Lymphoma, Multiple Myeloma
Conditions
Brief summary
The purpose of the study is to determine whether the addition of Elotuzumab to Lenalidomide/low-dose Dexamethasone will increase the progression free survival (PFS).
Interventions
DRUGLenalidomide
Capsules, Oral, 25 mg, once daily, on Days 1-21, Repeat every 28 days until subject meets criteria for discontinuation of study drug
DRUGDexamethasone
Tablets, Oral, 40 mg, weekly, on Days 1, 8, 15, 22, Repeat every 28 days until subject meets criteria for discontinuation of study drug
On weeks without Elotuzumab dosing: Tablets, Oral, 40mg, Repeat every 28 days until subject meets criteria for discontinuation of study drug. On weeks with Elotuzumab dosing: Tablets, Oral, 28 mg, Repeat every 28 days until subject meets criteria for discontinuation of study drug
On weeks without Elotuzumab dosing: Not Applicable (N/A) On weeks with Elotuzumab dosing: Solution, Intravenous (IV), 8 mg, weekly, Repeat every 28 days until subject meets criteria for discontinuation of study drug
BIOLOGICALElotuzumab (BMS-901608; HuLuc63)
Solution, IV, 10 mg/kg, weekly, on Days 1, 8, 15, 22 (cycles 1&2); Days 1 and 15 (cycles 3 and beyond), Repeat every 28 days until subject meets criteria for discontinuation of study drug
Sponsors
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: * Documented progression from most recent line of therapy * 1-3 prior lines of therapy * Measurable disease * Life expectancy ≥3 months * Prior treatment with Lenalidomide permitted if: 1. Best response achieved was ≥Partial Response (PR) 2. Patient was not refractory 3. Patient did not discontinue due to a Grade ≥3 related adverse event 4. Subject did not receive more than 9 cycles of Lenalidomide and had at least 9 months between the last dose of Lenalidomide and progression
Exclusion criteria
* Subjects with non-secretory or oligo-secretory or serum free light-chain only myeloma * Active plasma cell leukemia * Known Human immunodeficiency virus (HIV) infection or active hepatitis A, B, or C
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Median Progression Free Survival (PFS) | From randomization up to 326 events (up to approximately 38 months) | Primary definition of Progression-free survival (PFS) defined as the time from randomization to the date of first documented tumor progression or death due to any cause. Participants were censored at the last adequate assessment prior to the start of any subsequent systemic-therapy or at the last adequate assessment prior to 2 missing assessments (\> 10 weeks). Participants who died more than 10 weeks after the randomization date and had no on-treatment assessment were censored at the randomization date. Clinical deterioration was not considered progression. The primary analysis of PFS was based on the primary definition using the Independent Review Committee (IRC) tumor assessment using the European Group for Blood and Bone Marrow Transplant (EBMT) criteria. Tumor assessments were made every 4 weeks (±1 week) relative to the first dose of study medication. |
| Objective Response Rate (ORR) | From randomization up to approximately 38 months | Objective response rate (ORR) defined as the percentage of participants with a best response on-study of partial response (PR) or better (stringent CR \[sCR\], complete response \[CR\], very good partial response \[VGPR\], and partial response \[PR\]) based on the Independent Review Committee (IRC) assessment of best response using the European Group for Blood and Bone Marrow Transplant (EBMT) assessment criteria. Participants were censored at the last adequate assessment prior to the start of any subsequent systemic-therapy or at the last adequate assessment prior to 2 missing assessments (\> 10 weeks). Participants who died more than 10 weeks after the randomization date and had no on-treatment assessment were censored at the randomization date. Clinical deterioration was not considered progression. Assessments were made every 4 weeks. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Overall Survival (OS) | Randomization to the date of death from any cause (up to approximately 9 years) | Overall survival is defined as the time from randomization to the date of death from any cause. If a subject has not died, their survival time will be censored at the date of last contact (last known alive date). A subject will be censored at the date of randomization if they were randomized but had no follow-up. (Based on Kaplan Meier estimates) |
