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

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ClinicalTrials.gov Identifier: NCT01668719

Recruitment Status : Active, not recruiting

First Posted : August 20, 2012

Results First Posted : October 27, 2021

Last Update Posted : May 23, 2023

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Sponsor:

Collaborator:

National Cancer Institute (NCI)

Information provided by (Responsible Party):

SWOG Cancer Research Network

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Conditions	DS Stage I Plasma Cell Myeloma DS Stage II Plasma Cell Myeloma DS Stage III Plasma Cell Myeloma
Interventions	Drug: Bortezomib Drug: Dexamethasone Biological: Elotuzumab Other: Laboratory Biomarker Analysis Drug: Lenalidomide
Enrollment	142

Participant Flow

Recruitment Details

Pre-assignment Details

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.


Arm/Group Title	Phase I Dose Level 1 (Elotuzumab, 10mg, and Bortezomib, Lenalidomide and Dexamethasone)	Arm I (Bortezomib, Lenalidomide, Dexamethasone)	Arm II (Bortezomib, Lenalidomide, Dexamethasone, Elotuzumab)
Arm/Group Description	INDUCTION: Participants receive bor...	INDUCTION: Participants receive bor...	INDUCTION: Participants receive bor...
Arm/Group Description	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.	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	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
Period Title: Phase I
Started	6	0	0
Completed	0	0	0
Not Completed	6	0	0
Reason Not Completed
On treatment	1	0	0
Adverse Event	2	0	0
Progression/relapse	1	0	0
not protocol specified	2	0	0
Period Title: Phase II
Started	0	52	48
Completed	0	0	0
Not Completed	0	52	48
Reason Not Completed
On treatment	0	4	3
Adverse Event	0	18	18
Refusal unrelated to adverse event	0	4	1
Progression/relapse	0	13	17
Death	0	0	2
not protocol specified	0	13	7

Baseline Characteristics

Arm/Group Title		Phase I Dose Level 1 (Elotuzumab, 10mg, and Bortezomib, Lenalidomide and Dexamethasone)	Arm I (Bortezomib, Lenalidomide, Dexamethasone)	Arm II (Bortezomib, Lenalidomide, Dexamethasone, Elotuzumab)	Total
Arm/Group Description		INDUCTION: Participants receive bor...	INDUCTION: Participants receive bor...	INDUCTION: Participants receive bor...	Total of all reporting groups
Arm/Group Description		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.	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	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 of all reporting groups
Overall Number of Baseline Participants		6	52	48	106
Baseline Analysis Population Description		...
Baseline Analysis Population Description		All eligible participants
Age, Continuous Median (Full Range) Unit of measure: Years
	Number Analyzed	6 participants	52 participants	48 participants	106 participants
		67.6 (56.1 to 79.3)	65.6 (36.1 to 84.5)	62.3 (40.0 to 78.6)	64.2 (36.1 to 84.5)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	6 participants	52 participants	48 participants	106 participants
	Female	3 50.0%	21 40.4%	19 39.6%	43 40.6%
	Male	3 50.0%	31 59.6%	29 60.4%	63 59.4%
Ethnicity (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	6 participants	52 participants	48 participants	106 participants
	Hispanic or Latino	1 16.7%	0 0.0%	2 4.2%	3 2.8%
	Not Hispanic or Latino	5 83.3%	48 92.3%	45 93.8%	98 92.5%
	Unknown or Not Reported	0 0.0%	4 7.7%	1 2.1%	5 4.7%
Race (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	6 participants	52 participants	48 participants	106 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Asian	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Black or African American	1 16.7%	8 15.4%	6 12.5%	15 14.2%
	White	3 50.0%	44 84.6%	41 85.4%	88 83.0%
	More than one race	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	2 33.3%	0 0.0%	1 2.1%	3 2.8%
PCL and/or high LDH ^[1] Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	6 participants	52 participants	48 participants	106 participants
	Yes	1 16.7%	9 17.3%	6 12.5%	16 15.1%
	No	5 83.3%	43 82.7%	42 87.5%	90 84.9%
		[1] Measure Description: PCL- plasma cell leukemia LDH- lactate dehydrogenase

Outcome Measures

1.Primary Outcome


Title	Phase I: Maximum Tolerated Dose (MTD) of Elotuzumab in Combination With Bortezomib, Lenalidomide and Dexamethasone
Description	Assess safety of elotuzumab in combination with bortezomib, lenalidomi...
Description	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
Time Frame	time from first participants randomized until at least 6 patients were evaluable for DLTs. DLTs were assessed only during Cycle 1 (21 days)

Outcome Measure Data

Analysis Population Description

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).


Arm/Group Title	Phase I Dose Level 1 (Elotuzumab, 10mg, and Bortezomib, Lenalidomide and Dexamethasone)
Arm/Group Description:	INDUCTION: Participants receive bor...
Arm/Group Description:	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.
Overall Number of Participants Analyzed	6
Measure Type: Number Unit of Measure: mg/kg (Phase II dosing for elotuzumab)
	10

2.Primary Outcome


Title	Progression-free Survival
Description	From date of registration to date of first documentation of progressio...
Description	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
Time Frame	Up to 6 years post registration

Outcome Measure Data

Analysis Population Description

Eligible and analyzable participants


Arm/Group Title	Arm I (Bortezomib, Lenalidomide, Dexamethasone)	Arm II (Bortezomib, Lenalidomide, Dexamethasone, Elotuzumab)
Arm/Group Description:	INDUCTION: Participants receive bor...	INDUCTION: Participants receive bor...
Arm/Group Description:	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	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 Number of Participants Analyzed	52	48
Median (95% Confidence Interval) Unit of Measure: months
	33.6 ^[1] (19.6 to NA)	31.5 (18.6 to 54.0)

[1]

not reached

3.Secondary Outcome


Title	Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs
Description	Adverse Events (AEs) are reported by CTCAE Version 4.0. Only adverse e...
Description	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.
Time Frame	Duration of treatment and follow up until death or 6 years post registration, whichever occurs first.

