Trial Outcomes & Findings for Safety Study of Elotuzumab in Combination With Thalidomide and Dexamethasone in Relapsed and/or Refractory Multiple Myeloma (NCT NCT01632150)

Last Updated: 2017-04-14

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

51 participants

Primary outcome timeframe

From the first dose of study drug until the last dose of treatment, including cyclophosphamide treatment

Results posted on

2017-04-14

Participant Flow

Of 51 participants enrolled, 40 received treatment. Of those 40, 11 had cyclophosphamide added to their regimens.

Participant milestones

Participant milestones
Measure	Thalidomide + Elotuzumab + Dexamethasone + Cyclophosphamide 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 Study STARTED	40
Overall Study Received Cyclophosphamide	11
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	40

Reasons for withdrawal

Reasons for withdrawal
Measure	Thalidomide + Elotuzumab + Dexamethasone + Cyclophosphamide 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 Study Disease progression	27
Overall Study Study drug toxicity	1
Overall Study Unrelated adverse event	7
Overall Study Withdrawal by Subject	2
Overall Study Patient underwent autologous transplant	1
Overall Study Moved to compassionate program	2

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Thalidomide + Elotuzumab + Dexamethasone + Cyclophosphamide n=40 Participants 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.
Age, Continuous	64.3 Years STANDARD_DEVIATION 8.47 • n=5 Participants
Age, Customized Younger than 65 years	22 Participants n=5 Participants
Age, Customized 65 years and older to younger than 75 years	12 Participants n=5 Participants
Age, Customized 75 years and older	6 Participants n=5 Participants
Sex: Female, Male Female	15 Participants n=5 Participants
Sex: Female, Male Male	25 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	40 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Myeloma type Immunoglobulin (Ig)G	15 Participants n=5 Participants
Myeloma type IGA	7 Participants n=5 Participants
Myeloma type IGM	0 Participants n=5 Participants
Myeloma type IGD	0 Participants n=5 Participants
Myeloma type Light chain disease	9 Participants n=5 Participants
Myeloma type Not reported	9 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) performance status Score 0	17 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) performance status Score 1	21 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) performance status Score 2	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: From the first dose of study drug until the last dose of treatment, including cyclophosphamide treatment

Population: All participants who received thalidomide, elotuzumab, and dexamethasone (40) including those who had cyclophosphamide added to the regimen (11).

Outcome measures

Outcome measures
Measure	Thalidomide + Elotuzumab + Dexamethasone + Cyclophosphamide n=40 Participants 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.
Percentage of Participants Who Received Treatment Including Cyclophosphamide and Had Grade 3 or Higher Nonhematologic Adverse Events (AEs)	62.5 Percentage of participants Interval to 72.9 Only the upper bound of the CI was calculated

PRIMARY outcome

Timeframe: From the first dose of study drug until the earlier of discontinuation from E-Td or the time when cyclophosphamide was initiated

Population: All participants who received thalidomide + elotuzumab + dexamethasone regimen, from first dose of study drug until discontinuation or until cyclophosphamide was initiated, whichever came first.

Outcome measures

Outcome measures
Measure	Thalidomide + Elotuzumab + Dexamethasone + Cyclophosphamide n=40 Participants 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.
Percentage of All Participants Who Received Treatment Without Cyclophosphamide and Had Grade 3 or Higher Nonhematologic Adverse Events (AEs)	55.0 Percentage of participants Interval to 65.9 Only the upper bound of the CI was calculated

SECONDARY outcome

Timeframe: From the first dose of study drug until the last dose of treatment, including cyclophosphamide treatment

Population: All participants who received thalidomide, elotuzumab, and dexamethasone (40), including those who had cyclophosphamide added to the regimen (11).

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.

Outcome measures

Outcome measures
Measure	Thalidomide + Elotuzumab + Dexamethasone + Cyclophosphamide n=40 Participants 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.
Percentage of All Participants Who Received Treatment Including Cyclophosphamide and Had 1 Dose Reduction or Discontinued Due to an Adverse Event	65.0 Percentage of participants Interval 48.3 to 79.4

SECONDARY outcome

Timeframe: From the first dose of study drug until the earlier of discontinuation from E-Td or the time when cyclophosphamide was initiated

Outcome measures

Outcome measures
Measure	Thalidomide + Elotuzumab + Dexamethasone + Cyclophosphamide n=40 Participants 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.
Percentage of All Participants Who Received Treatment Without Cyclophosphamide and Had 1 Dose Reduction or Discontinued Due to an Adverse Event	57.5 Percentage of participants Interval 40.9 to 73.0

