Multiple Myeloma
Conditions
Keywords
Newly Diagnosed, Previously Untreated
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
BIOLOGICALElotuzumab (BMS-901608; HuLuc63)
Solution, Intravenous (IV), 10 mg/kg, weekly, on Days 1, 8, 15, 22 (cycles 1&2); Days 1 and 15 (cycles 3-18), 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: * Subjects who are newly diagnosed with symptomatic Multiple Myeloma (MM) and who: * have not received any prior systemic anti-myeloma therapy AND * have measurable disease AND * 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 CA204006 for a subject \< 65 years old. There must be a comorbidity that prevents SCT for a subject \< 65 years old
Exclusion criteria
* Subjects with non-secretory or oligo-secretory or free light-chain only 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 |
|---|---|---|
| Progression-Free Survival (PFS) | From randomization to date of first documented tumor progression or death due to any cause (up to 8 years) | PFS is defined as the time from randomization to the date of the first documented tumor progression (as determined by the Independent Review Committee (IRC)) or death due to any cause. The IRC conducted a blinded, independent review of the tumor assessments based on the European Group for Blood and Bone Marrow Transplant (EBMT) criteria. Censoring rules applied: * Participants receiving subsequent systemic anti-myeloma therapy prior to documented progression were censored at the date of the last adequate tumor assessment prior to new therapy. * Participants who had an event (progression or death) \> 10 weeks after their last tumor assessment were censored at their last adequate tumor assessment prior to the event. * Participants without progression or death (and not receiving subsequent therapy prior to progression) were censored at their last adequate tumor assessment. * Participants without any post-baseline tumor assessments were censored on the date of randomization |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | From randomization to primary completion date (approximately 8 years) | ORR is defined as the percentage of participants with objective response among all randomized subjects. Participants with an objective response are those participants experiencing a partial response (PR) or better, based on Independent Review Committee (IRC) assessment, as per EBMT criteria. |
| Overall Survival (OS) | From randomization to the date of death (up to 8 years) | Survival is defined as the time from randomization to the date of death. A participant who did not die had his or her survival duration censored at the date of last contact ('last known date alive). |
| Mean Change From Baseline of Pain Severity Score and Pain Interference Score | From Baseline to End of Treatment (approximately 8 years) | Pain severity (sensory dimension) and pain interference (reactive dimension, assessing the degree to which pain interferes with function) are measured using the Brief Pain Inventory- Short Form (BPI-SF). BPI-SF numeric rating scale goes from 0 (No pain) to 10 (Pain as bad as you can imagine). |
| Progression Free Survival (PFS) Rate at Specific Time-points | From randomization to the specified time-point (up to 5 years) | PFS rate is defined as the percentage of participants experiencing PFS at the defined time-points. |
Countries
Australia, Austria, Belgium, Canada, Czechia, Germany, Greece, Hungary, Ireland, Israel, Italy, Poland, Puerto Rico, Romania, Russia, Spain, Switzerland, Turkey (Türkiye), United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| E-Ld Cohort Participants receiving a combination of Elotuzumab (E) Lenalidomide (L) Dexamethasone (d) in a 28 day cycle | 374 |
| Ld Cohort Participants receiving a combination of Lenalidomide (L) Dexamethasone (d) in a 28 day cycle | 374 |
| Total | 748 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Pre-treatment Period | Adverse event unrelated to study drug | 0 | 1 |
| Pre-treatment Period | Consent withdrawal | 3 | 0 |
| Pre-treatment Period | No longer meeting study criteria | 0 | 1 |
| Pre-treatment Period | Participant request to discontinue | 0 | 1 |
| Treatment Period | Administrative reasons by Sponsor | 8 | 16 |
| Treatment Period | Adverse event unrelated to study drug | 110 | 73 |
| Treatment Period | Consent withdrawal | 10 | 7 |
| Treatment Period | Death | 7 | 6 |
| Treatment Period | Disease progression | 117 | 145 |
| Treatment Period | Lost to Follow-up | 2 | 2 |
| Treatment Period | Maximum clinical benefit | 1 | 1 |
| Treatment Period | No longer meet study criteria | 1 | 1 |
| Treatment Period | Other reasons | 30 | 30 |
| Treatment Period | Participant request to discontinue | 30 | 22 |
| Treatment Period | Poor/Non-compliance | 3 | 4 |
| Treatment Period | Study drug toxicity | 52 | 64 |
Baseline characteristics
| Characteristic | Ld Cohort | Total | E-Ld Cohort |
|---|---|---|---|
| Age, Continuous | 73.1 Years STANDARD_DEVIATION 6.7 | 73.0 Years STANDARD_DEVIATION 6.63 | 72.9 Years STANDARD_DEVIATION 6.58 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants | 17 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 87 Participants | 157 Participants | 70 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 279 Participants | 574 Participants | 295 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 5 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 16 Participants | 29 Participants | 13 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) White | 351 Participants | 711 Participants | 360 Participants |
| Sex: Female, Male Female | 173 Participants | 336 Participants | 163 Participants |