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose of protocol treatment.


Arm/Group Title	Arm I (Bortezomib, Lenalidomide, Dexamethasone)	Arm II (Bortezomib, Lenalidomide, Dexamethasone, Elotuzumab)
Arm/Group Description:	INDUCTION: Participants receive bor...	INDUCTION: Participants receive bor...
Arm/Group Description:	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 Lenalidomide: Given PO	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 Lenalidomide: Given PO
Overall Number of Participants Analyzed	52	48
Measure Type: Number Unit of Measure: Participants
Abdominal pain	1	0
Acute kidney injury	1	0
Agitation	0	1
Alanine aminotransferase increased	0	2
Alkaline phosphatase increased	0	1
Allergic reaction	0	1
Anemia	8	6
Aspartate aminotransferase increased	0	2
Atrial fibrillation	3	0
Back pain	0	1
Blood bilirubin increased	0	1
Bone pain	0	2
Cataract	0	1
Creatinine increased	0	1
Diarrhea	5	1
Dizziness	1	0
Dry skin	1	0
Dyspnea	0	2
Edema limbs	2	0
Encephalopathy	1	0
Eye disorders - Other, specify	0	1
Fall	1	0
Fatigue	6	5
Febrile neutropenia	2	1
Fracture	0	1
Gait disturbance	1	0
Gastrointestinal disorders - Other, specify	0	1
Generalized muscle weakness	1	1
Hyperglycemia	2	4
Hyperkalemia	1	1
Hypertension	2	1
Hypoalbuminemia	0	1
Hypokalemia	0	4
Hyponatremia	3	1
Hypophosphatemia	1	0
Hypotension	2	4
Hypoxia	1	1
INR increased	0	1
Infections and infestations - Other, specify	3	4
Infusion related reaction	0	3
Insomnia	0	2
Lung infection	3	5
Lymphocyte count decreased	14	13
Multi-organ failure	0	1
Muscle weakness lower limb	2	0
Muscle weakness trunk	0	1
Musculoskeletal and connective tiss disorder - Other	1	0
Nausea	1	0
Neck pain	0	1
Neuralgia	0	1
Neutrophil count decreased	8	5
Osteonecrosis of jaw	1	0
Pain	0	1
Pain in extremity	1	0
Peripheral motor neuropathy	1	4
Peripheral sensory neuropathy	4	6
Platelet count decreased	10	10
Pneumonitis	0	1
Portal vein thrombosis	0	1
Pulmonary edema	1	0
Rash acneiform	1	0
Rash maculo-papular	2	3
Resp, thoracic and mediastinal disorders - Other	0	1
Respiratory failure	2	1
Sepsis	2	1
Skin infection	0	1
Stroke	0	1
Supraventricular tachycardia	0	1
Syncope	1	2
Thromboembolic event	4	1
Tremor	1	0
Urinary tract infection	2	0
Urine output decreased	0	1
Vomiting	1	0
Weight loss	0	1
White blood cell decreased	4	5

4.Secondary Outcome


Title	Overall Survival
Description	From date of registration to date of death due to any cause
Description	From date of registration to date of death due to any cause
Time Frame	Up to 6 years post registration

Outcome Measure Data

Analysis Population Description

Eligible and evaluable participants


Arm/Group Title	Arm I (Bortezomib, Lenalidomide, Dexamethasone)	Arm II (Bortezomib, Lenalidomide, Dexamethasone, Elotuzumab)
Arm/Group Description:	INDUCTION: Participants receive bor...	INDUCTION: Participants receive bor...
Arm/Group Description:	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	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 Number of Participants Analyzed	52	48
Median (95% Confidence Interval) Unit of Measure: months
	NA ^[1] (NA to NA)	68 (61 to 68)

[1]

median overall survival was not reached

5.Secondary Outcome


Title	Response (Partial Response [PR] or Better) Rate
Description	Percentage of participants with PR or better to treatment per the Inte...
Description	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
Time Frame	Up to 6 years post registration

Outcome Measure Data

Analysis Population Description

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


Arm/Group Title	Arm I (Bortezomib, Lenalidomide, Dexamethasone)	Arm II (Bortezomib, Lenalidomide, Dexamethasone, Elotuzumab)
Arm/Group Description:	INDUCTION: Participants receive bor...	INDUCTION: Participants receive bor...
Arm/Group Description:	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	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 Number of Participants Analyzed	52	47
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: Percentage of participants
	88 (76 to 95)	83 (69 to 92)

Adverse Events

Time Frame	Duration of treatment and follow up until death or 6 years post registration, whichever occurs first.
Adverse Event Reporting Description	6 participants in Phase I and 100 participants in Phase II were evaluable and assessed for AEs.

