Trial Outcomes & Findings for S1211 Bortezomib, Dexamethasone, and Lenalidomide With or Without Elotuzumab in Treating Patients With Newly Diagnosed High-Risk Multiple Myeloma (NCT NCT01668719)

Last Updated: 2025-06-10

Results Overview

Assess safety of elotuzumab in combination with bortezomib, lenalidomide and dexamethasone and select the optimal dose of elotuzumab for the Phase II portion from 10mg/kg on each cycle, to 5mg/kg on each cycle MTD reflects the highest dose that had a dose-limiting toxicity (DLT) rate of ≤ 1/6 participants. DLTs were defined as treatment regimen related: grade ≥ 3 non-hematologic toxicity; grade 3 nausea or diarrhea despite anti-emetic and anti-diarrheal therapy; grade 3 hyperglycemia if symptomatic or glucose level \> 300mg/ml despite insulin and/or oral diabetic therapy; grade 4 neutropenia ≥ 7 days or grade 3/4 neutropenia with fever (≥ 38.5 oC); grade 4 thrombocytopenia ≥ 7 days or associated with hemorrhage; delay of treatment with any agent by \> 2 weeks due to drug related toxicity. DLT were graded using the NCI CTCAE version 4.0 Note: i) the second, lower dose level was not tested as the first dose level was deemed safe ii) 6 participants were evaluable at phase I analysis

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE1/PHASE2

Target enrollment

142 participants

Primary outcome timeframe

time from first participants randomized until at least 6 patients were evaluable for DLTs. DLTs were assessed only during Cycle 1 (21 days)

Results posted on

2025-06-10

Participant Flow

8 participants were enrolled to the Phase 1 Level 1 dose arm. 2 were ineligible, so 6 participants were assessed for DLT. In Phase II, 68 participants were enrolled on RVD and 66 to RVD/Elo arm. of these, 16 and 18 respectively were ineligible. Thus, 52 participants on RVD and 48 participants on RVD/Elo arm were eligible and evaluable for analyses.

Participant milestones

Participant milestones
Measure	Phase I Dose Level 1 (Elotuzumab, 10mg, and Bortezomib, Lenalidomide and Dexamethasone) INDUCTION: Participants receive bortezomib subcutaneously (SC) or intravenously (IV) on days 1, 4, 8, and 11; lenalidomide orally (PO) once daily (QD) on days 1-14; and dexamethasone PO or IV on days 1, 2, 4, 5, 8, 9, 11, and 12 (and on day 15 of courses 1 and 2 only). Participants also receive elotuzumab IV on days 1, 8, and 15 of courses 1 and 2 and on days 1 and 11 of courses 3-8. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Participants receive bortezomib SC or IV on days 1, 8, and 15; lenalidomide PO QD on days 1-21; dexamethasone PO on days 1, 8, and 15; and elotuzumab IV on days 1 and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.	Arm I (Bortezomib, Lenalidomide, Dexamethasone) INDUCTION: Participants receive bortezomib SC or IV on days 1, 4, 8, and 11; lenalidomide PO QD on days 1-14; and dexamethasone PO or IV on days 1, 2, 4, 5, 8, 9, 11, and 12. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity (participants who received a course of chemotherapy prior to registration will begin protocol treatment with course 2 and receive a total of 7 courses of protocol therapy). MAINTENANCE: Participants receive bortezomib SC or IV on days 1, 8, and 15; lenalidomide PO QD on days 1-21; and dexamethasone PO on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Bortezomib: Given SC or IV Dexamethasone: Given PO or IV Laboratory Biomarker Analysis: Correlative studies Lenalidomide: Given PO	Arm II (Bortezomib, Lenalidomide, Dexamethasone, Elotuzumab) INDUCTION: Participants receive bortezomib, lenalidomide, and dexamethasone as in Arm I. Participants also receive elotuzumab IV on days 1, 8, and 15 of courses 1 and 2 and on days 1 and 11 of courses 3-8. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Participants receive bortezomib, lenalidomide, and dexamethasone as in Arm I. Participants also receive elotuzumab IV on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Bortezomib: Given SC or IV Dexamethasone: Given PO or IV Elotuzumab: Given IV Laboratory Biomarker Analysis: Correlative studies Lenalidomide: Given PO
Phase I STARTED	6	0	0
Phase I COMPLETED	0	0	0
Phase I NOT COMPLETED	6	0	0
Phase II STARTED	0	52	48
Phase II COMPLETED	0	0	0
Phase II NOT COMPLETED	0	52	48

