Smoldering Multiple Myeloma
Conditions
Brief summary
The purpose of this study is to determine whether elotuzumab will improve response in patients with high risk smoldering myeloma who have more CD56\^dim cells (a marker for the health of the body's immune system)
Detailed description
Intervention model: Dosing is sequential
Interventions
BIOLOGICALElotuzumab (BMS-901608; HuLuc63)
Sponsors
AbbVie
Bristol-Myers Squibb
Study design
Allocation
NON_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. Key Inclusion Criteria: Participants with a confirmed diagnosis, according to criteria of the International Myeloma Working Group, of smoldering multiple myeloma, considered high risk according to the following: * Serum monoclonal (M) protein ≥3 gm/dL and bone marrow plasma cells (BMPC) ≥10% or * Serum M protein 1-3 g/dL and BMPC ≥10% and abnormal free light chain ratio of \<0.125 or \>8.0 * Urine M protein \>200 mg/24 hours, ≥10% BMPC, and serum free light chain ratio ≤0.125 or ≥8.0 Key
Exclusion criteria
* Active multiple myeloma * Monoclonal gammopathy of undetermined significance * Active plasma cell leukemia * Positive for hepatitis B or C virus or HIV infection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Linear Regression of Maximal Percent Reduction in Serum Monoclonal (M) Protein on Baseline Percent CD56^Dim Cells in Bone Marrow | From day of last patient, first dose to 6 months | Estimated using linear regression model, with baseline CD56\^dim cells as the independent covariate, and maximal percent reduction in serum M protein as the dependent variable. For 1 patient who had nonmeasurable disease at baseline, the percent change in serum kappa-lambda difference was used instead of the percent change in serum M protein. Unit of measure=percent change from baseline in M protein cells/ percent change in CD56\^dim cells (% chg from BL in M pro/% chg CD56\^dim cs) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) Rate | Up to 2 years from the initiation of study therapy by dose cohort (approximately 24 months) | The probability was estimated from the K-M curve of subjects being alive and without disease progression (modified IMWG criteria) at 2 years from the initiation of study therapy by dose cohort |
| Number of Participants Who Died and With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Infusion Reactions | From day of last patient, first dose to 6 months | AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. |
| Number of Participants With Laboratory Test Results Meeting the Criteria for Grade 3-4 Abnormality | From date of first dose to date of last dose plus 60 days (assessed up to August 2017, approximately 59 months | Clinical laboratory evaluations included hematology, chemistry, and liver and renal functioning. |
| Number of Participants With a Dose- or Concentration-related Effect on QTcF Interval, PR Interval, QRS Interval, and Heart Rate | cycle 1 to first day of cycle 3 assessed up to 08/17, approximately 59 months | All on-treatment electrocardiograms (ECGs) were performed in triplicates ( 1 ECG test equaled 3 consecutive individual 12-lead ECGs performed within a 4-minute period). The timing of the ECG was critical to the endpoint of the study. The investigative site documented any deviations from the protocol or procedures related to ECG collection or serum sampling. No ECGs were excluded due to timing deviations; no deviations were considered clinically relevant and all ECG data were included. |
| Objective Response Rate (ORR) | From first dose to date of progression or objective response (assessed up to August 2017, approximately 59 months) | ORR is defined as the number of participants with stringent compete response \[SCR\], complete response \[CR\], very good partial response \[VGPR\], and partial response \[PR\])/number of participants in arm, expressed as a percentage. Confidence intervals computed using the Clopper and Pearson method. SCR=CR plus normal free light chain ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence. CR=Negative immunofixation on serum and urine and 5% or fewer plasma cells in bone marrow. VGPR=Serum and urine monoclonal (M) protein detectable by immunofixation but not on electrophoresis or 90% reduction in serum M protein level plus urine M protein level \<100 mg/24 hour. PR=50% reduction of serum M protein and reduction in 24-hour urinary M protein by 90% or to \<200 mg/24 hour |
Countries
United States
Participant flow
Pre-assignment details
The study enrolled a total of 41 participants, and 31 received treatment. The 10 participants enrolled who did not receive treatment failed to meet the inclusion criteria.
