Conditions: Multiple Myeloma
Keywords: B-cell tumors autologous stem cell transplantation blood cancers
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 53
Healthy volunteers: no

Brief summary:
This is a phase 2, single arm, open-label, multicenter study to evaluate the feasibility and tolerance of the combination of elotuzumab, lenalidomide, and dexamethasone in the induction, consolidation, and maintenance treatment of transplant eligible, newly diagnosed multiple myeloma patients.

Detailed description:
The primary purpose of this study is to evaluate the feasibility of using the combination of elotuzumab, lenalidomide, and dexamethasone (ERd) as induction therapy and the ability of the combination to facilitate the start of autologous stem cell transplantation (ASCT) in transplant-eligible patients newly diagnosed with multiple myeloma. In addition to induction, the efficacy, safety, and tolerability of ERd as consolidation and maintenance therapy in these patients will be observed.

Eligible patients will undergo four 28-day cycles of an induction regimen of elotuzumab, lenalidomide, and dexamethasone. Following completion of 4 cycles of induction therapy, all patients will undergo standard mobilization, collection of stem cells, and then ASCT using a melphalan conditioning regimen as per institutional guidelines.

Toxicity evaluation will be interrupted during the stem cell procedure and will resume with the onset of consolidation. Adverse events will be collected, however, from the end of induction up to mobilization.

Consolidation therapy will begin 70 to 120 days following ASCT and will consist of four 28-day cycles of elotuzumab, lenalidomide, and dexamethasone. All patients that do not experience progressive disease will begin maintenance therapy of elotuzumab, lenalidomide, and dexamethasone. The duration of maintenance will be 24 months.

Arms:
arm 1: INDUCTION:

Cycles 1-2: elotuzumab 10mg/kg IV days 1, 8, 15, 22; lenalidomide (len) 25mg orally (PO), once daily (QD) on days 1-21; dexamethasone (dex) 28 mg PO (3-24 hrs before elotuzumab IV) and 8mg IV (45-90 minutes before elotuzumab) days 1, 8, 15, 22.

Cycles 3-4: elotuzumab 10mg/kg IV days 1 and 15; len 25mg PO QD days 1-21; dex 8mg PO (3-24 hrs before elotuzumab IV) and 8mg IV (45-90 minutes before elotuzumab) days 1 and 15; dex 40mg PO days 8 and 22.

CONSOLIDATION:

Four 28-day cycles: elotuzumab 10mg/kg IV days 1 and 15; len 15mg PO QD days 1-21; dex 28mg PO (3-24 hrs before elotuzumab) and 8mg IV (45-90 minutes before elotuzumab) days 1 and 15; dex 40mg PO days 8 and 22.

MAINTENANCE:

After completing consolidation therapy patients without progressive disease will receive, for up to 24 months, 28-day cycles of elotuzumab 20mg/kg IV day 1; len 10mg +/- 5mg PO QD days 1-21; dex 28mg PO (3-24 hrs before elotuzumab) and 8mg IV (45-90 minutes prior to elotuzumab) day 1.

Interventions: intervention 1: elotuzumab intervention 2: Lenalidomide intervention 3: Dexamethasone intervention 4: autologous stem cell transplantation
Intervention descriptions: intervention 1: Given intravenously (IV) intervention 2: Given by IV intervention 3: Given orally (PO) or by IV intervention 4: None

Protocol document:
Prot_SAP_000.pdf: 
 
CONFIDENTIAL 
This document is confidential and is the property of the Sarah Cannon Development Innovations.  No part of this 
document may be transmitted, reproduced, published, or used by other persons without prior written authorization 
from Sarah Cannon Development Innovations. 
 
 
MM 61 
A Phase 2 Study to Assess the Feasibility and Tolerance of the Combination of 
Elotuzumab, Lenalidomide, and Dexamethasone (ERd) in the Induction, 
Consolidation, and Maintenance Treatment of Transplant-Eligible Patients 
Newly Diagnosed with Multiple Myeloma (MM) 
SARAH CANNON DEVELOPMENT 
INNOVATIONS STUDY NUMBER: 
 
MM 61 
BRISTOL-MYERS SQUIBB STUDY NUMBER: 
CA204-154 
STUDY DRUG: 
Elotuzumab 
SPONSOR: 
Sarah Cannon Development Innovations 
1100 Charlotte Avenue, Suite 800 
Nashville, TN  37203 
1-877-MY-1-SCRI 
asksarah@sarahcannon.com 
 
STUDY CHAIR: 
Jesus Berdeja, MD 
Sarah Cannon Research Institute 
1100 Charlotte Avenue, Suite 800 
Nashville, TN  37203 
1-877-MY-1-SCRI 
 
DATE FINAL: 
10 May 2016 
AMENDMENT NUMBER 1: 
05 July 2016 
AMENDMENT NUMBER 2: 
07 December 2016 


 
 
CONFIDENTIAL 
STUDY DRUG(S):  ELOTUZUMAB 
  
              SARAH CANNON DEVELOPMENT INNOVATIONS  
 
  
 
 
 
STUDY NUMBER:  MM 61 
AMENDMENT 2 DATE:  07 DECEMBER 2016 
 
 
 
 
VERSION 3.0 
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Clinical Study Statement of Compliance 
A Phase 2 Study to Assess the Feasibility and Tolerance of the Combination of 
Elotuzumab, Lenalidomide, and Dexamethasone (ERd) in the Induction, 
Consolidation, and Maintenance Treatment of Transplant-Eligible Patients 
Newly Diagnosed with Multiple Myeloma (MM) 
 
 This clinical study shall be conducted in compliance with the protocol, as referenced herein, 
and all applicable local, national, and international regulatory requirements to include, but not 
be limited to: 
 
International Conference on Harmonisation (ICH) Guidelines on Good Clinical 
Practice (GCP) 
 
Ethical principles that have their origins in the Declaration of Helsinki 
 
The US Food and Drug Administration (FDA) Code of Federal Regulation (CFR): 
o 
Title 21CFR Part 50 & 45 CFR Part 46, Protection of Human Subjects 
o 
Title 21CFR Part 54, Financial Disclosure by Clinical Investigators 
o 
Title 21CFR Part 56, Institutional Review Boards 
o 
Title 21CFR Part 312, Investigational New Drug Application 
o 
Title 45 CFR Parts 160, 162, and 164, Health Insurance Portability and 
Accountability Act (HIPAA) 
 
 
As the Study Chair and/or Principal Investigator, I understand that my signature on the 
protocol constitutes my agreement and understanding of my responsibilities to conduct the 
clinical study in accordance to the protocol and applicable regulations.  Furthermore, it 
constitutes my understanding and agreement that any changes initiated by myself, without 
prior agreement in writing from the Sponsor, shall be defined as a deviation from the protocol, 
and shall be formally documented as such. 
 


 
 
CONFIDENTIAL 
STUDY DRUG(S):  ELOTUZUMAB 
  
              SARAH CANNON DEVELOPMENT INNOVATIONS  
 
  
 
 
 
STUDY NUMBER:  MM 61 
AMENDMENT 2 DATE:  07 DECEMBER 2016 
 
 
 
 
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Clinical Study Signature Approval Page 
 
SARAH CANNON DEVELOPMENT 
INNOVATIONS STUDY NUMBER: 
 
MM 61 
BRISTOL-MYERS SQUIBB STUDY 
NUMBER: 
CA204-154 
STUDY DRUG(S): 
Elotuzumab 
DATE FINAL: 
10 May 2016 
AMENDMENT NUMBER 1: 
05 July 2016 
AMENDMENT NUMBER 2: 
07 December 2016 
 
 
 
__________________________ 
__________________________         ______________  
Study Chair 
Sarah Cannon Research Institute 
Study Chair Signature 
 
Date 
 
 
 
 
__________________________ 
__________________________         ______________  
Sponsor Representative 
Sarah Cannon Development 
Innovations, LLC 
 
 
Sponsor Representative Signature  
 
Date 
 
 
 
Jesus Berdeja, MD 
Sheetal Khedkar, MD, MSPH 


 
 
 
CONFIDENTIAL 
STUDY DRUG(S):  ELOTUZUMAB 
  
              SARAH CANNON DEVELOPMENT INNOVATIONS  
 
  
 
 
 
STUDY NUMBER:  MM 61 
AMENDMENT 2 DATE:  07 DECEMBER 2016 
 
 
 
 
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Page 4 of 96 
 
Clinical Study Principal Investigator Signature Form 
A Phase 2 Study to Assess the Feasibility and Tolerance of the Combination of 
Elotuzumab, Lenalidomide, and Dexamethasone (ERd) in the Induction, 
Consolidation, and Maintenance Treatment of Transplant-Eligible Patients 
Newly Diagnosed with Multiple Myeloma (MM) 
 
SARAH CANNON DEVELOPMENT 
INNOVATIONS STUDY NUMBER: 
 
MM 61 
BRISTOL-MYERS SQUIBB STUDY 
NUMBER: 
CA204-154 
DATE FINAL: 
10 May 2016 
AMENDMENT NUMBER 1: 
05 July 2016 
AMENDMENT NUMBER 2: 
07 December 2016 
 
 
By signing this protocol acceptance page, I confirm I have read, understand, and agree to conduct the 
study in accordance with the current protocol. 
 