| Change From Baseline of Mean Score Pain Severity (BPI-SF) | From baseline up to approximately 38 months | The change from baseline of the mean score of pain severity at the end of treatment using the Brief Pain Inventory-Short Form (BPI-SF). The BPI-SF is a self administered questionnaire developed to assess the severity of pain (the sensory dimension) as well as the degree to which pain interferes with function (the reactive dimension). The BPI-SF uses 0 (No pain, No interference) to 10 (Pain as bad as you can imagine, Highest imaginable interference) numeric rating scale. |
| Change From Baseline of Mean Score Pain Interference (BPI-SF) | From baseline up to approximately 38 months | The change from baseline of the mean score of pain interference at the end of treatment using the Brief Pain Inventory-Short Form (BPI-SF). The BPI-SF is a self administered questionnaire developed to assess the severity of pain (the sensory dimension) as well as the degree to which pain interferes with function (the reactive dimension). The BPI-SF uses 0 (No pain, No interference) to 10 (Pain as bad as you can imagine, Highest imaginable interference) numeric rating scale. |
Countries
Australia, Austria, Belgium, Canada, Czechia, Denmark, France, Germany, Greece, Hungary, Ireland, Israel, Italy, Japan, Poland, Puerto Rico, Romania, Spain, Switzerland, Turkey (Türkiye), United Arab Emirates, United Kingdom, United States
Participant flow
Pre-assignment details
646 participants were randomized and 635 were treated
Participants by arm
| Arm | Count |
|---|---|
| Lenalidomide + Dexamethasone + Elotuzumab Lenalidomide: Capsules, Oral, 25 mg, once daily, on Days 1-21 Repeat every 28 days until participants met criteria for discontinuation of study drug Dexamethasone (Oral): On weeks without Elotuzumab dosing: Tablets, Oral, 40mg Repeat every 28 days until participants met criteria for discontinuation of study drug On weeks with Elotuzumab dosing: Tablets, Oral, 28 mg Repeat every 28 days until participants met criteria for discontinuation of study drug Dexamethasone (IV): On weeks without Elotuzumab dosing: Not Applicable (N/A) On weeks with Elotuzumab dosing: Solution, Intravenous (IV), 8 mg, weekly Repeat every 28 days until participants met criteria for discontinuation of study drug Elotuzumab (BMS-901608; HuLuc63): Solution, IV, 10 mg/kg, weekly, on Days 1, 8, 15, 22 (cycles 1&2); Days 1 and 15 (cycles 3 and beyond) Repeat every 28 days until participants met criteria for discontinuation of study drug | 321 |
| Lenalidomide + Dexamethasone Lenalidomide: Capsules, Oral, 25 mg, once daily, on Days 1-21 Regimen repeated every 28 days until participants met criteria for discontinuation of study drug Dexamethasone: Tablets, Oral, 40 mg, weekly, on Days 1, 8, 15, 22 Regimen repeated every 28 days until participants met criteria for discontinuation of study drug | 325 |
| Total | 646 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Randomized Participants | Adverse event unrelated to study drug | 0 | 1 |
| Randomized Participants | Participant no longer meets study criteria | 1 | 1 |
| Randomized Participants | Participant withdrew consent | 1 | 7 |
| Treated Participants | Administrative reason by sponsor | 13 | 4 |
| Treated Participants | Adverse event unrelated to study drug | 31 | 37 |
| Treated Participants | Death | 1 | 1 |
| Treated Participants | Disease progression | 185 | 185 |
| Treated Participants | Other reasons | 14 | 14 |
| Treated Participants | Participant no longer meets study criteria | 1 | 1 |
| Treated Participants | Participants request to discontinue study treatment | 28 | 18 |
| Treated Participants | Participant withdrew consent | 6 | 11 |
| Treated Participants | Poor/non-compliance | 0 | 1 |
| Treated Participants | Study drug toxicity | 39 | 45 |
Baseline characteristics
| Characteristic | Lenalidomide + Dexamethasone + Elotuzumab | Lenalidomide + Dexamethasone | Total |
|---|---|---|---|
| Age, Continuous | 66.2 years STANDARD_DEVIATION 9.34 | 65.3 years STANDARD_DEVIATION 10.26 | 65.7 years STANDARD_DEVIATION 9.81 |
| Age, Customized >= 65 and < 75 years old | 119 Participants | 122 Participants | 241 Participants |
| Age, Customized < 65 years old | 134 Participants | 142 Participants | 276 Participants |
