethasone (IV): On weeks without Elotuzumab dosing: Not Applicable (N/A) On weeks with Elotuzumab dosing: Solution, Intravenous (IV), 8 mg, weekly Repeat every 28 days until participants met criteria for discontinuation of study drug Elotuzumab (BMS-901608; HuLuc63): Solution, IV, 10 mg/kg, weekly, on Days 1, 8, 15, 22 (cycles 1&2); Days 1 and 15 (cycles 3 and beyond) Repeat every 28 days until participants met criteria for discontinuation of study drug Lenalidomide: Capsules, Oral, 25 mg, once daily, on Days 1-21 Regimen repeated every 28 days until participants met criteria for discontinuation of study drug Dexamethasone: Tablets, Oral, 40 mg, weekly, on Days 1, 8, 15, 22 Regimen repeated every 28 days until participants met criteria for discontinuation of study drug
    Measure Participants 321 325
    Number (95% Confidence Interval) [Percentage of participants]
    78.5
    24.5%
    65.5
    20.2%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Lenalidomide + Dexamethasone + Elotuzumab, Lenalidomide + Dexamethasone
    Comments Ratio of Lenalidomide + Dexamethasone + Elotuzumab to Lenalidomide + Dexamethasone
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0002
    Comments
    Method Cochran-Mantel-Haenszel
    Comments Stratified by B2 microglobulin (<3.5 mg/L vs >=3.5 mg/L), number of prior lines of therapy (1 vs >=2), and immunomodulatory drug use at randomization
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.95
    Confidence Interval (2-Sided) 95%
    1.36 to 2.78
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Lenalidomide + Dexamethasone + Elotuzumab, Lenalidomide + Dexamethasone
    Comments Difference of Lenalidomide + Dexamethasone + Elotuzumab minus Lenalidomide + Dexamethasone computed using the method of DerSimonian and Laird (weighted average over the strata)
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in ORR
    Estimated Value 12.7
    Confidence Interval (2-Sided) 95%
    6.2 to 19.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Secondary Outcome
    Title Median Overall Survival (OS)
    Description Overall survival is defined as the time from randomization to the date of death from any cause. If a subject has not died, their survival time will be censored at the date of last contact ("last known alive date"). A subject will be censored at the date of randomization if they were randomized but had no follow-up. (Based on Kaplan Meier estimates)
    Time Frame Randomization to the date of death from any cause (up to approximately 9 years)

    Outcome Measure Data

    Analysis Population Description
    All randomized participants
    Arm/Group Title Lenalidomide + Dexamethasone + Elotuzumab Lenalidomide + Dexamethasone
    Arm/Group Description Lenalidomide: Capsules, Oral, 25 mg, once daily, on Days 1-21 Repeat every 28 days until participants met criteria for discontinuation of study drug Dexamethasone (Oral): On weeks without Elotuzumab dosing: Tablets, Oral, 40mg Repeat every 28 days until participants met criteria for discontinuation of study drug On weeks with Elotuzumab dosing: Tablets, Oral, 28 mg Repeat every 28 days until participants met criteria for discontinuation of study drug Dexamethasone (IV): On weeks without Elotuzumab dosing: Not Applicable (N/A) On weeks with Elotuzumab dosing: Solution, Intravenous (IV), 8 mg, weekly Repeat every 28 days until participants met criteria for discontinuation of study drug Elotuzumab (BMS-901608; HuLuc63): Solution, IV, 10 mg/kg, weekly, on Days 1, 8, 15, 22 (cycles 1&2); Days 1 and 15 (cycles 3 and beyond) Repeat every 28 days until participants met criteria for discontinuation of study drug Lenalidomide: Capsules, Oral, 25 mg, once daily, on Days 1-21 Regimen repeated every 28 days until participants met criteria for discontinuation of study drug Dexamethasone: Tablets, Oral, 40 mg, weekly, on Days 1, 8, 15, 22 Regimen repeated every 28 days until participants met criteria for discontinuation of study drug
    Measure Participants 321 325
    Median (95% Confidence Interval) [Months]
    48.30
    39.62
    5. Secondary Outcome
    Title Change From Baseline of Mean Score Pain Severity (BPI-SF)
    Description The change from baseline of the mean score of pain severity at the end of treatment using the Brief Pain Inventory-Short Form (BPI-SF). The BPI-SF is a self administered questionnaire developed to assess the severity of pain (the sensory dimension) as well as the degree to which pain interferes with function (the reactive dimension). The BPI-SF uses 0 ("No pain", "No interference") to 10 ("Pain as bad as you can imagine", "Highest imaginable interference") numeric rating scale.
    Time Frame From baseline up to approximately 38 months

    Outcome Measure Data

    Analysis Population Description
    All randomized participants with baseline and end of treatment scores
    Arm/Group Title Lenalidomide + Dexamethasone + Elotuzumab Lenalidomide + Dexamethasone
    Arm/Group Description Lenalidomide: Capsules, Oral, 25 mg, once daily, on Days 1-21 Repeat every 28 days until participants met criteria for discontinuation of study drug Dexamethasone (Oral): On weeks without Elotuzumab dosing: Tablets, Oral, 40mg Repeat every 28 days until participants met criteria for discontinuation of study drug On weeks with Elotuzumab dosing: Tablets, Oral, 28 mg Repeat every 28 days until participants met criteria for discontinuation of study drug Dexamethasone (IV): On weeks without Elotuzumab dosing: Not Applicable (N/A) On weeks with Elotuzumab dosing: Solution, Intravenous (IV), 8 mg, weekly Repeat every 28 days until participants met criteria for discontinuation of study drug Elotuzumab (BMS-901608; HuLuc63): Solution, IV, 10 mg/kg, weekly, on Days 1, 8, 15, 22 (cycles 1&2); Days 1 and 15 (cycles 3 and beyond) Repeat every 28 days until participants met criteria for discontinuation of study drug Lenalidomide: Capsules, Oral, 25 mg, once daily, on Days 1-21 Regimen repeated every 28 days until participants met criteria for discontinuation of study drug Dexamethasone: Tablets, Oral, 40 mg, weekly, on Days 1, 8, 15, 22 Regimen repeated every 28 days until participants met criteria for discontinuation of study drug
    Measure Participants 114 152
    Mean (Standard Deviation) [Score on a scale]
    0.52
    (2.237)
    -0.04
    (2.408)
    6. Secondary Outcome
    Title Change From Baseline of Mean Score Pain Interference (BPI-SF)
    Description The change from baseline of the mean score of pain interference at the end of treatment using the Brief Pain Inventory-Short Form (BPI-SF). The BPI-SF is a self administered questionnaire developed to assess the severity of pain (the sensory dimension) as well as the degree to which pain interferes with function (the reactive dimension). The BPI-SF uses 0 ("No pain", "No interference") to 10 ("Pain as bad as you can imagine", "Highest imaginable interference") numeric rating scale.
