Multiple Myeloma
Conditions
Brief summary
The purpose of this study is to evaluate the safety and effectiveness of several combination therapies for Multiple Myeloma. Upon entry into the study, patients will be randomized (assigned by chance) to receive either: Group 1: nivolumab, pomalidomide and dexamethasone OR Group 2: pomalidomide and dexamethasone OR Group 3: nivolumab, elotuzumab, pomalidomide and dexamethasone. Enrollment is closed for all groups.
Interventions
BIOLOGICALNivolumab
Specified dose on specified days, IV (intravenous)
BIOLOGICALElotuzumab
Specified dose on specified days, IV
DRUGPomalidomide
Specified dose on specified days, PO (by mouth)
DRUGDexamethasone
Specified dose on specified days, PO
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
* Refractory or relapsed and refractory multiple myeloma * Measurable disease * Have received ≥ 2 lines of prior therapy which must have included an immune modulatory drug (IMiD) and a proteasome inhibitor alone or in combination
Exclusion criteria
* Solitary bone or extramedullary plasmacytoma disease only * Active plasma cell leukemia Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | From randomization to the date of the first documented tumor progression or death due to any cause, whichever occurred first (Up to approximately 64 month) | Randomization to first documented tumor progression or death due to any cause, whichever occurred first. Participants who die without reported prior progression are considered to have progressed on date of their death. Participants who did not progress or die will be censored at their last efficacy assessment. Participants who did not have on study efficacy assessments and alive will be censored on randomization date. Participants who started subsequent anti-cancer therapy without prior reported progression will be censored at last efficacy assessment prior to subsequent anti-cancer therapy. Progression is 1) increase of 25% from lowest confirmed response value in specific Serum M-protein and Urine M-protein criteria and increase of FLC for patients with no measurable M protein in blood or urine at baseline and/or 2) appearance of a new lesion(s), \>/= 50% increase from nadir in SPD of \> 1 lesion, or \>/= 50% increase in the longest diameter of a previous lesion \> 1 cm in short axis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | From randomization to the date of death due to any cause (up to approximately 64 months) | The time between the date of randomization and the date of death due to any cause. OS will be censored on the last date a participant was known to be alive. |
| Objective Response Rate (ORR) | From randomization up to approximately 64 months | The percentage of randomized 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 International Myeloma Working Group (IMWG) criteria. sCR= Complete response as defined below plus normal FLC ratio and absence of clonal cells in bone marrow biopsy by immunohistochemistry. CR = Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \< 5% plasma cells in bone marrow aspirates. VGPR = Serum and urine M-protein detectable by immunofixation but not on electrophoresis or \>/= 90% reduction in serum M-protein plus urine M-protein level \< 100 mg per 24 h. PR = \>/= 50% reduction of serum M-protein plus reduction in 24 h urinary M-protein by \>/= 90% or to \< 200 mg per 24 h. |
| Time to Objective Response (TTR) | From the date of randomization to the date of the first sCR, CR, VGPR, or PR (up to approximately 64 months) | The time from the date of randomization to the date of the first stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR). sCR= Complete response as defined below plus normal FLC ratio and absence of clonal cells in bone marrow biopsy by immunohistochemistry. CR = Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \< 5% plasma cells in bone marrow aspirates. VGPR = Serum and urine M-protein detectable by immunofixation but not on electrophoresis or \>/= 90% reduction in serum M-protein plus urine M-protein level \< 100 mg per 24 h. PR = \>/= 50% reduction of serum M-protein plus reduction in 24 h urinary M-protein by \>/= 90% or to \< 200 mg per 24 h. |
| Duration of Objective Response (DOR) | From randomization to the date of the first objectively documented tumor progression or death due to any cause prior to subsequent anti-cancer therapy (up to approximately 64 months) | The time between the date of first response to the date of the first objectively documented tumor progression as assessed by the investigator according to International Myeloma Working Group (IMWG) criteria or death due to any cause prior to subsequent anti-cancer therapy. Participants who neither progress nor die will be censored on the date of their last tumor assessment prior to subsequent anti-cancer therapy. Progression is 1) increase of 25% from lowest confirmed response value in specific Serum M-protein and Urine M-protein criteria and increase of FLC for patients with no measurable M protein in blood or urine at baseline and/or 2) appearance of a new lesion(s), \>/= 50% increase from nadir in SPD of \> 1 lesion, or \>/= 50% increase in the longest diameter of a previous lesion \> 1 cm in short axis. |
Countries
Austria, Canada, Czechia, Denmark, Germany, Greece, Israel, Italy, Norway, Portugal, Puerto Rico, Spain, Sweden, Switzerland, Turkey (Türkiye), United States
Participant flow
Pre-assignment details
This study contains an exploratory third arm evaluating the clinical benefit and the safety of the combination therapy of elotuzumab, nivolumab, pomalidomide and dexamethasone (Arm C: NE-Pd). Participants randomized to the Pd arm were allowed to cross over to this exploratory NE-Pd arm at the time of progression.
