Trial Outcomes & Findings for PH III Study of Lenalidomide and Dexamethasone With or Without Elotuzumab to Treat Previously Untreated Multiple Myeloma (ELO 1 Substudy) (NCT NCT01891643)

Last Updated: 2021-07-01

Results Overview

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)

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

23 participants

Primary outcome timeframe

From baseline (screening) to time of progression (up to approximately 54 months)

Results posted on

2021-07-01

Participant Flow

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.

Participant milestones

Participant milestones
Measure	E-Ld Cohort Participants receiving a combination of Elotuzumab (E) Lenalidomide (L) Dexamethasone (d) in a 28 day cycle	Ld Cohort Participants receiving a combination of Lenalidomide (L) Dexamethasone (d) in a 28 day cycle
Overall Study STARTED	13	10
Overall Study COMPLETED	3	0
Overall Study NOT COMPLETED	10	10

Reasons for withdrawal

Reasons for withdrawal
Measure	E-Ld Cohort Participants receiving a combination of Elotuzumab (E) Lenalidomide (L) Dexamethasone (d) in a 28 day cycle	Ld Cohort Participants receiving a combination of Lenalidomide (L) Dexamethasone (d) in a 28 day cycle
Overall Study Adverse event unrelated to study drug	2	5
Overall Study Disease Progression	4	3
Overall Study Study Drug Toxicity	3	0
Overall Study Maximum Clinical Benefit	0	1
Overall Study Poor/Non-compliance	0	1
Overall Study Participant request to discontinue	1	0

Baseline Characteristics

PH III Study of Lenalidomide and Dexamethasone With or Without Elotuzumab to Treat Previously Untreated Multiple Myeloma (ELO 1 Substudy)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	E-Ld Cohort n=13 Participants Participants receiving a combination of Elotuzumab (E) Lenalidomide (L) Dexamethasone (d) in a 28 day cycle	Ld Cohort n=10 Participants Participants receiving a combination of Lenalidomide (L) Dexamethasone (d) in a 28 day cycle	Total n=23 Participants Total of all reporting groups
Age, Continuous	74.8 Years STANDARD_DEVIATION 6.77 • n=93 Participants	71.3 Years STANDARD_DEVIATION 6.53 • n=4 Participants	73.3 Years STANDARD_DEVIATION 6.75 • n=27 Participants
Sex: Female, Male Female	6 Participants n=93 Participants	6 Participants n=4 Participants	12 Participants n=27 Participants
Sex: Female, Male Male	7 Participants n=93 Participants	4 Participants n=4 Participants	11 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2 Participants n=93 Participants	3 Participants n=4 Participants	5 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	11 Participants n=93 Participants	7 Participants n=4 Participants	18 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	1 Participants n=93 Participants	1 Participants n=4 Participants	2 Participants n=27 Participants
Race (NIH/OMB) White	12 Participants n=93 Participants	9 Participants n=4 Participants	21 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants

PRIMARY outcome

Timeframe: 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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Time of progression (up to approximately 54 months from pre-treatment screening)

Population: All treated participants with measurements available 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)

Outcome measures

Outcome measures
Measure	E-Ld Cohort n=4 Participants Participants receiving a combination of Elotuzumab (E) Lenalidomide (L) Dexamethasone (d) in a 28 day cycle	Ld Cohort n=1 Participants Participants receiving a combination of Lenalidomide (L) Dexamethasone (d) in a 28 day cycle
Percent of Bone Marrow-Derived Multiple Myeloma (MM) Cells Expressing Cell Surface CS1 at Time of Progression	46.59 Percent of cells expressing CS1 Interval 0.0 to 99.1	84.62 Percent of cells expressing CS1 Only 1 participant analyzed

SECONDARY outcome

Timeframe: 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.