Participants by arm
| Arm | Count |
|---|---|
| Elotuzumab, 20 mg/kg Participants in 2 arms were enrolled sequentially. The first group of participants received elotuzumab intravenously at a dose of 20 mg/kg on Days 1 and 8 per 28-day cycle for Cycle 1 and then on Day 1 only in subsequent cycles. | 15 |
| Elotuzumab, 10 mg/kg Participants in the second group received elotuzumab intravenously at a dose of 10 mg/kg weekly per 28-day cycle in Cycles 1 and 2, then on Days 1 and 15 in subsequent cycles. | 16 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative reason by sponsor | 3 | 5 |
| Overall Study | Adverse event unrelated to study drug | 3 | 2 |
| Overall Study | Disease progression | 8 | 6 |
| Overall Study | Participant request to discontinue | 1 | 1 |
| Overall Study | Participant withdrew consent | 0 | 1 |
| Overall Study | Poor compliance/noncompliance | 0 | 1 |
Baseline characteristics
| Characteristic | Elotuzumab, 20 mg/kg | Elotuzumab, 10 mg/kg | Total |
|---|---|---|---|
| Age, Continuous | 59.0 Years STANDARD_DEVIATION 9.75 | 59.3 Years STANDARD_DEVIATION 9.37 | 59.2 Years STANDARD_DEVIATION 9.4 |
| Age, Customized 65 years and older to younger than 75 years | 5 Participants | 2 Participants | 7 Participants |
| Age, Customized 75 years and older | 0 Participants | 1 Participants | 1 Participants |
| Age, Customized Younger than 65 years | 10 Participants | 13 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants | 15 Participants | 30 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 14 Participants | 15 Participants | 29 Participants |
| Serum monoclonal (M) protein | 29.5 g/L STANDARD_DEVIATION 15.19 | 21.9 g/L STANDARD_DEVIATION 11.46 | 25.6 g/L STANDARD_DEVIATION 13.72 |
| Sex: Female, Male Female | 5 Participants | 9 Participants | 14 Participants |
| Sex: Female, Male Male | 10 Participants | 7 Participants | 17 Participants |
| Time from diagnosis to enrollment | 31.75 Months STANDARD_DEVIATION 37.572 | 36.81 Months STANDARD_DEVIATION 35.103 | 34.37 Months STANDARD_DEVIATION 35.798 |
| Urine M protein | 0.208 g/day STANDARD_DEVIATION 0.6199 | 0.094 g/day STANDARD_DEVIATION 0.2131 | 0.149 g/day STANDARD_DEVIATION 0.4532 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 16 / 16 | 15 / 15 |
| serious Total, serious adverse events | 7 / 16 | 8 / 15 |
Outcome results
Primary
Linear Regression of Maximal Percent Reduction in Serum Monoclonal (M) Protein on Baseline Percent CD56^Dim Cells in Bone Marrow
Estimated using linear regression model, with baseline CD56\^dim cells as the independent covariate, and maximal percent reduction in serum M protein as the dependent variable. For 1 patient who had nonmeasurable disease at baseline, the percent change in serum kappa-lambda difference was used instead of the percent change in serum M protein. Unit of measure=percent change from baseline in M protein cells/ percent change in CD56\^dim cells (% chg from BL in M pro/% chg CD56\^dim cs)
Time frame: From day of last patient, first dose to 6 months
Population: All participants who received at least 1 dose of study drug and had the required data (4 participants did not have baseline data available).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Elotuzumab, 20 mg/kg | Linear Regression of Maximal Percent Reduction in Serum Monoclonal (M) Protein on Baseline Percent CD56^Dim Cells in Bone Marrow | -2.562 % chg from BL in M pro/% chg CD56^dim cs |
| Elotuzumab, 10 mg/kg | Linear Regression of Maximal Percent Reduction in Serum Monoclonal (M) Protein on Baseline Percent CD56^Dim Cells in Bone Marrow | 2.464 % chg from BL in M pro/% chg CD56^dim cs |
| Elotuzumab, All Dosages | Linear Regression of Maximal Percent Reduction in Serum Monoclonal (M) Protein on Baseline Percent CD56^Dim Cells in Bone Marrow | 0.274 % chg from BL in M pro/% chg CD56^dim cs |
Secondary
Number of Participants Who Died and With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Infusion Reactions
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.