    Time Frame From baseline up to approximately 38 months

    Outcome Measure Data

    Analysis Population Description
    All randomized participants with baseline and end of treatment scores
    Arm/Group Title Lenalidomide + Dexamethasone + Elotuzumab Lenalidomide + Dexamethasone
    Arm/Group Description Lenalidomide: Capsules, Oral, 25 mg, once daily, on Days 1-21 Repeat every 28 days until participants met criteria for discontinuation of study drug Dexamethasone (Oral): On weeks without Elotuzumab dosing: Tablets, Oral, 40mg Repeat every 28 days until participants met criteria for discontinuation of study drug On weeks with Elotuzumab dosing: Tablets, Oral, 28 mg Repeat every 28 days until participants met criteria for discontinuation of study drug Dexamethasone (IV): On weeks without Elotuzumab dosing: Not Applicable (N/A) On weeks with Elotuzumab dosing: Solution, Intravenous (IV), 8 mg, weekly Repeat every 28 days until participants met criteria for discontinuation of study drug Elotuzumab (BMS-901608; HuLuc63): Solution, IV, 10 mg/kg, weekly, on Days 1, 8, 15, 22 (cycles 1&2); Days 1 and 15 (cycles 3 and beyond) Repeat every 28 days until participants met criteria for discontinuation of study drug Lenalidomide: Capsules, Oral, 25 mg, once daily, on Days 1-21 Regimen repeated every 28 days until participants met criteria for discontinuation of study drug Dexamethasone: Tablets, Oral, 40 mg, weekly, on Days 1, 8, 15, 22 Regimen repeated every 28 days until participants met criteria for discontinuation of study drug
    Measure Participants 113 150
    Mean (Standard Deviation) [Score on a scale]
    0.95
    (2.466)
    0.48
    (2.868)

    Adverse Events

    Time Frame From first dose up to 60 days post last dose of study therapy (Up to approximately 9 years)
    Adverse Event Reporting Description Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed/monitored for the treated population. All-Cause Mortality was assessed for the randomized population.
    Arm/Group Title Lenalidomide + Dexamethasone + Elotuzumab Lenalidomide + Dexamethasone
    Arm/Group Description Lenalidomide: Capsules, Oral, 25 mg, once daily, on Days 1-21 Repeat every 28 days until participants met criteria for discontinuation of study drug Dexamethasone (Oral): On weeks without Elotuzumab dosing: Tablets, Oral, 40mg Repeat every 28 days until participants met criteria for discontinuation of study drug On weeks with Elotuzumab dosing: Tablets, Oral, 28 mg Repeat every 28 days until participants met criteria for discontinuation of study drug Dexamethasone (IV): On weeks without Elotuzumab dosing: Not Applicable (N/A) On weeks with Elotuzumab dosing: Solution, Intravenous (IV), 8 mg, weekly Repeat every 28 days until participants met criteria for discontinuation of study drug Elotuzumab (BMS-901608; HuLuc63): Solution, IV, 10 mg/kg, weekly, on Days 1, 8, 15, 22 (cycles 1&2); Days 1 and 15 (cycles 3 and beyond) Repeat every 28 days until participants met criteria for discontinuation of study drug Lenalidomide: Capsules, Oral, 25 mg, once daily, on Days 1-21 Regimen repeated every 28 days until participants met criteria for discontinuation of study drug Dexamethasone: Tablets, Oral, 40 mg, weekly, on Days 1, 8, 15, 22 Regimen repeated every 28 days until participants met criteria for discontinuation of study drug
    All Cause Mortality
    Lenalidomide + Dexamethasone + Elotuzumab Lenalidomide + Dexamethasone
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 226/321 (70.4%) 249/325 (76.6%)
    Serious Adverse Events
    Lenalidomide + Dexamethasone + Elotuzumab Lenalidomide + Dexamethasone
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 238/318 (74.8%) 194/317 (61.2%)
    Blood and lymphatic system disorders
    Anaemia 11/318 (3.5%) 8/317 (2.5%)
    Bone marrow failure 1/318 (0.3%) 0/317 (0%)
    Eosinophilia 1/318 (0.3%) 0/317 (0%)
    Febrile neutropenia 5/318 (1.6%) 4/317 (1.3%)
    Microangiopathic haemolytic anaemia 1/318 (0.3%) 0/317 (0%)
    Neutropenia 1/318 (0.3%) 4/317 (1.3%)
    Pancytopenia 2/318 (0.6%) 0/317 (0%)
    Splenic infarction 0/318 (0%) 1/317 (0.3%)