Expression levels of the free form of soluble CS1 were analyzed at different timepoints from serum samples derived from peripheral blood collection

Outcome measures

Outcome measures
Measure	E-Ld Cohort n=13 Participants Participants receiving a combination of Elotuzumab (E) Lenalidomide (L) Dexamethasone (d) in a 28 day cycle	Ld Cohort n=10 Participants Participants receiving a combination of Lenalidomide (L) Dexamethasone (d) in a 28 day cycle
Levels of CS1 Soluble Form (sCS1) in Serum Baseline	3.60 ug/L Interval 0.7 to 7.4	13.27 ug/L Interval 2.2 to 79.8
Levels of CS1 Soluble Form (sCS1) in Serum Cycle 3 day 1 of main study therapy	0.15 ug/L Interval 0.1 to 0.3	0.72 ug/L Interval 0.2 to 3.0
Levels of CS1 Soluble Form (sCS1) in Serum Time of progression	0.39 ug/L Interval 0.2 to 0.5	49.85 ug/L Only 1 participant analyzed

SECONDARY outcome

Timeframe: 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.

Expression levels of the free form of soluble CS1 were analyzed at different timepoints from serum samples derived from peripheral blood collection

Outcome measures

Outcome measures
Measure	E-Ld Cohort n=13 Participants Participants receiving a combination of Elotuzumab (E) Lenalidomide (L) Dexamethasone (d) in a 28 day cycle	Ld Cohort n=10 Participants Participants receiving a combination of Lenalidomide (L) Dexamethasone (d) in a 28 day cycle
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 Interval -6.9 to -0.6	-4.08 ug/L Interval -15.1 to -1.6
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 Interval -6.9 to -0.4	-17.41 ug/L Only 1 participant analyzed

SECONDARY outcome

Timeframe: 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.

Circulating MM cells isolated from peripheral blood

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Circulating MM cells isolated from peripheral blood

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome data not reported

Adverse Events

E-Ld Cohort

Serious events: 9 serious events

Other events: 13 other events

Deaths: 8 deaths

Ld Cohort

Serious events: 7 serious events

Other events: 10 other events

Deaths: 5 deaths

Serious adverse events

Other adverse events

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Phone: Please email

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Publication restrictions are in place

