Multiple Myeloma
Conditions
Brief summary
The purpose of this study is to determine the efficacy of Lenalidomide/Dexamethasone + Elotuzumab in the subjects with newly diagnosed, previously untreated Multiple Myeloma (MM) in Japan.
Interventions
DRUGLenalidomide
DRUGDexamethasone
BIOLOGICALElotuzumab (BMS-901608)
Sponsors
AbbVie
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: * Newly diagnosed with symptomatic Multiple Myeloma (MM) * Have not received any prior systemic anti-myeloma therapy * Have measurable disease * Are not candidates for high-dose therapy plus stem-cell transplantation (SCT) because of age (≥ 65 years) or coexisting conditions. Refusal to undergo high dose therapy with SCT is NOT sufficient for entry onto CA204-116 for a subject \< 65 years old. There must be a comorbidity that prevents SCT for a subject \< 65 years old
Exclusion criteria
* Non-secretory myeloma * Smoldering MM, defined as asymptomatic MM with absence of lytic bone lesions * Monoclonal Gammopathy of Undetermined Significance (MGUS) * Active plasma cell leukemia * Known Human Immunodeficiency Virus (HIV) infection or active hepatitis A, B, or C
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) of Participants Treated With Elotuzumab + Lenalidomide/Dexamethasone (E-Ld) | From first dose until documented response (assessed up to February 2017, approximately 24 months) | ORR is the proportion of randomized participants who achieve a stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or PR as determined by investigator using the International Myeloma Working Group (IMWG) response criteria. SCR: CR and normal free light chain (FLC) ratio and no clonal cells in bone marrow; CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein and urine M-protein level \< 100 mg/24 hours; PR: ≥ 50% reduction of serum M-Protein and reduction in urinary M-protein by ≥ 90% or to \< 200 mg/24 hours. In addition to the above, if present at baseline a ≥ 50% reduction in the size of soft tissue plasmacytomas is also required. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | From first dose until documented response, up to approximately 72 months | ORR is the percentage of randomized participants who achieve a stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR) as determined by investigator using the International Myeloma Working Group (IMWG) response criteria. SCR: CR and normal free light chain (FLC) ratio and no clonal cells in bone marrow; CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein and urine M-protein level \< 100 mg/24 hours; PR: ≥ 50% reduction of serum M-Protein and reduction in urinary M-protein by ≥ 90% or to \< 200 mg/24 hours. In addition to the above, if present at baseline a ≥ 50% reduction in the size of soft tissue plasmacytomas is also required. |
| Progression Free Survival (PFS) | From randomization to the date of first documented tumor progression or death due to any cause, up to approximately 72 months | PFS is defined as the time from randomization to the date of the first documented tumor progression, as determined by the investigator using the International Myeloma Working Group (IMWG) response criteria, or to death due to any cause, provided death does not occur more than 10 weeks (2 or more assessment visits) after the last tumor assessment. Clinical deterioration will not be considered progression. |
| Progression Free Survival (PFS) Rate | From randomization up to the specified timepoints, up to 3 years | PFS rate is defined as the percentage of participants who have neither progressed nor died at the specified timepoints |
Countries
Japan
Participant flow
Pre-assignment details
82 participants were randomized and treated.
Participants by arm
| Arm | Count |
|---|---|
| Arm A: Lenalidomide + Dexamethasone + Elotuzumab (BMS-901608) Lenalidomide
25 mg taken orally once daily, Days 1 - 21 of each cycle
Dexamethasone
Administered on Days 1, 8, 15, and 22 of each cycle:
On weeks when elotuzumab is administered:
* 28 mg taken orally (3 - 24 hours prior to start of elotuzumab infusion) AND
* 8 mg IV (at least 45 minutes prior to elotuzumab administration)
On weeks when elotuzumab is NOT administered:
\- 40 mg taken orally
Elotuzumab (BMS-901608)
* Cycle 1 - 2: 10 mg/kg IV, Days 1, 8, 15, 22
* Cycle 3 - 18: 10 mg/kg IV, Days 1 and 15
* Cycle 19 and beyond: 20 mg/kg IV, Day 1 | 40 |
| Arm B: Lenalidomide + Dexamethasone Lenalidomide
25 mg taken orally once a day, Days 1 - 21 of each cycle
Dexamethasone
40 mg taken orally, Days 1, 8, 15, and 22 of each cycle | 42 |
| Total | 82 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative reason by sponsor | 5 | 4 |
| Overall Study | Adverse Event unrelated to study drug | 3 | 5 |
| Overall Study | Death | 0 | 1 |
| Overall Study | Disease progression | 16 | 8 |
| Overall Study | Maximum clinical benefit | 4 | 2 |
| Overall Study | Other reasons | 1 | 3 |
| Overall Study | Participant request to discontinue study treatment | 3 | 7 |
| Overall Study | Poor/non-compliance | 2 | 2 |
