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Study of Bortezomib and Dexamethasone With or Without Elotuzumab to Treat Relapsed or Refractory Multiple Myeloma

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ClinicalTrials.gov Identifier: NCT01478048
Recruitment Status : Completed
First Posted : November 23, 2011
Results First Posted : January 26, 2016
Last Update Posted : May 21, 2018
Sponsor:
Collaborator:
AbbVie
Information provided by (Responsible Party):
Bristol-Myers Squibb

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Multiple Myeloma
Interventions Biological: Elotuzumab
Drug: Bortezomib
Drug: Dexamethasone
Enrollment 185
Recruitment Details  
Pre-assignment Details 185 participants were enrolled, 152 participants were randomized. Reasons not randomized: 23 no longer met study criteria, 5 withdrew consent, 2 died, 3 had poor/non-compliance. 150 were treated with study drug. 2 participants were not treated: 1 withdrawal by subject and 1 physician decision.
Arm/Group Title Elotuzumab + Bortezomib + Dexamethasone Bortezomib + Dexamethasone
Hide Arm/Group Description Elotuzumab: Solution; Intravenous (IV); 10 mg/kg; (Cycles 1 & 2: Days 1, 8 & 15; Cycles 3-8: Days 1 & 11; Cycle 9+: Days 1 & 15); Until participant meets criteria for discontinuation of drug Bortezomib: Solution; IV; 1.3 mg/m^2; (Cycles 1 - 8: Days 1, 4, 8, 11; Cycles 9+: Days 1, 8, 15); Until criteria met for discontinuation of drug. Days of Elotuzumab infusion: Dexamethasone (8mg IV + 8mg Oral) administered. Other days Dexamethasone 20 mg Oral administered Dexamethasone: Tablets; 20 mg; (Cycles 1& 2: once daily on Days 2, 4, 5, 8, 9, 11; Cycles 3-8: once daily on Days 2, 4, 5, 9, 12; Cycles 9+: once daily on Days 2, 8, 9, 16); Until criteria met for discontinuation. Dexamethasone: Tablets; 8 mg; (Cycles 1& 2: Days 1, 8, 15; Cycles 3-8: Days 1 &11; Cycles 9+; Days 1 & 15); Until criteria met for discontinuation of drug. Dexamethasone: Solution; IV; 8 mg; (Cycles 1& 2: Days 1, 8, 15; Cycles 3-8: Days 1 &11; Cycles 9+; Days 1 & 15); Until criteria met for discontinuation Bortezomib: Solution; IV; 1.3 mg/m^2; (Cycles 1 - 8: Days 1, 4, 8, 11; Cycles 9+: Days 1, 8, 15); Until criteria met for discontinuation of study drug. Dexamethasone: Tablets; 20 mg; (Cycles 1-8 once daily on Days 1, 2, 4, 5, 8, 9, 11, 12; Cycles 9+ once daily on Days 1, 2, 8, 9, 15, 16); Until criteria is met for discontinuation of study drug
Period Title: Overall Study
Started 77 75
Received Treatment 76 [1] 74 [1]
Completed [2] 0 0
Not Completed 77 75
Reason Not Completed
Disease Progression             52             35
study drug toxicity             11             14
Adverse Event             2             11
subject request to discontinue treatment             3             5
Withdrawal by Subject             2             5
non-specified             6             4
poor/non-compliance             0             1
no longer meets study criteria             1             0
[1]
1 randomized to E-Bd but received Bd. Included in E-Bd group for efficacy and Bd group for safety
[2]
Completed = Still on treatment
Arm/Group Title Elotuzumab + Bortezomib + Dexamethasone Bortezomib + Dexamethasone Total
Hide Arm/Group Description Elotuzumab: Solution; Intravenous (IV); 10 mg/kg; (Cycles 1 & 2: Days 1, 8 & 15; Cycles 3-8: Days 1 & 11; Cycle 9+: Days 1 & 15); Until participant meets criteria for discontinuation of drug Bortezomib: Solution; IV; 1.3 mg/m^2; (Cycles 1 - 8: Days 1, 4, 8, 11; Cycles 9+: Days 1, 8, 15); Until criteria met for discontinuation of drug. Days of Elotuzumab infusion: Dexamethasone (8mg IV + 8mg Oral) administered. Other days Dexamethasone 20 mg Oral administered Dexamethasone: Tablets; 20 mg; (Cycles 1& 2: once daily on Days 2, 4, 5, 8, 9, 11; Cycles 3-8: once daily on Days 2, 4, 5, 9, 12; Cycles 9+: once daily on Days 2, 8, 9, 16); Until criteria met for discontinuation. Dexamethasone: Tablets; 8 mg; (Cycles 1& 2: Days 1, 8, 15; Cycles 3-8: Days 1 &11; Cycles 9+; Days 1 & 15); Until criteria met for discontinuation of drug. Dexamethasone: Solution; IV; 8 mg; (Cycles 1& 2: Days 1, 8, 15; Cycles 3-8: Days 1 &11; Cycles 9+; Days 1 & 15); Until criteria met for discontinuation Bortezomib: Solution; IV; 1.3 mg/m^2; (Cycles 1 - 8: Days 1, 4, 8, 11; Cycles 9+: Days 1, 8, 15); Until criteria met for discontinuation of study drug. Dexamethasone: Tablets; 20 mg; (Cycles 1-8 once daily on Days 1, 2, 4, 5, 8, 9, 11, 12; Cycles 9+ once daily on Days 1, 2, 8, 9, 15, 16); Until criteria is met for discontinuation of study drug Total of all reporting groups
Overall Number of Baseline Participants 77 75 152
Hide Baseline Analysis Population Description
All enrolled participants who were randomized to a treatment arm were summarized.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 77 participants 75 participants 152 participants
65.4  (9.48) 65.1  (10.34) 65.3  (9.88)
Age, Customized   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 77 participants 75 participants 152 participants
< 65 years
34
  44.2%
33
  44.0%
67
  44.1%
≥65 and <75 years
28
  36.4%
28
  37.3%
56
  36.8%
>= 75 years
15
  19.5%
14
  18.7%
29
  19.1%
[1]
Measure Description: Less than (<); Greater than, equal to (≥).