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase I Dose Level 1 (Elotuzumab, 10mg, and Bortezomib, Lenalidomide and Dexamethasone) INDUCTION: Participants receive bortezomib subcutaneously (SC) or intravenously (IV) on days 1, 4, 8, and 11; lenalidomide orally (PO) once daily (QD) on days 1-14; and dexamethasone PO or IV on days 1, 2, 4, 5, 8, 9, 11, and 12 (and on day 15 of courses 1 and 2 only). Participants also receive elotuzumab IV on days 1, 8, and 15 of courses 1 and 2 and on days 1 and 11 of courses 3-8. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Participants receive bortezomib SC or IV on days 1, 8, and 15; lenalidomide PO QD on days 1-21; dexamethasone PO on days 1, 8, and 15; and elotuzumab IV on days 1 and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.	Arm I (Bortezomib, Lenalidomide, Dexamethasone) INDUCTION: Participants receive bortezomib SC or IV on days 1, 4, 8, and 11; lenalidomide PO QD on days 1-14; and dexamethasone PO or IV on days 1, 2, 4, 5, 8, 9, 11, and 12. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity (participants who received a course of chemotherapy prior to registration will begin protocol treatment with course 2 and receive a total of 7 courses of protocol therapy). MAINTENANCE: Participants receive bortezomib SC or IV on days 1, 8, and 15; lenalidomide PO QD on days 1-21; and dexamethasone PO on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Bortezomib: Given SC or IV Dexamethasone: Given PO or IV Laboratory Biomarker Analysis: Correlative studies Lenalidomide: Given PO	Arm II (Bortezomib, Lenalidomide, Dexamethasone, Elotuzumab) INDUCTION: Participants receive bortezomib, lenalidomide, and dexamethasone as in Arm I. Participants also receive elotuzumab IV on days 1, 8, and 15 of courses 1 and 2 and on days 1 and 11 of courses 3-8. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Participants receive bortezomib, lenalidomide, and dexamethasone as in Arm I. Participants also receive elotuzumab IV on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Bortezomib: Given SC or IV Dexamethasone: Given PO or IV Elotuzumab: Given IV Laboratory Biomarker Analysis: Correlative studies Lenalidomide: Given PO
Phase I On treatment	1	0	0
Phase I Adverse Event	2	0	0
Phase I Progression/relapse	1	0	0
Phase I not protocol specified	2	0	0
Phase II On treatment	0	4	3
Phase II Adverse Event	0	18	18
Phase II Refusal unrelated to adverse event	0	4	1
Phase II Progression/relapse	0	13	17
Phase II Death	0	0	2
Phase II not protocol specified	0	13	7