 
__________________________ _            _______________________________     _______  
Principal Investigator Name 
(Please Print) 
 
Principal Investigator Signature 
 
Date 
 
Please retain a copy of this page for your study files and return the original signed and dated 
form to: 
Sarah Cannon Development Innovations, LLC 
1100 Charlotte Avenue, Suite 800 
Attention:  MM 61 Study Team 
Nashville, TN 37203 
 


 
CONFIDENTIAL 
STUDY DRUG(S):  ELOTUZUMAB 
  
              SARAH CANNON DEVELOPMENT INNOVATIONS  
 
  
 
 
 
STUDY NUMBER:  MM 61 
AMENDMENT 2 DATE:  07 DECEMBER 2016 
 
 
 
 
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MM 61 PROTOCOL SYNOPSIS 
Title of Study: 
A Phase 2 Study to Assess the Feasibility and Tolerance of the Combination of 
Elotuzumab, Lenalidomide, and Dexamethasone (ERd) in the Induction, Consolidation, 
and Maintenance Treatment of Transplant-Eligible Patients Newly Diagnosed with 
Multiple Myeloma (MM) 
Sarah Cannon 
Development 
Innovations Study 
Number: 
MM 61 
Bristol-Myers Squibb 
Study Number 
CA204-154 
Sponsor: 
Sarah Cannon Development Innovations, LLC, Nashville, Tennessee 
Study Duration: 
The total duration of the study is planned to be 2 years for 
enrollment and up to 3.5 years maximum follow up per patient 
to complete the full treatment plan. 
Phase of Study:  2 
Study Centers: 
This study is planned to be conducted at 8 centers in the United States. 
Number of Patients: 
Approximately 53 patients are planned to be enrolled in this study.  Recruitment will end 
when 48 patients are evaluable for the primary endpoint (have completed 4 cycles of 
induction treatment with ERd and are able to start ASCT). 
Objectives: 
Primary objective 
The primary objective of this study is to: 
 
Evaluate the feasibility of using the combination of elotuzumab, lenalidomide, 
and dexamethasone (ERd) as induction therapy (induction feasibility rate [IFR]) 
and the ability of the combination to facilitate the start of autologous stem cell 
transplantation (ASCT) in transplant-eligible patients newly diagnosed with MM. 
Secondary objectives 
The secondary objectives of this study are to: 
 
Evaluate the efficacy of the combination of ERd as induction, consolidation, and 
maintenance therapy in transplant-eligible patients newly diagnosed with MM 
 
Evaluate the safety and tolerability of the combination of ERd as induction, 
consolidation, and maintenance therapy in transplant-eligible patients newly 
diagnosed with MM. 
Exploratory objectives 
The exploratory objectives of this study are to: 
 
Determine minimal residual disease (MRD) by multi-parameter-flow cytometry 
per institutional guidelines 
 
Evaluation of gene expression profiling (GEP) at diagnosis per institutional 
guidelines and correlation of outcomes. 


 
CONFIDENTIAL 
STUDY DRUG(S):  ELOTUZUMAB 
  
              SARAH CANNON DEVELOPMENT INNOVATIONS  
 
  
 
 
 
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MM 61 PROTOCOL SYNOPSIS 
Study Design: 
This is a multi-center, open-label, Phase 2 study to assess the feasibility and tolerance of 
the combination of ERd in the induction, consolidation, and maintenance treatment of 
transplant-eligible patients newly diagnosed with MM according to the following schema: 
Newly Diagnosed Multiple Myeloma in Transplant-Eligible Patients
ERd Induction Therapy - Four 28-day Cycles
ERd Consolidation Therapy  – Four 28-day Cycles
Mobilization and ASCT - Toxicity Evaluation Interrupted
70 to 120 days
ERd Maintenance Therapy – 28-day Cycles for up to 24 Months
 
Study Drugs, Doses, 
and Modes of 
Administration: 
Induction 
All patients will undergo four 28-day cycles of the following induction treatments: 
 
Cycles 1 and 2 
- Elotuzumab 10 mg/kg IV on Days 1, 8, 15, and 22 
- Lenalidomide 25 mg orally on Days 1 through 21 
- Dexamethasone 28 mg orally (3 to 24 hours prior to start of elotuzumab infusion) 
AND 8 mg IV (45 to 90 minutes prior to elotuzumab) on Days 1, 8, 15, and 
22. 
- H1 blockers, H2 blockers, and acetaminophen as pre-medications for elotuzumab. 
 
 
Cycles 3 and 4 
- Elotuzumab 10 mg/kg IV on Days 1 and 15 only 
- Lenalidomide 25 mg orally on Days 1 through 21 
- Dexamethasone 28 mg orally (3 to 24 hours prior to start of elotuzumab infusion) 
AND 8 mg IV (45 to 90 minutes prior to elotuzumab) on Days 1 and 15 
- Dexamethasone 40 mg orally on Days 8 and 22 
- H1 blockers, H2 blockers, and acetaminophen as pre-medications for elotuzumab. 
Mobilization and ASCT 
If a patient is unable to proceed to transplant, but the treating Investigator believes he/she 
would benefit from continued study treatment, the patient will be allowed to continue 
uninterrupted on to consolidation and maintenance without transplant. 
Toxicity evaluations are suspended during the stem cell procedure. 
Consolidation 
Consolidation is to begin 70 to 120 days following ASCT. 
All patients will undergo four 28-day cycles of the following consolidation treatment: 
 
Cycles 5 through 8 
- 
Elotuzumab 10 mg/kg IV on Days 1 and 15 
- 
Lenalidomide 15 mg orally on Days 1 through 21 
 
Lenalidomide can be escalated as tolerated to the maximum-tolerated dose 


 
CONFIDENTIAL 
STUDY DRUG(S):  ELOTUZUMAB 
  
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AMENDMENT 2 DATE:  07 DECEMBER 2016 
 
 
 
 
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MM 61 PROTOCOL SYNOPSIS 
administered during induction. 
Study Drugs, Doses, 
and Modes of 
Administration 
(continued): 
 
Lenalidomide can continue with dose unchanged from induction in patients 
who remain on study, but do not proceed to transplant. 
- 
Dexamethasone 28 mg orally (3 to 24 hours prior to start of elotuzumab 
infusion) AND 8 mg IV (45 to 90 minutes prior to elotuzumab infusion) on 
Days 1 and 15 
- 
Dexamethasone 40 mg orally on Days 8 and 22 
- 
H1 blockers, H2 blockers, and acetaminophen as pre-medications for 
elotuzumab. 
Maintenance 
All patients will proceed to 28-day cycles during maintenance to continue for up to 
24 months: 
 
Cycles 9+ 
- 
Elotuzumab 20 mg/kg IV on Day 1 
- 
Lenalidomide 10 mg ±5 mg orally on Days 1 through 21 
- 
Dexamethasone 28 mg orally (3 to 24 hours prior to start of elotuzumab 
infusion) AND 8 mg IV (45 to 90 minutes prior to elotuzumab) on Day 1 
- 
H1 blockers, H2 blockers, and acetaminophen as pre-medications for 
elotuzumab. 
Any patient who comes off elotuzumab for whatever reason, or completes the 24 months 
of maintenance allowed by the protocol, can continue therapy with FDA-approved 
therapies at the discretion of the treating physician, but will no longer be on study 
following their 60-day post maintenance safety follow-up. 
Inclusion Criteria: 
Patients must meet all of the following criteria in order to be included in the research 
study: 
1. Newly diagnosed myeloma requiring systemic chemotherapy as per International 
Myeloma Working Group (IMWG) uniform criteria (Appendix A) and 
Diagnostic Criteria and Staging for Multiple Myeloma (Appendix B): 
- 
Ideally, no prior therapy, or 
- 
No more than 1 cycle of therapy for emergent control of disease prior to 
enrolling on study, including prior treatment of hypercalcemia, spinal cord 
compression, or active and/or aggressively progressing myeloma with 
corticosteroids or lenalidomide or bortezomib-based regimens (the treatment 
dose should not exceed the equivalent of 160 mg of dexamethasone in a 4 
week period, or not more than 1 cycle) 
- 
Bisphosphonates are permitted. 
2. Eligible and plan to undergo ASCT in first remission (refer to Section 5.1.2) 
3. Measurable disease, prior to initial treatment as indicated by one or more of the 
following: 
- 
Serum M-protein ≥1.0 g/dL 
- 
Urine M-protein ≥200 mg/24 hours 
- 
Serum free light chain assay: involved free light chain level ≥10 mg/dL 
(≥100 mg/L) provided the serum free light chain ratio is abnormal. 


 
CONFIDENTIAL 
STUDY DRUG(S):  ELOTUZUMAB 
  
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MM 61 PROTOCOL SYNOPSIS 
4. Males and females ≥18 years-of-age. 
Inclusion Criteria 
(continued): 
5. Ability to take aspirin or other venous thromboembolism (VTE) anticoagulant therapy 
6. An Eastern Cooperative Oncology Group (ECOG) Performance Status score of 
0 through 2 (see Appendix C) 
7. Adequate hematologic function defined as: 
- 
Absolute neutrophil count (ANC) ≥1.0 x 109/L 
- 
Hemoglobin (Hgb) ≥8 g/dL 
- 
Platelets ≥75 x 109/L.  Screening platelet count should be independent of 
platelet transfusions for at least 2 weeks. 
8. Adequate liver function defined as: 
- 
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 
x the upper limit of normal (ULN) 
- 
Total bilirubin ≤1.5 x ULN (unless the patient has Grade 1 bilirubin 
elevation due to Gilbert’s disease or a similar syndrome involving slow 
conjugation of bilirubin) 
9. Adequate renal function defined as serum creatinine ≤1.5 x ULN OR calculated 
creatinine clearance ≥50 mL/min as calculated by Cockcroft and Gault Formula. 
10. All study participants must be registered into the mandatory Revlimid REMS® 
program and must be willing and able to comply with the requirements of that 
program. 
11. Females of reproductive potential must adhere to the scheduled pregnancy testing as 
required in the Revlimid REMS® program. 
12. Male patients with female partners of childbearing potential and female patients of 
childbearing potential are required to use two forms of acceptable contraception, 
including one barrier method, during their participation in the study and for 28 days 
following last dose of study drugs.  Male patients must also refrain from donating 
semen or sperm during their participation in the study.  Details of mandatory 
contraception measures are presented in Appendix E. 
13. Willingness and ability to comply with study and follow-up procedures. 
14. Ability to understand the nature of this study and give written informed consent. 
Exclusion Criteria: 
Patients who meet any of the following criteria will be excluded from study entry: 
1. Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin 
changes (POEMS) syndrome 
2. Plasma cell leukemia 
3. Waldenström’s macroglobulinemia or IgM myeloma 
4. Presence of other active cancers, or history of treatment for invasive cancer ≤5 years.  
Patients with Stage I cancer who have received definitive local treatment and are 
considered unlikely to recur are eligible.  All patients with previously treated in situ 
carcinoma (i.e., non-invasive) are eligible, as are patients with a history of non-
melanoma skin cancer. 