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 77 participants 75 participants 152 participants
Female
35
  45.5%
38
  50.7%
73
  48.0%
Male
42
  54.5%
37
  49.3%
79
  52.0%
Region of Enrollment   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 77 participants 75 participants 152 participants
United States
25
  32.5%
23
  30.7%
48
  31.6%
Italy
34
  44.2%
32
  42.7%
66
  43.4%
France
10
  13.0%
11
  14.7%
21
  13.8%
Spain
8
  10.4%
9
  12.0%
17
  11.2%
[1]
Measure Description: Number of participants enrolled, by country, were summarized.
Prior Protease Inhibitor Use   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 77 participants 75 participants 152 participants
Yes
38
  49.4%
37
  49.3%
75
  49.3%
No
39
  50.6%
38
  50.7%
77
  50.7%
[1]
Measure Description: Categories presented as they were at randomization based on information collected via the Interactive Voice Recognition System (IVRS) system.
Presence of At Least 1 FcγRIIIa V allele   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 77 participants 75 participants 152 participants
Yes
55
  71.4%
54
  72.0%
109
  71.7%
No
22
  28.6%
21
  28.0%
43
  28.3%
[1]
Measure Description: An allele is any one of a series of 2 or more different genes that may be on a specific chromosome. Categories presented as they were at randomization based on information collected via the Interactive Voice Recognition System (IVRS) system.
Number of Prior Lines of Therapy   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 77 participants 75 participants 152 participants
1 line of prior therapy
55
  71.4%
51
  68.0%
106
  69.7%
2 or 3 lines of prior therapy
22
  28.6%
24
  32.0%
46
  30.3%
[1]
Measure Description: Categories presented as they were at randomization based on information collected via the Interactive Voice Recognition System (IVRS) system.
1.Primary Outcome
Title Median Investigator-Assessed Progression-free Survival (PFS) Time (Months) From Randomization to Date of First Tumor Progression or Death Due to Any Cause - Randomized Participants
Hide Description PE was planned for after at least 103 events; it was analyzed after 111 events. Response was assessed: Day 1 (± 7 days) of each cycle per modified International Myeloma Working Group (IMWG) criteria; assessed using adequate tumor assessment (ATA) (ie, serum and urine M-protein tests performed within 14 days of each other; imaging if baseline measurable extramedullary plasmacytoma existed). Progression: Any of following: Increase of 25% from lowest response in 1 or more: serum and/or urine M-component; in those without measurable serum and urine M-protein levels, difference between involved and uninvolved free light chain (FLC) levels (absolute increase > 100 mg/L); Bone marrow plasma cell percentage (≥10%). Definite new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing lesions or plasmacytomas. Development of hypercalcemia attributed solely to the plasma cell proliferative disorder.
Time Frame Randomization until 111 events (disease progression or death), up to May 2014, approximately 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat (ITT), all randomized participants were analyzed.
Arm/Group Title Elotuzumab + Bortezomib + Dexamethasone Bortezomib + Dexamethasone
Hide Arm/Group Description:
Elotuzumab: Solution; Intravenous (IV); 10 mg/kg; (Cycles 1 & 2: Days 1, 8 & 15; Cycles 3-8: Days 1 & 11; Cycle 9+: Days 1 & 15); Until participant meets criteria for discontinuation of drug Bortezomib: Solution; IV; 1.3 mg/m^2; (Cycles 1 - 8: Days 1, 4, 8, 11; Cycles 9+: Days 1, 8, 15); Until criteria met for discontinuation of drug. Days of Elotuzumab infusion: Dexamethasone (8mg IV + 8mg Oral) administered. Other days Dexamethasone 20 mg Oral administered Dexamethasone: Tablets; 20 mg; (Cycles 1& 2: once daily on Days 2, 4, 5, 8, 9, 11; Cycles 3-8: once daily on Days 2, 4, 5, 9, 12; Cycles 9+: once daily on Days 2, 8, 9, 16); Until criteria met for discontinuation. Dexamethasone: Tablets; 8 mg; (Cycles 1& 2: Days 1, 8, 15; Cycles 3-8: Days 1 &11; Cycles 9+; Days 1 & 15); Until criteria met for discontinuation of drug. Dexamethasone: Solution; IV; 8 mg; (Cycles 1& 2: Days 1, 8, 15; Cycles 3-8: Days 1 &11; Cycles 9+; Days 1 & 15); Until criteria met for discontinuation
Bortezomib: Solution; IV; 1.3 mg/m^2; (Cycles 1 - 8: Days 1, 4, 8, 11; Cycles 9+: Days 1, 8, 15); Until criteria met for discontinuation of study drug. Dexamethasone: Tablets; 20 mg; (Cycles 1-8 once daily on Days 1, 2, 4, 5, 8, 9, 11, 12; Cycles 9+ once daily on Days 1, 2, 8, 9, 15, 16); Until criteria is met for discontinuation of study drug
Overall Number of Participants Analyzed 77 75
Median (95% Confidence Interval)
Unit of Measure: Months
9.7
(7.4 to 12.2)
6.9
(5.1 to 10.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Elotuzumab + Bortezomib + Dexamethasone, Bortezomib + Dexamethasone
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0923
Comments Log Rank test was stratified by prior proteasome inhibitor use (Yes versus No), presence of at least 1 FcγRIIIa V allele (Yes versus No) and number of prior lines of therapy (1 versus 2 or 3) at randomization
Method Log Rank
Comments Adjusted alpha level= 0.30
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.72
Confidence Interval (2-Sided) 95%
0.49 to 1.06
Estimation Comments [Not Specified]
2.Primary Outcome
Title Number of Investigator-Assessed Progression-free Survival Events From Randomization to Date of First Tumor Progression or Death Due to Any Cause - All Randomized Participants
Hide Description PE planned for after at least 103 events (progression/death); analyzed at 111 events. Those who neither progressed nor died were censored on the date of last adequate tumor assessment (ATA), which requires both serum and urine M-protein tests. If no post-baseline tumor assessments/no death, then censored on randomization day. Response assessed: Day 1 (± 7 days) each cycle; 30 and 60 days post treatment. Modified IMWG criteria used. Progression: Any of following: Increase of 25% in serum and/or urine M-component; if no measurable serum, urine M-protein levels, then difference between involved and uninvolved free light chain (FLC) levels (absolute increase > 100 mg/L) ; Bone marrow plasma cell percentage (≥10%). New bone lesions or soft tissue plasmacytomas or increase in size of existing lesions, plasmacytomas. Development of hypercalcemia attributed solely to plasma cell proliferative disorder. First dose occurs within 3 days of randomization.