Arm/Group Title	Phase I Dose Level 1 (Elotuzumab, 10mg, and Bortezomib, Lenali	Arm I (Bortezomib, Lenalidomide, Dexamethasone)	Arm II (Bortezomib, Lenalidomide, Dexamethasone, Elotuzumab)
Arm/Group Description	INDUCTION: Participants receive bor...	INDUCTION: Participants receive bor...	INDUCTION: Participants receive bor...
Arm/Group Description	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.	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 Lenalidomide: Given PO	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 Lenalidomide: Given PO
All-Cause Mortality
	Phase I Dose Level 1 (Elotuzumab, 10mg, and Bortezomib, Lenali	Arm I (Bortezomib, Lenalidomide, Dexamethasone)	Arm II (Bortezomib, Lenalidomide, Dexamethasone, Elotuzumab)
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	2/6 (33.33%)	19/52 (36.54%)	16/48 (33.33%)
Serious Adverse Events Serious Adverse Events
	Phase I Dose Level 1 (Elotuzumab, 10mg, and Bortezomib, Lenali	Arm I (Bortezomib, Lenalidomide, Dexamethasone)	Arm II (Bortezomib, Lenalidomide, Dexamethasone, Elotuzumab)
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	3/6 (50.00%)	6/52 (11.54%)	24/48 (50.00%)
Blood and lymphatic system disorders
Anemia ^†	0/6 (0.00%)	0/52 (0.00%)	4/48 (8.33%)
Febrile neutropenia ^†	0/6 (0.00%)	1/52 (1.92%)	1/48 (2.08%)
Cardiac disorders
Atrial fibrillation ^†	0/6 (0.00%)	1/52 (1.92%)	1/48 (2.08%)
Sinus bradycardia ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Gastrointestinal disorders
Diarrhea ^†	0/6 (0.00%)	0/52 (0.00%)	3/48 (6.25%)
Nausea ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Vomiting ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
General disorders
Chills ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Edema limbs ^†	0/6 (0.00%)	0/52 (0.00%)	2/48 (4.17%)
Flu like symptoms ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Infusion related reaction ^†	0/6 (0.00%)	0/52 (0.00%)	2/48 (4.17%)
Malaise ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Multi-organ failure ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Pain ^†	0/6 (0.00%)	0/52 (0.00%)	2/48 (4.17%)
Infections and infestations
Infections and infestations-Other ^†	1/6 (16.67%)	1/52 (1.92%)	5/48 (10.42%)
Lung infection ^†	0/6 (0.00%)	0/52 (0.00%)	7/48 (14.58%)
Sepsis ^†	0/6 (0.00%)	1/52 (1.92%)	1/48 (2.08%)
Skin infection ^†	1/6 (16.67%)	0/52 (0.00%)	0/48 (0.00%)
Urinary tract infection ^†	0/6 (0.00%)	0/52 (0.00%)	3/48 (6.25%)
Injury, poisoning and procedural complications
Fall ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Spinal fracture ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Investigations
Alanine aminotransferase increased ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Aspartate aminotransferase increased ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Blood bilirubin increased ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Creatinine increased ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
INR increased ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Lymphocyte count decreased ^†	0/6 (0.00%)	0/52 (0.00%)	2/48 (4.17%)
Neutrophil count decreased ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Platelet count decreased ^†	0/6 (0.00%)	0/52 (0.00%)	4/48 (8.33%)
Urine output decreased ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
White blood cell decreased ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Metabolism and nutrition disorders
Hyperglycemia ^†	0/6 (0.00%)	0/52 (0.00%)	2/48 (4.17%)
Hyperkalemia ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Hypoalbuminemia ^†	0/6 (0.00%)	0/52 (0.00%)	2/48 (4.17%)
Hypocalcemia ^†	0/6 (0.00%)	0/52 (0.00%)	3/48 (6.25%)
Hypokalemia ^†	0/6 (0.00%)	0/52 (0.00%)	2/48 (4.17%)
Hypophosphatemia ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Musculoskeletal and connective tissue disorders
Back pain ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Generalized muscle weakness ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Muscle weakness lower limb ^†	0/6 (0.00%)	0/52 (0.00%)	2/48 (4.17%)
Muscle weakness trunk ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Muscle weakness upper limb ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Neck pain ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Osteonecrosis of jaw ^†	0/6 (0.00%)	1/52 (1.92%)	0/48 (0.00%)
Pain in extremity ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified - Other ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Treatment related secondary malignancy ^†	2/6 (33.33%)	0/52 (0.00%)	0/48 (0.00%)
Nervous system disorders
Nervous system disorders-Other ^†	1/6 (16.67%)	0/52 (0.00%)	0/48 (0.00%)