| Overall Study | Study drug toxicity | 4 | 9 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | Arm B: Lenalidomide + Dexamethasone | Total | Arm A: Lenalidomide + Dexamethasone + Elotuzumab (BMS-901608) |
|---|---|---|---|
| Age, Continuous | 74.0 years STANDARD_DEVIATION 6.32 | 73.3 years STANDARD_DEVIATION 5.69 | 72.6 years STANDARD_DEVIATION 4.91 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 42 Participants | 82 Participants | 40 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 20 Participants | 43 Participants | 23 Participants |
| Sex: Female, Male Male | 22 Participants | 39 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 40 | 6 / 42 |
| other Total, other adverse events | 39 / 40 | 42 / 42 |
| serious Total, serious adverse events | 26 / 40 | 27 / 42 |
Outcome results
Primary
Objective Response Rate (ORR) of Participants Treated With Elotuzumab + Lenalidomide/Dexamethasone (E-Ld)
ORR is the proportion of randomized participants who achieve a stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or PR as determined by investigator using the International Myeloma Working Group (IMWG) response criteria. SCR: CR and normal free light chain (FLC) ratio and no clonal cells in bone marrow; CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein and urine M-protein level \< 100 mg/24 hours; PR: ≥ 50% reduction of serum M-Protein and reduction in urinary M-protein by ≥ 90% or to \< 200 mg/24 hours. In addition to the above, if present at baseline a ≥ 50% reduction in the size of soft tissue plasmacytomas is also required.
Time frame: From first dose until documented response (assessed up to February 2017, approximately 24 months)
Population: Participants treated with E-Ld
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A: Lenalidomide + Dexamethasone + Elotuzumab (BMS-901608) | Objective Response Rate (ORR) of Participants Treated With Elotuzumab + Lenalidomide/Dexamethasone (E-Ld) | 87.5 Percentage of participants |
Secondary
Objective Response Rate (ORR)
ORR is the percentage of randomized participants who achieve a stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR) as determined by investigator using the International Myeloma Working Group (IMWG) response criteria. SCR: CR and normal free light chain (FLC) ratio and no clonal cells in bone marrow; CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein and urine M-protein level \< 100 mg/24 hours; PR: ≥ 50% reduction of serum M-Protein and reduction in urinary M-protein by ≥ 90% or to \< 200 mg/24 hours. In addition to the above, if present at baseline a ≥ 50% reduction in the size of soft tissue plasmacytomas is also required.
Time frame: From first dose until documented response, up to approximately 72 months
Population: All randomized participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A: Lenalidomide + Dexamethasone + Elotuzumab (BMS-901608) | Objective Response Rate (ORR) | 92.5 Percentage of participants |
| Arm B: Lenalidomide + Dexamethasone | Objective Response Rate (ORR) | 73.8 Percentage of participants |
Secondary
Progression Free Survival (PFS)
PFS is defined as the time from randomization to the date of the first documented tumor progression, as determined by the investigator using the International Myeloma Working Group (IMWG) response criteria, or to death due to any cause, provided death does not occur more than 10 weeks (2 or more assessment visits) after the last tumor assessment. Clinical deterioration will not be considered progression.
Time frame: From randomization to the date of first documented tumor progression or death due to any cause, up to approximately 72 months
Population: All randomized participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: Lenalidomide + Dexamethasone + Elotuzumab (BMS-901608) | Progression Free Survival (PFS) | NA Months |
| Arm B: Lenalidomide + Dexamethasone | Progression Free Survival (PFS) | 43.33 Months |
95% CI: [0.41, 1.67]
Secondary
Progression Free Survival (PFS) Rate
PFS rate is defined as the percentage of participants who have neither progressed nor died at the specified timepoints
Time frame: From randomization up to the specified timepoints, up to 3 years
Population: All randomized participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A: Lenalidomide + Dexamethasone + Elotuzumab (BMS-901608) | Progression Free Survival (PFS) Rate | 1 year | 0.87 Percentage of Participants |
| Arm A: Lenalidomide + Dexamethasone + Elotuzumab (BMS-901608) | Progression Free Survival (PFS) Rate | 2 years | 0.67 Percentage of Participants |
| Arm A: Lenalidomide + Dexamethasone + Elotuzumab (BMS-901608) | Progression Free Survival (PFS) Rate | 3 years | 0.61 Percentage of Participants |
| Arm B: Lenalidomide + Dexamethasone | Progression Free Survival (PFS) Rate | 1 year | 0.89 Percentage of Participants |
| Arm B: Lenalidomide + Dexamethasone | Progression Free Survival (PFS) Rate | 2 years | 0.60 Percentage of Participants |
| Arm B: Lenalidomide + Dexamethasone | Progression Free Survival (PFS) Rate | 3 years | 0.56 Percentage of Participants |