Participants by arm
| Arm | Count |
|---|---|
| Arm A: N-Pd Nivolumab:
* Cycles 1 through 4: 240 mg IV Days 1, 15 of each 28-day cycle.
* Cycles 5 and beyond: 480 mg IV Day 1 of each 28-day cycle.
Pomalidomide:
\- 4 mg PO QD Days 1-21 of each 28-day cycle.
Dexamethasone:
* Participants \</= 75 years old: 40 mg PO Days (1, 8, 15, and 22) of each cycle
* Participants \> 75 years old: 20 mg PO Days (1, 8, 15, and 22) of each cycle. | 75 |
| Arm B: Pd Pomalidomide:
\- 4 mg PO QD Days 1-21 of each 28-day cycle.
Dexamethasone:
* Participants \</= 75 years old: 40 mg PO Days (1, 8, 15, and 22) of each cycle
* Participants \> 75 years old: 20 mg PO Days (1, 8, 15, and 22) of each cycle. | 71 |
| Arm C: NE-Pd Nivolumab:
* Cycles 1 through 4: 240 mg IV Days 1, 15 of each 28-day cycle.
* Cycles 5 and beyond: 480 mg IV Day 1 of each 28-day cycle.
Elotuzumab:
* Cycles 1 - 2: 10 mg/kg IV Days 1, 8, 15, and 22 of each 28-day cycle.
* Cycle 3 and 4: 10mg/kg IV Day 1 and 15 of each 28-day cycle.
* Cycles 5 and beyond: 20 mg/kg IV Day 1 of each 28-day cycle.
Pomalidomide:
4 mg PO QD Days 1-21 of each 28-day cycle.
Dexamethasone:
Days 1, 8, 15, and 22 of each cycle.
* Participants \</= 75 years old: weeks with elotuzumab dosing: 28 mg PO + 8 mg IV and 40 mg PO on non-elotuzumab dosing weeks.
* Participants \> 75 years old: weeks with elotuzumab dosing: 8 mg PO + 8 mg IV and 20 mg PO on non-elotuzumab dosing weeks. | 24 |
| Total | 170 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Pre-Treatment Period | Administrative reason by sponsor | 2 | 0 | 0 |
| Pre-Treatment Period | Participant no longer meets study criteria | 1 | 0 | 0 |
| Pre-Treatment Period | Participant request to discontinue study treatment | 0 | 1 | 0 |
| Treatment Period | Adverse event unrelated to study drug | 4 | 4 | 2 |
| Treatment Period | Death | 1 | 0 | 0 |
| Treatment Period | Disease progression | 47 | 50 | 16 |
| Treatment Period | Maximum clinical benefit | 0 | 2 | 0 |
| Treatment Period | Other reasons | 9 | 8 | 2 |
| Treatment Period | Participant no longer meets study criteria | 0 | 1 | 0 |
| Treatment Period | Participant request to discontinue study treatment | 1 | 1 | 1 |
| Treatment Period | Participant withdrew consent | 3 | 1 | 1 |
| Treatment Period | Poor/non-compliance | 1 | 0 | 0 |
| Treatment Period | Study drug toxicity | 6 | 3 | 2 |
Baseline characteristics
| Characteristic | Arm A: N-Pd | Arm B: Pd | Arm C: NE-Pd | Total |
|---|---|---|---|---|
| Age, Continuous | 65.9 Years STANDARD_DEVIATION 9.4 | 65.5 Years STANDARD_DEVIATION 8.7 | 66.2 Years STANDARD_DEVIATION 11.5 | 65.8 Years STANDARD_DEVIATION 9.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 4 Participants | 1 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 40 Participants | 41 Participants | 15 Participants | 96 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 34 Participants | 26 Participants | 8 Participants | 68 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 5 Participants | 5 Participants | 13 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 72 Participants | 64 Participants | 19 Participants | 155 Participants |
| Sex: Female, Male Female | 24 Participants | 25 Participants | 8 Participants | 57 Participants |
| Sex: Female, Male Male | 51 Participants | 46 Participants | 16 Participants | 113 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 47 / 75 | 49 / 71 | 17 / 24 | 5 / 8 |
| other Total, other adverse events | 70 / 72 | 65 / 70 | 24 / 24 | 7 / 8 |
| serious Total, serious adverse events | 52 / 72 | 41 / 70 | 18 / 24 | 5 / 8 |
Outcome results
Primary
Progression Free Survival (PFS)
Randomization to first documented tumor progression or death due to any cause, whichever occurred first. Participants who die without reported prior progression are considered to have progressed on date of their death. Participants who did not progress or die will be censored at their last efficacy assessment. Participants who did not have on study efficacy assessments and alive will be censored on randomization date. Participants who started subsequent anti-cancer therapy without prior reported progression will be censored at last efficacy assessment prior to subsequent anti-cancer therapy. Progression is 1) increase of 25% from lowest confirmed response value in specific Serum M-protein and Urine M-protein criteria and increase of FLC for patients with no measurable M protein in blood or urine at baseline and/or 2) appearance of a new lesion(s), \>/= 50% increase from nadir in SPD of \> 1 lesion, or \>/= 50% increase in the longest diameter of a previous lesion \> 1 cm in short axis.