 
CONFIDENTIAL 
STUDY DRUG(S):  ELOTUZUMAB 
  
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MM 61 PROTOCOL SYNOPSIS 
5. Radiotherapy to multiple sites or immunotherapy within 4 weeks before start of 
protocol treatment (localized radiotherapy to a single site at least 1 week before start 
is permissible) 
Exclusion Criteria 
(continued): 
6. Major surgical procedures ≤28 days of beginning study drug, or minor surgical 
procedures ≤7 days.  No waiting required following port-a-cath placement. 
7. Acute active infection requiring systemic antibiotics, antivirals, or antifungals within 
2 weeks prior to first dose of study treatment 
 
8. Presence of active gastrointestinal disease or other condition that will interfere 
significantly with the absorption, distribution, metabolism, or excretion of oral 
therapy (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea Grade ≥2, 
and malabsorption syndrome) 
9. Any of the following cardiac diseases currently or within the last 6 months: 
- 
Left ventricular ejection fraction (LVEF) <40% as determined by 
echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan 
- 
Unstable angina pectoris 
- 
Congestive heart failure (New York Heart Association ≥ Grade 2, see 
Appendix D) 
- 
Acute myocardial infarction 
- 
Conduction abnormality not controlled with pacemaker or medication 
- 
Significant ventricular or supraventricular arrhythmias (patients with chronic 
rate-controlled atrial fibrillation in the absence of other cardiac abnormalities 
are eligible) 
- 
Valvular disease with significant compromise in cardiac function. 
10. Known seropositive for or active viral infection with human immunodeficiency virus 
or hepatitis A, B, or C virus.  Patients who are seropositive because of hepatitis B 
virus vaccine are eligible. 
11. Any clinically significant medical disease or condition that, in the treating 
Investigator’s opinion, may interfere with protocol adherence or a patient’s ability to 
give informed consent 
12. Pregnant or lactating females 
13. Contraindication to any of the required concomitant drugs, including dexamethasone, 
H1 and H2 blockers, and acetaminophen, or if patient has a history of prior thrombotic 
disease, warfarin or low molecular weight heparin 
14. No health coverage, or if the copay for lenalidomide is not acceptable to the patient 
15. Psychological, familial, sociological, or geographical conditions that do not permit 
compliance with the protocol. 
Correlative Studies: 
Bone marrow aspirates collected as standard of care will be used for MRD analysis and 
GEP to correlate with response. 
Minimal residual disease analysis will be conducted per institutional guidelines at any 


 
CONFIDENTIAL 
STUDY DRUG(S):  ELOTUZUMAB 
  
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MM 61 PROTOCOL SYNOPSIS 
time bone marrow is collected as standard of care. 
Gene expression profiling will be conducted per institutional guidelines on bone marrow 
collected as standard of care at diagnosis. 
Statistical 
Considerations: 
In order to test the null hypothesis of an IFR of 65% versus an alternative hypothesis with 
an IFR of 80%, 48 patients are required in order to have 85% power to test the null 
hypothesis using a one-sided exact binomial test at the 0.1 significance level.  To allow for 
a possible 10% drop-out rate the sample size has been inflated to 53 patients. 
 
Primary endpoint: 
 
IFR, defined as the percentage of patients successfully completing 4 cycles of 
induction treatment with ERd and able to start ASCT. 
Secondary endpoints: 
 
Complete response rate (CRR), defined as the percentage of patients who achieve 
a complete response (CR) or near complete response (nCR) to treatment at each 
stage of the study, i.e., induction, ASCT, consolidation, end of study as per 
IMWG and European Group for Blood and Marrow Transplantation (EBMT) 
criteria 
 
Overall response rate (ORR), defined as the percentage of patients who achieve 
at least a partial response (PR) to treatment at each stage of the study, i.e., 
induction, ASCT, consolidation, end of study as per IMWG and EBMT criteria 
 
Progression-free survival (PFS), defined as the time from start of induction 
treatment to documented progressive disease (PD) or death from any cause up to 
3 years post first study treatment 
 
Overall survival (OS), defined as the time from start of induction treatment to 
3 years post first study treatment or death from any cause, whichever comes first 
 
Consolidation feasibility rate (CFR), defined as the percentage of patients starting 
induction treatment with ERd successfully completing treatment to end of 
consolidation 
 
Maintenance feasibility rate (MFR), defined as the percentage of patients starting 
induction treatment with ERd successfully completing treatment to end of 
maintenance. 


 
CONFIDENTIAL 
STUDY DRUG(S):  ELOTUZUMAB 
  
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MM 61 PROTOCOL SYNOPSIS 
 
 
Safety endpoints including 1) treatment-emergent adverse events (TEAEs), 
serious adverse events (SAEs), and deaths, and 2) clinically significant changes 
in safety-related laboratory parameters according to National Cancer Institute 
Common Terminology Criteria for Adverse Events (NCI CTCAE Volume 4.03) 
and abnormal vital signs. 
Exploratory endpoint: 
 
To evaluate MRD: defined as the proportion of patients who are MRD positive 
versus those who are MRD negative. 
 
All efficacy analyses will be performed using the response evaluation population.  The 
IFR will be computed and presented together with the exact 90% confidence interval (CI) 
using the method of Clopper and Pearson.  The null hypothesis of 65% IFR will be 
rejected if at least 36 patients are able to complete 4 cycles of induction treatment and start 
ASCT.  The CRR, ORR, CFR, and MFR will be computed and presented together with the 
exact 90% Clopper and Pearson CIs. 
 
The Kaplan-Meier product limit method will be used to estimate PFS and OS.  Median 
values and rates at clinically relevant time points will be provided with the 90% CIs.  A 
Cox Proportional Hazards Model may also be utilized to estimate the effects of patient 
baseline characteristics or known prognostic factors on PFS and OS. 


 
CONFIDENTIAL 
STUDY DRUG(S):  ELOTUZUMAB 
  
              SARAH CANNON DEVELOPMENT INNOVATIONS  
 
  
 
 
 
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MM 61 CONTACT INFORMATION 
Sarah Cannon Development Innovations 
Contact Information: 
Sarah Cannon Development Innovations 
1100 Charlotte Avenue, Suite 800 
Nashville, TN  37203 
1-877-MY-1-SCRI 
asksarah@sarahcannon.com 
 
Study Chair: 
Jesus Berdeja, MD 
Sarah Cannon Research Institute 
1100 Charlotte Avenue, Suite 800 
Nashville, TN  37203 
1-877-MY-1-SCRI 
asksarah@sarahcannon.com 
 
Safety Department Fax #: 
Safety Department Email: 
1-866-807-4325 
CANN.SAE@SCRI-Innovations.com 
Regulatory Phone #: 
Regulatory Email: 
1-877-MY-1-SCRI (1-877-691-7274) 
SCRIRegulatory@SCRI-Innovations.com 
Sarah Cannon Development Innovations 
Enrollment Phone #: 
Sarah Cannon Development Innovations 
Enrollment Fax #: 
1-877-MY-1-SCRI (1-877-691-7274) 
1-866-699-0258 
 
 
 


 
CONFIDENTIAL 
STUDY DRUG(S):  ELOTUZUMAB 
  
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LIST OF ABBREVIATIONS 
AE 
Adverse event 
ALP 
Alkaline phosphatase 
ALT 
Alanine aminotransferase 
ANC 
Absolute neutrophil count 
aPTT 
Activated partial thromboplastin time 
ASCT 
Autologous stem cell transplantation 
AST 
Aspartate aminotransferase 
CBC 
Complete blood count 
CFR 
Consolidation feasibility rate 
CI 
Confidence interval 
CMP 
Comprehensive metabolic profile 
CR 
Complete response/remission 
CRF 
Case Report Form 
CRP 
C-reactive protein 
CRR 
Complete response rate 
CS1 
CD2-subset-1, also known as CRACC and SLAMF7 
ECG 
Electrocardiogram 
ECHO 
Echocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
Electronic Case Report Form 
EMBT 
European Group for Blood and Marrow Transplantation 
ERd 
Elotuzumab, lenalidomide, and dexamethasone 
FDA 
US Food and Drug Administration 
FISH 
Fluorescence in-situ hybridization 
GCP 
Good Clinical Practice 
GEP 
Gene expression profiling 
HIPAA 
Health Insurance Portability and Accountability Act 
ICH 
International Conference on Harmonization 
IFR 
Induction feasibility rate 
IgG1 
Immunoglobulin G 1 
IMiD 
Immunomodulatory drugs 
IMWG 
International Myeloma Working Group 
INR 
International Normalized Ratio 
IRB 
Institutional Review Board 
IV 
Intravenous 
LVEF 
Left ventricular ejection fraction 
MFR 
Maintenance feasibility rate 
MM 
Multiple myeloma 
MRD 
Minimal residual disease 
MTD 
Maximum-tolerated dose 
MUGA 
Multi-gated acquisition (scan) 
NCI CTCAE 
National Cancer Institute Common Terminology Criteria for Adverse Events 
ORR 
Objective response rate 