| Sex: Female, Male Male | 201 Participants | 412 Participants | 211 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 240 / 374 | 232 / 374 |
| other Total, other adverse events | 364 / 371 | 365 / 371 |
| serious Total, serious adverse events | 293 / 371 | 279 / 371 |
Outcome results
Primary
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 Independent Review Committee (IRC)) or death due to any cause. The IRC conducted a blinded, independent review of the tumor assessments based on the European Group for Blood and Bone Marrow Transplant (EBMT) criteria. Censoring rules applied: * Participants receiving subsequent systemic anti-myeloma therapy prior to documented progression were censored at the date of the last adequate tumor assessment prior to new therapy. * Participants who had an event (progression or death) \> 10 weeks after their last tumor assessment were censored at their last adequate tumor assessment prior to the event. * Participants without progression or death (and not receiving subsequent therapy prior to progression) were censored at their last adequate tumor assessment. * Participants without any post-baseline tumor assessments were censored on the date of randomization
Time frame: From randomization to date of first documented tumor progression or death due to any cause (up to 8 years)
Population: All randomized participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| E-Ld Cohort | Progression-Free Survival (PFS) | 31.38 Months |
| Ld Cohort | Progression-Free Survival (PFS) | 29.47 Months |
p-value: 0.4358Stratified Log Rank
95.71% CI: [0.77, 1.12]
Secondary
Mean Change From Baseline of Pain Severity Score and Pain Interference Score
Pain severity (sensory dimension) and pain interference (reactive dimension, assessing the degree to which pain interferes with function) are measured using the Brief Pain Inventory- Short Form (BPI-SF). BPI-SF numeric rating scale goes from 0 (No pain) to 10 (Pain as bad as you can imagine).
Time frame: From Baseline to End of Treatment (approximately 8 years)
Population: All randomized participants
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| E-Ld Cohort | Mean Change From Baseline of Pain Severity Score and Pain Interference Score | Pain Severity | 0.02 Rating score | Standard Deviation 2.645 |
| E-Ld Cohort | Mean Change From Baseline of Pain Severity Score and Pain Interference Score | Pain Interference | 0.33 Rating score | Standard Deviation 3.077 |
| Ld Cohort | Mean Change From Baseline of Pain Severity Score and Pain Interference Score | Pain Severity | -0.25 Rating score | Standard Deviation 2.721 |
| Ld Cohort | Mean Change From Baseline of Pain Severity Score and Pain Interference Score | Pain Interference | -0.18 Rating score | Standard Deviation 3.082 |
Secondary
Objective Response Rate (ORR)
ORR is defined as the percentage of participants with objective response among all randomized subjects. Participants with an objective response are those participants experiencing a partial response (PR) or better, based on Independent Review Committee (IRC) assessment, as per EBMT criteria.
Time frame: From randomization to primary completion date (approximately 8 years)
Population: All randomized participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| E-Ld Cohort | Objective Response Rate (ORR) | 82.9 Percent of Participants |
| Ld Cohort | Objective Response Rate (ORR) | 79.4 Percent of Participants |
p-value: 0.223295% CI: [0.87, 1.82]CMH ESTIMATE OF COMMON ODDS RATIO
Secondary
Overall Survival (OS)
Survival is defined as the time from randomization to the date of death. A participant who did not die had his or her survival duration censored at the date of last contact ('last known date alive).
Time frame: From randomization to the date of death (up to 8 years)
Population: All randomized participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| E-Ld Cohort | Overall Survival (OS) | 60.42 Months |
| Ld Cohort | Overall Survival (OS) | 57.56 Months |
p-value: 0.893295% CI: [0.82, 1.19]Stratified log rank test
Secondary
Progression Free Survival (PFS) Rate at Specific Time-points
PFS rate is defined as the percentage of participants experiencing PFS at the defined time-points.
Time frame: From randomization to the specified time-point (up to 5 years)
Population: All randomized participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| E-Ld Cohort | Progression Free Survival (PFS) Rate at Specific Time-points | 2 year | 0.59 Percent of participants |
| E-Ld Cohort | Progression Free Survival (PFS) Rate at Specific Time-points | 4 year | 0.36 Percent of participants |
| E-Ld Cohort | Progression Free Survival (PFS) Rate at Specific Time-points | 3 year | 0.46 Percent of participants |
| E-Ld Cohort | Progression Free Survival (PFS) Rate at Specific Time-points | 5 year | 0.26 Percent of participants |
| E-Ld Cohort | Progression Free Survival (PFS) Rate at Specific Time-points | 1 year | 0.77 Percent of participants |
| Ld Cohort | Progression Free Survival (PFS) Rate at Specific Time-points | 5 year | 0.25 Percent of participants |
| Ld Cohort | Progression Free Survival (PFS) Rate at Specific Time-points | 1 year | 0.76 Percent of participants |
| Ld Cohort | Progression Free Survival (PFS) Rate at Specific Time-points | 2 year | 0.55 Percent of participants |
| Ld Cohort | Progression Free Survival (PFS) Rate at Specific Time-points | 3 year | 0.41 Percent of participants |
| Ld Cohort | Progression Free Survival (PFS) Rate at Specific Time-points | 4 year | 0.33 Percent of participants |
p-value: 0.435895% CI: [0.78, 1.12]Hazard Ratio