Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Safety Study of Elotuzumab in Combination With Thalidomide and Dexamethasone in Relapsed and/or Refractory Multiple Myeloma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01632150
Recruitment Status : Completed
First Posted : July 2, 2012
Results First Posted : February 26, 2016
Last Update Posted : April 14, 2017
Sponsor:
Collaborator:
AbbVie
Information provided by (Responsible Party):
Bristol-Myers Squibb

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Relapsed and/or Refractory Multiple Myeloma
Interventions Biological: Elotuzumab
Biological: Thalidomide
Biological: Dexamethasone
Biological: Cyclophosphamide
Enrollment 51
Recruitment Details  
Pre-assignment Details Of 51 participants enrolled, 40 received treatment. Of those 40, 11 had cyclophosphamide added to their regimens.
Arm/Group Title Thalidomide + Elotuzumab + Dexamethasone + Cyclophosphamide
Hide Arm/Group Description Participants received thalidomide in 28-day cycles: 50 mg, for the first 2 weeks, escalated to 100 mg for the next 2 weeks and beginning with Cycle 2, to 200 mg once daily. Elotuzumab, 10 mg/kg, was administered as an intravenous infusion weekly for the first 2 cycles and beginning with Cycle 3, every 2 weeks. Dexamethasone, 40 mg, was administered weekly on those weeks when elotuzumab was not administered. On weeks when elotuzumab was also given, participants received dexamethasone as a split dose of 28 mg, 3 to 24 hours before the elotuzumab infusion, and 8 mg intravenously at least 45 minutes before the infusion. Those patients with suboptimal response, defined as evidence of progressive disease between end of Cycle 2 and end of Cycle 4 or inability to achieve partial response or better by end of Cycle 4, also received cyclophosphamide, 50 mg. Cyclophosphamide could not be added beyond Cycle 5.
Period Title: Overall Study
Started 40
Received Cyclophosphamide 11
Completed 0 [1]
Not Completed 40
Reason Not Completed
Disease progression             27
Study drug toxicity             1
Unrelated adverse event             7
Withdrawal by Subject             2
Patient underwent autologous transplant             1
Moved to compassionate program             2
[1]
Completed=still receiving treatment
Arm/Group Title Thalidomide + Elotuzumab + Dexamethasone + Cyclophosphamide
Hide Arm/Group Description Participants received thalidomide in 28-day cycles: 50 mg, for the first 2 weeks, escalated to 100 mg for the next 2 weeks and beginning with Cycle 2, to 200 mg once daily. Elotuzumab, 10 mg/kg, was administered as an intravenous infusion weekly for the first 2 cycles and beginning with Cycle 3, every 2 weeks. Dexamethasone, 40 mg, was administered weekly on those weeks when elotuzumab was not administered. On weeks when elotuzumab was also given, participants received dexamethasone as a split dose of 28 mg, 3 to 24 hours before the elotuzumab infusion, and 8 mg intravenously at least 45 minutes before the infusion. Those patients with suboptimal response, defined as evidence of progressive disease between end of Cycle 2 and end of Cycle 4 or inability to achieve partial response or better by end of Cycle 4, also received cyclophosphamide, 50 mg. Cyclophosphamide could not be added beyond Cycle 5.
Overall Number of Baseline Participants 40
Hide Baseline Analysis Population Description
All participants who received thalidomide +elotuzumab + dexamethose (40) and had cyclophosphamide added to the regimen (11).
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 40 participants
64.3  (8.47)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 40 participants
Younger than 65 years 22
65 years and older to younger than 75 years 12
75 years and older 6
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 40 participants
Female
15
  37.5%
Male
25
  62.5%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 40 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
0
   0.0%
White
40
 100.0%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Myeloma type  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 40 participants
Immunoglobulin (Ig)G 15
IGA 7
IGM 0
IGD 0
Light chain disease 9
Not reported 9
Eastern Cooperative Oncology Group (ECOG) performance status   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 40 participants
Score 0 17
Score 1 21
Score 2 2
[1]
Measure Description: ECOG is a 6-item scale used to assess disease progression, daily functioning, appropriate treatment, and prognosis. Performance status is scored on a scale ranging from 0-5, with (best score) 0=fully active and able to carry on all predisease performance without restriction and (worst score) 5=death.