Adverse Events

All Treated Subjects

Serious events: 23 serious events

Other events: 39 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	All Treated Subjects n=40 participants at risk
Cardiac disorders Cardio-respiratory arrest	2.5% 1/40 • From date of first dose to 60 days post last dose
Cardiac disorders Myocarditis	2.5% 1/40 • From date of first dose to 60 days post last dose
Gastrointestinal disorders Pancreatitis	2.5% 1/40 • From date of first dose to 60 days post last dose
General disorders Cardiac death	2.5% 1/40 • From date of first dose to 60 days post last dose
General disorders Disease progression	2.5% 1/40 • From date of first dose to 60 days post last dose
General disorders Sudden death	2.5% 1/40 • From date of first dose to 60 days post last dose
Infections and infestations Aspergillus infection	2.5% 1/40 • From date of first dose to 60 days post last dose
Infections and infestations Bronchopulmonary aspergillosis	2.5% 1/40 • From date of first dose to 60 days post last dose
Infections and infestations Cellulitis	2.5% 1/40 • From date of first dose to 60 days post last dose
Infections and infestations Herpes zoster	5.0% 2/40 • From date of first dose to 60 days post last dose
Infections and infestations Lung infection	2.5% 1/40 • From date of first dose to 60 days post last dose
Infections and infestations Pneumonia	5.0% 2/40 • From date of first dose to 60 days post last dose
Infections and infestations Respiratory tract infection	10.0% 4/40 • From date of first dose to 60 days post last dose
Infections and infestations Septic shock	7.5% 3/40 • From date of first dose to 60 days post last dose
Infections and infestations Upper respiratory tract infection	2.5% 1/40 • From date of first dose to 60 days post last dose
Injury, poisoning and procedural complications Femur fracture	2.5% 1/40 • From date of first dose to 60 days post last dose
Injury, poisoning and procedural complications Spinal fracture	2.5% 1/40 • From date of first dose to 60 days post last dose
Investigations Aspiration bronchial	2.5% 1/40 • From date of first dose to 60 days post last dose
Musculoskeletal and connective tissue disorders Back pain	2.5% 1/40 • From date of first dose to 60 days post last dose
Musculoskeletal and connective tissue disorders Spinal pain	2.5% 1/40 • From date of first dose to 60 days post last dose
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	5.0% 2/40 • From date of first dose to 60 days post last dose
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Plasma cell myeloma	5.0% 2/40 • From date of first dose to 60 days post last dose
Nervous system disorders Spinal cord compression	2.5% 1/40 • From date of first dose to 60 days post last dose
Psychiatric disorders Confusional state	5.0% 2/40 • From date of first dose to 60 days post last dose
Renal and urinary disorders Acute kidney injury	2.5% 1/40 • From date of first dose to 60 days post last dose
Renal and urinary disorders Renal failure	2.5% 1/40 • From date of first dose to 60 days post last dose
Respiratory, thoracic and mediastinal disorders Epistaxis	2.5% 1/40 • From date of first dose to 60 days post last dose
Respiratory, thoracic and mediastinal disorders Pneumonitis	5.0% 2/40 • From date of first dose to 60 days post last dose
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	2.5% 1/40 • From date of first dose to 60 days post last dose
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	2.5% 1/40 • From date of first dose to 60 days post last dose
Respiratory, thoracic and mediastinal disorders Respiratory failure	2.5% 1/40 • From date of first dose to 60 days post last dose
Vascular disorders Hypertension	2.5% 1/40 • From date of first dose to 60 days post last dose