Restriction type: OTHER

Measure	E-Ld Cohort n=13 participants at risk Participants receiving a combination of Elotuzumab (E) Lenalidomide (L) Dexamethasone (d) in a 28 day cycle	Ld Cohort n=10 participants at risk Participants receiving a combination of Lenalidomide (L) Dexamethasone (d) in a 28 day cycle
Blood and lymphatic system disorders Anaemia	7.7% 1/13 • From first dose to 60 days following last dose (up to approximately 80 months)	10.0% 1/10 • From first dose to 60 days following last dose (up to approximately 80 months)
Cardiac disorders Atrial flutter	7.7% 1/13 • From first dose to 60 days following last dose (up to approximately 80 months)	0.00% 0/10 • From first dose to 60 days following last dose (up to approximately 80 months)
Cardiac disorders Cardiac arrest	7.7% 1/13 • From first dose to 60 days following last dose (up to approximately 80 months)	0.00% 0/10 • From first dose to 60 days following last dose (up to approximately 80 months)
Cardiac disorders Sinus tachycardia	0.00% 0/13 • From first dose to 60 days following last dose (up to approximately 80 months)	10.0% 1/10 • From first dose to 60 days following last dose (up to approximately 80 months)
Eye disorders Cataract	7.7% 1/13 • From first dose to 60 days following last dose (up to approximately 80 months)	10.0% 1/10 • From first dose to 60 days following last dose (up to approximately 80 months)
Gastrointestinal disorders Colitis	7.7% 1/13 • From first dose to 60 days following last dose (up to approximately 80 months)	0.00% 0/10 • From first dose to 60 days following last dose (up to approximately 80 months)
Gastrointestinal disorders Inguinal hernia	7.7% 1/13 • From first dose to 60 days following last dose (up to approximately 80 months)	0.00% 0/10 • From first dose to 60 days following last dose (up to approximately 80 months)
General disorders Multiple organ dysfunction syndrome	0.00% 0/13 • From first dose to 60 days following last dose (up to approximately 80 months)	10.0% 1/10 • From first dose to 60 days following last dose (up to approximately 80 months)
Infections and infestations Bronchitis	7.7% 1/13 • From first dose to 60 days following last dose (up to approximately 80 months)	10.0% 1/10 • From first dose to 60 days following last dose (up to approximately 80 months)
Infections and infestations Pneumonia	7.7% 1/13 • From first dose to 60 days following last dose (up to approximately 80 months)	20.0% 2/10 • From first dose to 60 days following last dose (up to approximately 80 months)
Infections and infestations Septic shock	7.7% 1/13 • From first dose to 60 days following last dose (up to approximately 80 months)	0.00% 0/10 • From first dose to 60 days following last dose (up to approximately 80 months)
Infections and infestations Urinary tract infection	7.7% 1/13 • From first dose to 60 days following last dose (up to approximately 80 months)	0.00% 0/10 • From first dose to 60 days following last dose (up to approximately 80 months)
Injury, poisoning and procedural complications Femur fracture	0.00% 0/13 • From first dose to 60 days following last dose (up to approximately 80 months)	20.0% 2/10 • From first dose to 60 days following last dose (up to approximately 80 months)
Injury, poisoning and procedural complications Pelvic fracture	7.7% 1/13 • From first dose to 60 days following last dose (up to approximately 80 months)	0.00% 0/10 • From first dose to 60 days following last dose (up to approximately 80 months)
Metabolism and nutrition disorders Electrolyte imbalance	0.00% 0/13 • From first dose to 60 days following last dose (up to approximately 80 months)	10.0% 1/10 • From first dose to 60 days following last dose (up to approximately 80 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute lymphocytic leukaemia	0.00% 0/13 • From first dose to 60 days following last dose (up to approximately 80 months)	10.0% 1/10 • From first dose to 60 days following last dose (up to approximately 80 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Refractory anaemia with ringed sideroblasts	7.7% 1/13 • From first dose to 60 days following last dose (up to approximately 80 months)	0.00% 0/10 • From first dose to 60 days following last dose (up to approximately 80 months)
Nervous system disorders Syncope	7.7% 1/13 • From first dose to 60 days following last dose (up to approximately 80 months)	0.00% 0/10 • From first dose to 60 days following last dose (up to approximately 80 months)
Nervous system disorders Transient ischaemic attack	0.00% 0/13 • From first dose to 60 days following last dose (up to approximately 80 months)	10.0% 1/10 • From first dose to 60 days following last dose (up to approximately 80 months)
Psychiatric disorders Delusional disorder, unspecified type	7.7% 1/13 • From first dose to 60 days following last dose (up to approximately 80 months)	0.00% 0/10 • From first dose to 60 days following last dose (up to approximately 80 months)
Renal and urinary disorders Acute kidney injury	0.00% 0/13 • From first dose to 60 days following last dose (up to approximately 80 months)	10.0% 1/10 • From first dose to 60 days following last dose (up to approximately 80 months)
Renal and urinary disorders Renal failure	7.7% 1/13 • From first dose to 60 days following last dose (up to approximately 80 months)	0.00% 0/10 • From first dose to 60 days following last dose (up to approximately 80 months)
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/13 • From first dose to 60 days following last dose (up to approximately 80 months)	10.0% 1/10 • From first dose to 60 days following last dose (up to approximately 80 months)
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/13 • From first dose to 60 days following last dose (up to approximately 80 months)	10.0% 1/10 • From first dose to 60 days following last dose (up to approximately 80 months)
Respiratory, thoracic and mediastinal disorders Pulmonary congestion	0.00% 0/13 • From first dose to 60 days following last dose (up to approximately 80 months)	10.0% 1/10 • From first dose to 60 days following last dose (up to approximately 80 months)
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/13 • From first dose to 60 days following last dose (up to approximately 80 months)	10.0% 1/10 • From first dose to 60 days following last dose (up to approximately 80 months)
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/13 • From first dose to 60 days following last dose (up to approximately 80 months)	10.0% 1/10 • From first dose to 60 days following last dose (up to approximately 80 months)
Respiratory, thoracic and mediastinal disorders Restrictive pulmonary disease	7.7% 1/13 • From first dose to 60 days following last dose (up to approximately 80 months)	0.00% 0/10 • From first dose to 60 days following last dose (up to approximately 80 months)
Vascular disorders Deep vein thrombosis	0.00% 0/13 • From first dose to 60 days following last dose (up to approximately 80 months)	10.0% 1/10 • From first dose to 60 days following last dose (up to approximately 80 months)
Vascular disorders Thrombosis	0.00% 0/13 • From first dose to 60 days following last dose (up to approximately 80 months)	10.0% 1/10 • From first dose to 60 days following last dose (up to approximately 80 months)