    Thrombocytopenia 5/318 (1.6%) 2/317 (0.6%)
    Cardiac disorders
    Acute coronary syndrome 1/318 (0.3%) 2/317 (0.6%)
    Acute left ventricular failure 1/318 (0.3%) 0/317 (0%)
    Acute myocardial infarction 1/318 (0.3%) 2/317 (0.6%)
    Angina pectoris 1/318 (0.3%) 0/317 (0%)
    Angina unstable 1/318 (0.3%) 0/317 (0%)
    Arrhythmia 0/318 (0%) 1/317 (0.3%)
    Atrial fibrillation 6/318 (1.9%) 9/317 (2.8%)
    Atrioventricular block complete 2/318 (0.6%) 0/317 (0%)
    Brugada syndrome 1/318 (0.3%) 0/317 (0%)
    Cardiac aneurysm 0/318 (0%) 1/317 (0.3%)
    Cardiac arrest 3/318 (0.9%) 1/317 (0.3%)
    Cardiac failure 3/318 (0.9%) 3/317 (0.9%)
    Cardiac failure congestive 2/318 (0.6%) 1/317 (0.3%)
    Cardio-respiratory arrest 1/318 (0.3%) 0/317 (0%)
    Cardiogenic shock 2/318 (0.6%) 0/317 (0%)
    Left ventricular failure 0/318 (0%) 1/317 (0.3%)
    Myocardial infarction 0/318 (0%) 3/317 (0.9%)
    Myocardial ischaemia 0/318 (0%) 2/317 (0.6%)
    Pericarditis 1/318 (0.3%) 1/317 (0.3%)
    Sinus node dysfunction 0/318 (0%) 1/317 (0.3%)
    Supraventricular tachycardia 1/318 (0.3%) 0/317 (0%)
    Endocrine disorders
    Hypothyroidism 0/318 (0%) 1/317 (0.3%)
    Eye disorders
    Cataract 6/318 (1.9%) 6/317 (1.9%)
    Cataract nuclear 1/318 (0.3%) 0/317 (0%)
    Visual impairment 1/318 (0.3%) 0/317 (0%)
    Gastrointestinal disorders
    Abdominal pain 3/318 (0.9%) 0/317 (0%)
    Abdominal pain upper 2/318 (0.6%) 0/317 (0%)
    Colitis 1/318 (0.3%) 2/317 (0.6%)
    Constipation 1/318 (0.3%) 2/317 (0.6%)
    Diarrhoea 7/318 (2.2%) 12/317 (3.8%)
    Diverticulum 1/318 (0.3%) 0/317 (0%)
    Enteritis 2/318 (0.6%) 0/317 (0%)
    Enterocolitis 1/318 (0.3%) 0/317 (0%)
    Enterocutaneous fistula 0/318 (0%) 1/317 (0.3%)
    Gastric haemorrhage 1/318 (0.3%) 0/317 (0%)
    Gastric ulcer 0/318 (0%) 1/317 (0.3%)
    Gastrointestinal haemorrhage 2/318 (0.6%) 1/317 (0.3%)
    Haemorrhoids 0/318 (0%) 1/317 (0.3%)
    Hiatus hernia 0/318 (0%) 1/317 (0.3%)
    Ileus 0/318 (0%) 1/317 (0.3%)
    Ileus paralytic 0/318 (0%) 1/317 (0.3%)
    Inguinal hernia 1/318 (0.3%) 1/317 (0.3%)
    Inguinal hernia, obstructive 0/318 (0%) 1/317 (0.3%)
    Intestinal haemorrhage 0/318 (0%) 1/317 (0.3%)
    Intestinal ischaemia 1/318 (0.3%) 0/317 (0%)
    Intestinal obstruction 1/318 (0.3%) 0/317 (0%)
    Irritable bowel syndrome 0/318 (0%) 1/317 (0.3%)
    Large intestinal ulcer 0/318 (0%) 1/317 (0.3%)
    Large intestine perforation 1/318 (0.3%) 0/317 (0%)
    Lower gastrointestinal haemorrhage 0/318 (0%) 1/317 (0.3%)
    Mouth haemorrhage 1/318 (0.3%) 0/317 (0%)
    Nausea 1/318 (0.3%) 1/317 (0.3%)
    Pancreatitis 1/318 (0.3%) 1/317 (0.3%)
    Pancreatitis acute 2/318 (0.6%) 0/317 (0%)
    Rectal haemorrhage 1/318 (0.3%) 0/317 (0%)
    Subileus 0/318 (0%) 1/317 (0.3%)
    Upper gastrointestinal haemorrhage 0/318 (0%) 1/317 (0.3%)
    Vomiting 2/318 (0.6%) 4/317 (1.3%)
    General disorders
    Asthenia 4/318 (1.3%) 0/317 (0%)
    Chest pain 1/318 (0.3%) 0/317 (0%)
    Chills 0/318 (0%) 1/317 (0.3%)
    Death 1/318 (0.3%) 1/317 (0.3%)
    Disease progression 15/318 (4.7%) 10/317 (3.2%)
    Fatigue 1/318 (0.3%) 0/317 (0%)
    General physical health deterioration 5/318 (1.6%) 4/317 (1.3%)
    Hernia 0/318 (0%) 1/317 (0.3%)
    Malaise 1/318 (0.3%) 0/317 (0%)
    Multiple organ dysfunction syndrome 1/318 (0.3%) 0/317 (0%)
    Pain 1/318 (0.3%) 0/317 (0%)
    Pyrexia 25/318 (7.9%) 17/317 (5.4%)
    Hepatobiliary disorders
    Cholangitis 1/318 (0.3%) 0/317 (0%)
    Cholecystitis 1/318 (0.3%) 0/317 (0%)
    Cholecystitis acute 4/318 (1.3%) 0/317 (0%)
    Cholecystitis chronic 1/318 (0.3%) 0/317 (0%)
    Cholelithiasis 1/318 (0.3%) 0/317 (0%)
    Hepatic failure 1/318 (0.3%) 0/317 (0%)
    Hepatic function abnormal 0/318 (0%) 1/317 (0.3%)
    Hepatitis 1/318 (0.3%) 0/317 (0%)
    Hyperbilirubinaemia 2/318 (0.6%) 0/317 (0%)
    Immune system disorders
    Haemophagocytic lymphohistiocytosis 1/318 (0.3%) 1/317 (0.3%)
    Infections and infestations
    Abdominal abscess 0/318 (0%) 1/317 (0.3%)
    Abscess oral 0/318 (0%) 1/317 (0.3%)
    Acute sinusitis 0/318 (0%) 1/317 (0.3%)