| Age, Customized >= 75 years old | 68 Participants | 61 Participants | 129 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 1 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 28 Participants | 33 Participants | 61 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 288 Participants | 291 Participants | 579 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 33 Participants | 31 Participants | 64 Participants |
| Race/Ethnicity, Customized Black or African American | 13 Participants | 10 Participants | 23 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 9 Participants | 4 Participants | 13 Participants |
| Race/Ethnicity, Customized White | 264 Participants | 280 Participants | 544 Participants |
| Sex: Female, Male Female | 129 Participants | 132 Participants | 261 Participants |
| Sex: Female, Male Male | 192 Participants | 193 Participants | 385 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 226 / 321 | 249 / 325 |
| other Total, other adverse events | 314 / 318 | 309 / 317 |
| serious Total, serious adverse events | 238 / 318 | 194 / 317 |
Outcome results
Primary
Median Progression Free Survival (PFS)
Primary definition of Progression-free survival (PFS) defined as the time from randomization to the date of first documented tumor progression or death due to any cause. Participants were censored at the last adequate assessment prior to the start of any subsequent systemic-therapy or at the last adequate assessment prior to 2 missing assessments (\> 10 weeks). Participants who died more than 10 weeks after the randomization date and had no on-treatment assessment were censored at the randomization date. Clinical deterioration was not considered progression. The primary analysis of PFS was based on the primary definition using the Independent Review Committee (IRC) tumor assessment using the European Group for Blood and Bone Marrow Transplant (EBMT) criteria. Tumor assessments were made every 4 weeks (±1 week) relative to the first dose of study medication.
Time frame: From randomization up to 326 events (up to approximately 38 months)
Population: All randomized participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lenalidomide + Dexamethasone + Elotuzumab | Median Progression Free Survival (PFS) | 19.35 Months |
| Lenalidomide + Dexamethasone | Median Progression Free Survival (PFS) | 14.85 Months |
Comparison: Hazard Ratio of Lenalidomide + Dexamethasone + Elotuzumab to Lenalidomide + Dexamethasonep-value: 0.001495% CI: [0.6, 0.89]Log Rank
Primary
Objective Response Rate (ORR)
Objective response rate (ORR) defined as the percentage of participants with a best response on-study of partial response (PR) or better (stringent CR \[sCR\], complete response \[CR\], very good partial response \[VGPR\], and partial response \[PR\]) based on the Independent Review Committee (IRC) assessment of best response using the European Group for Blood and Bone Marrow Transplant (EBMT) assessment criteria. Participants were censored at the last adequate assessment prior to the start of any subsequent systemic-therapy or at the last adequate assessment prior to 2 missing assessments (\> 10 weeks). Participants who died more than 10 weeks after the randomization date and had no on-treatment assessment were censored at the randomization date. Clinical deterioration was not considered progression. Assessments were made every 4 weeks.
Time frame: From randomization up to approximately 38 months
Population: All randomized participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lenalidomide + Dexamethasone + Elotuzumab | Objective Response Rate (ORR) | 78.5 Percentage of participants |
| Lenalidomide + Dexamethasone | Objective Response Rate (ORR) | 65.5 Percentage of participants |
Comparison: Ratio of Lenalidomide + Dexamethasone + Elotuzumab to Lenalidomide + Dexamethasonep-value: 0.000295% CI: [1.36, 2.78]Cochran-Mantel-Haenszel
Comparison: Difference of Lenalidomide + Dexamethasone + Elotuzumab minus Lenalidomide + Dexamethasone computed using the method of DerSimonian and Laird (weighted average over the strata)95% CI: [6.2, 19.3]
Secondary
Change From Baseline of Mean Score Pain Interference (BPI-SF)
The change from baseline of the mean score of pain interference at the end of treatment using the Brief Pain Inventory-Short Form (BPI-SF). The BPI-SF is a self administered questionnaire developed to assess the severity of pain (the sensory dimension) as well as the degree to which pain interferes with function (the reactive dimension). The BPI-SF uses 0 (No pain, No interference) to 10 (Pain as bad as you can imagine, Highest imaginable interference) numeric rating scale.