 
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LIST OF ABBREVIATIONS 
OS 
Overall survival 
PBMC 
Peripheral blood mononuclear cells 
PD 
Progressive disease 
PFS 
Progression-free survival 
PHI 
Protected health information 
PO 
per os (orally) 
POEMS 
Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin 
PR 
Partial response/remission 
PT 
Prothrombin time 
QA 
Quality assurance 
RBC 
Red blood cell 
SAE 
Serious adverse event 
SAR 
Suspected adverse reaction 
SD 
Stable disease 
SFLC 
Serum-free light chains 
SLAMF7 
Signaling lymphocyte activation molecule family 7 
SUSAR 
Suspected unexpected serious adverse reaction 
TLS 
Tumor lysis syndrome 
ULN 
Upper limit of normal 
UPEP 
Urine protein electrophoresis 
VGPR 
Very good partial response 
VTE 
Venous thromboembolism 


 
CONFIDENTIAL 
STUDY DRUG(S):  ELOTUZUMAB 
  
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TABLE OF CONTENTS 
1. 
INTRODUCTION ................................................................................................. 20 
1.1 
Background ........................................................................................................... 20 
1.2 
Treatment for multiple myeloma ........................................................................... 20 
1.3 
Elotuzumab ............................................................................................................ 20 
1.3.1 
Summary of non-clinical experience ..................................................................... 21 
1.3.2 
Summary of relevant clinical experience .............................................................. 22 
1.4 
Lenalidomide and dexamethasone ........................................................................ 23 
1.5 
Rationale for the study .......................................................................................... 24 
2. 
STUDY OBJECTIVES ......................................................................................... 24 
2.1 
Primary objective .................................................................................................. 24 
2.2 
Secondary objectives ............................................................................................. 25 
2.3 
Exploratory objectives ........................................................................................... 26 
3. 
STUDY PATIENT POPULATION AND DISCONTINUATION ...................... 26 
3.1 
Inclusion criteria .................................................................................................... 26 
3.2 
Exclusion criteria ................................................................................................... 27 
3.3 
Discontinuation from study treatment ................................................................... 29 
4. 
STUDY REGISTRATION.................................................................................... 29 
5. 
STUDY DESIGN .................................................................................................. 30 
5.1 
Treatment plan ....................................................................................................... 30 
5.1.1 
Induction ................................................................................................................ 31 
5.1.2 
Mobilization/ASCT ............................................................................................... 31 
5.1.3 
Consolidation......................................................................................................... 32 
5.1.4 
Maintenance .......................................................................................................... 33 
5.2 
Treatment duration ................................................................................................ 33 
5.3 
Concomitant medications ...................................................................................... 33 
5.3.1 
Permitted concomitant medications ...................................................................... 34 
5.3.2 
Prohibited concomitant medications ..................................................................... 36 
5.4 
Correlative studies ................................................................................................. 36 
6. 
DOSE MODIFICATIONS AND PERMANENT DISCONTINUATION ........... 36 
6.1 
Discontinuation of study treatments ...................................................................... 36 
6.2 
Dose modifications ................................................................................................ 37 
6.2.1 
Elotuzumab ............................................................................................................ 37 
6.2.2 
Lenalidomide ......................................................................................................... 37 


 
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STUDY DRUG(S):  ELOTUZUMAB 
  
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6.2.3 
Dexamethasone ..................................................................................................... 37 
6.2.4 
Dose modifications due to hematologic toxicity ................................................... 38 
6.2.5 
Dose modifications/management guidelines due to non-hematologic toxicities .. 40 
6.2.6 
Dose modifications due to dexamethasone toxicity .............................................. 43 
7. 
STUDY ASSESSMENTS AND EVALUATIONS .............................................. 45 
7.1 
Overview ............................................................................................................... 45 
7.2 
Baseline study assessments (screening) ................................................................ 45 
7.3 
Study treatment assessments ................................................................................. 46 
7.3.1 
ERd Induction Cycles 1 and 2, Day 1 ................................................................... 46 
7.3.2 
ERd Induction Cycles 1 and 2, Days 8, 15, and 22 ............................................... 47 
7.3.3 
Restaging ............................................................................................................... 47 
7.3.4 
ERd Induction Cycles 3 and 4, Day 1 ................................................................... 47 
7.3.5 
ERd Induction Cycles 3 and 4, Day 15 ................................................................. 48 
7.3.6 
End of Cycle 4 through start of mobilization ........................................................ 48 
7.3.7 
Post ASCT evaluation (at 70 to 120 days following transplant) – preference 
would be to perform evaluation on the earlier side (Day 70) and initiate 
consolidation shortly thereafter. ............................................................................ 49 
7.3.8 
ERd Consolidation Cycles 6 through 8, Day 1 ..................................................... 50 
7.3.9 
ERd Consolidation Cycles 5 through 8, Day 15 ................................................... 50 
7.3.10 
End of Cycle 8 ....................................................................................................... 51 
7.3.11 
Maintenance Cycles 9+, Day 1 ............................................................................. 51 
7.3.12 
Maintenance Cycles 9+, Day 15 ........................................................................... 52 
7.4 
End-of-treatment visit............................................................................................ 52 
7.5 
Follow-up visits ..................................................................................................... 53 
7.5.1 
Off-study follow-up before disease progression ................................................... 53 
7.5.2 
Off-study follow-up after disease progression ...................................................... 54 
8. 
DRUG FORMULATION, AVAILABILITY, ADMINISTRATION, AND 
TOXICITY INFORMATION ............................................................................... 54 
8.1 
Elotuzumab ............................................................................................................ 54 
8.1.1 
Labeling, packaging, and supply ........................................................................... 54 
8.1.2 
Preparation and administration of elotuzumab ...................................................... 54 
8.1.3 
Storage and use of elotuzumab .............................................................................. 55 
8.1.4 
Precautions and risks associated with elotuzumab ................................................ 56 
8.2 
Lenalidomide ......................................................................................................... 57 
8.3 
Dexamethasone ..................................................................................................... 57 
8.4 
Accountability for all study drugs ......................................................................... 57 
9. 
RESPONSE EVALUATIONS AND MEASUREMENTS .................................. 58 
10. 
STATISTICAL CONSIDERATIONS .................................................................. 58 


 
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STUDY DRUG(S):  ELOTUZUMAB 
  
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AMENDMENT 2 DATE:  07 DECEMBER 2016 
 
 
 
 
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10.1 
Statistical design .................................................................................................... 58 
10.2 
Sample size considerations .................................................................................... 58 
10.3 
Analysis population ............................................................................................... 58 
10.4 
Data analysis.......................................................................................................... 58 
10.4.1 
Timing of analyses ................................................................................................ 58 
10.4.2 
Demographics and baseline characteristics ........................................................... 59 
10.4.3 
Efficacy analysis.................................................................................................... 59 
10.4.4 
Safety analysis ....................................................................................................... 60 
11. 
SAFETY REPORTING AND ANALYSES ......................................................... 61 
11.1 
Definitions ............................................................................................................. 61 
11.1.1 
Adverse events ...................................................................................................... 61 
11.1.2 
Serious adverse events........................................................................................... 61 
11.1.3 
Adverse reaction .................................................................................................... 62 
11.1.4 
Suspected adverse reaction .................................................................................... 62 
11.1.5 
Recording and reporting of adverse events ........................................................... 62 
11.1.6 
Assessment of adverse events ............................................................................... 63 
11.2 
Serious adverse event reporting by Investigators .................................................. 64 
11.3 
Recording of adverse events and serious adverse events ...................................... 64 
11.3.1 
Diagnosis versus signs and symptoms .................................................................. 64 
11.3.2 
Persistent or recurrent adverse events ................................................................... 65 
11.3.3 
Abnormal laboratory values .................................................................................. 65 
11.3.4 
Deaths .................................................................................................................... 65 
11.3.5 
Hospitalization, prolonged hospitalization, or surgery ......................................... 66 
11.3.6 
Pre-existing medical conditions ............................................................................ 66 
11.3.7 
New cancers .......................................................................................................... 66 
11.3.8 
Pregnancy, abortion, birth defects/congenital anomalies ...................................... 66 
11.3.9 
Elotuzumab overdose ............................................................................................ 67 
11.4 
Protocol-defined events of special interest ............................................................ 67 
11.5 
Serious adverse event reporting requirements to BMS ......................................... 67 
11.5.1 
Bristol-Myers Squibb-specific requirements for adverse event reporting ............ 67 
11.5.2 
Sponsor assessment of unexpected........................................................................ 68 
11.5.3 
Sponsor reporting for clinical studies under an Investigational New Drug 
Application ............................................................................................................ 68 
12. 
QUALITY ASSURANCE AND QUALITY CONTROL .................................... 69 
12.1 
Study monitoring, auditing, and inspecting........................................................... 69 
13. 
ETHICAL, FINANCIAL, AND REGULATORY CONSIDERATIONS ............ 69 
13.1 
Institutional Review Board approval ..................................................................... 69 
13.2 
Regulatory approval .............................................................................................. 69 