Baseline Characteristics

S1211 Bortezomib, Dexamethasone, and Lenalidomide With or Without Elotuzumab in Treating Patients With Newly Diagnosed High-Risk Multiple Myeloma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase I Dose Level 1 (Elotuzumab, 10mg, and Bortezomib, Lenalidomide and Dexamethasone) n=6 Participants INDUCTION: Participants receive bortezomib subcutaneously (SC) or intravenously (IV) on days 1, 4, 8, and 11; lenalidomide orally (PO) once daily (QD) on days 1-14; and dexamethasone PO or IV on days 1, 2, 4, 5, 8, 9, 11, and 12 (and on day 15 of courses 1 and 2 only). Participants also receive elotuzumab IV on days 1, 8, and 15 of courses 1 and 2 and on days 1 and 11 of courses 3-8. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Participants receive bortezomib SC or IV on days 1, 8, and 15; lenalidomide PO QD on days 1-21; dexamethasone PO on days 1, 8, and 15; and elotuzumab IV on days 1 and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.	Arm I (Bortezomib, Lenalidomide, Dexamethasone) n=52 Participants INDUCTION: Participants receive bortezomib SC or IV on days 1, 4, 8, and 11; lenalidomide PO QD on days 1-14; and dexamethasone PO or IV on days 1, 2, 4, 5, 8, 9, 11, and 12. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity (participants who received a course of chemotherapy prior to registration will begin protocol treatment with course 2 and receive a total of 7 courses of protocol therapy). MAINTENANCE: Participants receive bortezomib SC or IV on days 1, 8, and 15; lenalidomide PO QD on days 1-21; and dexamethasone PO on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Bortezomib: Given SC or IV Dexamethasone: Given PO or IV Laboratory Biomarker Analysis: Correlative studies Lenalidomide: Given PO	Arm II (Bortezomib, Lenalidomide, Dexamethasone, Elotuzumab) n=48 Participants INDUCTION: Participants receive bortezomib, lenalidomide, and dexamethasone as in Arm I. Participants also receive elotuzumab IV on days 1, 8, and 15 of courses 1 and 2 and on days 1 and 11 of courses 3-8. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE:Participants receive bortezomib, lenalidomide, and dexamethasone as in Arm I. Participants also receive elotuzumab IV on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Bortezomib: Given SC or IV Dexamethasone: Given PO or IV Elotuzumab: Given IV Laboratory Biomarker Analysis: Correlative studies Lenalidomide: Given PO	Total n=106 Participants Total of all reporting groups
Age, Continuous	67.6 years n=5 Participants	65.6 years n=7 Participants	62.3 years n=5 Participants	64.2 years n=4 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	21 Participants n=7 Participants	19 Participants n=5 Participants	43 Participants n=4 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	31 Participants n=7 Participants	29 Participants n=5 Participants	63 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants n=5 Participants	48 Participants n=7 Participants	45 Participants n=5 Participants	98 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	4 Participants n=7 Participants	1 Participants n=5 Participants	5 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	8 Participants n=7 Participants	6 Participants n=5 Participants	15 Participants n=4 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants	44 Participants n=7 Participants	41 Participants n=5 Participants	88 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants
PCL and/or high LDH Yes	1 Participants n=5 Participants	9 Participants n=7 Participants	6 Participants n=5 Participants	16 Participants n=4 Participants
PCL and/or high LDH No	5 Participants n=5 Participants	43 Participants n=7 Participants	42 Participants n=5 Participants	90 Participants n=4 Participants

PRIMARY outcome

Timeframe: time from first participants randomized until at least 6 patients were evaluable for DLTs. DLTs were assessed only during Cycle 1 (21 days)

Population: At the time of the phase I analysis, six participants were evaluable for DLTs (i.e. were eligible and received at least one dose of study drug).

Outcome measures

Outcome measures
Measure	Phase I Dose Level 1 (Elotuzumab, 10mg, and Bortezomib, Lenalidomide and Dexamethasone) n=6 Participants INDUCTION: Participants receive bortezomib subcutaneously (SC) or intravenously (IV) on days 1, 4, 8, and 11; lenalidomide orally (PO) once daily (QD) on days 1-14; and dexamethasone PO or IV on days 1, 2, 4, 5, 8, 9, 11, and 12 (and on day 15 of courses 1 and 2 only). Participants also receive elotuzumab IV on days 1, 8, and 15 of courses 1 and 2 and on days 1 and 11 of courses 3-8. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Participants receive bortezomib SC or IV on days 1, 8, and 15; lenalidomide PO QD on days 1-21; dexamethasone PO on days 1, 8, and 15; and elotuzumab IV on days 1 and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.	Arm II (Bortezomib, Lenalidomide, Dexamethasone, Elotuzumab) INDUCTION: Participants receive bortezomib, lenalidomide, and dexamethasone as in Arm I. Participants also receive elotuzumab IV on days 1, 8, and 15 of courses 1 and 2 and on days 1 and 11 of courses 3-8. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE:Participants receive bortezomib, lenalidomide, and dexamethasone as in Arm I. Participants also receive elotuzumab IV on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Bortezomib: Given SC or IV Dexamethasone: Given PO or IV Elotuzumab: Given IV Laboratory Biomarker Analysis: Correlative studies Lenalidomide: Given PO
Phase I: Maximum Tolerated Dose (MTD) of Elotuzumab in Combination With Bortezomib, Lenalidomide and Dexamethasone	10 mg/kg (Phase II dosing for elotuzumab)	—