Time Frame Randomization until 111 events, up to May 2014, approximately 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat (ITT), all randomized participants were analyzed.
Arm/Group Title Elotuzumab + Bortezomib + Dexamethasone Bortezomib + Dexamethasone
Hide Arm/Group Description:
Elotuzumab: Solution; Intravenous (IV); 10 mg/kg; (Cycles 1 & 2: Days 1, 8 & 15; Cycles 3-8: Days 1 & 11; Cycle 9+: Days 1 & 15); Until participant meets criteria for discontinuation of drug Bortezomib: Solution; IV; 1.3 mg/m^2; (Cycles 1 - 8: Days 1, 4, 8, 11; Cycles 9+: Days 1, 8, 15); Until criteria met for discontinuation of drug. Days of Elotuzumab infusion: Dexamethasone (8mg IV + 8mg Oral) administered. Other days Dexamethasone 20 mg Oral administered Dexamethasone: Tablets; 20 mg; (Cycles 1& 2: once daily on Days 2, 4, 5, 8, 9, 11; Cycles 3-8: once daily on Days 2, 4, 5, 9, 12; Cycles 9+: once daily on Days 2, 8, 9, 16); Until criteria met for discontinuation. Dexamethasone: Tablets; 8 mg; (Cycles 1& 2: Days 1, 8, 15; Cycles 3-8: Days 1 &11; Cycles 9+; Days 1 & 15); Until criteria met for discontinuation of drug. Dexamethasone: Solution; IV; 8 mg; (Cycles 1& 2: Days 1, 8, 15; Cycles 3-8: Days 1 &11; Cycles 9+; Days 1 & 15); Until criteria met for discontinuation
Bortezomib: Solution; IV; 1.3 mg/m^2; (Cycles 1 - 8: Days 1, 4, 8, 11; Cycles 9+: Days 1, 8, 15); Until criteria met for discontinuation of study drug. Dexamethasone: Tablets; 20 mg; (Cycles 1-8 once daily on Days 1, 2, 4, 5, 8, 9, 11, 12; Cycles 9+ once daily on Days 1, 2, 8, 9, 15, 16); Until criteria is met for discontinuation of study drug
Overall Number of Participants Analyzed 77 75
Measure Type: Number
Unit of Measure: Events (progression or death)
52 59
3.Primary Outcome
Title 1 Year Progression-Free Survival Rate - Randomized Participants
Hide Description PFS rate=Percentage probability of participants experiencing no progression or death up to 1 year, estimated using the Kaplan-Meier method. Response assessed by the investigator: Day 1 (± 7 days) of each cycle per modified IMWG criteria; assessed using ATA (ie, serum and urine M-protein tests performed within 14 days of each other; imaging done if baseline measurable extramedullary plasmacytoma existed). Progression: Any of the following: Increase of 25% from lowest response in 1 or more: serum and/or urine M-component; in those without measurable serum and urine M-protein levels, difference between involved and uninvolved FLC levels (absolute increase > 100 mg/L) ; Bone marrow plasma cell percentage (≥10%). Definite new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing lesions or plasmacytomas. Development of hypercalcemia attributed solely to the plasma cell proliferative disorder.
Time Frame Year 1 after last participant was randomized
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants were analyzed.