 
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STUDY DRUG(S):  ELOTUZUMAB 
  
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13.3 
Informed consent ................................................................................................... 70 
13.3.1 
Confidentiality ....................................................................................................... 70 
13.4 
Financial information ............................................................................................ 71 
14. 
RESEARCH RETENTION AND DOCUMENTATION OF THE STUDY ........ 71 
14.1 
Amendments to the protocol ................................................................................. 71 
14.2 
Documentation required to initiate the study ........................................................ 72 
14.3 
Study documentation and storage.......................................................................... 73 
14.4 
Data collection ....................................................................................................... 74 
14.5 
Disclosure and publication policy ......................................................................... 75 
15. 
REFERENCES ...................................................................................................... 76 
16. 
APPENDICES ....................................................................................................... 78 
 
LIST OF TABLES 
Table 1 
Corticosteroid premedicationa for previous infusion reactions ................ 34 
Table 2 
Dose reduction steps for lenalidomide ..................................................... 37 
Table 3 
Dose reduction steps for dexamethasone ................................................. 38 
Table 4 
Dose modifications due to hematologic toxicities ................................... 39 
Table 5 
 Dose reductions for non-hematologic toxicities other than infusion 
reactions ................................................................................................... 41 
Table 6 
Dose modifications due to dexamethasone toxicity................................. 44 
Table 7 
Elotuzumab infusion rates........................................................................ 55 
LIST OF FIGURES 
Figure 1 
Study schema ........................................................................................... 30 
 


 
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STUDY DRUG(S):  ELOTUZUMAB 
  
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STUDY NUMBER:  MM 61 
AMENDMENT 2 DATE:  07 DECEMBER 2016 
 
 
 
 
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LIST OF APPENDICES 
Appendix A: 
Response Criteria for Multiple Myeloma ................................................ 78 
Appendix B: 
Diagnostic Criteria and Staging for Multiple Myeloma .......................... 83 
Appendix C: 
ECOG and Karnofsky Performance Status Scales................................... 86 
Appendix D: 
New York Heart Association (NYHA) Classification of Cardiac 
Disease ..................................................................................................... 87 
Appendix E: 
Guidelines for Female Patients of Childbearing Potential and Fertile 
Male Patients ............................................................................................ 88 
Appendix F: 
Neurotoxicity Questionnaire .................................................................... 93 
Appendix G: 
Schedule of assessments MM 61 ............................................................. 94 
 


 
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STUDY DRUG(S):  ELOTUZUMAB 
  
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STUDY NUMBER:  MM 61 
AMENDMENT 2 DATE:  07 DECEMBER 2016 
 
 
 
 
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1. 
INTRODUCTION 
1.1 
Background 
Multiple myeloma (MM), a B-cell tumor of malignant plasma cells within the bone marrow, is 
characterized by the accumulation of plasma cells in the bone marrow (and other organs) and 
commonly results in anemia, bone marrow failure, bone destruction, hypercalcemia, renal 
failure, and increased susceptibility to infections.  The disease accounts for approximately 1.4% 
of all new cancer cases in the United States (US) and approximately 13% of hematologic cancers 
worldwide (Palumbo and Anderson 2011).  There are approximately 24,000 new cases of MM 
diagnosed in the US each year with over 11,000 deaths annually due to the disease (Howlader et 
al 2014). 
1.2 
Treatment for multiple myeloma 
Although MM is considered fatal, survival has dramatically improved over the last 2 decades 
with the introduction of more effective treatment options.  Multiple myeloma is sensitive to a 
number of cytotoxic drugs (e.g., alkylating agents and anthracyclines) and corticosteroids that 
are commonly used for initial treatment and for relapsed disease.  Younger patients are 
consolidated with high-dose therapy (ablative chemotherapy or radiation) with autologous stem 
cell transplantation (ASCT).  In addition, the introduction of novel agents such as proteasome 
inhibitors and immunomodulatory drugs (IMiDs) has revolutionized treatment and improved 
survival rates for this disease. 
Current treatments include combination chemotherapy with regimens using melphalan 
(Alkeran®), bortezomib (Velcade®), thalidomide (Thalomid®), lenalidomide (Revlimid®), 
elotuzumab (EMPLICITI™), and their combinations with and without corticosteroids.  Although 
improvements in progression-free survival (PFS) and overall survival (OS) have occurred in the 
past 5 years, even with the best available approved agents, 10% to 30% of patients fail to 
respond to the primary therapy, and almost all patients eventually relapse, with a median OS of 
44.8 months (Kumar et al 2008). 
1.3 
Elotuzumab 
On 30 November 2015, the U.S. Food and Drug Administration (FDA) approved elotuzumab 
(EMPLICITI, Bristol-Myers Squibb Company) in combination with lenalidomide and 
dexamethasone for the treatment of patients with MM who have received 1 to 3 prior therapies.  
The full package insert can be viewed at:  
http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/761035s000lbl.pdf. 
Elotuzumab is a humanized IgG1 monoclonal antibody that specifically targets the SLAMF7 
(Signaling Lymphocytic Activation Molecule Family member 7) protein.  SLAMF7 is expressed 
on myeloma cells independent of cytogenetic abnormalities, and is also expressed on natural 
killer cells, plasma cells, and at lower levels on specific immune cell subsets of differentiated 
cells within the hematopoietic lineage. 


 
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AMENDMENT 2 DATE:  07 DECEMBER 2016 
 
 
 
 
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Elotuzumab directly activates natural killer cells through both the SLAMF7 pathway and Fc 
receptors.  Elotuzumab also targets SLAMF7 on myeloma cells and facilitates the interaction 
with natural killer cells to mediate the killing of myeloma cells through antibody-dependent 
cellular cytotoxicity.  In preclinical models, the combination of elotuzumab and lenalidomide 
resulted in enhanced activation of natural killer cells that was greater than the effects of either 
agent alone and increased anti-tumor activity in vitro and in vivo. 
1.3.1 
Summary of non-clinical experience 
The expression of the elotuzumab target, SLAMF7, is restricted to malignant myeloma cells and 
subsets of normal leukocytes in humans (natural killer, natural killer-like T cells, a subset of 
CD8+ T cells, and tissue plasma cells).  No significant expression was detected in resting CD4+ 
T cells, B cells, resting monocytes, neutrophils, and granulocytes.  Elotuzumab binding was not 
observed on epithelia, vessels, or smooth muscle cells of any of the organs examined. 
No SLAMF7 expression was noted with immunohistochemical staining in a variety of normal 
and neoplastic tissues.  Except for infiltrating cells, no SLAMF7 expression was noted in brain, 
breast, colon, heart, kidney, liver, lung, ovary, pancreas, prostate, skin, small intestine, spleen, 
stomach, testis, tonsil, uterus, and urinary bladder.  Additionally, no SLAMF7 expression was 
noted in tumor samples, including ductal breast adenocarcinoma, lobular breast adenocarcinoma, 
renal cell carcinoma, prostate carcinoma, endometrial adenocarcinoma, gastric adenocarcinoma, 
urothelial carcinoma, small cell lung carcinoma, non-small cell lung carcinoma, ovarian 
carcinoma, testicular germ cell tumor, head and neck squamous cell carcinoma, melanoma, and 
pancreatic adenocarcinoma (Hsi et al 2008). 
Elotuzumab only recognizes human SLAMF7 protein and does not appear to bind SLAMF7 
from other species, including chimpanzee, cynomolgus monkey, dog, mini pig, mouse, rabbit, 
rat, and rhesus monkey.  Due to the lack of species-specific cross-reactivity, there are no relevant 
animal species in which to conduct toxicological studies.  Therefore, the nonclinical studies 
consisted primarily of in vitro safety assessments and selected in vivo biological activity 
assessment to address the selectivity of elotuzumab and potential toxicities.  In addition, a 
limited non-Good Laboratory Practice exploratory single-dose intravenous (IV) toxicity and 
toxicokinetics study in rhesus monkeys was conducted and no potential non-target effects were 
identified. 
Elotuzumab (100 and 200 μg/mL) in vitro had no effect on lymphocytes, CD3, CD4, CD8, and B 
cell counts in blood samples from healthy human donors.  The natural killer cell counts were 
decreased on average by 20% at both doses of elotuzumab.  The observed decline was variable 
between donors and ranged between 0% and 45%. 
Elotuzumab, at concentrations up to 500 μg/mL, did not adversely affect the ability of human 
bone marrow-derived hematopoietic stem cells to differentiate down the erythroid and myeloid 
pathways. 
In nonclinical models, elotuzumab plus either bortezomib or lenalidomide had greater antitumor 
activity than either agent alone.  In addition, elotuzumab plus mAbs that enhance natural killer 
cell function either by antagonizing a negative regulatory molecule, KIR2DL3, or by agonizing 