Neuralgia ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Presyncope ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Stroke ^†	0/6 (0.00%)	1/52 (1.92%)	1/48 (2.08%)
Syncope ^†	0/6 (0.00%)	0/52 (0.00%)	3/48 (6.25%)
Renal and urinary disorders
Cystitis noninfective ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Reproductive system and breast disorders
Pelvic pain ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Respiratory, thoracic and mediastinal disorders
Atelectasis ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Dyspnea ^†	0/6 (0.00%)	0/52 (0.00%)	3/48 (6.25%)
Hypoxia ^†	0/6 (0.00%)	1/52 (1.92%)	2/48 (4.17%)
Pneumonitis ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Productive cough ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Pulmonary edema ^†	0/6 (0.00%)	1/52 (1.92%)	0/48 (0.00%)
Respiratory failure ^†	0/6 (0.00%)	2/52 (3.85%)	1/48 (2.08%)
Wheezing ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Skin and subcutaneous tissue disorders
Erythroderma ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Rash maculo-papular ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Vascular disorders
Hypotension ^†	0/6 (0.00%)	1/52 (1.92%)	1/48 (2.08%)
Thromboembolic event ^†	1/6 (16.67%)	1/52 (1.92%)	1/48 (2.08%)
† Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Phase I Dose Level 1 (Elotuzumab, 10mg, and Bortezomib, Lenali	Arm I (Bortezomib, Lenalidomide, Dexamethasone)	Arm II (Bortezomib, Lenalidomide, Dexamethasone, Elotuzumab)
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	6/6 (100.00%)	52/52 (100.00%)	47/48 (97.92%)
Blood and lymphatic system disorders
Anemia ^†	1/6 (16.67%)	39/52 (75.00%)	21/48 (43.75%)
Blood and lymphatic system disorders - Other ^†	1/6 (16.67%)	1/52 (1.92%)	0/48 (0.00%)
Febrile neutropenia ^†	0/6 (0.00%)	1/52 (1.92%)	0/48 (0.00%)
Leukocytosis ^†	1/6 (16.67%)	0/52 (0.00%)	0/48 (0.00%)
Cardiac disorders
Atrial fibrillation ^†	0/6 (0.00%)	3/52 (5.77%)	1/48 (2.08%)
Cardiac disorders-Other ^†	1/6 (16.67%)	0/52 (0.00%)	0/48 (0.00%)
Chest pain - cardiac ^†	0/6 (0.00%)	2/52 (3.85%)	0/48 (0.00%)
Heart failure ^†	0/6 (0.00%)	4/52 (7.69%)	0/48 (0.00%)
Myocardial infarction ^†	0/6 (0.00%)	1/52 (1.92%)	0/48 (0.00%)
Palpitations ^†	0/6 (0.00%)	1/52 (1.92%)	1/48 (2.08%)
Paroxysmal atrial tachycardia ^†	0/6 (0.00%)	1/52 (1.92%)	0/48 (0.00%)
Sinus bradycardia ^†	1/6 (16.67%)	4/52 (7.69%)	3/48 (6.25%)
Sinus tachycardia ^†	0/6 (0.00%)	2/52 (3.85%)	4/48 (8.33%)
Supraventricular tachycardia ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Ear and labyrinth disorders
Ear and labyrinth disorders-Other ^†	1/6 (16.67%)	1/52 (1.92%)	1/48 (2.08%)
Ear pain ^†	0/6 (0.00%)	3/52 (5.77%)	0/48 (0.00%)
Hearing impaired ^†	0/6 (0.00%)	0/52 (0.00%)	3/48 (6.25%)
Tinnitus ^†	2/6 (33.33%)	3/52 (5.77%)	1/48 (2.08%)
Vertigo ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Endocrine disorders
Cushingoid ^†	0/6 (0.00%)	1/52 (1.92%)	0/48 (0.00%)
Endocrine disorders-Other ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Hyperparathyroidism ^†	0/6 (0.00%)	1/52 (1.92%)	0/48 (0.00%)
Hyperthyroidism ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Hypothyroidism ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Eye disorders
Blurred vision ^†	2/6 (33.33%)	10/52 (19.23%)	11/48 (22.92%)
Cataract ^†	1/6 (16.67%)	2/52 (3.85%)	2/48 (4.17%)
Conjunctivitis ^†	1/6 (16.67%)	1/52 (1.92%)	1/48 (2.08%)
Dry eye ^†	0/6 (0.00%)	2/52 (3.85%)	2/48 (4.17%)
Eye disorders-Other ^†	0/6 (0.00%)	5/52 (9.62%)	6/48 (12.50%)
Flashing lights ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Floaters ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Optic nerve disorder ^†	1/6 (16.67%)	0/52 (0.00%)	0/48 (0.00%)
Photophobia ^†	0/6 (0.00%)	1/52 (1.92%)	0/48 (0.00%)
Scleral disorder ^†	0/6 (0.00%)	1/52 (1.92%)	0/48 (0.00%)
Watering eyes ^†	0/6 (0.00%)	1/52 (1.92%)	1/48 (2.08%)
Gastrointestinal disorders
Abdominal distension ^†	1/6 (16.67%)	1/52 (1.92%)	2/48 (4.17%)
Abdominal pain ^†	3/6 (50.00%)	7/52 (13.46%)	7/48 (14.58%)
Bloating ^†	1/6 (16.67%)	2/52 (3.85%)	3/48 (6.25%)
Colitis ^†	0/6 (0.00%)	1/52 (1.92%)	0/48 (0.00%)
Constipation ^†	3/6 (50.00%)	37/52 (71.15%)	24/48 (50.00%)
Dental caries ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Diarrhea ^†	5/6 (83.33%)	29/52 (55.77%)	24/48 (50.00%)
Dry mouth ^†	0/6 (0.00%)	3/52 (5.77%)	8/48 (16.67%)
Dyspepsia ^†	2/6 (33.33%)	12/52 (23.08%)	5/48 (10.42%)
Dysphagia ^†	0/6 (0.00%)	4/52 (7.69%)	5/48 (10.42%)
Enterocolitis ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Esophagitis ^†	0/6 (0.00%)	0/52 (0.00%)	2/48 (4.17%)
Fecal incontinence ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Flatulence ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Gastritis ^†	0/6 (0.00%)	2/52 (3.85%)	0/48 (0.00%)