Arm/Group Title Elotuzumab + Bortezomib + Dexamethasone Bortezomib + Dexamethasone
Hide Arm/Group Description:
Elotuzumab: Solution; Intravenous (IV); 10 mg/kg; (Cycles 1 & 2: Days 1, 8 & 15; Cycles 3-8: Days 1 & 11; Cycle 9+: Days 1 & 15); Until participant meets criteria for discontinuation of drug Bortezomib: Solution; IV; 1.3 mg/m^2; (Cycles 1 - 8: Days 1, 4, 8, 11; Cycles 9+: Days 1, 8, 15); Until criteria met for discontinuation of drug. Days of Elotuzumab infusion: Dexamethasone (8mg IV + 8mg Oral) administered. Other days Dexamethasone 20 mg Oral administered Dexamethasone: Tablets; 20 mg; (Cycles 1& 2: once daily on Days 2, 4, 5, 8, 9, 11; Cycles 3-8: once daily on Days 2, 4, 5, 9, 12; Cycles 9+: once daily on Days 2, 8, 9, 16); Until criteria met for discontinuation. Dexamethasone: Tablets; 8 mg; (Cycles 1& 2: Days 1, 8, 15; Cycles 3-8: Days 1 &11; Cycles 9+; Days 1 & 15); Until criteria met for discontinuation of drug. Dexamethasone: Solution; IV; 8 mg; (Cycles 1& 2: Days 1, 8, 15; Cycles 3-8: Days 1 &11; Cycles 9+; Days 1 & 15); Until criteria met for discontinuation
Bortezomib: Solution; IV; 1.3 mg/m^2; (Cycles 1 - 8: Days 1, 4, 8, 11; Cycles 9+: Days 1, 8, 15); Until criteria met for discontinuation of study drug. Dexamethasone: Tablets; 20 mg; (Cycles 1-8 once daily on Days 1, 2, 4, 5, 8, 9, 11, 12; Cycles 9+ once daily on Days 1, 2, 8, 9, 15, 16); Until criteria is met for discontinuation of study drug
Overall Number of Participants Analyzed 77 75
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage probability
0.39
(0.28 to 0.50)
0.33
(0.22 to 0.44)
4.Secondary Outcome
Title Median Progression-free Survival Time (Months) From Randomization to Date of First Tumor Progression or Death Due to Any Cause, in Randomized Participants With at Least One FcγRIIIa V Allele
Hide Description PE was planned for after at least 103 events; it was analyzed after 111 events. Response was assessed: Day 1 (± 7 days) of each cycle per modified IMWG criteria; assessed using adequate tumor assessment (ATA) (ie, serum and urine M-protein tests performed within 14 days of each other; imaging if baseline measurable extramedullary plasmacytoma existed). Progression: Any of following: Increase of 25% from lowest response in 1 or more: serum and/or urine M-component; in those without measurable serum and urine M-protein levels, difference between involved and uninvolved FLC levels (absolute increase > 100 mg/L); Bone marrow plasma cell percentage (≥10%). Definite new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing lesions or plasmacytomas. Development of hypercalcemia attributed solely to the plasma cell proliferative disorder. Randomized participants with at least 1 FcγRIIIa V allele were a sub-set of all randomized participants.
Time Frame Randomization until 111 events, up to May 2014, approximately 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had at least one FcγRIIIa V allele were analyzed.
Arm/Group Title Elotuzumab + Bortezomib + Dexamethasone Bortezomib + Dexamethasone
Hide Arm/Group Description:
Elotuzumab: Solution; Intravenous (IV); 10 mg/kg; (Cycles 1 & 2: Days 1, 8 & 15; Cycles 3-8: Days 1 & 11; Cycle 9+: Days 1 & 15); Until participant meets criteria for discontinuation of drug Bortezomib: Solution; IV; 1.3 mg/m^2; (Cycles 1 - 8: Days 1, 4, 8, 11; Cycles 9+: Days 1, 8, 15); Until criteria met for discontinuation of drug. Days of Elotuzumab infusion: Dexamethasone (8mg IV + 8mg Oral) administered. Other days Dexamethasone 20 mg Oral administered Dexamethasone: Tablets; 20 mg; (Cycles 1& 2: once daily on Days 2, 4, 5, 8, 9, 11; Cycles 3-8: once daily on Days 2, 4, 5, 9, 12; Cycles 9+: once daily on Days 2, 8, 9, 16); Until criteria met for discontinuation. Dexamethasone: Tablets; 8 mg; (Cycles 1& 2: Days 1, 8, 15; Cycles 3-8: Days 1 &11; Cycles 9+; Days 1 & 15); Until criteria met for discontinuation of drug. Dexamethasone: Solution; IV; 8 mg; (Cycles 1& 2: Days 1, 8, 15; Cycles 3-8: Days 1 &11; Cycles 9+; Days 1 & 15); Until criteria met for discontinuation
Bortezomib: Solution; IV; 1.3 mg/m^2; (Cycles 1 - 8: Days 1, 4, 8, 11; Cycles 9+: Days 1, 8, 15); Until criteria met for discontinuation of study drug. Dexamethasone: Tablets; 20 mg; (Cycles 1-8 once daily on Days 1, 2, 4, 5, 8, 9, 11, 12; Cycles 9+ once daily on Days 1, 2, 8, 9, 15, 16); Until criteria is met for discontinuation of study drug
Overall Number of Participants Analyzed 55 54
Median (95% Confidence Interval)
Unit of Measure: Months
9.9
(6.1 to 13.9)
8.1
(5.0 to 11.1)
5.Secondary Outcome
Title Investigator-Assessed Objective Response Rate (ORR) - All Randomized Participants
Hide Description ORR was calculated for participants with a best overall response (BOR) of partial response (PR) or better, including stringent complete response (sCR), complete response (CR), and very good partial response (VGPR). BOR was determined by the investigator based on myeloma tumor assessments using IMWG criteria: CR=Negative immunofixation of serum and urine and disappearance of any soft tissue plasmacytomas, and < 5% plasma cells in bone marrow; sCR= CR + normal FLC ratio and absence of clonal cells in bone marrow; VGPR=Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein level + urine M-protein level < 100 mg per 24 hour; PR= ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥ 90% or to < 200 mg per 24 hour. ORR= number of participants responding divided by total number of participants randomized, measured as a percentage.
Time Frame Randomization until 111 events, up to May 2014, approximately 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants were analyzed.