    Appendicitis 0/318 (0%) 1/317 (0.3%)
    Arthritis bacterial 0/318 (0%) 2/317 (0.6%)
    Atypical pneumonia 3/318 (0.9%) 0/317 (0%)
    Bacteraemia 1/318 (0.3%) 1/317 (0.3%)
    Bacterial sepsis 1/318 (0.3%) 0/317 (0%)
    Biliary sepsis 1/318 (0.3%) 0/317 (0%)
    Brain abscess 1/318 (0.3%) 0/317 (0%)
    Bronchitis 8/318 (2.5%) 8/317 (2.5%)
    Bronchopulmonary aspergillosis 1/318 (0.3%) 0/317 (0%)
    Bursitis infective 0/318 (0%) 1/317 (0.3%)
    Campylobacter gastroenteritis 0/318 (0%) 1/317 (0.3%)
    Catheter site abscess 0/318 (0%) 1/317 (0.3%)
    Cellulitis 8/318 (2.5%) 1/317 (0.3%)
    Cerebral aspergillosis 1/318 (0.3%) 0/317 (0%)
    Clostridium colitis 1/318 (0.3%) 0/317 (0%)
    Clostridium difficile colitis 1/318 (0.3%) 0/317 (0%)
    Clostridium difficile infection 0/318 (0%) 1/317 (0.3%)
    Cytomegalovirus chorioretinitis 1/318 (0.3%) 0/317 (0%)
    Cytomegalovirus infection 1/318 (0.3%) 0/317 (0%)
    Device related infection 1/318 (0.3%) 0/317 (0%)
    Device related sepsis 0/318 (0%) 1/317 (0.3%)
    Diverticulitis 2/318 (0.6%) 0/317 (0%)
    Endocarditis 1/318 (0.3%) 2/317 (0.6%)
    Enteritis infectious 1/318 (0.3%) 0/317 (0%)
    Enterocolitis viral 1/318 (0.3%) 0/317 (0%)
    Epididymitis 1/318 (0.3%) 0/317 (0%)
    Escherichia urinary tract infection 1/318 (0.3%) 0/317 (0%)
    Febrile infection 1/318 (0.3%) 0/317 (0%)
    Gastroenteritis 1/318 (0.3%) 2/317 (0.6%)
    Gastroenteritis clostridial 1/318 (0.3%) 0/317 (0%)
    Gastroenteritis norovirus 0/318 (0%) 1/317 (0.3%)
    Gastroenteritis viral 1/318 (0.3%) 4/317 (1.3%)
    Genital abscess 0/318 (0%) 1/317 (0.3%)
    H1N1 influenza 1/318 (0.3%) 1/317 (0.3%)
    Hepatitis B 1/318 (0.3%) 0/317 (0%)
    Herpes zoster 4/318 (1.3%) 1/317 (0.3%)
    Herpes zoster reactivation 0/318 (0%) 1/317 (0.3%)
    Infection 3/318 (0.9%) 1/317 (0.3%)
    Infective exacerbation of chronic obstructive airways disease 0/318 (0%) 1/317 (0.3%)
    Influenza 3/318 (0.9%) 4/317 (1.3%)
    Intervertebral discitis 0/318 (0%) 1/317 (0.3%)
    Large intestine infection 1/318 (0.3%) 0/317 (0%)
    Listeriosis 0/318 (0%) 1/317 (0.3%)
    Localised infection 0/318 (0%) 1/317 (0.3%)
    Lower respiratory tract infection 8/318 (2.5%) 4/317 (1.3%)
    Lung abscess 0/318 (0%) 1/317 (0.3%)
    Meningitis staphylococcal 1/318 (0.3%) 0/317 (0%)
    Metapneumovirus infection 1/318 (0.3%) 0/317 (0%)
    Neutropenic sepsis 1/318 (0.3%) 1/317 (0.3%)
    Ophthalmic herpes zoster 0/318 (0%) 1/317 (0.3%)
    Osteomyelitis 1/318 (0.3%) 1/317 (0.3%)
    Otitis media chronic 0/318 (0%) 1/317 (0.3%)
    Parvovirus B19 infection 0/318 (0%) 1/317 (0.3%)
    Periodontitis 0/318 (0%) 1/317 (0.3%)
    Peritonitis 0/318 (0%) 1/317 (0.3%)
    Pharyngitis 1/318 (0.3%) 2/317 (0.6%)
    Pneumococcal sepsis 1/318 (0.3%) 0/317 (0%)
    Pneumocystis jirovecii pneumonia 2/318 (0.6%) 1/317 (0.3%)
    Pneumonia 56/318 (17.6%) 40/317 (12.6%)
    Pneumonia bacterial 1/318 (0.3%) 0/317 (0%)
    Pneumonia fungal 2/318 (0.6%) 0/317 (0%)
    Pneumonia influenzal 2/318 (0.6%) 2/317 (0.6%)
    Pneumonia pneumococcal 3/318 (0.9%) 1/317 (0.3%)
    Post procedural infection 0/318 (0%) 1/317 (0.3%)
    Pseudomonal sepsis 1/318 (0.3%) 0/317 (0%)
    Pseudomonas infection 1/318 (0.3%) 0/317 (0%)
    Pulmonary sepsis 1/318 (0.3%) 0/317 (0%)
    Pyelonephritis 1/318 (0.3%) 0/317 (0%)
    Pyelonephritis acute 0/318 (0%) 1/317 (0.3%)
    Respiratory syncytial virus infection 1/318 (0.3%) 1/317 (0.3%)
    Respiratory tract infection 11/318 (3.5%) 4/317 (1.3%)
    Retinitis 1/318 (0.3%) 0/317 (0%)
    Rotavirus infection 1/318 (0.3%) 0/317 (0%)
    Sepsis 5/318 (1.6%) 8/317 (2.5%)
    Septic shock 2/318 (0.6%) 5/317 (1.6%)
    Sinusitis 2/318 (0.6%) 1/317 (0.3%)
    Skin infection 0/318 (0%) 1/317 (0.3%)
    Staphylococcal bacteraemia 0/318 (0%) 1/317 (0.3%)
    Staphylococcal sepsis 1/318 (0.3%) 1/317 (0.3%)
    Streptococcal bacteraemia 0/318 (0%) 1/317 (0.3%)
    Systemic infection 1/318 (0.3%) 0/317 (0%)
    Tooth abscess 0/318 (0%) 1/317 (0.3%)
    Upper respiratory tract infection 2/318 (0.6%) 1/317 (0.3%)
    Urinary tract infection 3/318 (0.9%) 5/317 (1.6%)