Time frame: From day of last patient, first dose to 6 months
Population: All participants who received at least 1 dose of study drug
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Elotuzumab, 20 mg/kg | Number of Participants Who Died and With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Infusion Reactions | Deaths | 0 Participants |
| Elotuzumab, 20 mg/kg | Number of Participants Who Died and With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Infusion Reactions | SAEs | 8 Participants |
| Elotuzumab, 20 mg/kg | Number of Participants Who Died and With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Infusion Reactions | AEs leading to discontinuation | 4 Participants |
| Elotuzumab, 20 mg/kg | Number of Participants Who Died and With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Infusion Reactions | Infusion reactions | 4 Participants |
| Elotuzumab, 10 mg/kg | Number of Participants Who Died and With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Infusion Reactions | Infusion reactions | 1 Participants |
| Elotuzumab, 10 mg/kg | Number of Participants Who Died and With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Infusion Reactions | Deaths | 0 Participants |
| Elotuzumab, 10 mg/kg | Number of Participants Who Died and With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Infusion Reactions | AEs leading to discontinuation | 2 Participants |
| Elotuzumab, 10 mg/kg | Number of Participants Who Died and With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Infusion Reactions | SAEs | 7 Participants |
| Elotuzumab, All Dosages | Number of Participants Who Died and With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Infusion Reactions | Infusion reactions | 5 Participants |
| Elotuzumab, All Dosages | Number of Participants Who Died and With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Infusion Reactions | SAEs | 15 Participants |
| Elotuzumab, All Dosages | Number of Participants Who Died and With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Infusion Reactions | AEs leading to discontinuation | 6 Participants |
| Elotuzumab, All Dosages | Number of Participants Who Died and With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Infusion Reactions | Deaths | 0 Participants |
Secondary
Number of Participants With a Dose- or Concentration-related Effect on QTcF Interval, PR Interval, QRS Interval, and Heart Rate
All on-treatment electrocardiograms (ECGs) were performed in triplicates ( 1 ECG test equaled 3 consecutive individual 12-lead ECGs performed within a 4-minute period). The timing of the ECG was critical to the endpoint of the study. The investigative site documented any deviations from the protocol or procedures related to ECG collection or serum sampling. No ECGs were excluded due to timing deviations; no deviations were considered clinically relevant and all ECG data were included.
Time frame: cycle 1 to first day of cycle 3 assessed up to 08/17, approximately 59 months
Population: All participants who received at least 1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Elotuzumab, 20 mg/kg | Number of Participants With a Dose- or Concentration-related Effect on QTcF Interval, PR Interval, QRS Interval, and Heart Rate | 0 Participants |
| Elotuzumab, 10 mg/kg | Number of Participants With a Dose- or Concentration-related Effect on QTcF Interval, PR Interval, QRS Interval, and Heart Rate | 0 Participants |
| Elotuzumab, All Dosages | Number of Participants With a Dose- or Concentration-related Effect on QTcF Interval, PR Interval, QRS Interval, and Heart Rate | 0 Participants |
Secondary
Number of Participants With Laboratory Test Results Meeting the Criteria for Grade 3-4 Abnormality
Clinical laboratory evaluations included hematology, chemistry, and liver and renal functioning.