Arm/Group Title Elotuzumab + Bortezomib + Dexamethasone Bortezomib + Dexamethasone
Hide Arm/Group Description:
Elotuzumab: Solution; Intravenous (IV); 10 mg/kg; (Cycles 1 & 2: Days 1, 8 & 15; Cycles 3-8: Days 1 & 11; Cycle 9+: Days 1 & 15); Until participant meets criteria for discontinuation of drug Bortezomib: Solution; IV; 1.3 mg/m^2; (Cycles 1 - 8: Days 1, 4, 8, 11; Cycles 9+: Days 1, 8, 15); Until criteria met for discontinuation of drug. Days of Elotuzumab infusion: Dexamethasone (8mg IV + 8mg Oral) administered. Other days Dexamethasone 20 mg Oral administered Dexamethasone: Tablets; 20 mg; (Cycles 1& 2: once daily on Days 2, 4, 5, 8, 9, 11; Cycles 3-8: once daily on Days 2, 4, 5, 9, 12; Cycles 9+: once daily on Days 2, 8, 9, 16); Until criteria met for discontinuation. Dexamethasone: Tablets; 8 mg; (Cycles 1& 2: Days 1, 8, 15; Cycles 3-8: Days 1 &11; Cycles 9+; Days 1 & 15); Until criteria met for discontinuation of drug. Dexamethasone: Solution; IV; 8 mg; (Cycles 1& 2: Days 1, 8, 15; Cycles 3-8: Days 1 &11; Cycles 9+; Days 1 & 15); Until criteria met for discontinuation
Bortezomib: Solution; IV; 1.3 mg/m^2; (Cycles 1 - 8: Days 1, 4, 8, 11; Cycles 9+: Days 1, 8, 15); Until criteria met for discontinuation of study drug. Dexamethasone: Tablets; 20 mg; (Cycles 1-8 once daily on Days 1, 2, 4, 5, 8, 9, 11, 12; Cycles 9+ once daily on Days 1, 2, 8, 9, 15, 16); Until criteria is met for discontinuation of study drug
Overall Number of Participants Analyzed 77 75
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
64.9
(53.2 to 75.5)
62.7
(50.7 to 73.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Elotuzumab + Bortezomib + Dexamethasone, Bortezomib + Dexamethasone
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference using Chan-Zhang method
Estimated Value 2.3
Confidence Interval (2-Sided) 95%
-13.2 to 17.8
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Investigator-Assessed Objective Response Rate in Randomized Participants With at Least One FcγRIIIa V Allele
Hide Description ORR was calculated for participants with a BOR of PR or better, sCR, CR, and VGPR. BOR was determined by the investigator based on myeloma tumor assessments using IMWG criteria: CR=Negative immunofixation of serum and urine and disappearance of any soft tissue plasmacytomas, and < 5% plasma cells in bone marrow; sCR= CR + normal FLC ratio and absence of clonal cells in bone marrow; VGPR=Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein level + urine M-protein level < 100 mg per 24 hour; PR= ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥ 90% or to < 200 mg per 24 hour. ORR= number of participants responding divided by total number of participants randomized, measured as a percentage. Randomized participants with at least 1 FcγRIIIa V allele were a sub-set of all randomized participants.
Time Frame Randomization until 111 events, up to May 2014, approximately 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had at least one FcγRIIIa V allele at randomization were analyzed.
Arm/Group Title Elotuzumab + Bortezomib + Dexamethasone Bortezomib + Dexamethasone
Hide Arm/Group Description:
Elotuzumab: Solution; Intravenous (IV); 10 mg/kg; (Cycles 1 & 2: Days 1, 8 & 15; Cycles 3-8: Days 1 & 11; Cycle 9+: Days 1 & 15); Until participant meets criteria for discontinuation of drug Bortezomib: Solution; IV; 1.3 mg/m^2; (Cycles 1 - 8: Days 1, 4, 8, 11; Cycles 9+: Days 1, 8, 15); Until criteria met for discontinuation of drug. Days of Elotuzumab infusion: Dexamethasone (8mg IV + 8mg Oral) administered. Other days Dexamethasone 20 mg Oral administered Dexamethasone: Tablets; 20 mg; (Cycles 1& 2: once daily on Days 2, 4, 5, 8, 9, 11; Cycles 3-8: once daily on Days 2, 4, 5, 9, 12; Cycles 9+: once daily on Days 2, 8, 9, 16); Until criteria met for discontinuation. Dexamethasone: Tablets; 8 mg; (Cycles 1& 2: Days 1, 8, 15; Cycles 3-8: Days 1 &11; Cycles 9+; Days 1 & 15); Until criteria met for discontinuation of drug. Dexamethasone: Solution; IV; 8 mg; (Cycles 1& 2: Days 1, 8, 15; Cycles 3-8: Days 1 &11; Cycles 9+; Days 1 & 15); Until criteria met for discontinuation