1.Primary Outcome
Title Percentage of Participants Who Received Treatment Including Cyclophosphamide and Had Grade 3 or Higher Nonhematologic Adverse Events (AEs)
Hide Description AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or unknown relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death.
Time Frame From the first dose of study drug until the last dose of treatment, including cyclophosphamide treatment
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received thalidomide, elotuzumab, and dexamethasone (40) including those who had cyclophosphamide added to the regimen (11).
Arm/Group Title Thalidomide + Elotuzumab + Dexamethasone + Cyclophosphamide
Hide Arm/Group Description:
Participants received thalidomide in 28-day cycles: 50 mg, for the first 2 weeks, escalated to 100 mg for the next 2 weeks and beginning with Cycle 2, to 200 mg once daily. Elotuzumab, 10 mg/kg, was administered as an intravenous infusion weekly for the first 2 cycles and beginning with Cycle 3, every 2 weeks. Dexamethasone, 40 mg, was administered weekly on those weeks when elotuzumab was not administered. On weeks when elotuzumab was also given, participants received dexamethasone as a split dose of 28 mg, 3 to 24 hours before the elotuzumab infusion, and 8 mg intravenously at least 45 minutes before the infusion. Those patients with suboptimal response, defined as evidence of progressive disease between end of Cycle 2 and end of Cycle 4 or inability to achieve partial response or better by end of Cycle 4, also received cyclophosphamide, 50 mg. Cyclophosphamide could not be added beyond Cycle 5.
Overall Number of Participants Analyzed 40
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Percentage of participants
62.5 [1] 
(NA to 72.9)
[1]
Only the upper bound of the CI was calculated
2.Primary Outcome
Title Percentage of All Participants Who Received Treatment Without Cyclophosphamide and Had Grade 3 or Higher Nonhematologic Adverse Events (AEs)
Hide Description AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or unknown relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death.
Time Frame From the first dose of study drug until the earlier of discontinuation from E-Td or the time when cyclophosphamide was initiated
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received thalidomide + elotuzumab + dexamethasone regimen, from first dose of study drug until discontinuation or until cyclophosphamide was initiated, whichever came first.
Arm/Group Title Thalidomide + Elotuzumab + Dexamethasone
Hide Arm/Group Description:
Participants received thalidomide in 28-day cycles: 50 mg, for the first 2 weeks, escalated to 100 mg for the next 2 weeks and beginning with Cycle 2, to 200 mg once daily. Elotuzumab, 10 mg/kg, was administered as an intravenous infusion weekly for the first 2 cycles, then beginning with Cycle 3, every 2 weeks. Dexamethasone, 40 mg, was administered weekly on those weeks when elotuzumab was not administered. On weeks when elotuzumab was also given, participants received dexamethasone as a split dose of 28 mg, 3 to 24 hours before the elotuzumab infusion, and 8 mg intravenously at least 45 minutes before the infusion.
Overall Number of Participants Analyzed 40
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Percentage of participants
55.0 [1] 
(NA to 65.9)
[1]
Only the upper bound of the CI was calculated
3.Secondary Outcome
Title Percentage of All Participants Who Received Treatment Including Cyclophosphamide and Had 1 Dose Reduction or Discontinued Due to an Adverse Event
Hide Description Elotuzumab dose reduction was not permitted. Thalidomide dose reduction, delay, interruptions, or discontinuation was permitted in the event of toxicity. Dexamethasone dose reduction was also permitted in the event of toxicity and in the setting of infusion reactions;dose delays were allowed as clinically indicated at the discretion of the investigator. Cyclophosphamide dose reduction, delay, interruption, or discontinuation was permitted in the event of toxicity.
Time Frame From the first dose of study drug until the last dose of treatment, including cyclophosphamide treatment
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received thalidomide, elotuzumab, and dexamethasone (40), including those who had cyclophosphamide added to the regimen (11).