Gastroesophageal reflux disease ^†	3/6 (50.00%)	7/52 (13.46%)	6/48 (12.50%)
Gastrointestinal disorders-Other ^†	0/6 (0.00%)	4/52 (7.69%)	3/48 (6.25%)
Gingival pain ^†	0/6 (0.00%)	1/52 (1.92%)	1/48 (2.08%)
Hemorrhoidal hemorrhage ^†	0/6 (0.00%)	2/52 (3.85%)	1/48 (2.08%)
Hemorrhoids ^†	0/6 (0.00%)	1/52 (1.92%)	0/48 (0.00%)
Ileus ^†	0/6 (0.00%)	1/52 (1.92%)	0/48 (0.00%)
Lower gastrointestinal hemorrhage ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Mucositis oral ^†	0/6 (0.00%)	6/52 (11.54%)	6/48 (12.50%)
Nausea ^†	3/6 (50.00%)	26/52 (50.00%)	25/48 (52.08%)
Oral pain ^†	0/6 (0.00%)	2/52 (3.85%)	0/48 (0.00%)
Rectal hemorrhage ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Small intestinal obstruction ^†	0/6 (0.00%)	1/52 (1.92%)	0/48 (0.00%)
Stomach pain ^†	0/6 (0.00%)	3/52 (5.77%)	2/48 (4.17%)
Toothache ^†	0/6 (0.00%)	2/52 (3.85%)	1/48 (2.08%)
Vomiting ^†	3/6 (50.00%)	8/52 (15.38%)	9/48 (18.75%)
General disorders
Chills ^†	3/6 (50.00%)	9/52 (17.31%)	8/48 (16.67%)
Edema face ^†	0/6 (0.00%)	4/52 (7.69%)	3/48 (6.25%)
Edema limbs ^†	6/6 (100.00%)	33/52 (63.46%)	29/48 (60.42%)
Fatigue ^†	6/6 (100.00%)	41/52 (78.85%)	34/48 (70.83%)
Fever ^†	3/6 (50.00%)	11/52 (21.15%)	13/48 (27.08%)
Flu like symptoms ^†	4/6 (66.67%)	0/52 (0.00%)	3/48 (6.25%)
Gait disturbance ^†	0/6 (0.00%)	6/52 (11.54%)	2/48 (4.17%)
General disorders and admin site conditions - Other ^†	4/6 (66.67%)	3/52 (5.77%)	3/48 (6.25%)
Infusion related reaction ^†	0/6 (0.00%)	0/52 (0.00%)	2/48 (4.17%)
Infusion site extravasation ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Injection site reaction ^†	2/6 (33.33%)	1/52 (1.92%)	3/48 (6.25%)
Irritability ^†	1/6 (16.67%)	1/52 (1.92%)	2/48 (4.17%)
Localized edema ^†	0/6 (0.00%)	4/52 (7.69%)	1/48 (2.08%)
Malaise ^†	0/6 (0.00%)	3/52 (5.77%)	2/48 (4.17%)
Non-cardiac chest pain ^†	0/6 (0.00%)	5/52 (9.62%)	3/48 (6.25%)
Pain ^†	3/6 (50.00%)	14/52 (26.92%)	14/48 (29.17%)
Hepatobiliary disorders
Portal vein thrombosis ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Immune system disorders
Allergic reaction ^†	0/6 (0.00%)	1/52 (1.92%)	2/48 (4.17%)
Autoimmune disorder ^†	1/6 (16.67%)	0/52 (0.00%)	0/48 (0.00%)
Immune system disorders-Other ^†	2/6 (33.33%)	0/52 (0.00%)	0/48 (0.00%)
Infections and infestations
Bladder infection ^†	1/6 (16.67%)	0/52 (0.00%)	0/48 (0.00%)
Bronchial infection ^†	2/6 (33.33%)	2/52 (3.85%)	1/48 (2.08%)
Conjunctivitis infective ^†	0/6 (0.00%)	1/52 (1.92%)	0/48 (0.00%)
Endocarditis infective ^†	0/6 (0.00%)	1/52 (1.92%)	0/48 (0.00%)
Eye infection ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Gum infection ^†	1/6 (16.67%)	1/52 (1.92%)	0/48 (0.00%)
Infections and infestations-Other ^†	3/6 (50.00%)	11/52 (21.15%)	5/48 (10.42%)
Lung infection ^†	0/6 (0.00%)	7/52 (13.46%)	4/48 (8.33%)
Mucosal infection ^†	1/6 (16.67%)	1/52 (1.92%)	2/48 (4.17%)
Nail infection ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Papulopustular rash ^†	0/6 (0.00%)	1/52 (1.92%)	0/48 (0.00%)
Peripheral nerve infection ^†	0/6 (0.00%)	1/52 (1.92%)	0/48 (0.00%)
Rhinitis infective ^†	0/6 (0.00%)	1/52 (1.92%)	1/48 (2.08%)
Sepsis ^†	0/6 (0.00%)	3/52 (5.77%)	0/48 (0.00%)
Sinusitis ^†	0/6 (0.00%)	2/52 (3.85%)	2/48 (4.17%)
Skin infection ^†	1/6 (16.67%)	2/52 (3.85%)	3/48 (6.25%)
Soft tissue infection ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Tooth infection ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Upper respiratory infection ^†	5/6 (83.33%)	8/52 (15.38%)	8/48 (16.67%)
Urinary tract infection ^†	1/6 (16.67%)	5/52 (9.62%)	6/48 (12.50%)
Injury, poisoning and procedural complications
Ankle fracture ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Bruising ^†	1/6 (16.67%)	3/52 (5.77%)	6/48 (12.50%)
Burn ^†	0/6 (0.00%)	1/52 (1.92%)	0/48 (0.00%)
Fall ^†	2/6 (33.33%)	8/52 (15.38%)	7/48 (14.58%)
Fracture ^†	1/6 (16.67%)	1/52 (1.92%)	2/48 (4.17%)
Hip fracture ^†	0/6 (0.00%)	1/52 (1.92%)	0/48 (0.00%)
Injury, poison and procedural complications - Other ^†	2/6 (33.33%)	0/52 (0.00%)	6/48 (12.50%)
Spinal fracture ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Tracheal obstruction ^†	0/6 (0.00%)	1/52 (1.92%)	0/48 (0.00%)
Investigations
Activated partial thromboplastin time prolonged ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Alanine aminotransferase increased ^†	1/6 (16.67%)	15/52 (28.85%)	14/48 (29.17%)
Alkaline phosphatase increased ^†	1/6 (16.67%)	13/52 (25.00%)	12/48 (25.00%)
Aspartate aminotransferase increased ^†	1/6 (16.67%)	9/52 (17.31%)	10/48 (20.83%)
Blood bilirubin increased ^†	1/6 (16.67%)	6/52 (11.54%)	1/48 (2.08%)
Cholesterol high ^†	0/6 (0.00%)	2/52 (3.85%)	4/48 (8.33%)
Creatinine increased ^†	1/6 (16.67%)	14/52 (26.92%)	9/48 (18.75%)
Ejection fraction decreased ^†	0/6 (0.00%)	1/52 (1.92%)	0/48 (0.00%)