Time frame: From baseline up to approximately 38 months
Population: All randomized participants with baseline and end of treatment scores
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lenalidomide + Dexamethasone + Elotuzumab | Change From Baseline of Mean Score Pain Interference (BPI-SF) | 0.95 Score on a scale | Standard Deviation 2.466 |
| Lenalidomide + Dexamethasone | Change From Baseline of Mean Score Pain Interference (BPI-SF) | 0.48 Score on a scale | Standard Deviation 2.868 |
Secondary
Change From Baseline of Mean Score Pain Severity (BPI-SF)
The change from baseline of the mean score of pain severity at the end of treatment using the Brief Pain Inventory-Short Form (BPI-SF). The BPI-SF is a self administered questionnaire developed to assess the severity of pain (the sensory dimension) as well as the degree to which pain interferes with function (the reactive dimension). The BPI-SF uses 0 (No pain, No interference) to 10 (Pain as bad as you can imagine, Highest imaginable interference) numeric rating scale.
Time frame: From baseline up to approximately 38 months
Population: All randomized participants with baseline and end of treatment scores
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lenalidomide + Dexamethasone + Elotuzumab | Change From Baseline of Mean Score Pain Severity (BPI-SF) | 0.52 Score on a scale | Standard Deviation 2.237 |
| Lenalidomide + Dexamethasone | Change From Baseline of Mean Score Pain Severity (BPI-SF) | -0.04 Score on a scale | Standard Deviation 2.408 |
Secondary
Median Overall Survival (OS)
Overall survival is defined as the time from randomization to the date of death from any cause. If a subject has not died, their survival time will be censored at the date of last contact (last known alive date). A subject will be censored at the date of randomization if they were randomized but had no follow-up. (Based on Kaplan Meier estimates)
Time frame: Randomization to the date of death from any cause (up to approximately 9 years)
Population: All randomized participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lenalidomide + Dexamethasone + Elotuzumab | Median Overall Survival (OS) | 48.30 Months |
| Lenalidomide + Dexamethasone | Median Overall Survival (OS) | 39.62 Months |
Post Hoc
Median Progression Free Survival (PFS) - Extended Collection
The time from randomization to the date of first documented tumor progression or death due to any cause. Participants were censored at the last adequate assessment prior to the start of any subsequent systemic-therapy or at the last adequate assessment prior to 2 missing assessments (\> 10 weeks). Participants who died more than 10 weeks after the randomization date and had no on-treatment assessment were censored at the randomization date. Clinical deterioration was not considered progression. Tumor assessments were made every 4 weeks (±1 week) relative to the first dose of study medication based on Independent Review Committee (IRC) tumor assessment using the European Group for Blood and Bone Marrow Transplant (EBMT) criteria. Note: This outcome measure represents an updated version of the primary endpoint to include additional data collection that has occurred after the primary completion date. (Assessments were made until 06-Jul-2018)
Time frame: From randomization up to to the date of first documented tumor progression or death (up to approximately 85 months)
Population: All randomized participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lenalidomide + Dexamethasone + Elotuzumab | Median Progression Free Survival (PFS) - Extended Collection | 19.42 Months |
| Lenalidomide + Dexamethasone | Median Progression Free Survival (PFS) - Extended Collection | 14.92 Months |
Comparison: Hazard Ratio of Lenalidomide + Dexamethasone + Elotuzumab to Lenalidomide + Dexamethasonep-value: 0.000595% CI: [0.6, 0.87]Log Rank