    Urinary tract infection enterococcal 0/318 (0%) 1/317 (0.3%)
    Urosepsis 1/318 (0.3%) 0/317 (0%)
    Varicella zoster virus infection 2/318 (0.6%) 0/317 (0%)
    Viral diarrhoea 1/318 (0.3%) 0/317 (0%)
    Viral infection 1/318 (0.3%) 0/317 (0%)
    Wound infection 1/318 (0.3%) 0/317 (0%)
    Injury, poisoning and procedural complications
    Accidental overdose 1/318 (0.3%) 0/317 (0%)
    Ankle fracture 0/318 (0%) 1/317 (0.3%)
    Chemical burn 1/318 (0.3%) 0/317 (0%)
    Compression fracture 0/318 (0%) 1/317 (0.3%)
    Craniocerebral injury 0/318 (0%) 2/317 (0.6%)
    Fall 1/318 (0.3%) 1/317 (0.3%)
    Femoral neck fracture 1/318 (0.3%) 1/317 (0.3%)
    Femur fracture 1/318 (0.3%) 1/317 (0.3%)
    Hip fracture 2/318 (0.6%) 2/317 (0.6%)
    Humerus fracture 2/318 (0.6%) 0/317 (0%)
    Ilium fracture 1/318 (0.3%) 0/317 (0%)
    Joint dislocation 1/318 (0.3%) 0/317 (0%)
    Limb injury 1/318 (0.3%) 0/317 (0%)
    Lip injury 1/318 (0.3%) 0/317 (0%)
    Lumbar vertebral fracture 2/318 (0.6%) 1/317 (0.3%)
    Overdose 1/318 (0.3%) 1/317 (0.3%)
    Pelvic fracture 1/318 (0.3%) 2/317 (0.6%)
    Post procedural haemorrhage 0/318 (0%) 2/317 (0.6%)
    Procedural pain 0/318 (0%) 1/317 (0.3%)
    Rib fracture 2/318 (0.6%) 0/317 (0%)
    Road traffic accident 0/318 (0%) 1/317 (0.3%)
    Seroma 0/318 (0%) 1/317 (0.3%)
    Skin laceration 0/318 (0%) 1/317 (0.3%)
    Soft tissue injury 0/318 (0%) 1/317 (0.3%)
    Spinal compression fracture 3/318 (0.9%) 1/317 (0.3%)
    Spinal fracture 1/318 (0.3%) 0/317 (0%)
    Stenosis of vesicourethral anastomosis 0/318 (0%) 1/317 (0.3%)
    Subdural haematoma 0/318 (0%) 1/317 (0.3%)
    Tendon rupture 0/318 (0%) 1/317 (0.3%)
    Thoracic vertebral fracture 0/318 (0%) 1/317 (0.3%)
    Toxicity to various agents 0/318 (0%) 1/317 (0.3%)
    Traumatic fracture 0/318 (0%) 2/317 (0.6%)
    Upper limb fracture 1/318 (0.3%) 0/317 (0%)
    Investigations
    Blood creatinine increased 0/318 (0%) 1/317 (0.3%)
    Clostridium test positive 1/318 (0.3%) 0/317 (0%)
    Escherichia test positive 1/318 (0.3%) 0/317 (0%)
    General physical condition abnormal 1/318 (0.3%) 0/317 (0%)
    Haemoglobin decreased 0/318 (0%) 1/317 (0.3%)
    Hepatic enzyme increased 0/318 (0%) 1/317 (0.3%)
    Influenza A virus test positive 1/318 (0.3%) 1/317 (0.3%)
    Influenza B virus test positive 2/318 (0.6%) 1/317 (0.3%)
    International normalised ratio increased 1/318 (0.3%) 0/317 (0%)
    Liver function test abnormal 1/318 (0.3%) 0/317 (0%)
    Polymerase chain reaction positive 0/318 (0%) 1/317 (0.3%)
    Viral test positive 1/318 (0.3%) 0/317 (0%)
    Metabolism and nutrition disorders
    Decreased appetite 2/318 (0.6%) 1/317 (0.3%)
    Dehydration 2/318 (0.6%) 1/317 (0.3%)
    Diabetes mellitus 1/318 (0.3%) 0/317 (0%)
    Failure to thrive 1/318 (0.3%) 0/317 (0%)
    Fluid retention 1/318 (0.3%) 0/317 (0%)
    Hypercalcaemia 3/318 (0.9%) 2/317 (0.6%)
    Hyperglycaemia 3/318 (0.9%) 1/317 (0.3%)
    Hypocalcaemia 0/318 (0%) 1/317 (0.3%)
    Hypoglycaemia 0/318 (0%) 1/317 (0.3%)
    Hypokalaemia 3/318 (0.9%) 2/317 (0.6%)
    Hyponatraemia 0/318 (0%) 1/317 (0.3%)
    Ketoacidosis 1/318 (0.3%) 0/317 (0%)
    Tumour lysis syndrome 0/318 (0%) 1/317 (0.3%)
    Type 2 diabetes mellitus 1/318 (0.3%) 0/317 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 2/318 (0.6%) 2/317 (0.6%)
    Arthritis 1/318 (0.3%) 0/317 (0%)
    Back pain 7/318 (2.2%) 5/317 (1.6%)
    Bone cyst 1/318 (0.3%) 0/317 (0%)
    Bone lesion 1/318 (0.3%) 0/317 (0%)
    Bone pain 3/318 (0.9%) 0/317 (0%)
    Cervical spinal stenosis 0/318 (0%) 1/317 (0.3%)
    Exostosis 0/318 (0%) 1/317 (0.3%)
    Muscle mass 1/318 (0.3%) 0/317 (0%)
    Muscular weakness 2/318 (0.6%) 0/317 (0%)
    Musculoskeletal chest pain 1/318 (0.3%) 1/317 (0.3%)
    Musculoskeletal pain 1/318 (0.3%) 0/317 (0%)
    Osteoarthritis 1/318 (0.3%) 0/317 (0%)
    Osteonecrosis 1/318 (0.3%) 1/317 (0.3%)
    Osteonecrosis of jaw 0/318 (0%) 6/317 (1.9%)
    Pain in extremity 1/318 (0.3%) 0/317 (0%)
    Pathological fracture 0/318 (0%) 1/317 (0.3%)
    Rhabdomyolysis 0/318 (0%) 3/317 (0.9%)
