Multiple Myeloma
Conditions
Brief summary
The purpose of this study is to determine if adding Elotuzumab to Pomalidomide and low-dose dexamethasone is a more effective treatment of relapsed and refractory multiple myeloma compared to pomalidomide and low-dose dexamethasone by itself.
Interventions
DRUGElotuzumab
DRUGPomalidomide
DRUGDexamethasone
Sponsors
Celgene
AbbVie
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
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 Inclusion Criteria: * ≥ 2 prior lines of therapy which must have included at least 2 consecutive cycles of lenalidomide and a proteosome inhibitor alone or in combination * Documented refractory or relapsed and refractory multiple myeloma * Refractory to proteosome inhibitor and lenalidomide, and to last treatment * Relapsed and refractory patients must have achieved at least a partial response to previous treatment with proteosome inhibitor or lenalidomide, or both, but progressed within 6 months, and were refractory to their last treatment * Measurable disease at screening * Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
Exclusion criteria
* Active plasma cell leukemia * Prior treatment with pomalidomide * Unable to tolerate thromboembolic prophylaxis while on the study * Prior autologous stem cell transplant within 12 weeks * Known Human Immunodeficiency Virus (HIV) infection or active hepatitis A, B, or C
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | From randomization to date of progression or death (up to approximately 21 months) | PFS is defined as the time from randomization to the date of the first documented tumor progression or death due to any cause. Progressive disease response criteria were defined as an increase of 25% from lowest response value in any one or more of the following: 1\. Serum M-component and/or 2. Urine M-component and/or 3. Only in patients without measurable serum and urine M-protein levels: the difference between involved and uninvolved FLC levels 4. Bone marrow plasma cell percentage; Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcemia that can be attributed solely to the plasma cell proliferative disorder |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | From first dose to disease progression (up to approximately 21 months) | ORR is defined as the percentage of participants who achieved a best overall response (BOR) of stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR) using the modified International Myeloma Working Group (IMWG) criteria described as follows, as per investigator's assessment * CR: Negative immunofixation of serum and urine and disappearance of any soft tissue plasmacytomas, and \< 5% plasma cells in bone marrow * sCR: CR, as defined above, plus the following: Normal FLC ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence * VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or \>= 90% reduction in serum M-protein level plus 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. |
| Overall Survival (OS) | From randomization to death (up to approximately 52 months) | OS is the time from randomization to the date of death from any cause. The survival time for participants who had not died was censored at the last known alive date. OS was censored at the date of randomization for subjects who were randomized but had no follow-up. |
Countries
Australia, Canada, France, Germany, Greece, Italy, Japan, Netherlands, Poland, Spain, United States
Participant flow
Pre-assignment details
117 participants were randomized, and 115 participants were treated.
Participants by arm
| Arm | Count |
|---|---|
| E-Pd Cohort Elotuzumab + Pomalidomide + Dexamethasone | 60 |
| Pd Cohort Pomalidomide + Dexamethasone | 57 |
| Total | 117 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Pre-Treatment Period | Participant Withdrew Consent | 0 | 2 |
| Treatment Period | Administrative reasons by sponsor | 0 | 1 |
| Treatment Period | Adverse Event unrelated to study drug | 6 | 9 |
| Treatment Period | Death | 1 | 0 |
| Treatment Period | Disease progression | 43 | 38 |
| Treatment Period | Maximum Clinical Benefit | 0 | 2 |
| Treatment Period | Other reasons | 4 | 2 |
| Treatment Period | Participant request to discontinue | 2 | 0 |
| Treatment Period | Study drug toxicity | 2 | 2 |
| Treatment Period | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | E-Pd Cohort | Pd Cohort | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 38 Participants | 35 Participants | 73 Participants |
| Age, Categorical Between 18 and 65 years | 22 Participants | 22 Participants | 44 Participants |
| Age, Continuous | 66.2 Years STANDARD_DEVIATION 9.92 | 65.5 Years STANDARD_DEVIATION 9.95 | 65.9 Years STANDARD_DEVIATION 9.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 18 Participants | 28 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 49 Participants | 39 Participants | 88 Participants |
| Race/Ethnicity, Customized Asian | 15 Participants | 9 Participants | 24 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 45 Participants | 45 Participants | 90 Participants |
| Sex: Female, Male Female | 28 Participants | 22 Participants | 50 Participants |
| Sex: Female, Male Male | 32 Participants | 35 Participants | 67 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 41 / 60 | 41 / 57 |
| other Total, other adverse events | 56 / 60 | 49 / 55 |
| serious Total, serious adverse events | 42 / 60 | 33 / 55 |
Outcome results
Primary
Progression Free Survival (PFS)
PFS is defined as the time from randomization to the date of the first documented tumor progression or death due to any cause. Progressive disease response criteria were defined as an increase of 25% from lowest response value in any one or more of the following: 1\. Serum M-component and/or 2. Urine M-component and/or 3. Only in patients without measurable serum and urine M-protein levels: the difference between involved and uninvolved FLC levels 4. Bone marrow plasma cell percentage; Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcemia that can be attributed solely to the plasma cell proliferative disorder
Time frame: From randomization to date of progression or death (up to approximately 21 months)
Population: All randomized participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| E-Pd Cohort | Progression Free Survival (PFS) | 10.25 Months |
| Pd Cohort | Progression Free Survival (PFS) | 4.70 Months |
p-value: 0.004395% CI: [0.32, 0.82]Log Rank
Secondary
Objective Response Rate (ORR)
ORR is defined as the percentage of participants who achieved a best overall response (BOR) of stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR) using the modified International Myeloma Working Group (IMWG) criteria described as follows, as per investigator's assessment * CR: Negative immunofixation of serum and urine and disappearance of any soft tissue plasmacytomas, and \< 5% plasma cells in bone marrow * sCR: CR, as defined above, plus the following: Normal FLC ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence * VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or \>= 90% reduction in serum M-protein level plus 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.
Time frame: From first dose to disease progression (up to approximately 21 months)
Population: All randomized participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| E-Pd Cohort | Objective Response Rate (ORR) | 58.3 Percent of participants |
| Pd Cohort | Objective Response Rate (ORR) | 24.6 Percent of participants |
p-value: 0.000295% CI: [2.05, 10.43]Cochran-Mantel-Haenszel
Secondary
Overall Survival (OS)
OS is the time from randomization to the date of death from any cause. The survival time for participants who had not died was censored at the last known alive date. OS was censored at the date of randomization for subjects who were randomized but had no follow-up.
Time frame: From randomization to death (up to approximately 52 months)
Population: All randomized participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| E-Pd Cohort | Overall Survival (OS) | 29.80 Months |
| Pd Cohort | Overall Survival (OS) | 17.41 Months |
p-value: 0.021795% CI: [0.37, 0.93]Log Rank