Bortezomib: Solution; IV; 1.3 mg/m^2; (Cycles 1 - 8: Days 1, 4, 8, 11; Cycles 9+: Days 1, 8, 15); Until criteria met for discontinuation of study drug. Dexamethasone: Tablets; 20 mg; (Cycles 1-8 once daily on Days 1, 2, 4, 5, 8, 9, 11, 12; Cycles 9+ once daily on Days 1, 2, 8, 9, 15, 16); Until criteria is met for discontinuation of study drug
Overall Number of Participants Analyzed 55 54
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
60.0
(45.9 to 73.0)
61.1
(46.9 to 74.1)
Time Frame From first dose to last dose plus 60 days (assessed up to April 2017, approximately 63 months)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Elotuzumab + Bortezomib + Dexamethasone Bortezomib + Dexamethasone
Hide Arm/Group Description Elotuzumab: Solution; Intravenous (IV); 10 mg/kg; (Cycles 1 & 2: Days 1, 8 & 15; Cycles 3-8: Days 1 & 11; Cycle 9+: Days 1 & 15); Until participant meets criteria for discontinuation of drug Bortezomib: Solution; IV; 1.3 mg/m^2; (Cycles 1 - 8: Days 1, 4, 8, 11; Cycles 9+: Days 1, 8, 15); Until criteria met for discontinuation of drug. Days of Elotuzumab infusion: Dexamethasone (8mg IV + 8mg Oral) administered. Other days Dexamethasone 20 mg Oral administered Dexamethasone: Tablets; 20 mg; (Cycles 1& 2: once daily on Days 2, 4, 5, 8, 9, 11; Cycles 3-8: once daily on Days 2, 4, 5, 9, 12; Cycles 9+: once daily on Days 2, 8, 9, 16); Until criteria met for discontinuation. Dexamethasone: Tablets; 8 mg; (Cycles 1& 2: Days 1, 8, 15; Cycles 3-8: Days 1 &11; Cycles 9+; Days 1 & 15); Until criteria met for discontinuation of drug. Dexamethasone: Solution; IV; 8 mg; (Cycles 1& 2: Days 1, 8, 15; Cycles 3-8: Days 1 &11; Cycles 9+; Days 1 & 15); Until criteria met for discontinuation Bortezomib: Solution; IV; 1.3 mg/m^2; (Cycles 1 - 8: Days 1, 4, 8, 11; Cycles 9+: Days 1, 8, 15); Until criteria met for discontinuation of study drug. Dexamethasone: Tablets; 20 mg; (Cycles 1-8 once daily on Days 1, 2, 4, 5, 8, 9, 11, 12; Cycles 9+ once daily on Days 1, 2, 8, 9, 15, 16); Until criteria is met for discontinuation of study drug
All-Cause Mortality
Elotuzumab + Bortezomib + Dexamethasone Bortezomib + Dexamethasone
Affected / at Risk (%) Affected / at Risk (%)
Total   37/75 (49.33%)   39/75 (52.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Elotuzumab + Bortezomib + Dexamethasone Bortezomib + Dexamethasone
Affected / at Risk (%) Affected / at Risk (%)
Total   39/75 (52.00%)   31/75 (41.33%) 
Blood and lymphatic system disorders     
Thrombocytopenia  1  1/75 (1.33%)  0/75 (0.00%) 
Cardiac disorders     
Angina pectoris  1  0/75 (0.00%)  1/75 (1.33%) 
Atrial fibrillation  1  1/75 (1.33%)  0/75 (0.00%) 
Atrial flutter  1  0/75 (0.00%)  1/75 (1.33%) 
Cardio-respiratory arrest  1  0/75 (0.00%)  2/75 (2.67%) 
Coronary artery disease  1  1/75 (1.33%)  0/75 (0.00%) 
Myocardial infarction  1  0/75 (0.00%)  1/75 (1.33%) 
Sinus tachycardia  1  0/75 (0.00%)  1/75 (1.33%) 
Tachycardia  1  0/75 (0.00%)  1/75 (1.33%) 
Eye disorders     
Cataract  1  2/75 (2.67%)  0/75 (0.00%) 
Diplopia  1  1/75 (1.33%)  0/75 (0.00%) 
Gastrointestinal disorders     
Abdominal pain  1  2/75 (2.67%)  1/75 (1.33%) 
Colitis  1  2/75 (2.67%)  0/75 (0.00%) 
Constipation  1  1/75 (1.33%)  1/75 (1.33%) 
Diarrhoea  1  4/75 (5.33%)  1/75 (1.33%) 
Gastritis  1  0/75 (0.00%)  1/75 (1.33%) 
Gastrointestinal haemorrhage  1  0/75 (0.00%)  1/75 (1.33%) 
Ileus  1  1/75 (1.33%)  0/75 (0.00%) 
Ileus paralytic  1  0/75 (0.00%)  1/75 (1.33%) 
Impaired gastric emptying  1  0/75 (0.00%)  1/75 (1.33%) 
Nausea  1  2/75 (2.67%)  1/75 (1.33%) 
Oesophagitis  1  0/75 (0.00%)  1/75 (1.33%) 
Pancreatitis  1  1/75 (1.33%)  0/75 (0.00%) 
Small intestinal obstruction  1  0/75 (0.00%)  2/75 (2.67%) 
Vomiting  1  1/75 (1.33%)  2/75 (2.67%) 
General disorders     
Asthenia  1  0/75 (0.00%)  1/75 (1.33%) 
Gait disturbance  1  0/75 (0.00%)  1/75 (1.33%) 
General physical health deterioration  1  1/75 (1.33%)  0/75 (0.00%) 
Non-cardiac chest pain  1  0/75 (0.00%)  1/75 (1.33%) 
Oedema peripheral  1  2/75 (2.67%)  0/75 (0.00%) 