    Spinal stenosis 1/318 (0.3%) 0/317 (0%)
    Tendonitis 1/318 (0.3%) 0/317 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute erythroid leukaemia 1/318 (0.3%) 0/317 (0%)
    Acute myeloid leukaemia 1/318 (0.3%) 0/317 (0%)
    Adenocarcinoma of colon 1/318 (0.3%) 1/317 (0.3%)
    Atypical fibroxanthoma 1/318 (0.3%) 0/317 (0%)
    Basal cell carcinoma 10/318 (3.1%) 4/317 (1.3%)
    Bladder transitional cell carcinoma 1/318 (0.3%) 0/317 (0%)
    Breast cancer stage I 1/318 (0.3%) 0/317 (0%)
    Cervix carcinoma 1/318 (0.3%) 0/317 (0%)
    Chronic lymphocytic leukaemia 1/318 (0.3%) 0/317 (0%)
    Colorectal adenocarcinoma 1/318 (0.3%) 0/317 (0%)
    Endometrial cancer 0/318 (0%) 1/317 (0.3%)
    External ear neoplasm malignant 0/318 (0%) 1/317 (0.3%)
    Gastrointestinal neoplasm 1/318 (0.3%) 0/317 (0%)
    Haemangioma 0/318 (0%) 1/317 (0.3%)
    Haemangioma of bone 0/318 (0%) 1/317 (0.3%)
    Lip squamous cell carcinoma 0/318 (0%) 1/317 (0.3%)
    Lung cancer metastatic 0/318 (0%) 1/317 (0.3%)
    Lung neoplasm malignant 4/318 (1.3%) 0/317 (0%)
    Malignant melanoma in situ 0/318 (0%) 1/317 (0.3%)
    Malignant neoplasm of unknown primary site 0/318 (0%) 1/317 (0.3%)
    Malignant neoplasm progression 5/318 (1.6%) 4/317 (1.3%)
    Malignant pleural effusion 1/318 (0.3%) 0/317 (0%)
    Meningioma 1/318 (0.3%) 0/317 (0%)
    Mesothelioma 1/318 (0.3%) 0/317 (0%)
    Myelodysplastic syndrome 2/318 (0.6%) 3/317 (0.9%)
    Neoplasm malignant 1/318 (0.3%) 0/317 (0%)
    Non-small cell lung cancer 1/318 (0.3%) 0/317 (0%)
    Plasma cell myeloma 6/318 (1.9%) 5/317 (1.6%)
    Plasma cell myeloma recurrent 0/318 (0%) 1/317 (0.3%)
    Plasmacytoma 2/318 (0.6%) 3/317 (0.9%)
    Prostate cancer 1/318 (0.3%) 2/317 (0.6%)
    Prostatic adenoma 1/318 (0.3%) 1/317 (0.3%)
    Rectal adenocarcinoma 0/318 (0%) 1/317 (0.3%)
    Sarcoma 1/318 (0.3%) 0/317 (0%)
    Squamous cell carcinoma 2/318 (0.6%) 3/317 (0.9%)
    Squamous cell carcinoma of skin 12/318 (3.8%) 3/317 (0.9%)
    Tonsil cancer 0/318 (0%) 1/317 (0.3%)
    Tumour associated fever 0/318 (0%) 1/317 (0.3%)
    Vulval cancer 1/318 (0.3%) 0/317 (0%)
    Nervous system disorders
    Cerebral haemorrhage 0/318 (0%) 1/317 (0.3%)
    Cerebral infarction 1/318 (0.3%) 0/317 (0%)
    Cerebral ischaemia 2/318 (0.6%) 1/317 (0.3%)
    Cerebrospinal fluid leakage 1/318 (0.3%) 0/317 (0%)
    Cerebrovascular accident 2/318 (0.6%) 3/317 (0.9%)
    Dementia 2/318 (0.6%) 0/317 (0%)
    Dizziness 2/318 (0.6%) 0/317 (0%)
    Encephalopathy 0/318 (0%) 2/317 (0.6%)
    Hemiparesis 0/318 (0%) 1/317 (0.3%)
    Hepatic encephalopathy 1/318 (0.3%) 0/317 (0%)
    Hypoaesthesia 1/318 (0.3%) 0/317 (0%)
    Ischaemic stroke 1/318 (0.3%) 0/317 (0%)
    Nervous system disorder 1/318 (0.3%) 0/317 (0%)
    Neuropathy peripheral 0/318 (0%) 1/317 (0.3%)
    Optic neuritis 1/318 (0.3%) 0/317 (0%)
    Paraesthesia 0/318 (0%) 1/317 (0.3%)
    Paraparesis 1/318 (0.3%) 1/317 (0.3%)
    Presyncope 1/318 (0.3%) 0/317 (0%)
    Sciatica 1/318 (0.3%) 0/317 (0%)
    Seizure 1/318 (0.3%) 0/317 (0%)
    Somnolence 1/318 (0.3%) 0/317 (0%)
    Spinal cord compression 1/318 (0.3%) 2/317 (0.6%)
    Spinal cord disorder 0/318 (0%) 1/317 (0.3%)
    Status epilepticus 0/318 (0%) 1/317 (0.3%)
    Syncope 3/318 (0.9%) 2/317 (0.6%)
    Transient ischaemic attack 2/318 (0.6%) 1/317 (0.3%)
    Product Issues
    Device dislocation 0/318 (0%) 1/317 (0.3%)
    Psychiatric disorders
    Completed suicide 1/318 (0.3%) 0/317 (0%)
    Confusional state 4/318 (1.3%) 1/317 (0.3%)
    Delirium 1/318 (0.3%) 0/317 (0%)
    Depression 1/318 (0.3%) 0/317 (0%)
    Mental status changes 1/318 (0.3%) 0/317 (0%)
    Renal and urinary disorders
    Acute kidney injury 11/318 (3.5%) 8/317 (2.5%)
    Haematuria 0/318 (0%) 1/317 (0.3%)
    Haemorrhage urinary tract 1/318 (0.3%) 0/317 (0%)
    Myeloma cast nephropathy 1/318 (0.3%) 0/317 (0%)
    Nephrolithiasis 0/318 (0%) 1/317 (0.3%)
    Neurogenic bladder 1/318 (0.3%) 0/317 (0%)
    Prerenal failure 1/318 (0.3%) 0/317 (0%)
    Renal failure 4/318 (1.3%) 5/317 (1.6%)
    Renal impairment 3/318 (0.9%) 0/317 (0%)
    Renal tubular acidosis 1/318 (0.3%) 0/317 (0%)