Arm/Group Title Thalidomide + Elotuzumab + Dexamethasone + Cyclophosphamide
Hide Arm/Group Description:
Participants received thalidomide in 28-day cycles: 50 mg, for the first 2 weeks, escalated to 100 mg for the next 2 weeks, then beginning with Cycle 2, to 200 mg once daily. Elotuzumab, 10 mg/kg, was administered as an intravenous infusion weekly for the first 2 cycles, then beginning with Cycle 3, every 2 weeks. Dexamethasone, 40 mg, was administered weekly on those weeks when elotuzumab was not administered. On weeks when elotuzumab was also given, participants received dexamethasone as a split dose of 28 mg, 3 to 24 hours before the elotuzumab infusion, and 8 mg intravenously at least 45 minutes before the infusion. Those patients with suboptimal response, defined as evidence of progressive disease between end of Cycle 2 and end of Cycle 4 or inability to achieve partial response or better by end of Cycle 4, also received cyclophosphamide, 50 mg. Cyclophosphamide could not be added beyond Cycle 5.
Overall Number of Participants Analyzed 40
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
65.0
(48.3 to 79.4)
4.Secondary Outcome
Title Percentage of All Participants Who Received Treatment Without Cyclophosphamide and Had 1 Dose Reduction or Discontinued Due to an Adverse Event
Hide Description Elotuzumab dose reduction was not permitted. Thalidomide dose reduction, delay, interruptions, or discontinuation was permitted in the event of toxicity. Dexamethasone dose reduction was also permitted in the event of toxicity and in the setting of infusion reactions;dose delays were allowed as clinically indicated at the discretion of the investigator.
Time Frame From the first dose of study drug until the earlier of discontinuation from E-Td or the time when cyclophosphamide was initiated
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received thalidomide + elotuzumab + dexamethasone regimen, from first dose of study drug until discontinuation or until cyclophosphamide was initiated, whichever came first.
Arm/Group Title Thalidomide + Elotuzumab + Dexamethasone
Hide Arm/Group Description:
Participants received thalidomide in 28-day cycles: 50 mg, for the first 2 weeks, escalated to 100 mg for the next 2 weeks, then beginning with Cycle 2, to 200 mg once daily. Elotuzumab, 10 mg/kg, was administered as an intravenous infusion weekly for the first 2 cycles, then beginning with Cycle 3, every 2 weeks. Dexamethasone, 40 mg, was administered weekly on those weeks when elotuzumab was not administered. On weeks when elotuzumab was also given, participants received dexamethasone as a split dose of 28 mg, 3 to 24 hours before the elotuzumab infusion, and 8 mg intravenously at least 45 minutes before the infusion.
Overall Number of Participants Analyzed 40
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
57.5
(40.9 to 73.0)
Time Frame From date of first dose to 60 days post last dose
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title All Treated Subjects
Hide Arm/Group Description [Not Specified]
All-Cause Mortality
All Treated Subjects
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
All Treated Subjects
Affected / at Risk (%)
Total   23/40 (57.50%) 
Cardiac disorders   
Cardio-respiratory arrest  1  1/40 (2.50%) 
Myocarditis  1  1/40 (2.50%) 
Gastrointestinal disorders   
Pancreatitis  1  1/40 (2.50%) 
General disorders   
Cardiac death  1  1/40 (2.50%) 
Disease progression  1  1/40 (2.50%) 
Sudden death  1  1/40 (2.50%) 
Infections and infestations   
Aspergillus infection  1  1/40 (2.50%) 
Bronchopulmonary aspergillosis  1  1/40 (2.50%) 
Cellulitis  1  1/40 (2.50%) 
Herpes zoster  1  2/40 (5.00%) 
Lung infection  1  1/40 (2.50%) 
Pneumonia  1  2/40 (5.00%) 
Respiratory tract infection  1  4/40 (10.00%) 
Septic shock  1  3/40 (7.50%) 