Pyrexia  1  1/75 (1.33%)  3/75 (4.00%) 
Hepatobiliary disorders     
Hepatitis  1  1/75 (1.33%)  0/75 (0.00%) 
Infections and infestations     
Aspergillus infection  1  1/75 (1.33%)  0/75 (0.00%) 
Bacteraemia  1  1/75 (1.33%)  0/75 (0.00%) 
Bacterial pyelonephritis  1  0/75 (0.00%)  1/75 (1.33%) 
Bronchitis  1  1/75 (1.33%)  0/75 (0.00%) 
Cellulitis  1  2/75 (2.67%)  0/75 (0.00%) 
Cytomegalovirus colitis  1  1/75 (1.33%)  0/75 (0.00%) 
Cytomegalovirus infection  1  1/75 (1.33%)  0/75 (0.00%) 
Diverticulitis  1  0/75 (0.00%)  1/75 (1.33%) 
Hepatitis b  1  1/75 (1.33%)  0/75 (0.00%) 
Pneumonia  1  7/75 (9.33%)  5/75 (6.67%) 
Pneumonia bacterial  1  0/75 (0.00%)  1/75 (1.33%) 
Pneumonia fungal  1  1/75 (1.33%)  1/75 (1.33%) 
Pneumonia pneumococcal  1  1/75 (1.33%)  0/75 (0.00%) 
Respiratory tract infection  1  0/75 (0.00%)  1/75 (1.33%) 
Sepsis  1  1/75 (1.33%)  2/75 (2.67%) 
Septic shock  1  1/75 (1.33%)  1/75 (1.33%) 
Urinary tract infection  1  1/75 (1.33%)  0/75 (0.00%) 
Injury, poisoning and procedural complications     
Femur fracture  1  0/75 (0.00%)  1/75 (1.33%) 
Humerus fracture  1  1/75 (1.33%)  0/75 (0.00%) 
Limb injury  1  0/75 (0.00%)  1/75 (1.33%) 
Rib fracture  1  0/75 (0.00%)  1/75 (1.33%) 
Sternal fracture  1  0/75 (0.00%)  1/75 (1.33%) 
Subdural haematoma  1  1/75 (1.33%)  1/75 (1.33%) 
Wrist fracture  1  0/75 (0.00%)  1/75 (1.33%) 
Investigations     
Blood creatinine increased  1  1/75 (1.33%)  0/75 (0.00%) 
Platelet count decreased  1  1/75 (1.33%)  1/75 (1.33%) 
Metabolism and nutrition disorders     
Diabetes mellitus inadequate control  1  1/75 (1.33%)  0/75 (0.00%) 
Hyperglycaemia  1  2/75 (2.67%)  0/75 (0.00%) 
Hypernatraemia  1  1/75 (1.33%)  0/75 (0.00%) 
Hyperuricaemia  1  0/75 (0.00%)  1/75 (1.33%) 
Hypokalaemia  1  1/75 (1.33%)  0/75 (0.00%) 
Hyponatraemia  1  1/75 (1.33%)  0/75 (0.00%) 
Lactic acidosis  1  1/75 (1.33%)  0/75 (0.00%) 
Musculoskeletal and connective tissue disorders     
Arthritis  1  1/75 (1.33%)  1/75 (1.33%) 
Back pain  1  1/75 (1.33%)  0/75 (0.00%) 
Musculoskeletal chest pain  1  0/75 (0.00%)  1/75 (1.33%) 
Osteoarthritis  1  0/75 (0.00%)  1/75 (1.33%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Basal cell carcinoma  1  2/75 (2.67%)  0/75 (0.00%) 
Malignant neoplasm progression  1  2/75 (2.67%)  1/75 (1.33%) 
Plasma cell myeloma  1  1/75 (1.33%)  1/75 (1.33%) 
Plasmacytoma  1  0/75 (0.00%)  1/75 (1.33%) 
Squamous cell carcinoma  1  0/75 (0.00%)  1/75 (1.33%) 
Nervous system disorders     
Dizziness  1  0/75 (0.00%)  1/75 (1.33%) 
Syncope  1  3/75 (4.00%)  1/75 (1.33%) 
Renal and urinary disorders     
Acute kidney injury  1  0/75 (0.00%)  2/75 (2.67%) 
Renal failure  1  2/75 (2.67%)  1/75 (1.33%) 
Reproductive system and breast disorders     
Genital prolapse  1  1/75 (1.33%)  0/75 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Acute pulmonary oedema  1  0/75 (0.00%)  1/75 (1.33%) 
Dyspnoea  1  1/75 (1.33%)  0/75 (0.00%) 
Haemothorax  1  0/75 (0.00%)  1/75 (1.33%) 
Interstitial lung disease  1  1/75 (1.33%)  0/75 (0.00%) 
Organising pneumonia  1  1/75 (1.33%)  0/75 (0.00%) 
Pleural effusion  1  1/75 (1.33%)  0/75 (0.00%) 
Pneumonitis  1  0/75 (0.00%)  1/75 (1.33%) 
Pulmonary hypertension  1  0/75 (0.00%)  1/75 (1.33%) 
Respiratory failure  1  1/75 (1.33%)  0/75 (0.00%) 
Vascular disorders     
Orthostatic hypotension  1  0/75 (0.00%)  1/75 (1.33%) 
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Elotuzumab + Bortezomib + Dexamethasone Bortezomib + Dexamethasone
Affected / at Risk (%) Affected / at Risk (%)
Total   72/75 (96.00%)   71/75 (94.67%) 
Blood and lymphatic system disorders     
Anaemia  1  25/75 (33.33%)  20/75 (26.67%) 
Lymphopenia  1  5/75 (6.67%)  3/75 (4.00%) 
Neutropenia  1  4/75 (5.33%)  7/75 (9.33%) 
Thrombocytopenia  1  13/75 (17.33%)  22/75 (29.33%) 
Cardiac disorders     
Tachycardia  1  3/75 (4.00%)  4/75 (5.33%) 
Eye disorders     
Cataract  1  3/75 (4.00%)  4/75 (5.33%) 
Vision blurred  1  4/75 (5.33%)  5/75 (6.67%) 
Gastrointestinal disorders     
Abdominal distension  1  9/75 (12.00%)  2/75 (2.67%) 