    Urinary retention 1/318 (0.3%) 3/317 (0.9%)
    Urinary tract obstruction 1/318 (0.3%) 1/317 (0.3%)
    Reproductive system and breast disorders
    Benign prostatic hyperplasia 0/318 (0%) 1/317 (0.3%)
    Ovarian cyst 0/318 (0%) 1/317 (0.3%)
    Respiratory, thoracic and mediastinal disorders
    Acute pulmonary oedema 0/318 (0%) 1/317 (0.3%)
    Acute respiratory distress syndrome 1/318 (0.3%) 1/317 (0.3%)
    Acute respiratory failure 1/318 (0.3%) 0/317 (0%)
    Asthma 1/318 (0.3%) 1/317 (0.3%)
    Bronchial disorder 0/318 (0%) 1/317 (0.3%)
    Bronchial hyperreactivity 2/318 (0.6%) 0/317 (0%)
    Chronic obstructive pulmonary disease 5/318 (1.6%) 3/317 (0.9%)
    Cough 1/318 (0.3%) 0/317 (0%)
    Dyspnoea 4/318 (1.3%) 4/317 (1.3%)
    Epistaxis 1/318 (0.3%) 0/317 (0%)
    Haemoptysis 0/318 (0%) 1/317 (0.3%)
    Hypoxia 1/318 (0.3%) 1/317 (0.3%)
    Interstitial lung disease 1/318 (0.3%) 3/317 (0.9%)
    Lung disorder 4/318 (1.3%) 1/317 (0.3%)
    Obliterative bronchiolitis 1/318 (0.3%) 0/317 (0%)
    Organising pneumonia 2/318 (0.6%) 0/317 (0%)
    Pleural effusion 2/318 (0.6%) 1/317 (0.3%)
    Pneumonitis 1/318 (0.3%) 2/317 (0.6%)
    Pulmonary alveolar haemorrhage 1/318 (0.3%) 0/317 (0%)
    Pulmonary artery thrombosis 1/318 (0.3%) 0/317 (0%)
    Pulmonary embolism 11/318 (3.5%) 8/317 (2.5%)
    Pulmonary fibrosis 1/318 (0.3%) 0/317 (0%)
    Respiratory failure 2/318 (0.6%) 1/317 (0.3%)
    Skin and subcutaneous tissue disorders
    Dermal cyst 1/318 (0.3%) 0/317 (0%)
    Pustular psoriasis 1/318 (0.3%) 0/317 (0%)
    Rash maculo-papular 1/318 (0.3%) 0/317 (0%)
    Skin haemorrhage 1/318 (0.3%) 0/317 (0%)
    Skin ulcer 0/318 (0%) 1/317 (0.3%)
    Surgical and medical procedures
    Hip arthroplasty 1/318 (0.3%) 0/317 (0%)
    Vascular disorders
    Aortic aneurysm rupture 1/318 (0.3%) 0/317 (0%)
    Deep vein thrombosis 10/318 (3.1%) 4/317 (1.3%)
    Embolism 0/318 (0%) 1/317 (0.3%)
    Hypotension 1/318 (0.3%) 1/317 (0.3%)
    Hypovolaemic shock 1/318 (0.3%) 0/317 (0%)
    Orthostatic hypotension 0/318 (0%) 1/317 (0.3%)
    Pelvic venous thrombosis 1/318 (0.3%) 0/317 (0%)
    Peripheral artery thrombosis 1/318 (0.3%) 0/317 (0%)
    Peripheral ischaemia 1/318 (0.3%) 0/317 (0%)
    Subclavian vein thrombosis 1/318 (0.3%) 0/317 (0%)
    Thrombophlebitis 0/318 (0%) 2/317 (0.6%)
    Thrombophlebitis superficial 0/318 (0%) 1/317 (0.3%)
    Thrombosis 0/318 (0%) 1/317 (0.3%)
    Venous thrombosis 0/318 (0%) 2/317 (0.6%)
    Venous thrombosis limb 1/318 (0.3%) 0/317 (0%)
    Other (Not Including Serious) Adverse Events
    Lenalidomide + Dexamethasone + Elotuzumab Lenalidomide + Dexamethasone
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 314/318 (98.7%) 309/317 (97.5%)
    Blood and lymphatic system disorders
    Anaemia 135/318 (42.5%) 118/317 (37.2%)
    Leukopenia 26/318 (8.2%) 26/317 (8.2%)
    Lymphopenia 41/318 (12.9%) 23/317 (7.3%)
    Neutropenia 114/318 (35.8%) 137/317 (43.2%)
    Thrombocytopenia 91/318 (28.6%) 72/317 (22.7%)
    Eye disorders
    Cataract 58/318 (18.2%) 36/317 (11.4%)
    Vision blurred 31/318 (9.7%) 18/317 (5.7%)
    Gastrointestinal disorders
    Abdominal pain 44/318 (13.8%) 31/317 (9.8%)
    Abdominal pain upper 30/318 (9.4%) 20/317 (6.3%)
    Constipation 115/318 (36.2%) 89/317 (28.1%)
    Diarrhoea 159/318 (50%) 122/317 (38.5%)
    Dry mouth 16/318 (5%) 10/317 (3.2%)
    Dyspepsia 36/318 (11.3%) 19/317 (6%)
    Nausea 82/318 (25.8%) 73/317 (23%)
    Stomatitis 30/318 (9.4%) 14/317 (4.4%)
    Toothache 18/318 (5.7%) 11/317 (3.5%)
    Vomiting 58/318 (18.2%) 32/317 (10.1%)
    General disorders
    Asthenia 80/318 (25.2%) 54/317 (17%)
    Chest pain 28/318 (8.8%) 14/317 (4.4%)
    Chills 31/318 (9.7%) 12/317 (3.8%)
    Fatigue 154/318 (48.4%) 131/317 (41.3%)
    Influenza like illness 27/318 (8.5%) 16/317 (5%)
    Malaise 19/318 (6%) 12/317 (3.8%)
    Oedema peripheral 97/318 (30.5%) 78/317 (24.6%)
    Pain 17/318 (5.3%) 7/317 (2.2%)
    Pyrexia 121/318 (38.1%) 74/317 (23.3%)
    Infections and infestations
    Bronchitis 66/318 (20.8%) 52/317 (16.4%)
    Gastroenteritis 18/318 (5.7%) 9/317 (2.8%)
