Relapsed and/or Refractory Multiple Myeloma
Conditions
Brief summary
The purpose of this study is to determine the safety and tolerability of elotuzumab administered in combination with thalidomide and dexamethasone in the treatment of relapsed and/or refractory multiple myeloma.
Interventions
BIOLOGICALElotuzumab
Powder for solution, 400-mg vials, for infusion
BIOLOGICALThalidomide
50-mg capsules administered orally
BIOLOGICALDexamethasone
2- and 4-mg tablets (and various other strengths, as needed) administered orally and in 4- and 8-mg/mL (and various other strengths, as needed) solutions for intravenous administration
BIOLOGICALCyclophosphamide
50-mg tablets administered orally
Sponsors
AbbVie
Bristol-Myers Squibb
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com. Key Inclusion Criteria: * Confirmed diagnosis of previously treated multiple myeloma with progression documented by criteria of the International Myeloma Working Group after or during the most recent therapy * Patient received 5 or fewer prior lines of therapy * Eastern Cooperative Oncology Group performance status of 0 or 1 (safety lead-in cohort) or 0 to 2 (additional patients) * Measurable disease as defined by at least 1 of the following: * Serum immunoglobulin (Ig)G, IgA, IgM, or monoclonal (M) protein level ≥0.5 g/dL or serum IgD M protein level ≥0.05 g/dL; or * Urine M protein level ≥200 mg excreted in a 24-hour collection sample; or * Involved serum free light chain level ≥10 mg/dL, provided the free light chain ratio is abnormal Key
Exclusion criteria
* Solitary bone or solitary extramedullary plasmacytoma as the only evidence of plasma cell dyscrasia * Monoclonal gammopathy of undetermined significance, smoldering myeloma, or Waldenström's macroglobulinemia * Left ventricular ejection fraction by echocardiogram or Multi Gated Acquisition ≤50% * Electrocardiogram finding of QTc ≥450 msec * Active plasma cell leukemia (defined as either 20% of peripheral white blood cells, composed of plasma/CD138+ cells or an absolute plasma cell count of 2\*10\^9/L) * Diagnosis of nonsecretory myeloma * Active hepatitis A, B, or C virus infection * Grade ≥2 neuropathy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Received Treatment Including Cyclophosphamide and Had Grade 3 or Higher Nonhematologic Adverse Events (AEs) | From the first dose of study drug until the last dose of treatment, including cyclophosphamide treatment | 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. |
| Percentage of All Participants Who Received Treatment Without Cyclophosphamide and Had Grade 3 or Higher Nonhematologic Adverse Events (AEs) | From the first dose of study drug until the earlier of discontinuation from E-Td or the time when cyclophosphamide was initiated | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of All Participants Who Received Treatment Without Cyclophosphamide and Had 1 Dose Reduction or Discontinued Due to an Adverse Event | From the first dose of study drug until the earlier of discontinuation from E-Td or the time when cyclophosphamide was initiated | 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. |
| Percentage of All Participants Who Received Treatment Including Cyclophosphamide and Had 1 Dose Reduction or Discontinued Due to an Adverse Event | From the first dose of study drug until the last dose of treatment, including cyclophosphamide treatment | 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. |
Countries
Spain
Participant flow
Pre-assignment details
Of 51 participants enrolled, 40 received treatment. Of those 40, 11 had cyclophosphamide added to their regimens.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 40 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Disease progression | 27 |
| Overall Study | Moved to compassionate program | 2 |
| Overall Study | Patient underwent autologous transplant | 1 |
| Overall Study | Study drug toxicity | 1 |
| Overall Study | Unrelated adverse event | 7 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Thalidomide + Elotuzumab + Dexamethasone + Cyclophosphamide |
|---|---|
| Age, Continuous | 64.3 Years STANDARD_DEVIATION 8.47 |
| Age, Customized 65 years and older to younger than 75 years | 12 Participants |
| Age, Customized 75 years and older | 6 Participants |
| Age, Customized Younger than 65 years | 22 Participants |
| Eastern Cooperative Oncology Group (ECOG) performance status Score 0 | 17 Participants |
| Eastern Cooperative Oncology Group (ECOG) performance status Score 1 | 21 Participants |
| Eastern Cooperative Oncology Group (ECOG) performance status Score 2 | 2 Participants |
| Myeloma type IGA | 7 Participants |
| Myeloma type IGD | 0 Participants |
| Myeloma type IGM | 0 Participants |
| Myeloma type Immunoglobulin (Ig)G | 15 Participants |
| Myeloma type Light chain disease | 9 Participants |
| Myeloma type Not reported | 9 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 40 Participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 39 / 40 |
| serious Total, serious adverse events | 23 / 40 |
Outcome results
Primary
Percentage of All Participants Who Received Treatment Without Cyclophosphamide and Had Grade 3 or Higher Nonhematologic Adverse Events (AEs)
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
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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Thalidomide + Elotuzumab + Dexamethasone + Cyclophosphamide | Percentage of All Participants Who Received Treatment Without Cyclophosphamide and Had Grade 3 or Higher Nonhematologic Adverse Events (AEs) | 55.0 Percentage of participants |
Primary
Percentage of Participants Who Received Treatment Including Cyclophosphamide and Had Grade 3 or Higher Nonhematologic Adverse Events (AEs)
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
Population: All participants who received thalidomide, elotuzumab, and dexamethasone (40) including those who had cyclophosphamide added to the regimen (11).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Thalidomide + Elotuzumab + Dexamethasone + Cyclophosphamide | Percentage of Participants Who Received Treatment Including Cyclophosphamide and Had Grade 3 or Higher Nonhematologic Adverse Events (AEs) | 62.5 Percentage of participants |
Secondary
Percentage of All Participants Who Received Treatment Including Cyclophosphamide and Had 1 Dose Reduction or Discontinued Due to an Adverse Event
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
Population: All participants who received thalidomide, elotuzumab, and dexamethasone (40), including those who had cyclophosphamide added to the regimen (11).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Thalidomide + Elotuzumab + Dexamethasone + Cyclophosphamide | 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 |
Secondary
Percentage of All Participants Who Received Treatment Without Cyclophosphamide and Had 1 Dose Reduction or Discontinued Due to an Adverse Event
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
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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Thalidomide + Elotuzumab + Dexamethasone + Cyclophosphamide | 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 |