 
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STUDY DRUG(S):  ELOTUZUMAB 
  
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the immune cell costimulatory molecule, CD137, had greater antitumor activity than either agent 
alone. 
Significant antibody-dependent killing of MM cells was observed when elotuzumab was 
incubated with L363 or OPM2 human MM cells in the presence of human PBMCs isolated from 
the blood of healthy donors or from the blood of patients with MM.  No complement-dependent 
cytotoxicity was detected. 
Elotuzumab treatment of mice bearing human xenograft MM tumors resulted in significant 
antitumor activity and eradication of tumors in many of the treated mice. 
Experiments using an in vivo mouse xenograft model suggest that, while maximal antitumor 
activity is reached at elotuzumab serum levels of 70 to 430 μg/mL, minimal biological activity is 
seen at 2 to 13 μg/mL.  In vitro experiments suggested that the elotuzumab concentration 
required to achieve saturation of SLAMF7 on PBMCs from healthy donors was approximately 
20 μg/mL. 
1.3.2 
Summary of relevant clinical experience 
The first 3 elotuzumab clinical trials were Phase I studies in patients with relapsed MM with 
elotuzumab as monotherapy or combined with bortezomib or lenalidomide. 
Results of the monotherapy Phase I trial (Zonder et al 2012) demonstrated acceptable safety with 
no maximum tolerated dose (MTD) identified up to 20 mg/kg.  The most common adverse 
events (AEs), regardless of attribution, were cough, headache, back pain, fever, and chills.  
Adverse events were generally mild to moderate in severity, and AEs attributed to elotuzumab 
were primarily infusion-related.  Stable disease was reported for 27% of the 35 patients treated.  
Plasma elotuzumab levels and terminal half-life increased with dose whereas clearance 
decreased, suggesting target-mediated clearance. 
Results of the Phase I trial of the combination of elotuzumab with bortezomib/dexamethasone 
demonstrated adequate safety with no MTD observed up to 20 mg/kg.  Twenty-eight patients 
were treated: each were treated with the 2.5-, 5.0-, and 10-mg/kg dose cohorts, and 19 subjects 
were treated with the 20-mg/kg cohort.  Objective responses were obtained in 48% of treated 
patients. 
Results of a Phase I trial of the combination of elotuzumab with lenalidomide/dexamethasone 
demonstrated acceptable safety with no MTD observed up to 20 mg/kg (Lonial et al 2012).  
Twenty-eight patients were treated: 3 each in the 5.0- and 10-mg/kg cohorts, and 22 in the 
20-mg/kg cohort.  No dose-limiting toxicities were observed up to the maximum proposed dose 
of 20 mg/kg.  The most frequent Grade 3 to 4 toxicities were neutropenia (36%) and 
thrombocytopenia (21%).  Two patients experienced a serious infusion reaction during the first 
treatment cycle.  Objective responses were obtained in 82% (23 of 28) of treated patients.  After 
a median of 16.4 months follow-up, the median time to progression was not reached for patients 
in the 20-mg/kg cohort who were treated until disease progression.  This trial also included a 
Phase 2 portion that is ongoing.  Preliminary data from this portion of the trial demonstrated an 
objective response rate of 84% among all 73 treated patients, 92% among the 36 subjects treated 
with 10 mg/kg of elotuzumab.  Median PFS was 33 months with the 10 mg/kg dose and 
18.6 months with the 20-mg/kg dose. 


 
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STUDY DRUG(S):  ELOTUZUMAB 
  
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In a randomized portion of a Phase Ib/II trial, the combination of elotuzumab with 
lenalidomide/dexamethasone was studied in patients with relapsed MM who were randomly 
assigned to either 10-mg/kg (36 patients) or 20-mg/kg (37 patients) doses of elotuzumab plus 
oral lenalidomide/dexamethasone (Richardson et al 2015).  Of the 73 patients randomized, 
61 (84%) achieved an objective response (33 [92%] with 10 mg/kg, 28 [76%] with 20 mg/kg); 
31 (42%) a very good partial response (17 [47%] with 10 mg/kg, 14 [38%] with 20 mg/kg); and 
20 (27%) a partial response (10 [28%] with 10 mg/kg, 10 [27%] with 20 mg/kg).  The most 
common treatment-emergent AEs of any grade were diarrhea (48 [66%]), muscle spasms 
(45 [62%]), and fatigue (41 [56%]).  Fifty-seven (78%) patients had Grade 3 or 4 events, the 
most common of which were lymphopenia (15 [21%]) and neutropenia (14 [19%]). 
In a randomized, open-label Phase III clinical trial, patients with previously treated MM were 
assigned to receive either 10 mg/kg elotuzumab plus lenalidomide/dexamethasone (elotuzumab 
group) or lenalidomide/dexamethasone alone (control group) (Lonial et al 2015, EMPLICITI).  
Overall, 321 patients were assigned to the elotuzumab group and 325 to the control group.  After 
a median follow-up of 24.5 months, the rate of PFS at 1 year in the elotuzumab group was 68%, 
as compared with 57% in the control group; at 2 years, the rates were 41% and 27%, 
respectively.  Median PFS in the elotuzumab group was 19.4 months versus 14.9 months in the 
control group (hazard ratio for progression or death in the elotuzumab group, 0.70; 95% 
confidence interval, 0.57 to 0.85; P<0.001).  The overall response rate in the elotuzumab group 
was 79% versus 66% in the control group (P<0.001).  Common Grade 3 or 4 AEs in the 2 groups 
were lymphocytopenia, neutropenia, fatigue, and pneumonia.  Infusion reactions occurred in 
33 patients (10%) in the elotuzumab group, and were Grade 1 or 2 in 29 (88%) patients.  The 
conclusion derived from these results was that patients with relapsed or refractory MM receiving 
a combination of elotuzumab, lenalidomide, and dexamethasone had a significant relative 
reduction of 30% in the risk of disease progression or death over those who received 
lenalidomide and dexamethasone alone. 
Precautions and risks with elotuzumab are presented in Section 8.1.4. 
1.4 
Lenalidomide and dexamethasone 
Lenalidomide is an immunomodulatory derivative of thalidomide and has both immunomodulatory 
and anti-angiogenic properties that are considered to confer anti-tumor effects.  Two pivotal 
randomized Phase 3 trials established that lenalidomide in combination with high-dose 
dexamethasone produced a significant improvement in ORR and time to progression (TTP) versus 
high-dose dexamethasone alone in patients with relapsed MM who had had up to 3 prior therapies 
(Dimopoulos et al 2007, Weber et al 2007). 
The combination of lenalidomide and high-dose dexamethasone has shown impressive activity in 
untreated disease.  In a Phase 2 study of 34 patients with newly diagnosed MM, patients received 
lenalidomide (25 mg Days 1 to 21 of a 28-day cycle) and high-dose dexamethasone (40 mg Days 
1 to 4, 9 to 12, and 17 to 20).  The ORR was 91%, with 6% complete responders (CR), 32% near 
CR plus very good partial response (VGPR), and 53% partial responses (PR) (Arastu-Kapur et al 
2008).  However, when this regimen was compared with a more conventional delivery of 
dexamethasone (40 mg Days 1, 8, 15, and 22) in a 445-patient study, the more intensive 
dexamethasone schedule was associated with significantly shorter OS relative to the less 
intensive regimen (1-year survival rates 86% vs. 96.5%, respectively) (Kirk et al 2008).  The 


 
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dexamethasone-intensive regimen was associated with higher incidences of thromboembolism 
and hyperglycemia, and higher incidences of Grades 3 and 4 toxicities overall.  Clearly, better 
and safer combination regimens for newly diagnosed disease are warranted. 
1.5 
Rationale for the study 
Despite many advances in the treatment of MM, the optimal front-line treatment and duration of 
treatment of transplant-eligible patients with MM remains controversial.  It appears that the use 
of a triplet such as bortezomib, lenalidomide, and dexamethasone, and the incorporation of the 
newer generation of drugs such as carfilzomib, lenalidomide, and dexamethasone, can yield a 
higher percentage of CRs than seen with less aggressive therapies.  It is also clear that the 
duration of therapy is important with respect to PFS and OS in the transplant-ineligible 
population, and likely the transplant-eligible population, as well.  Thus, it is imperative to find a 
balance with an aggressive regimen that will result in good disease control to allow stem cell 
transplantation, but that will also be well tolerated so that it can translate to more prolonged 
treatment duration without significantly impacting patients’ quality of life.  The combination of 
10 mg/kg elotuzumab, lenalidomide, and dexamethasone (ERd) is active, well-tolerated, and 
approved for patients with MM who have had prior treatments, based on data from a large 
randomized trial of elotuzumab in combination with lenalidomide and dexamethasone in newly 
diagnosed transplant-ineligible patients with MM (Lonial et al 2015).  There are currently no 
studies looking at this combination in the transplant-eligible population. 
In this study, we will determine the feasibility of incorporating ERd into the treatment paradigm 
of transplant-eligible patients with MM.  All patients will undergo 4 cycles of induction therapy, 
followed by stem cell mobilization and collection.  Patients will then undergo ASCT followed by 
consolidation therapy with ERd for 8 more cycles, and then maintenance with elotuzumab and 
lenalidomide for up to 2 years.  Elotuzumab 10 mg/kg will be dosed every 2 weeks for all phases 
of the study with the exception of the maintenance phase.  During maintenance, the frequency of 
elotuzumab dosing drops to once every 4 weeks.  Therefore, the dose of elotuzumab is increased 
to 20 mg/kg for that phase to maintain as much of the receptor saturation as possible, as reflected 
by the PK data from the Phase I studies (Zonder et al 2012, Lonial et al 2012).  The t1/2 increased 
with an increased dose of elotuzumab from 0.5 mg/kg to 20 mg/kg, and saturation of the CS1 by 
elotuzumab on bone marrow target cells increased as the dose of elotuzumab increased.  At doses 
of 10 mg/kg and 20 mg/kg elotuzumab, CS1 receptors on bone marrow–derived myeloma cells 
were consistently saturated.  Lower dose groups exhibited more variation in the level of target 
cell saturation achieved.  Since the 20-mg/kg dose of elotuzumab, both as monotherapy and in 
combination with lenalidomide and dexamethasone, has been shown to be well tolerated when 
dosed every 2 weeks, no increase in toxicity would be expected with the less frequent dosing 
schedule of once every 4 weeks.  This maintenance strategy is being used in several large studies 
in front-line MM in both the transplant and non-transplant settings. 
2. 
STUDY OBJECTIVES 
2.1 
Primary objective 
The primary objective of this study is to: 