PRIMARY outcome

Timeframe: Up to 6 years post registration

Population: Eligible and analyzable participants

From date of registration to date of first documentation of progression or death due to any cause. Per the International Uniform Response Criteria for Multiple Myeloma, progression is defined as \>=1 of Serum M protein increase \>= 25% from lowest response level, with an absolute increase of \>= 0.5g/dL; Urine M protein increase \>= 25% from lowest response level, with an absolute increase of \>= 200 mg/24 hrs; If participant had serum M protein \<1 g/dL, urine M protein \<200 mg/24 hrs, and an involved serum free light chain level \>= 10mg/dL at baseline: \>= 25% increase in the difference between involved and uninvolved serum free light chain level with an absolute increase of \>= 10 mg/dL; Bone marrow plasma cell % increase =25% from baseline with the absolute plasma cell % \>=10%; New bone lesions or soft tissue plasmocytomas, or definite increase in size of existing bone lesions or soft tissue plasmocytomas; Development of hypercalcemia that can be attributed solely to multiple myeloma

Outcome measures

Outcome measures
Measure	Phase I Dose Level 1 (Elotuzumab, 10mg, and Bortezomib, Lenalidomide and Dexamethasone) n=52 Participants INDUCTION: Participants receive bortezomib subcutaneously (SC) or intravenously (IV) on days 1, 4, 8, and 11; lenalidomide orally (PO) once daily (QD) on days 1-14; and dexamethasone PO or IV on days 1, 2, 4, 5, 8, 9, 11, and 12 (and on day 15 of courses 1 and 2 only). Participants also receive elotuzumab IV on days 1, 8, and 15 of courses 1 and 2 and on days 1 and 11 of courses 3-8. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Participants receive bortezomib SC or IV on days 1, 8, and 15; lenalidomide PO QD on days 1-21; dexamethasone PO on days 1, 8, and 15; and elotuzumab IV on days 1 and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.	Arm II (Bortezomib, Lenalidomide, Dexamethasone, Elotuzumab) n=48 Participants INDUCTION: Participants receive bortezomib, lenalidomide, and dexamethasone as in Arm I. Participants also receive elotuzumab IV on days 1, 8, and 15 of courses 1 and 2 and on days 1 and 11 of courses 3-8. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE:Participants receive bortezomib, lenalidomide, and dexamethasone as in Arm I. Participants also receive elotuzumab IV on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Bortezomib: Given SC or IV Dexamethasone: Given PO or IV Elotuzumab: Given IV Laboratory Biomarker Analysis: Correlative studies Lenalidomide: Given PO
Progression-free Survival	33.6 months Interval 19.6 to not reached	31.5 months Interval 18.6 to 54.0

SECONDARY outcome

Timeframe: Duration of treatment and follow up until death or 6 years post registration, whichever occurs first.

Population: Participants who received at least one dose of protocol treatment.

Adverse Events (AEs) are reported by CTCAE Version 4.0. Only adverse events that are possibly, probably or definitely related to study drug are reported.