Time frame: From randomization to the date of the first documented tumor progression or death due to any cause, whichever occurred first (Up to approximately 64 month)
Population: All randomized participants in Arm A and B. Data was pre-specified to be collected only in the N-Pd and Pd arms.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: N-Pd | Progression Free Survival (PFS) | 8.38 Months |
| Arm B: Pd | Progression Free Survival (PFS) | 7.33 Months |
95% CI: [0.62, 1.3]
Secondary
Duration of Objective Response (DOR)
The time between the date of first response to the date of the first objectively documented tumor progression as assessed by the investigator according to International Myeloma Working Group (IMWG) criteria or death due to any cause prior to subsequent anti-cancer therapy. Participants who neither progress nor die will be censored on the date of their last tumor assessment prior to subsequent anti-cancer therapy. Progression is 1) increase of 25% from lowest confirmed response value in specific Serum M-protein and Urine M-protein criteria and increase of FLC for patients with no measurable M protein in blood or urine at baseline and/or 2) appearance of a new lesion(s), \>/= 50% increase from nadir in SPD of \> 1 lesion, or \>/= 50% increase in the longest diameter of a previous lesion \> 1 cm in short axis.
Time frame: From randomization to the date of the first objectively documented tumor progression or death due to any cause prior to subsequent anti-cancer therapy (up to approximately 64 months)
Population: All responders (sCR, CR, VGPR, or PR) in Arm A and B. Data was pre-specified to be collected only in the N-Pd and Pd arms.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: N-Pd | Duration of Objective Response (DOR) | 8.51 Months |
| Arm B: Pd | Duration of Objective Response (DOR) | 6.47 Months |
Secondary
Objective Response Rate (ORR)
The percentage of randomized 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 International Myeloma Working Group (IMWG) criteria. sCR= Complete response as defined below plus normal FLC ratio and absence of clonal cells in bone marrow biopsy by immunohistochemistry. CR = Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \< 5% plasma cells in bone marrow aspirates. VGPR = Serum and urine M-protein detectable by immunofixation but not on electrophoresis or \>/= 90% reduction in serum M-protein plus urine M-protein level \< 100 mg per 24 h. PR = \>/= 50% reduction of serum M-protein plus reduction in 24 h urinary M-protein by \>/= 90% or to \< 200 mg per 24 h.
Time frame: From randomization up to approximately 64 months
Population: All randomized participants in Arm A and B. Data was pre-specified to be collected only in the N-Pd and Pd arms.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A: N-Pd | Objective Response Rate (ORR) | 48.0 Percentage of participants |
| Arm B: Pd | Objective Response Rate (ORR) | 54.9 Percentage of participants |
95% CI: [0.39, 1.46]
Secondary
Overall Survival (OS)
The time between the date of randomization and the date of death due to any cause. OS will be censored on the last date a participant was known to be alive.
Time frame: From randomization to the date of death due to any cause (up to approximately 64 months)
Population: All randomized participants in Arm A and B. Data was pre-specified to be collected only in the N-Pd and Pd arms.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: N-Pd | Overall Survival (OS) | 24.87 Months |
| Arm B: Pd | Overall Survival (OS) | 21.39 Months |
95% CI: [0.53, 1.19]
Secondary
Time to Objective Response (TTR)
The time from the date of randomization to the date of the first stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR). sCR= Complete response as defined below plus normal FLC ratio and absence of clonal cells in bone marrow biopsy by immunohistochemistry. CR = Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \< 5% plasma cells in bone marrow aspirates. VGPR = Serum and urine M-protein detectable by immunofixation but not on electrophoresis or \>/= 90% reduction in serum M-protein plus urine M-protein level \< 100 mg per 24 h. PR = \>/= 50% reduction of serum M-protein plus reduction in 24 h urinary M-protein by \>/= 90% or to \< 200 mg per 24 h.
Time frame: From the date of randomization to the date of the first sCR, CR, VGPR, or PR (up to approximately 64 months)
Population: All responders (sCR, CR, VGPR, or PR) in Arm A and B. Data was pre-specified to be collected only in the N-Pd and Pd arms.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm A: N-Pd | Time to Objective Response (TTR) | 5.91 Months | Standard Deviation 9.09 |
| Arm B: Pd | Time to Objective Response (TTR) | 4.37 Months | Standard Deviation 5.63 |