Time frame: From date of first dose to date of last dose plus 60 days (assessed up to August 2017, approximately 59 months
Population: All participants who received at least 1 dose of study drug
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Elotuzumab, 20 mg/kg | Number of Participants With Laboratory Test Results Meeting the Criteria for Grade 3-4 Abnormality | Lymphocytes | 2 Participants |
| Elotuzumab, 20 mg/kg | Number of Participants With Laboratory Test Results Meeting the Criteria for Grade 3-4 Abnormality | Hyponatremia | 1 Participants |
| Elotuzumab, 20 mg/kg | Number of Participants With Laboratory Test Results Meeting the Criteria for Grade 3-4 Abnormality | Hyperkalemia | 0 Participants |
| Elotuzumab, 20 mg/kg | Number of Participants With Laboratory Test Results Meeting the Criteria for Grade 3-4 Abnormality | Hyperglycemia | 1 Participants |
| Elotuzumab, 10 mg/kg | Number of Participants With Laboratory Test Results Meeting the Criteria for Grade 3-4 Abnormality | Hyperglycemia | 2 Participants |
| Elotuzumab, 10 mg/kg | Number of Participants With Laboratory Test Results Meeting the Criteria for Grade 3-4 Abnormality | Lymphocytes | 1 Participants |
| Elotuzumab, 10 mg/kg | Number of Participants With Laboratory Test Results Meeting the Criteria for Grade 3-4 Abnormality | Hyperkalemia | 1 Participants |
| Elotuzumab, 10 mg/kg | Number of Participants With Laboratory Test Results Meeting the Criteria for Grade 3-4 Abnormality | Hyponatremia | 1 Participants |
| Elotuzumab, All Dosages | Number of Participants With Laboratory Test Results Meeting the Criteria for Grade 3-4 Abnormality | Hyperglycemia | 3 Participants |
| Elotuzumab, All Dosages | Number of Participants With Laboratory Test Results Meeting the Criteria for Grade 3-4 Abnormality | Hyponatremia | 2 Participants |
| Elotuzumab, All Dosages | Number of Participants With Laboratory Test Results Meeting the Criteria for Grade 3-4 Abnormality | Hyperkalemia | 1 Participants |
| Elotuzumab, All Dosages | Number of Participants With Laboratory Test Results Meeting the Criteria for Grade 3-4 Abnormality | Lymphocytes | 3 Participants |
Secondary
Objective Response Rate (ORR)
ORR is defined as the number of participants with stringent compete response \[SCR\], complete response \[CR\], very good partial response \[VGPR\], and partial response \[PR\])/number of participants in arm, expressed as a percentage. Confidence intervals computed using the Clopper and Pearson method. SCR=CR plus normal free light chain ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence. CR=Negative immunofixation on serum and urine and 5% or fewer plasma cells in bone marrow. VGPR=Serum and urine monoclonal (M) protein detectable by immunofixation but not on electrophoresis or 90% reduction in serum M protein level plus urine M protein level \<100 mg/24 hour. PR=50% reduction of serum M protein and reduction in 24-hour urinary M protein by 90% or to \<200 mg/24 hour
Time frame: From first dose to date of progression or objective response (assessed up to August 2017, approximately 59 months)
Population: All treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Elotuzumab, 20 mg/kg | Objective Response Rate (ORR) | 13.3 Percentage of participants |
| Elotuzumab, 10 mg/kg | Objective Response Rate (ORR) | 6.3 Percentage of participants |
| Elotuzumab, All Dosages | Objective Response Rate (ORR) | 9.7 Percentage of participants |
Secondary
Progression Free Survival (PFS) Rate
The probability was estimated from the K-M curve of subjects being alive and without disease progression (modified IMWG criteria) at 2 years from the initiation of study therapy by dose cohort
Time frame: Up to 2 years from the initiation of study therapy by dose cohort (approximately 24 months)
Population: All treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Elotuzumab, 20 mg/kg | Progression Free Survival (PFS) Rate | 0.71 Probability of Progression Free Survival |
| Elotuzumab, 10 mg/kg | Progression Free Survival (PFS) Rate | 0.54 Probability of Progression Free Survival |
| Elotuzumab, All Dosages | Progression Free Survival (PFS) Rate | 0.62 Probability of Progression Free Survival |