Other adverse events

Other adverse events
Measure	All Treated Subjects n=40 participants at risk
Blood and lymphatic system disorders Anaemia	37.5% 15/40 • From date of first dose to 60 days post last dose
Blood and lymphatic system disorders Neutropenia	15.0% 6/40 • From date of first dose to 60 days post last dose
Blood and lymphatic system disorders Thrombocytopenia	22.5% 9/40 • From date of first dose to 60 days post last dose
Eye disorders Diplopia	5.0% 2/40 • From date of first dose to 60 days post last dose
Eye disorders Vision blurred	5.0% 2/40 • From date of first dose to 60 days post last dose
Gastrointestinal disorders Abdominal distension	5.0% 2/40 • From date of first dose to 60 days post last dose
Gastrointestinal disorders Abdominal pain	5.0% 2/40 • From date of first dose to 60 days post last dose
Gastrointestinal disorders Constipation	20.0% 8/40 • From date of first dose to 60 days post last dose
Gastrointestinal disorders Diarrhoea	7.5% 3/40 • From date of first dose to 60 days post last dose
Gastrointestinal disorders Dysphagia	5.0% 2/40 • From date of first dose to 60 days post last dose
Gastrointestinal disorders Nausea	5.0% 2/40 • From date of first dose to 60 days post last dose
Gastrointestinal disorders Vomiting	5.0% 2/40 • From date of first dose to 60 days post last dose
General disorders Asthenia	42.5% 17/40 • From date of first dose to 60 days post last dose
General disorders Chest pain	5.0% 2/40 • From date of first dose to 60 days post last dose
General disorders Chills	5.0% 2/40 • From date of first dose to 60 days post last dose
General disorders Crepitations	5.0% 2/40 • From date of first dose to 60 days post last dose
General disorders Fatigue	7.5% 3/40 • From date of first dose to 60 days post last dose
General disorders Gait disturbance	5.0% 2/40 • From date of first dose to 60 days post last dose
General disorders Oedema peripheral	30.0% 12/40 • From date of first dose to 60 days post last dose
General disorders Pain	7.5% 3/40 • From date of first dose to 60 days post last dose
General disorders Pyrexia	32.5% 13/40 • From date of first dose to 60 days post last dose
Infections and infestations Gastroenteritis	5.0% 2/40 • From date of first dose to 60 days post last dose
Infections and infestations Herpes zoster	7.5% 3/40 • From date of first dose to 60 days post last dose
Infections and infestations Influenza	10.0% 4/40 • From date of first dose to 60 days post last dose
Infections and infestations Lower respiratory tract infection	5.0% 2/40 • From date of first dose to 60 days post last dose
Infections and infestations Nasopharyngitis	12.5% 5/40 • From date of first dose to 60 days post last dose
Infections and infestations Respiratory tract infection	22.5% 9/40 • From date of first dose to 60 days post last dose
Infections and infestations Upper respiratory tract infection	12.5% 5/40 • From date of first dose to 60 days post last dose
Investigations Blood creatinine increased	7.5% 3/40 • From date of first dose to 60 days post last dose
Investigations Blood glucose increased	5.0% 2/40 • From date of first dose to 60 days post last dose
Investigations Laboratory test abnormal	5.0% 2/40 • From date of first dose to 60 days post last dose
Investigations Weight decreased	7.5% 3/40 • From date of first dose to 60 days post last dose
Metabolism and nutrition disorders Decreased appetite	10.0% 4/40 • From date of first dose to 60 days post last dose
Metabolism and nutrition disorders Hyperglycaemia	20.0% 8/40 • From date of first dose to 60 days post last dose
Metabolism and nutrition disorders Iron deficiency	5.0% 2/40 • From date of first dose to 60 days post last dose
Musculoskeletal and connective tissue disorders Arthralgia	5.0% 2/40 • From date of first dose to 60 days post last dose
Musculoskeletal and connective tissue disorders Back pain	30.0% 12/40 • From date of first dose to 60 days post last dose
Musculoskeletal and connective tissue disorders Bone pain	12.5% 5/40 • From date of first dose to 60 days post last dose
Musculoskeletal and connective tissue disorders Muscle spasms	5.0% 2/40 • From date of first dose to 60 days post last dose
Musculoskeletal and connective tissue disorders Muscular weakness	5.0% 2/40 • From date of first dose to 60 days post last dose
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	5.0% 2/40 • From date of first dose to 60 days post last dose
Musculoskeletal and connective tissue disorders Myalgia	5.0% 2/40 • From date of first dose to 60 days post last dose
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Plasmacytoma	5.0% 2/40 • From date of first dose to 60 days post last dose
Nervous system disorders Dizziness	17.5% 7/40 • From date of first dose to 60 days post last dose
Nervous system disorders Neuropathy peripheral	27.5% 11/40 • From date of first dose to 60 days post last dose
Nervous system disorders Paraesthesia	12.5% 5/40 • From date of first dose to 60 days post last dose
Nervous system disorders Somnolence	10.0% 4/40 • From date of first dose to 60 days post last dose
Nervous system disorders Tremor	12.5% 5/40 • From date of first dose to 60 days post last dose
Psychiatric disorders Anxiety	12.5% 5/40 • From date of first dose to 60 days post last dose
Psychiatric disorders Confusional state	5.0% 2/40 • From date of first dose to 60 days post last dose
Respiratory, thoracic and mediastinal disorders Catarrh	5.0% 2/40 • From date of first dose to 60 days post last dose
Respiratory, thoracic and mediastinal disorders Cough	22.5% 9/40 • From date of first dose to 60 days post last dose
Respiratory, thoracic and mediastinal disorders Dyspnoea	12.5% 5/40 • From date of first dose to 60 days post last dose
Respiratory, thoracic and mediastinal disorders Productive cough	5.0% 2/40 • From date of first dose to 60 days post last dose
Vascular disorders Deep vein thrombosis	10.0% 4/40 • From date of first dose to 60 days post last dose
Vascular disorders Hypertension	10.0% 4/40 • From date of first dose to 60 days post last dose
Vascular disorders Hypotension	5.0% 2/40 • From date of first dose to 60 days post last dose

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER