Newly Diagnosed, Previously Untreated Multiple Myeloma
Conditions
Brief summary
The purpose of the study is to look at subjects who receive Lenalidomide, Dexamethasone, and Elotuzumab and determine if they will have lower surface CS1 expression on malignant plasma cells at the time of progression than those who receive Lenalidomide and Dexamethasone without Elotuzumab
Interventions
DRUGLenalidomide
DRUGDexamethasone
BIOLOGICALElotuzumab
Sponsors
Abbott
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
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 MM and who: * Have not received any prior systemic anti-myeloma therapy * 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 CA204-006 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 |
|---|---|---|
| Change From Baseline to Progression of the Cell Surface Expression of CS1 From Bone Marrow-Derived Multiple Myeloma (MM) Cells | From baseline (screening) to time of progression (up to approximately 54 months) | CS1 (CD2 subset-1, also known as CRACC, SLAMF7, CD319) expression levels in multiple myeloma cells were analyzed from bone-marrow aspirates collected at baseline and at time of progression through mean fluorescent intensity. The following conditions were considered to describe multiple myeloma cells expressing CS1 (CS1+/CD38++/CD138+/CD56+/CD19-/CD45DIM) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Levels of CS1 Soluble Form (sCS1) in Serum | At baseline (screening), during main study therapy (cycle 3 day 1, up to 64 days) and at time of progression (up to approximately 31 months) | Expression levels of the free form of soluble CS1 were analyzed at different timepoints from serum samples derived from peripheral blood collection |
| Change From Baseline in the Levels of CS1 Soluble Form (sCS1) in Serum During Therapy and At Progression | From baseline (screening) to cycle 3 day 1 of the main study therapy (up to 64 days) and from baseline (screening) to time of progression (up to approximately 31 months) | Expression levels of the free form of soluble CS1 were analyzed at different timepoints from serum samples derived from peripheral blood collection |
| Percent of Bone Marrow-Derived Multiple Myeloma (MM) Cells Expressing Cell Surface CS1 at Time of Progression | Time of progression (up to approximately 54 months from pre-treatment screening) | CS1 (CD2 subset-1, also known as CRACC, SLAMF7, CD319) expression levels in multiple myeloma cells were analyzed from bone-marrow aspirates collected at time of progression. The following conditions were considered to describe multiple myeloma cells expressing CS1 (CS1+/CD38++/CD138+/CD56+/CD19-/CD45DIM) |
| Change From Baseline in Cell Surface CS1 Expression Levels in Circulating Multiple Myeloma (MM) Cells | From baseline (screening) to cycle 3 day 1 of the main study therapy (up to 64 days) and from baseline (screening) to the time of progression (up to approximately 54 months) | Circulating MM cells isolated from peripheral blood |
| CS1 Expression Levels in Matched Samples of Bone Marrow-Derived Multiple Myeloma (MM) Cells and Circulating MM Cells | At baseline (screening), during main study therapy (cycle 3 day 1) and at time of progression (up to approximately 54 months) | CS1 expression levels analyzed from matching bone marrow aspirates (for bone marrow-derived MM cells) and from peripheral blood (for circulating tumor cells) collected from the same participants |
| Change From Baseline in the Number of Circulating Multiple Myeloma (MM) Cells | From baseline (screening) to cycle 3 day 1 of the main study therapy (up to 64 days) and from baseline (screening) to the time of progression (up to approximately 54 months) | Circulating MM cells isolated from peripheral blood |
Countries
Greece, Italy, Poland, United States
Participant flow
Pre-assignment details
23 participants treated in the main CA204-006 study (NCT01335399) were recruited for the CA204-006 biomarker sub-study (NCT01891643). No additional treatment (other than what administered in the main study) was dosed during the biomarker sub-study.