Outcome measures

Outcome measures
Measure	Phase I Dose Level 1 (Elotuzumab, 10mg, and Bortezomib, Lenalidomide and Dexamethasone) n=52 Participants INDUCTION: Participants receive bortezomib subcutaneously (SC) or intravenously (IV) on days 1, 4, 8, and 11; lenalidomide orally (PO) once daily (QD) on days 1-14; and dexamethasone PO or IV on days 1, 2, 4, 5, 8, 9, 11, and 12 (and on day 15 of courses 1 and 2 only). Participants also receive elotuzumab IV on days 1, 8, and 15 of courses 1 and 2 and on days 1 and 11 of courses 3-8. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Participants receive bortezomib SC or IV on days 1, 8, and 15; lenalidomide PO QD on days 1-21; dexamethasone PO on days 1, 8, and 15; and elotuzumab IV on days 1 and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.	Arm II (Bortezomib, Lenalidomide, Dexamethasone, Elotuzumab) n=48 Participants INDUCTION: Participants receive bortezomib, lenalidomide, and dexamethasone as in Arm I. Participants also receive elotuzumab IV on days 1, 8, and 15 of courses 1 and 2 and on days 1 and 11 of courses 3-8. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE:Participants receive bortezomib, lenalidomide, and dexamethasone as in Arm I. Participants also receive elotuzumab IV on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Bortezomib: Given SC or IV Dexamethasone: Given PO or IV Elotuzumab: Given IV Laboratory Biomarker Analysis: Correlative studies Lenalidomide: Given PO
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Vomiting	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Dizziness	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Abdominal pain	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Acute kidney injury	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Agitation	0 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Alanine aminotransferase increased	0 Participants	2 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Alkaline phosphatase increased	0 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Allergic reaction	0 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Anemia	8 Participants	6 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Aspartate aminotransferase increased	0 Participants	2 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Atrial fibrillation	3 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Back pain	0 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Blood bilirubin increased	0 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Bone pain	0 Participants	2 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Cataract	0 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Creatinine increased	0 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Diarrhea	5 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Dry skin	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Dyspnea	0 Participants	2 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Edema limbs	2 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Encephalopathy	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Eye disorders - Other, specify	0 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Fall	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Fatigue	6 Participants	5 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Febrile neutropenia	2 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Fracture	0 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Gait disturbance	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Gastrointestinal disorders - Other, specify	0 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Generalized muscle weakness	1 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Hyperglycemia	2 Participants	4 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Hyperkalemia	1 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Hypertension	2 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Hypoalbuminemia	0 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Hypokalemia	0 Participants	4 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Hyponatremia	3 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Hypophosphatemia	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Hypotension	2 Participants	4 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Hypoxia	1 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs INR increased	0 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Infections and infestations - Other, specify	3 Participants	4 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Infusion related reaction	0 Participants	3 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Insomnia	0 Participants	2 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Lung infection	3 Participants	5 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Lymphocyte count decreased	14 Participants	13 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Multi-organ failure	0 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Muscle weakness lower limb	2 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Muscle weakness trunk	0 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Musculoskeletal and connective tiss disorder - Other	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Nausea	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Neck pain	0 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Neuralgia	0 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Neutrophil count decreased	8 Participants	5 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Osteonecrosis of jaw	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Pain	0 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Pain in extremity	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Peripheral motor neuropathy	1 Participants	4 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Peripheral sensory neuropathy	4 Participants	6 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Platelet count decreased	10 Participants	10 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Pneumonitis	0 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Portal vein thrombosis	0 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Pulmonary edema	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Rash acneiform	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Rash maculo-papular	2 Participants	3 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Resp, thoracic and mediastinal disorders - Other	0 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Respiratory failure	2 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Sepsis	2 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Skin infection	0 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Stroke	0 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Supraventricular tachycardia	0 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Syncope	1 Participants	2 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Thromboembolic event	4 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Tremor	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Urinary tract infection	2 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Urine output decreased	0 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Weight loss	0 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs White blood cell decreased	4 Participants	5 Participants

SECONDARY outcome

Timeframe: Up to 6 years post registration

Population: Eligible and evaluable participants

From date of registration to date of death due to any cause

Outcome measures

Outcome measures
Measure	Phase I Dose Level 1 (Elotuzumab, 10mg, and Bortezomib, Lenalidomide and Dexamethasone) n=52 Participants INDUCTION: Participants receive bortezomib subcutaneously (SC) or intravenously (IV) on days 1, 4, 8, and 11; lenalidomide orally (PO) once daily (QD) on days 1-14; and dexamethasone PO or IV on days 1, 2, 4, 5, 8, 9, 11, and 12 (and on day 15 of courses 1 and 2 only). Participants also receive elotuzumab IV on days 1, 8, and 15 of courses 1 and 2 and on days 1 and 11 of courses 3-8. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Participants receive bortezomib SC or IV on days 1, 8, and 15; lenalidomide PO QD on days 1-21; dexamethasone PO on days 1, 8, and 15; and elotuzumab IV on days 1 and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.	Arm II (Bortezomib, Lenalidomide, Dexamethasone, Elotuzumab) n=48 Participants INDUCTION: Participants receive bortezomib, lenalidomide, and dexamethasone as in Arm I. Participants also receive elotuzumab IV on days 1, 8, and 15 of courses 1 and 2 and on days 1 and 11 of courses 3-8. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE:Participants receive bortezomib, lenalidomide, and dexamethasone as in Arm I. Participants also receive elotuzumab IV on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Bortezomib: Given SC or IV Dexamethasone: Given PO or IV Elotuzumab: Given IV Laboratory Biomarker Analysis: Correlative studies Lenalidomide: Given PO
Overall Survival	NA months median overall survival was not reached	68 months Interval 61.0 to 68.0