    Herpes zoster 18/318 (5.7%) 5/317 (1.6%)
    Influenza 25/318 (7.9%) 17/317 (5.4%)
    Lower respiratory tract infection 32/318 (10.1%) 16/317 (5%)
    Nasopharyngitis 83/318 (26.1%) 60/317 (18.9%)
    Oral herpes 20/318 (6.3%) 13/317 (4.1%)
    Pharyngitis 17/318 (5.3%) 16/317 (5%)
    Pneumonia 30/318 (9.4%) 23/317 (7.3%)
    Respiratory tract infection 36/318 (11.3%) 32/317 (10.1%)
    Rhinitis 30/318 (9.4%) 13/317 (4.1%)
    Sinusitis 23/318 (7.2%) 15/317 (4.7%)
    Upper respiratory tract infection 86/318 (27%) 62/317 (19.6%)
    Urinary tract infection 36/318 (11.3%) 31/317 (9.8%)
    Viral infection 18/318 (5.7%) 10/317 (3.2%)
    Injury, poisoning and procedural complications
    Contusion 44/318 (13.8%) 28/317 (8.8%)
    Fall 21/318 (6.6%) 14/317 (4.4%)
    Investigations
    Alanine aminotransferase increased 25/318 (7.9%) 33/317 (10.4%)
    Aspartate aminotransferase increased 21/318 (6.6%) 31/317 (9.8%)
    Blood creatinine increased 36/318 (11.3%) 27/317 (8.5%)
    C-reactive protein increased 13/318 (4.1%) 16/317 (5%)
    Platelet count decreased 16/318 (5%) 5/317 (1.6%)
    Weight decreased 52/318 (16.4%) 20/317 (6.3%)
    Metabolism and nutrition disorders
    Decreased appetite 71/318 (22.3%) 42/317 (13.2%)
    Hyperglycaemia 61/318 (19.2%) 45/317 (14.2%)
    Hypoalbuminaemia 17/318 (5.3%) 11/317 (3.5%)
    Hypocalcaemia 48/318 (15.1%) 28/317 (8.8%)
    Hypokalaemia 67/318 (21.1%) 47/317 (14.8%)
    Hypomagnesaemia 22/318 (6.9%) 5/317 (1.6%)
    Hyponatraemia 18/318 (5.7%) 10/317 (3.2%)
    Hypophosphataemia 19/318 (6%) 10/317 (3.2%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 98/318 (30.8%) 63/317 (19.9%)
    Back pain 105/318 (33%) 97/317 (30.6%)
    Bone pain 33/318 (10.4%) 43/317 (13.6%)
    Muscle spasms 99/318 (31.1%) 85/317 (26.8%)
    Muscular weakness 42/318 (13.2%) 28/317 (8.8%)
    Musculoskeletal chest pain 39/318 (12.3%) 30/317 (9.5%)
    Myalgia 26/318 (8.2%) 22/317 (6.9%)
    Neck pain 23/318 (7.2%) 13/317 (4.1%)
    Pain in extremity 64/318 (20.1%) 35/317 (11%)
    Nervous system disorders
    Dizziness 48/318 (15.1%) 38/317 (12%)
    Headache 54/318 (17%) 29/317 (9.1%)
    Hypoaesthesia 28/318 (8.8%) 12/317 (3.8%)
    Neuropathy peripheral 51/318 (16%) 31/317 (9.8%)
    Paraesthesia 35/318 (11%) 29/317 (9.1%)
    Peripheral sensory neuropathy 33/318 (10.4%) 39/317 (12.3%)
    Taste disorder 18/318 (5.7%) 14/317 (4.4%)
    Tremor 30/318 (9.4%) 29/317 (9.1%)
    Psychiatric disorders
    Anxiety 26/318 (8.2%) 24/317 (7.6%)
    Confusional state 18/318 (5.7%) 10/317 (3.2%)
    Depression 18/318 (5.7%) 14/317 (4.4%)
    Insomnia 79/318 (24.8%) 83/317 (26.2%)
    Mood altered 23/318 (7.2%) 8/317 (2.5%)
    Renal and urinary disorders
    Dysuria 16/318 (5%) 9/317 (2.8%)
    Respiratory, thoracic and mediastinal disorders
    Cough 109/318 (34.3%) 62/317 (19.6%)
    Dysphonia 25/318 (7.9%) 32/317 (10.1%)
    Dyspnoea 72/318 (22.6%) 60/317 (18.9%)
    Dyspnoea exertional 20/318 (6.3%) 15/317 (4.7%)
    Epistaxis 22/318 (6.9%) 19/317 (6%)
    Oropharyngeal pain 32/318 (10.1%) 15/317 (4.7%)
    Productive cough 25/318 (7.9%) 5/317 (1.6%)
    Skin and subcutaneous tissue disorders
    Erythema 26/318 (8.2%) 16/317 (5%)
    Hyperhidrosis 38/318 (11.9%) 25/317 (7.9%)
    Night sweats 24/318 (7.5%) 10/317 (3.2%)
    Pruritus 36/318 (11.3%) 29/317 (9.1%)
    Rash 63/318 (19.8%) 58/317 (18.3%)
    Vascular disorders
    Deep vein thrombosis 19/318 (6%) 10/317 (3.2%)
    Flushing 16/318 (5%) 6/317 (1.9%)
    Haematoma 17/318 (5.3%) 8/317 (2.5%)
    Hypertension 40/318 (12.6%) 23/317 (7.3%)
    Hypotension 33/318 (10.4%) 12/317 (3.8%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.

    Results Point of Contact

    Name/Title Bristol-Myers Squibb Study Director
    Organization Bristol-Myers Squibb
    Phone
    Email Clinical.Trials@bms.com
    Responsible Party:
    Bristol-Myers Squibb
    ClinicalTrials.gov Identifier:
    NCT01239797
    Other Study ID Numbers:
    • CA204-004
    • 2010-020347-12
    First Posted:
    Nov 11, 2010
    Last Update Posted:
    Jun 1, 2022
    Last Verified:
    May 1, 2022