 
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 Evaluate the feasibility of using the combination of elotuzumab, lenalidomide, and 
dexamethasone (ERd) as induction therapy (induction feasibility rate [IFR]) and the 
ability of the combination to facilitate the start of autologous stem cell transplantation 
(ASCT) in transplant-eligible patients newly diagnosed with MM. 
The primary endpoint is: 
 IFR, defined as the percentage of patients successfully completing 4 cycles of induction 
treatment with ERd and able to start ASCT. 
2.2 
Secondary objectives 
The secondary objectives of this study are to: 
 Evaluate the efficacy of the combination of ERd as induction, consolidation, and 
maintenance therapy in transplant-eligible patients newly diagnosed with MM 
 Evaluate the safety and tolerability of the combination of ERd as induction, 
consolidation, and maintenance therapy in transplant-eligible patients newly diagnosed 
with MM. 
The secondary endpoints are: 
 Complete response rate (CRR), defined as the percentage of patients who achieve a 
complete response (CR) or near complete response (nCR) to treatment at each stage of 
the study, i.e., induction, ASCT, consolidation, end of study as per IMWG and European 
Group for Blood and Marrow Transplantation (EBMT) criteria 
 Overall response rate (ORR), defined as the percentage of patients who achieve at least a 
partial response (PR) to treatment at each stage of the study, i.e., induction, ASCT, 
consolidation, end of study as per IMWG and EBMT criteria 
 Progression-free survival (PFS), defined as the time from start of induction treatment to 
documented progressive disease (PD) or death from any cause up to 3 years post first 
study treatment 
 Overall survival (OS), defined as the time from start of induction treatment to 3 years 
post first study treatment or to death from any cause, whichever comes first 
 Consolidation feasibility rate (CFR), defined as the percentage of patients starting 
induction treatment with ERd successfully completing treatment to end of consolidation 
 Maintenance feasibility rate (MFR), defined as the percentage of patients starting 
induction treatment with ERd successfully completing treatment to end of maintenance. 
 Safety endpoints including 1) treatment-emergent adverse events (TEAEs), serious 
adverse events (SAEs), and deaths, and 2) clinically significant changes in safety-related 
laboratory parameters according to National Cancer Institute Common Terminology 
Criteria for Adverse Events (NCI CTCAE Volume 4.03) and abnormal vital signs. 


 
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2.3 
Exploratory objectives 
The exploratory objectives of this study are to: 
 Determine MRD by multi-parameter flow cytometry per institutional guidelines 
 Evaluate gene expression profiling (GEP) at diagnosis per institutional guidelines and 
correlation of outcomes. 
The exploratory endpoint is: 
 To evaluate MRD defined as the proportion of patients who are MRD-positive versus 
those who are MRD-negative. 
3. 
STUDY PATIENT POPULATION AND DISCONTINUATION 
3.1 
Inclusion criteria 
Patients must meet all of the following criteria in order to be included in the research study: 
1. Newly diagnosed myeloma requiring systemic chemotherapy as per International 
Myeloma Working Group (IMWG) uniform criteria (Appendix A) and Diagnostic 
Criteria and Staging for Multiple Myeloma (Appendix B): 
- Ideally, no prior therapy, or 
- No more than 1 cycle of therapy for emergent control of disease prior to enrolling 
on study, including prior treatment of hypercalcemia, spinal cord compression, or 
active and/or aggressively progressing myeloma with corticosteroids or 
lenalidomide or bortezomib-based regimens (the treatment dose should not 
exceed the equivalent of 160 mg of dexamethasone in a 4 week period, or not 
more than 1 cycle) 
- Bisphosphonates are permitted 
2. Eligible and plan to undergo ASCT in first remission (refer to Section 5.1.2) 
3. Measurable disease, prior to initial treatment as indicated by one or more of the 
following: 
- Serum M-protein ≥1.0 g/dL 
- Urine M-protein ≥200 mg/24 hours 
- Serum free light chain assay: involved free light chain level ≥10 mg/dL 
(≥100 mg/L) provided the serum free light chain ratio is abnormal. 
4. Males and females ≥18 years-of-age 
5. Ability to take aspirin or other venous thromboembolism (VTE) anticoagulant therapy 
6. An ECOG Performance Status score of 0 through 2 (see Appendix C) 
7. Adequate hematologic function defined as: 


 
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- Absolute neutrophil count (ANC) ≥1.0 x 109/L 
- Hemoglobin (Hgb) ≥8 g/dL 
- Platelets ≥75 x 109/L.  Screening platelet count should be independent of platelet 
transfusions for at least 2 weeks. 
8. Adequate liver function defined as: 
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 x the 
upper limit of normal (ULN) 
- Total bilirubin ≤1.5 x ULN (unless the patient has Grade 1 bilirubin elevation due 
to Gilbert’s disease or a similar syndrome involving slow conjugation of 
bilirubin) 
9. Adequate renal function defined as serum creatinine ≤1.5 x ULN OR calculated 
creatinine clearance ≥50 mL/min as calculated by Cockcroft and Gault Formula. 
10. All study participants must be registered into the mandatory Revlimid REMS® program 
and must be willing and able to comply with the requirements of that program. 
11. Females of reproductive potential must adhere to the scheduled pregnancy testing as 
required in the Revlimid REMS® program. 
12. Male patients with female partners of childbearing potential and female patients of 
childbearing potential are required to use two forms of acceptable contraception, 
including one barrier method, during their participation in the study and for 28 days 
following last dose of study drugs.  Male patients must also refrain from donating semen 
or sperm during their participation in the study.  Details of mandatory contraception 
measures are presented in Appendix E. 
13. Willingness and ability to comply with study and follow-up procedures. 
14. Ability to understand the nature of this study and give written informed consent. 
3.2 
Exclusion criteria 
Patients who meet any of the following criteria will be excluded from study entry: 
1. Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes 
(POEMS) syndrome 
2. Plasma cell leukemia 
3. Waldenström’s macroglobulinemia or IgM myeloma 
4. Presence of other active cancers, or history of treatment for invasive cancer ≤5 years.  
Patients with Stage I cancer who have received definitive local treatment and are 
considered unlikely to recur are eligible.  All patients with previously treated in situ 
carcinoma (i.e., non-invasive) are eligible, as are patients with a history of non-melanoma 
skin cancer. 


 
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5. Radiotherapy to multiple sites or immunotherapy within 4 weeks before start of protocol 
treatment (localized radiotherapy to a single site at least 1 week before start is 
permissible) 
6. Major surgical procedures ≤28 days of beginning study drug, or minor surgical 
procedures ≤7 days.  No waiting required following port-a-cath placement. 
7. Acute active infection requiring systemic antibiotics, antivirals, or antifungals within 
2 weeks prior to first dose of study treatment 
8. Presence of active gastrointestinal disease or other condition that will interfere 
significantly with the absorption, distribution, metabolism, or excretion of oral therapy 
(e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea Grade ≥2, and 
malabsorption syndrome) 
9. Any of the following cardiac diseases currently or within the last 6 months: 
- Left ventricular ejection fraction (LVEF) <40% as determined by echocardiogram 
(ECHO) or multiple-gated acquisition (MUGA) scan 
- Unstable angina pectoris 
- Congestive heart failure (New York Heart Association ≥ Grade 2, see Appendix 
D) 
- Acute myocardial infarction 
- Conduction abnormality not controlled with pacemaker or medication 
- Significant ventricular or supraventricular arrhythmias (patients with chronic rate-
controlled atrial fibrillation in the absence of other cardiac abnormalities are 
eligible) 
- Valvular disease with significant compromise in cardiac function 
10. Known seropositive for or active viral infection with human immunodeficiency virus or 
hepatitis A, B, or C virus.  Patients who are seropositive because of hepatitis B virus 
vaccine are eligible. 
11. Any clinically significant medical disease or condition that, in the treating Investigator’s 
opinion, may interfere with protocol adherence or a patient’s ability to give informed 
consent 
12. Pregnant or lactating females 
13. Contraindication to any of the required concomitant drugs, including dexamethasone, H1 
and H2 blockers, and acetaminophen, or if patient has a history of prior thrombotic 
disease, warfarin or low molecular weight heparin 
14. No health coverage, or if the copay for lenalidomide is not acceptable to the patient. 
15. Psychological, familial, sociological, or geographical conditions that do not permit 
compliance with the protocol. 