Electrocardiogram QT corrected interval prolonged ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Hemoglobin increased ^†	0/6 (0.00%)	1/52 (1.92%)	1/48 (2.08%)
INR increased ^†	0/6 (0.00%)	1/52 (1.92%)	3/48 (6.25%)
Investigations-Other ^†	1/6 (16.67%)	1/52 (1.92%)	0/48 (0.00%)
Lymphocyte count decreased ^†	4/6 (66.67%)	24/52 (46.15%)	18/48 (37.50%)
Lymphocyte count increased ^†	0/6 (0.00%)	1/52 (1.92%)	2/48 (4.17%)
Neutrophil count decreased ^†	2/6 (33.33%)	18/52 (34.62%)	17/48 (35.42%)
Platelet count decreased ^†	3/6 (50.00%)	30/52 (57.69%)	32/48 (66.67%)
Weight gain ^†	1/6 (16.67%)	8/52 (15.38%)	11/48 (22.92%)
Weight loss ^†	2/6 (33.33%)	9/52 (17.31%)	9/48 (18.75%)
White blood cell decreased ^†	4/6 (66.67%)	25/52 (48.08%)	23/48 (47.92%)
Metabolism and nutrition disorders
Acidosis ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Anorexia ^†	3/6 (50.00%)	20/52 (38.46%)	17/48 (35.42%)
Dehydration ^†	1/6 (16.67%)	7/52 (13.46%)	10/48 (20.83%)
Glucose intolerance ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Hypercalcemia ^†	0/6 (0.00%)	6/52 (11.54%)	7/48 (14.58%)
Hyperglycemia ^†	0/6 (0.00%)	15/52 (28.85%)	17/48 (35.42%)
Hyperkalemia ^†	1/6 (16.67%)	5/52 (9.62%)	4/48 (8.33%)
Hypermagnesemia ^†	0/6 (0.00%)	1/52 (1.92%)	1/48 (2.08%)
Hypernatremia ^†	0/6 (0.00%)	6/52 (11.54%)	2/48 (4.17%)
Hypertriglyceridemia ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Hyperuricemia ^†	0/6 (0.00%)	3/52 (5.77%)	0/48 (0.00%)
Hypoalbuminemia ^†	3/6 (50.00%)	15/52 (28.85%)	20/48 (41.67%)
Hypocalcemia ^†	1/6 (16.67%)	21/52 (40.38%)	21/48 (43.75%)
Hypoglycemia ^†	2/6 (33.33%)	6/52 (11.54%)	7/48 (14.58%)
Hypokalemia ^†	2/6 (33.33%)	18/52 (34.62%)	18/48 (37.50%)
Hypomagnesemia ^†	0/6 (0.00%)	6/52 (11.54%)	5/48 (10.42%)
Hyponatremia ^†	2/6 (33.33%)	14/52 (26.92%)	14/48 (29.17%)
Hypophosphatemia ^†	0/6 (0.00%)	6/52 (11.54%)	1/48 (2.08%)
Metabolism and nutrition disorders - Other, specify ^†	0/6 (0.00%)	1/52 (1.92%)	1/48 (2.08%)
Obesity ^†	0/6 (0.00%)	1/52 (1.92%)	0/48 (0.00%)
Musculoskeletal and connective tissue disorders
Arthralgia ^†	1/6 (16.67%)	12/52 (23.08%)	11/48 (22.92%)
Arthritis ^†	1/6 (16.67%)	4/52 (7.69%)	0/48 (0.00%)
Back pain ^†	4/6 (66.67%)	19/52 (36.54%)	20/48 (41.67%)
Bone pain ^†	1/6 (16.67%)	11/52 (21.15%)	9/48 (18.75%)
Buttock pain ^†	1/6 (16.67%)	1/52 (1.92%)	0/48 (0.00%)
Chest wall pain ^†	0/6 (0.00%)	3/52 (5.77%)	4/48 (8.33%)
Flank pain ^†	0/6 (0.00%)	3/52 (5.77%)	2/48 (4.17%)
Generalized muscle weakness ^†	2/6 (33.33%)	8/52 (15.38%)	11/48 (22.92%)
Joint effusion ^†	1/6 (16.67%)	1/52 (1.92%)	0/48 (0.00%)
Muscle weakness lower limb ^†	2/6 (33.33%)	6/52 (11.54%)	4/48 (8.33%)
Muscle weakness right-sided ^†	0/6 (0.00%)	1/52 (1.92%)	0/48 (0.00%)
Muscle weakness upper limb ^†	0/6 (0.00%)	1/52 (1.92%)	2/48 (4.17%)
Musculoskeletal and connective tiss disorder - Other ^†	3/6 (50.00%)	5/52 (9.62%)	3/48 (6.25%)
Myalgia ^†	0/6 (0.00%)	13/52 (25.00%)	10/48 (20.83%)
Neck pain ^†	1/6 (16.67%)	2/52 (3.85%)	6/48 (12.50%)
Osteonecrosis of jaw ^†	0/6 (0.00%)	1/52 (1.92%)	0/48 (0.00%)
Osteoporosis ^†	0/6 (0.00%)	2/52 (3.85%)	0/48 (0.00%)
Pain in extremity ^†	4/6 (66.67%)	21/52 (40.38%)	25/48 (52.08%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified - Other ^†	0/6 (0.00%)	1/52 (1.92%)	2/48 (4.17%)
Nervous system disorders
Akathisia ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Ataxia ^†	0/6 (0.00%)	1/52 (1.92%)	3/48 (6.25%)
Cognitive disturbance ^†	0/6 (0.00%)	1/52 (1.92%)	0/48 (0.00%)
Concentration impairment ^†	0/6 (0.00%)	1/52 (1.92%)	0/48 (0.00%)
Depressed level of consciousness ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Dizziness ^†	3/6 (50.00%)	22/52 (42.31%)	19/48 (39.58%)
Dysesthesia ^†	0/6 (0.00%)	1/52 (1.92%)	0/48 (0.00%)
Dysgeusia ^†	0/6 (0.00%)	13/52 (25.00%)	10/48 (20.83%)
Dysphasia ^†	0/6 (0.00%)	0/52 (0.00%)	2/48 (4.17%)
Encephalopathy ^†	0/6 (0.00%)	2/52 (3.85%)	0/48 (0.00%)
Headache ^†	2/6 (33.33%)	16/52 (30.77%)	14/48 (29.17%)
Hypersomnia ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Ischemia cerebrovascular ^†	1/6 (16.67%)	1/52 (1.92%)	0/48 (0.00%)
Memory impairment ^†	1/6 (16.67%)	2/52 (3.85%)	6/48 (12.50%)
Movements involuntary ^†	1/6 (16.67%)	0/52 (0.00%)	1/48 (2.08%)
Nervous system disorders-Other ^†	0/6 (0.00%)	1/52 (1.92%)	0/48 (0.00%)
Neuralgia ^†	0/6 (0.00%)	1/52 (1.92%)	2/48 (4.17%)
Paresthesia ^†	1/6 (16.67%)	5/52 (9.62%)	4/48 (8.33%)
Peripheral motor neuropathy ^†	1/6 (16.67%)	6/52 (11.54%)	13/48 (27.08%)
Peripheral sensory neuropathy ^†	5/6 (83.33%)	38/52 (73.08%)	35/48 (72.92%)
Presyncope ^†	0/6 (0.00%)	2/52 (3.85%)	2/48 (4.17%)
Radiculitis ^†	1/6 (16.67%)	4/52 (7.69%)	0/48 (0.00%)
Seizure ^†	0/6 (0.00%)	1/52 (1.92%)	0/48 (0.00%)
Sinus pain ^†	0/6 (0.00%)	1/52 (1.92%)	0/48 (0.00%)