Participants by arm
| Arm | Count |
|---|---|
| E-Ld Cohort Participants receiving a combination of Elotuzumab (E) Lenalidomide (L) Dexamethasone (d) in a 28 day cycle | 13 |
| Ld Cohort Participants receiving a combination of Lenalidomide (L) Dexamethasone (d) in a 28 day cycle | 10 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse event unrelated to study drug | 2 | 5 |
| Overall Study | Disease Progression | 4 | 3 |
| Overall Study | Maximum Clinical Benefit | 0 | 1 |
| Overall Study | Participant request to discontinue | 1 | 0 |
| Overall Study | Poor/Non-compliance | 0 | 1 |
| Overall Study | Study Drug Toxicity | 3 | 0 |
Baseline characteristics
| Characteristic | Ld Cohort | Total | E-Ld Cohort |
|---|---|---|---|
| Age, Continuous | 71.3 Years STANDARD_DEVIATION 6.53 | 73.3 Years STANDARD_DEVIATION 6.75 | 74.8 Years STANDARD_DEVIATION 6.77 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 5 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 7 Participants | 18 Participants | 11 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 1 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 | 9 Participants | 21 Participants | 12 Participants |
| Sex: Female, Male Female | 6 Participants | 12 Participants | 6 Participants |
| Sex: Female, Male Male | 4 Participants | 11 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 8 / 13 | 5 / 10 |
| other Total, other adverse events | 13 / 13 | 10 / 10 |
| serious Total, serious adverse events | 9 / 13 | 7 / 10 |
Outcome results
Primary
Change From Baseline to Progression of the Cell Surface Expression of CS1 From Bone Marrow-Derived Multiple Myeloma (MM) Cells
CS1 (CD2 subset-1, also known as CRACC, SLAMF7, CD319) expression levels in multiple myeloma cells were analyzed from bone-marrow aspirates collected at baseline and at time of progression through mean fluorescent intensity. The following conditions were considered to describe multiple myeloma cells expressing CS1 (CS1+/CD38++/CD138+/CD56+/CD19-/CD45DIM)
Time frame: From baseline (screening) to time of progression (up to approximately 54 months)
Population: All treated participants with measurements available at baseline and at time of progression.~No participants in any of the 2 cohorts had available measurements both at baseline and time of progression
Secondary
Change From Baseline in Cell Surface CS1 Expression Levels in Circulating Multiple Myeloma (MM) Cells
Circulating MM cells isolated from peripheral blood
Time frame: From baseline (screening) to cycle 3 day 1 of the main study therapy (up to 64 days) and from baseline (screening) to the time of progression (up to approximately 54 months)
Population: All treated participants with available circulating MM cells and CS1 expression levels.~Circulating MM cells were not collected for any of the participants.
| Arm | Measure | Group | Value |
|---|---|---|---|
| Unknown | Change From Baseline in Cell Surface CS1 Expression Levels in Circulating Multiple Myeloma (MM) Cells | From baseline to Cycle 3 day 1 of study therapy | — |
| Unknown | Change From Baseline in Cell Surface CS1 Expression Levels in Circulating Multiple Myeloma (MM) Cells | From baseline to time of progression | — |
Secondary
Change From Baseline in the Levels of CS1 Soluble Form (sCS1) in Serum During Therapy and At Progression
Expression levels of the free form of soluble CS1 were analyzed at different timepoints from serum samples derived from peripheral blood collection
Time frame: From baseline (screening) to cycle 3 day 1 of the main study therapy (up to 64 days) and from baseline (screening) to time of progression (up to approximately 31 months)
Population: All treated participants with measurements available at baseline and at cycle 3 day 1 of study therapy or at baseline and at the time of progression.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| E-Ld Cohort | Change From Baseline in the Levels of CS1 Soluble Form (sCS1) in Serum During Therapy and At Progression | From baseline to Cycle 3 day 1 of main study therapy | -3.51 ug/L |
| E-Ld Cohort | Change From Baseline in the Levels of CS1 Soluble Form (sCS1) in Serum During Therapy and At Progression | From baseline to time of progression | -0.85 ug/L |
| Ld Cohort | Change From Baseline in the Levels of CS1 Soluble Form (sCS1) in Serum During Therapy and At Progression | From baseline to Cycle 3 day 1 of main study therapy | -4.08 ug/L |
| Ld Cohort | Change From Baseline in the Levels of CS1 Soluble Form (sCS1) in Serum During Therapy and At Progression | From baseline to time of progression | -17.41 ug/L |
Secondary
Change From Baseline in the Number of Circulating Multiple Myeloma (MM) Cells
Circulating MM cells isolated from peripheral blood
Time frame: From baseline (screening) to cycle 3 day 1 of the main study therapy (up to 64 days) and from baseline (screening) to the time of progression (up to approximately 54 months)
Population: All treated participants with available circulating MM cells. Circulating MM cells were not collected for any of the participants.
| Arm | Measure | Group | Value |
|---|---|---|---|
| Unknown | Change From Baseline in the Number of Circulating Multiple Myeloma (MM) Cells | From baseline to Cycle 3 day 1 of study therapy | — |
| Unknown | Change From Baseline in the Number of Circulating Multiple Myeloma (MM) Cells | From baseline to time of progression | — |
Secondary
CS1 Expression Levels in Matched Samples of Bone Marrow-Derived Multiple Myeloma (MM) Cells and Circulating MM Cells
CS1 expression levels analyzed from matching bone marrow aspirates (for bone marrow-derived MM cells) and from peripheral blood (for circulating tumor cells) collected from the same participants
Time frame: At baseline (screening), during main study therapy (cycle 3 day 1) and at time of progression (up to approximately 54 months)
Population: All treated participants with matched samples of bone marrow-derived MM cells and circulating MM cells.~Circulating MM cells were not collected for any of the participants.
Secondary
Levels of CS1 Soluble Form (sCS1) in Serum
Expression levels of the free form of soluble CS1 were analyzed at different timepoints from serum samples derived from peripheral blood collection
Time frame: At baseline (screening), during main study therapy (cycle 3 day 1, up to 64 days) and at time of progression (up to approximately 31 months)
Population: All treated participants with measurements available either at baseline, at cycle 3 day 1 of study therapy or at time of progression.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| E-Ld Cohort | Levels of CS1 Soluble Form (sCS1) in Serum | Baseline | 3.60 ug/L |
| E-Ld Cohort | Levels of CS1 Soluble Form (sCS1) in Serum | Cycle 3 day 1 of main study therapy | 0.15 ug/L |
| E-Ld Cohort | Levels of CS1 Soluble Form (sCS1) in Serum | Time of progression | 0.39 ug/L |
| Ld Cohort | Levels of CS1 Soluble Form (sCS1) in Serum | Baseline | 13.27 ug/L |
| Ld Cohort | Levels of CS1 Soluble Form (sCS1) in Serum | Cycle 3 day 1 of main study therapy | 0.72 ug/L |
| Ld Cohort | Levels of CS1 Soluble Form (sCS1) in Serum | Time of progression | 49.85 ug/L |
Secondary
Percent of Bone Marrow-Derived Multiple Myeloma (MM) Cells Expressing Cell Surface CS1 at Time of Progression
CS1 (CD2 subset-1, also known as CRACC, SLAMF7, CD319) expression levels in multiple myeloma cells were analyzed from bone-marrow aspirates collected at time of progression. The following conditions were considered to describe multiple myeloma cells expressing CS1 (CS1+/CD38++/CD138+/CD56+/CD19-/CD45DIM)
Time frame: Time of progression (up to approximately 54 months from pre-treatment screening)
Population: All treated participants with measurements available at time of progression.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| E-Ld Cohort | Percent of Bone Marrow-Derived Multiple Myeloma (MM) Cells Expressing Cell Surface CS1 at Time of Progression | 46.59 Percent of cells expressing CS1 |
| Ld Cohort | Percent of Bone Marrow-Derived Multiple Myeloma (MM) Cells Expressing Cell Surface CS1 at Time of Progression | 84.62 Percent of cells expressing CS1 |