SECONDARY outcome

Timeframe: Up to 6 years post registration

Population: Eligible participants assessable for response at follow up. 1 participant on Arm II was not assessable for RR.

Percentage of participants with PR or better to treatment per the International Uniform Response Criteria for Multiple Myeloma stringent Complete Response- CR criteria + normal serum free light chain (FLC) ratio + absence of clonal cells in bone marrow (BM) by immunohistochemistry or immunofluorescence CR- Negative immunofixation (IFX) on serum \& urine M proteins + \<5% plasma cells in BM + disappearance of soft tissue plasmocytomas (STP) very good PR- PR criteria + serum \& urine M proteins detectable by IFX but not on electrophoresis or \>=90% reduction (RED) in serum M protein \& urine M protein \<100 g/24 hrs PR- \>=50% RED in size of STP, if present at baseline \& \>=50% RED in plasma cells, if \>=30% plasma cells in BM at baseline: \& RED in serum M protein of \>=50% \& in urine M protein of \>= 90% or to 200 mg/24hr OR if serum M protein \<1 g/dL, urine M protein \<200 mg/24 hrs, \& involved serum FLC level \>= 10 mg/dl at baseline: \>= 50% RED in (involved-uninvolved) serum FLC levels

Outcome measures

Outcome measures
Measure	Phase I Dose Level 1 (Elotuzumab, 10mg, and Bortezomib, Lenalidomide and Dexamethasone) n=52 Participants INDUCTION: Participants receive bortezomib subcutaneously (SC) or intravenously (IV) on days 1, 4, 8, and 11; lenalidomide orally (PO) once daily (QD) on days 1-14; and dexamethasone PO or IV on days 1, 2, 4, 5, 8, 9, 11, and 12 (and on day 15 of courses 1 and 2 only). Participants also receive elotuzumab IV on days 1, 8, and 15 of courses 1 and 2 and on days 1 and 11 of courses 3-8. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Participants receive bortezomib SC or IV on days 1, 8, and 15; lenalidomide PO QD on days 1-21; dexamethasone PO on days 1, 8, and 15; and elotuzumab IV on days 1 and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.	Arm II (Bortezomib, Lenalidomide, Dexamethasone, Elotuzumab) n=47 Participants INDUCTION: Participants receive bortezomib, lenalidomide, and dexamethasone as in Arm I. Participants also receive elotuzumab IV on days 1, 8, and 15 of courses 1 and 2 and on days 1 and 11 of courses 3-8. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE:Participants receive bortezomib, lenalidomide, and dexamethasone as in Arm I. Participants also receive elotuzumab IV on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Bortezomib: Given SC or IV Dexamethasone: Given PO or IV Elotuzumab: Given IV Laboratory Biomarker Analysis: Correlative studies Lenalidomide: Given PO
Response (Partial Response [PR] or Better) Rate	88 Percentage of participants Interval 76.0 to 95.0	83 Percentage of participants Interval 69.0 to 92.0

Adverse Events

Phase I Dose Level 1 (Elotuzumab, 10mg, and Bortezomib, Lenali

Serious events: 3 serious events

Other events: 6 other events

Deaths: 2 deaths

Arm I (Bortezomib, Lenalidomide, Dexamethasone)

Serious events: 6 serious events

Other events: 52 other events

Deaths: 19 deaths

Arm II (Bortezomib, Lenalidomide, Dexamethasone, Elotuzumab)

Serious events: 24 serious events

Other events: 47 other events

Deaths: 16 deaths

Serious adverse events

Other adverse events

Additional Information

Myeloma Committee Statistician

SWOG Statistics and Data Management Center

Phone: 2066674623

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60