Somnolence ^†	0/6 (0.00%)	1/52 (1.92%)	0/48 (0.00%)
Spasticity ^†	0/6 (0.00%)	1/52 (1.92%)	0/48 (0.00%)
Syncope ^†	0/6 (0.00%)	3/52 (5.77%)	2/48 (4.17%)
Tremor ^†	1/6 (16.67%)	4/52 (7.69%)	6/48 (12.50%)
Psychiatric disorders
Agitation ^†	0/6 (0.00%)	1/52 (1.92%)	4/48 (8.33%)
Anxiety ^†	2/6 (33.33%)	8/52 (15.38%)	10/48 (20.83%)
Confusion ^†	0/6 (0.00%)	2/52 (3.85%)	3/48 (6.25%)
Depression ^†	0/6 (0.00%)	5/52 (9.62%)	10/48 (20.83%)
Insomnia ^†	3/6 (50.00%)	16/52 (30.77%)	19/48 (39.58%)
Personality change ^†	0/6 (0.00%)	1/52 (1.92%)	0/48 (0.00%)
Restlessness ^†	1/6 (16.67%)	1/52 (1.92%)	1/48 (2.08%)
Renal and urinary disorders
Acute kidney injury ^†	0/6 (0.00%)	6/52 (11.54%)	1/48 (2.08%)
Chronic kidney disease ^†	0/6 (0.00%)	1/52 (1.92%)	2/48 (4.17%)
Hematuria ^†	0/6 (0.00%)	1/52 (1.92%)	3/48 (6.25%)
Proteinuria ^†	0/6 (0.00%)	4/52 (7.69%)	4/48 (8.33%)
Renal and urinary disorders-Other ^†	0/6 (0.00%)	1/52 (1.92%)	1/48 (2.08%)
Renal calculi ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Urinary frequency ^†	0/6 (0.00%)	4/52 (7.69%)	1/48 (2.08%)
Urinary incontinence ^†	1/6 (16.67%)	1/52 (1.92%)	2/48 (4.17%)
Urinary retention ^†	0/6 (0.00%)	2/52 (3.85%)	4/48 (8.33%)
Urinary tract pain ^†	1/6 (16.67%)	1/52 (1.92%)	2/48 (4.17%)
Urinary urgency ^†	0/6 (0.00%)	1/52 (1.92%)	1/48 (2.08%)
Urine discoloration ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Reproductive system and breast disorders
Erectile dysfunction ^†	0/6 (0.00%)	2/52 (3.85%)	2/48 (4.17%)
Pelvic pain ^†	0/6 (0.00%)	1/52 (1.92%)	2/48 (4.17%)
Prostatic obstruction ^†	0/6 (0.00%)	1/52 (1.92%)	0/48 (0.00%)
Testicular pain ^†	0/6 (0.00%)	1/52 (1.92%)	1/48 (2.08%)
Vaginal discharge ^†	0/6 (0.00%)	2/52 (3.85%)	0/48 (0.00%)
Vaginal hemorrhage ^†	1/6 (16.67%)	0/52 (0.00%)	0/48 (0.00%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis ^†	0/6 (0.00%)	3/52 (5.77%)	3/48 (6.25%)
Aspiration ^†	1/6 (16.67%)	0/52 (0.00%)	0/48 (0.00%)
Atelectasis ^†	1/6 (16.67%)	0/52 (0.00%)	0/48 (0.00%)
Cough ^†	5/6 (83.33%)	18/52 (34.62%)	22/48 (45.83%)
Dyspnea ^†	2/6 (33.33%)	21/52 (40.38%)	19/48 (39.58%)
Epistaxis ^†	0/6 (0.00%)	3/52 (5.77%)	2/48 (4.17%)
Hiccups ^†	0/6 (0.00%)	1/52 (1.92%)	0/48 (0.00%)
Hoarseness ^†	0/6 (0.00%)	3/52 (5.77%)	1/48 (2.08%)
Hypoxia ^†	0/6 (0.00%)	4/52 (7.69%)	1/48 (2.08%)
Nasal congestion ^†	2/6 (33.33%)	8/52 (15.38%)	7/48 (14.58%)
Pharyngeal mucositis ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Pleural effusion ^†	0/6 (0.00%)	2/52 (3.85%)	2/48 (4.17%)
Pleuritic pain ^†	0/6 (0.00%)	2/52 (3.85%)	0/48 (0.00%)
Pneumonitis ^†	1/6 (16.67%)	1/52 (1.92%)	0/48 (0.00%)
Postnasal drip ^†	1/6 (16.67%)	2/52 (3.85%)	2/48 (4.17%)
Productive cough ^†	1/6 (16.67%)	4/52 (7.69%)	11/48 (22.92%)
Pulmonary edema ^†	0/6 (0.00%)	1/52 (1.92%)	0/48 (0.00%)
Resp, thoracic and mediastinal disorders - Other ^†	1/6 (16.67%)	0/52 (0.00%)	1/48 (2.08%)
Retinoic acid syndrome ^†	0/6 (0.00%)	1/52 (1.92%)	0/48 (0.00%)
Sleep apnea ^†	1/6 (16.67%)	1/52 (1.92%)	2/48 (4.17%)
Sore throat ^†	0/6 (0.00%)	5/52 (9.62%)	4/48 (8.33%)
Wheezing ^†	1/6 (16.67%)	2/52 (3.85%)	1/48 (2.08%)
Skin and subcutaneous tissue disorders
Alopecia ^†	0/6 (0.00%)	2/52 (3.85%)	6/48 (12.50%)
Dry skin ^†	1/6 (16.67%)	7/52 (13.46%)	8/48 (16.67%)
Erythema multiforme ^†	1/6 (16.67%)	0/52 (0.00%)	5/48 (10.42%)
Hirsutism ^†	0/6 (0.00%)	0/52 (0.00%)	2/48 (4.17%)
Hyperhidrosis ^†	0/6 (0.00%)	3/52 (5.77%)	7/48 (14.58%)
Nail discoloration ^†	0/6 (0.00%)	1/52 (1.92%)	1/48 (2.08%)
Nail ridging ^†	0/6 (0.00%)	0/52 (0.00%)	1/48 (2.08%)
Periorbital edema ^†	0/6 (0.00%)	1/52 (1.92%)	1/48 (2.08%)
Pruritus ^†	3/6 (50.00%)	6/52 (11.54%)	6/48 (12.50%)
Purpura ^†	1/6 (16.67%)	0/52 (0.00%)	1/48 (2.08%)
Rash acneiform ^†	1/6 (16.67%)	3/52 (5.77%)	2/48 (4.17%)
Rash maculo-papular ^†	1/6 (16.67%)	18/52 (34.62%)	12/48 (25.00%)
Skin and subcutaneous tissue disorders - Other ^†	2/6 (33.33%)	6/52 (11.54%)	5/48 (10.42%)
Skin hyperpigmentation ^†	1/6 (16.67%)	1/52 (1.92%)	2/48 (4.17%)
Skin ulceration ^†	0/6 (0.00%)	3/52 (5.77%)	1/48 (2.08%)
Urticaria ^†	0/6 (0.00%)	1/52 (1.92%)	1/48 (2.08%)
Surgical and medical procedures
Surgical and medical procedures-Other ^†	1/6 (16.67%)	1/52 (1.92%)	2/48 (4.17%)
Vascular disorders
Flushing ^†	0/6 (0.00%)	0/52 (0.00%)	7/48 (14.58%)
Hematoma ^†	0/6 (0.00%)	2/52 (3.85%)	0/48 (0.00%)
Hot flashes ^†	0/6 (0.00%)	2/52 (3.85%)	6/48 (12.50%)
Hypertension ^†	1/6 (16.67%)	21/52 (40.38%)	17/48 (35.42%)
Hypotension ^†	1/6 (16.67%)	13/52 (25.00%)	14/48 (29.17%)
Superficial thrombophlebitis ^†	0/6 (0.00%)	1/52 (1.92%)	1/48 (2.08%)
Thromboembolic event ^†	2/6 (33.33%)	6/52 (11.54%)	6/48 (12.50%)
Vascular disorders-Other ^†	0/6 (0.00%)	0/52 (0.00%)	2/48 (4.17%)
† Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

