ELOQUENT - 2: Phase III Study of Lenalidomide and Dexamethasone With or Without Elotuzumab to Treat Relapsed or Refractory Multiple Myeloma
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
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:
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:
|
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:
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:
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:
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
- 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.
- 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
- 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)
- 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.
- 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
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:
-
Best response achieved was ≥Partial Response (PR)
-
Patient was not refractory
-
Patient did not discontinue due to a Grade ≥3 related adverse event
-
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.- CA204-004
- 2010-020347-12
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
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 |
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 |
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 |
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
|
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)
|
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
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 | |
Clinical.Trials@bms.com |
- CA204-004
- 2010-020347-12