Upper respiratory tract infection  1  1/40 (2.50%) 
Injury, poisoning and procedural complications   
Femur fracture  1  1/40 (2.50%) 
Spinal fracture  1  1/40 (2.50%) 
Investigations   
Aspiration bronchial  1  1/40 (2.50%) 
Musculoskeletal and connective tissue disorders   
Back pain  1  1/40 (2.50%) 
Spinal pain  1  1/40 (2.50%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Malignant neoplasm progression  1  2/40 (5.00%) 
Plasma cell myeloma  1  2/40 (5.00%) 
Nervous system disorders   
Spinal cord compression  1  1/40 (2.50%) 
Psychiatric disorders   
Confusional state  1  2/40 (5.00%) 
Renal and urinary disorders   
Acute kidney injury  1  1/40 (2.50%) 
Renal failure  1  1/40 (2.50%) 
Respiratory, thoracic and mediastinal disorders   
Epistaxis  1  1/40 (2.50%) 
Pneumonitis  1  2/40 (5.00%) 
Pulmonary embolism  1  1/40 (2.50%) 
Pulmonary oedema  1  1/40 (2.50%) 
Respiratory failure  1  1/40 (2.50%) 
Vascular disorders   
Hypertension  1  1/40 (2.50%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 19.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
All Treated Subjects
Affected / at Risk (%)
Total   39/40 (97.50%) 
Blood and lymphatic system disorders   
Anaemia  1  15/40 (37.50%) 
Neutropenia  1  6/40 (15.00%) 
Thrombocytopenia  1  9/40 (22.50%) 
Eye disorders   
Diplopia  1  2/40 (5.00%) 
Vision blurred  1  2/40 (5.00%) 
Gastrointestinal disorders   
Abdominal distension  1  2/40 (5.00%) 
Abdominal pain  1  2/40 (5.00%) 
Constipation  1  8/40 (20.00%) 
Diarrhoea  1  3/40 (7.50%) 
Dysphagia  1  2/40 (5.00%) 
Nausea  1  2/40 (5.00%) 
Vomiting  1  2/40 (5.00%) 
General disorders   
Asthenia  1  17/40 (42.50%) 
Chest pain  1  2/40 (5.00%) 
Chills  1  2/40 (5.00%) 
Crepitations  1  2/40 (5.00%) 
Fatigue  1  3/40 (7.50%) 
Gait disturbance  1  2/40 (5.00%) 
Oedema peripheral  1  12/40 (30.00%) 
Pain  1  3/40 (7.50%) 
Pyrexia  1  13/40 (32.50%) 
Infections and infestations   
Gastroenteritis  1  2/40 (5.00%) 
Herpes zoster  1  3/40 (7.50%) 
Influenza  1  4/40 (10.00%) 
Lower respiratory tract infection  1  2/40 (5.00%) 
Nasopharyngitis  1  5/40 (12.50%) 
Respiratory tract infection  1  9/40 (22.50%) 
Upper respiratory tract infection  1  5/40 (12.50%) 
Investigations   
Blood creatinine increased  1  3/40 (7.50%) 
Blood glucose increased  1  2/40 (5.00%) 
Laboratory test abnormal  1  2/40 (5.00%) 
Weight decreased  1  3/40 (7.50%) 
Metabolism and nutrition disorders   
Decreased appetite  1  4/40 (10.00%) 
Hyperglycaemia  1  8/40 (20.00%) 
Iron deficiency  1  2/40 (5.00%) 
Musculoskeletal and connective tissue disorders   
Arthralgia  1  2/40 (5.00%) 
Back pain  1  12/40 (30.00%) 
Bone pain  1  5/40 (12.50%) 
Muscle spasms  1  2/40 (5.00%) 
Muscular weakness  1  2/40 (5.00%) 
Musculoskeletal chest pain  1  2/40 (5.00%) 
Myalgia  1  2/40 (5.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Plasmacytoma  1  2/40 (5.00%) 
Nervous system disorders   
Dizziness  1  7/40 (17.50%) 
Neuropathy peripheral  1  11/40 (27.50%) 
Paraesthesia  1  5/40 (12.50%) 
Somnolence  1  4/40 (10.00%) 
Tremor  1  5/40 (12.50%) 
Psychiatric disorders   
Anxiety  1  5/40 (12.50%) 
Confusional state  1  2/40 (5.00%) 
Respiratory, thoracic and mediastinal disorders   
Catarrh  1  2/40 (5.00%) 
Cough  1  9/40 (22.50%) 
Dyspnoea  1  5/40 (12.50%) 
Productive cough  1  2/40 (5.00%) 
Vascular disorders   
Deep vein thrombosis  1  4/40 (10.00%) 
Hypertension  1  4/40 (10.00%) 
Hypotension  1  2/40 (5.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 19.0
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: NCT01632150     History of Changes
Other Study ID Numbers: CA204-010
2011-005121-49 ( EudraCT Number )
First Submitted: June 28, 2012
First Posted: July 2, 2012
Results First Submitted: December 22, 2015
Results First Posted: February 26, 2016
Last Update Posted: April 14, 2017