Abdominal pain  1  8/75 (10.67%)  8/75 (10.67%) 
Abdominal pain upper  1  2/75 (2.67%)  6/75 (8.00%) 
Constipation  1  28/75 (37.33%)  21/75 (28.00%) 
Diarrhoea  1  31/75 (41.33%)  24/75 (32.00%) 
Dyspepsia  1  7/75 (9.33%)  5/75 (6.67%) 
Gastrooesophageal reflux disease  1  1/75 (1.33%)  5/75 (6.67%) 
Nausea  1  19/75 (25.33%)  16/75 (21.33%) 
Vomiting  1  14/75 (18.67%)  7/75 (9.33%) 
General disorders     
Asthenia  1  20/75 (26.67%)  21/75 (28.00%) 
Chest pain  1  6/75 (8.00%)  2/75 (2.67%) 
Chills  1  4/75 (5.33%)  2/75 (2.67%) 
Face oedema  1  4/75 (5.33%)  4/75 (5.33%) 
Fatigue  1  22/75 (29.33%)  17/75 (22.67%) 
Influenza like illness  1  7/75 (9.33%)  4/75 (5.33%) 
Injection site erythema  1  3/75 (4.00%)  4/75 (5.33%) 
Oedema  1  5/75 (6.67%)  3/75 (4.00%) 
Oedema peripheral  1  21/75 (28.00%)  18/75 (24.00%) 
Pyrexia  1  25/75 (33.33%)  15/75 (20.00%) 
Infections and infestations     
Bronchitis  1  8/75 (10.67%)  7/75 (9.33%) 
Conjunctivitis  1  9/75 (12.00%)  4/75 (5.33%) 
Herpes zoster  1  6/75 (8.00%)  3/75 (4.00%) 
Influenza  1  3/75 (4.00%)  7/75 (9.33%) 
Pneumonia  1  1/75 (1.33%)  6/75 (8.00%) 
Upper respiratory tract infection  1  10/75 (13.33%)  4/75 (5.33%) 
Urinary tract infection  1  3/75 (4.00%)  5/75 (6.67%) 
Viral upper respiratory tract infection  1  6/75 (8.00%)  4/75 (5.33%) 
Injury, poisoning and procedural complications     
Rib fracture  1  5/75 (6.67%)  2/75 (2.67%) 
Investigations     
Blood creatinine increased  1  5/75 (6.67%)  4/75 (5.33%) 
Platelet count decreased  1  6/75 (8.00%)  8/75 (10.67%) 
Weight decreased  1  7/75 (9.33%)  3/75 (4.00%) 
Weight increased  1  4/75 (5.33%)  4/75 (5.33%) 
Metabolism and nutrition disorders     
Decreased appetite  1  12/75 (16.00%)  9/75 (12.00%) 
Hypercalcaemia  1  1/75 (1.33%)  4/75 (5.33%) 
Hyperglycaemia  1  10/75 (13.33%)  7/75 (9.33%) 
Hypocalcaemia  1  13/75 (17.33%)  3/75 (4.00%) 
Hypokalaemia  1  8/75 (10.67%)  5/75 (6.67%) 
Hyponatraemia  1  5/75 (6.67%)  2/75 (2.67%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  7/75 (9.33%)  12/75 (16.00%) 
Back pain  1  14/75 (18.67%)  15/75 (20.00%) 
Bone pain  1  12/75 (16.00%)  7/75 (9.33%) 
Muscle spasms  1  5/75 (6.67%)  5/75 (6.67%) 
Muscular weakness  1  6/75 (8.00%)  2/75 (2.67%) 
Musculoskeletal chest pain  1  7/75 (9.33%)  7/75 (9.33%) 
Pain in extremity  1  16/75 (21.33%)  12/75 (16.00%) 
Nervous system disorders     
Dizziness  1  9/75 (12.00%)  7/75 (9.33%) 
Dysgeusia  1  2/75 (2.67%)  4/75 (5.33%) 
Headache  1  8/75 (10.67%)  6/75 (8.00%) 
Neuralgia  1  5/75 (6.67%)  4/75 (5.33%) 
Neuropathy peripheral  1  28/75 (37.33%)  28/75 (37.33%) 
Paraesthesia  1  19/75 (25.33%)  13/75 (17.33%) 
Peripheral sensory neuropathy  1  8/75 (10.67%)  9/75 (12.00%) 
Somnolence  1  0/75 (0.00%)  6/75 (8.00%) 
Tremor  1  3/75 (4.00%)  5/75 (6.67%) 
Psychiatric disorders     
Anxiety  1  7/75 (9.33%)  2/75 (2.67%) 
Confusional state  1  4/75 (5.33%)  2/75 (2.67%) 
Depression  1  4/75 (5.33%)  1/75 (1.33%) 
Insomnia  1  20/75 (26.67%)  15/75 (20.00%) 
Renal and urinary disorders     
Pollakiuria  1  4/75 (5.33%)  1/75 (1.33%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  31/75 (41.33%)  18/75 (24.00%) 
Dysphonia  1  4/75 (5.33%)  1/75 (1.33%) 
Dyspnoea  1  12/75 (16.00%)  7/75 (9.33%) 
Epistaxis  1  9/75 (12.00%)  2/75 (2.67%) 
Oropharyngeal pain  1  5/75 (6.67%)  7/75 (9.33%) 
Productive cough  1  5/75 (6.67%)  5/75 (6.67%) 
Skin and subcutaneous tissue disorders     
Dry skin  1  2/75 (2.67%)  5/75 (6.67%) 
Hyperhidrosis  1  4/75 (5.33%)  2/75 (2.67%) 
Pruritus  1  4/75 (5.33%)  6/75 (8.00%) 
Rash  1  8/75 (10.67%)  5/75 (6.67%) 
Vascular disorders     
Hypertension  1  12/75 (16.00%)  3/75 (4.00%) 
Hypotension  1  7/75 (9.33%)  6/75 (8.00%) 
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01478048     History of Changes
Other Study ID Numbers: CA204-009
2011-002695-16 ( EudraCT Number )
First Submitted: November 2, 2011
First Posted: November 23, 2011
Results First Submitted: December 17, 2015
Results First Posted: January 26, 2016
Last Update Posted: May 21, 2018