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Name/Title:	Myeloma Committee Statistician
Organization:	SWOG Statistics and Data Management Center
Phone:	2066674623
EMail:	rachaels@crab.org

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Usmani SZ, Hoering A, Ailawadhi S, Sexton R, Lipe B, Hita SF, Valent J, Rosenzweig M, Zonder JA, Dhodapkar M, Callander N, Zimmerman T, Voorhees PM, Durie B, Rajkumar SV, Richardson PG, Orlowski RZ; SWOG1211 Trial Investigators. Bortezomib, lenalidomide, and dexamethasone with or without elotuzumab in patients with untreated, high-risk multiple myeloma (SWOG-1211): primary analysis of a randomised, phase 2 trial. Lancet Haematol. 2021 Jan;8(1):e45-e54. doi: 10.1016/S2352-3026(20)30354-9. Epub 2020 Dec 22.

Layout table for additonal information

Responsible Party:	SWOG Cancer Research Network
ClinicalTrials.gov Identifier:	NCT01668719
Other Study ID Numbers:	S1211 NCI-2012-01998 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) PS1211_A12PAMDREVW01 CDR0000738512 S1211 ( Other Identifier: SWOG ) S1211 ( Other Identifier: CTEP ) U10CA180888 ( U.S. NIH Grant/Contract ) U10CA032102 ( U.S. NIH Grant/Contract )
First Submitted:	August 16, 2012
First Posted:	August 20, 2012
Results First Submitted:	June 8, 2021
Results First Posted:	October 27, 2021
Last Update Posted:	May 23, 2023

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