 
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3.3 
Discontinuation from study treatment 
Patients will be discontinued from study treatment for any of the following reasons: 
 
Disease progression 
 
Irreversible or intolerable toxicity or abnormal laboratory values thought to be related to 
drug toxicity 
 
Conditions requiring therapeutic intervention not permitted by the protocol 
 
Intercurrent illness (this will be at the Investigator’s discretion) 
 
Inability of the patient to comply with study requirements (non-compliance) 
 
Patient requests to discontinue treatment 
 
Patient withdraws consent from the study 
 
Lost to follow-up 
 
Pregnancy 
After discontinuation from protocol treatment, patients must be followed for AEs for 30 days and 
SAEs for 60 days, after their last dose of study drugs.  All new AEs occurring during this period 
must be reported and followed until resolution, unless, in the opinion of the investigator, these 
values are not likely to improve, because of the underlying disease.  In this case, the investigator 
must record his or her reasoning for this decision in the patient’s medical records and as a 
comment in the electronic Case Report Form (eCRF). 
All patients who have Grade 3 or 4 laboratory abnormalities (per National Cancer Institute 
Common Terminology Criteria for Adverse Events [NCI CTCAE] Version 4.03) at the time of 
discontinuation must be followed until the laboratory values have returned to Grade 1 or 2, 
unless it is, in the opinion of the Investigator, not likely that these values are to improve.  In this 
case, the investigator must record his or her reasoning for making this decision in the patients’ 
medical records and as a comment in the eCRF. 
After 24 months of maintenance therapy, patients who have no recorded disease progression or 
death can continue treatment with FDA approved therapies at the discretion of the treating 
physician.  Patients who discontinue study treatment prior to the occurrence of disease 
progression will be followed for a total of up to 3 years post first study treatment or until they 
progress (see Section 7.5.1).  Patients with documented disease recurrence or progression will be 
followed for survival status only for up to 3 years or until death (see Section 7.5.2). 
4. 
STUDY REGISTRATION 
The patient must willingly consent to participate in this study after being informed of the 
procedures to be followed, the experimental nature of the treatment, potential benefits, treatment 
alternatives, side effects, risks, and discomforts.  Human protection committee (Institutional 
Review Board [IRB]) approval of this protocol and consent form is required.  Eligible patients 
who wish to participate in the study and sign the consent form will be enrolled into the study. 


 
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Registration must occur prior to the initiation of protocol therapy.  Patients eligible to participate 
in the study may be enrolled through the Sarah Cannon Development Innovations Central 
Enrollment Desk.  The enrollment desk may be reached by calling 877-MY-1-SCRI (877-691-
7274).  Registration may be done via fax 866-699-0258 Monday through Friday, 8:30 AM to 
4:30 PM, Central Standard Time.  Patient registration will be confirmed via email within 
24 hours, or by the next business day. 
5. 
STUDY DESIGN 
This is an open-label, Phase 2 study to assess the feasibility and tolerance of the combination of 
ERd in the induction, consolidation, and maintenance treatment of transplant-eligible patients 
newly diagnosed with MM.  The study is planned to be conducted at 8 centers in the United 
States. 
This study will enroll approximately 53 patients in the pre-ASCT induction portion of the study 
with the anticipation that most of them will resume protocol treatment at the 
consolidation/maintenance therapy post ASCT.  Recruitment will end when 48 patients are 
evaluable for the primary endpoint (have completed 4 cycles of induction treatment with ERd 
and are able to start ASCT).  Patients who decline transplant for reasons other than toxicities will 
be replaced.  The study schema is presented in Figure 1. 
 
Figure 1 
Study schema 
Newly Diagnosed Multiple Myeloma in Transplant-Eligible Patients
ERd Induction Therapy - Four 28-day Cycles
ERd Consolidation Therapy  – Four 28-day Cycles
Mobilization and ASCT - Toxicity Evaluation Interrupted
70 to 120 days
ERd Maintenance Therapy – 28-day Cycles for up to 24 Months
 
 
5.1 
Treatment plan 
Instructions for initiation of a new cycle during induction, consolidation, and maintenance 


 
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A new course of treatment may begin on the scheduled Day 1 of a new cycle if all of the 
following are met: 
 ANC ≥1.0 x 109/L 
 Platelet count ≥50 x 109/L 
 Any other study drug-related adverse event must have resolved to grades as specified in 
protocol (see Section 6.2). 
If these conditions are not met on Day 1 of a new cycle, the subject will be evaluated weekly, 
and a new treatment cycle will not be initiated until the toxicity has resolved, as described above. 
If either lenalidomide or dexamethasone are held for the remainder of the previous cycle or the 
new cycle is delayed due to residual toxicity on the planned Day 1 of the next cycle, then the 
new cycle will be started at 1 dose decrement of lenalidomide and/or dexamethasone, as 
applicable (see Table 2 and Table 3, respectively). 
5.1.1 
Induction 
All patients will undergo four 28-day cycles of the following induction treatments. 
 Cycles 1 and 2 
- Elotuzumab 10 mg/kg IV on Days 1, 8, 15, and 22 
- Lenalidomide 25 mg orally on Days 1 through 21 
- Dexamethasone 28 mg orally (3 to 24 hours prior to start of elotuzumab infusion) 
AND 8 mg IV (45 to 90 minutes prior to elotuzumab) on Days 1, 8, 15, and 22 
- H1 blockers, H2 blockers, and acetaminophen as pre-medications for elotuzumab 
(see Section 5.3.1.1). 
 Cycles 3 and 4 
- Elotuzumab 10 mg/kg IV on Days 1 and 15 only 
- Lenalidomide 25 mg orally on Days 1 through 21 
- Dexamethasone 28 mg orally (3 to 24 hours prior to start of elotuzumab infusion) 
AND 8 mg IV (45 to 90 minutes prior to elotuzumab) on Days 1 and 15 
- Dexamethasone 40 mg orally on Days 8 and 22 
- H1 blockers, H2 blockers, and acetaminophen as pre-medications for elotuzumab 
(see Section 5.3.1.1). 
5.1.2 
Mobilization/ASCT 
Following completion of 4 cycles of induction therapy, all patients will undergo standard 
mobilization, collection of stem cells, and then ASCT using a melphalan conditioning regimen as 
per individual transplant institutional guidelines. 
Mobilization with G-CSF should start 2 to 4 weeks from the last dose of lenalidomide (i.e., 
2 to 4 weeks after Cycle 4 Day 21).  In general, the scheduling of stem cell collection should 


 
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assure as limited a break as possible between the last dose of ERd treatment and ASCT, which 
should not exceed 6 weeks. 
Neupogen/Granix (G-CSF) should be used for stem cell mobilization according to standard 
practice.  If G-CSF alone is not sufficient for mobilization, the addition of plerixafor (Mozibil) 
should be used or as per institutional guidelines. 
During the apheresis procedure, correction of cytopenias and electrolyte abnormalities will be 
performed as per institutional guidelines. 
Conditioning chemotherapy will consist of melphalan 140 mg/m2 or 200 mg/m2 IV.  Sites should 
follow their standard protocol for hydration and antiemetic prophylaxis prior to melphalan 
infusion, antibiotic prophylaxis, platelet and packed red blood cell transfusions, and standard 
laboratory testing.  Administration of autologous peripheral stem cells will take place on Day 0 
according to standard unit protocol.  Patients will be monitored as per standard protocol until 
criteria for discharge from the transplant unit are met. 
If a patient is unable to proceed to transplant, but the treating Investigator believes he/she would 
benefit from continued study treatment, the patient will be allowed to continue uninterrupted on 
to consolidation and maintenance without transplant. 
All patients will be monitored and followed closely by the transplant team as per institutional 
guidelines during the stem cell procedure and full toxicity evaluations will resume with the onset 
of consolidation.  Standard, expected hematotoxicity and gastrointestinal toxicities well known 
from high-dose melphalan treatment will not be collected.  Any unexpected toxicity will be 
reviewed by the Medical Monitor in consultation with the Investigator and documented prior to a 
decision to proceed to the consolidation phase of treatment. 
5.1.3 
Consolidation 
Consolidation is to begin approximately 70 to 120 days from transplant.  Patients can begin 
consolidation if they have recovered from all transplant-related toxicities, do not have PD, and 
they meet the standards presented in Section 5.1. 
All patients will undergo four 28-day cycles of the following consolidation treatment: 
 Cycles 5 through 8 
- Elotuzumab 10 mg/kg IV on Days 1 and 15 
- Lenalidomide 15 mg orally on Days 1 through 21  
 Lenalidomide can be escalated as tolerated to the maximum-tolerated dose 
[MTD] administered during induction. 
 Lenalidomide can continue with dose unchanged from induction in 
patients who remain on study, but do not proceed to transplant. 
- Dexamethasone 28 mg orally (3 to 24 hours prior to start of elotuzumab infusion) 
AND 8 mg IV (45 to 90 minutes prior to elotuzumab infusion) on Days 1 and 15 
- Dexamethasone 40 mg orally on Days 8 and 22 


 
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- H1 blockers, H2 blockers, and acetaminophen as pre-medications for elotuzumab 
(see Section 5.3.1.1). 
In order for a patient’s data to be included in the calculation of CFR, they must have successfully 
completed all 4 consolidation cycles with or without dose reductions. 
5.1.4 
Maintenance 
All patients who do not have PD will automatically be switched to maintenance therapy (28-day 
cycles) following successful completion of 4 cycles of consolidation therapy.  Please note that 
the elotuzumab dose is increased here to 20 mg/kg from 10 mg/kg due to once per month dosing 
during this phase as opposed to twice a month dosing in the previous phases. 
 Cycles 9+ 
- Elotuzumab 20 mg/kg IV on Day 1 
- Lenalidomide 10 mg ±5 mg orally on Days 1 through 21 
- Dexamethasone 28 mg orally (3 to 24 hours prior to start of elotuzumab infusion) 
AND 8 mg IV (45 to 90 minutes prior to elotuzumab) on Day 1 
- H1 blockers, H2 blockers, and acetaminophen as pre-medications for elotuzumab 
(see Section 5.3.1.1). 
Any patient who comes off elotuzumab for whatever reason, or completes the 24 months of 
maintenance allowed by the protocol, can continue treatment with FDA approved therapies at the 
discretion of the treating physician, but will no longer be on study following their 60-day post 
maintenance safety follow up. 
5.2 
Treatment duration 
The end of the study is defined as the last visit of the last patient after 24 months of maintenance 
therapy.  The total duration of the study is planned to be 2 years for enrollment and up to 
3.5 years maximum follow up per patient to complete the full treatment plan. 
Patients will be evaluated for toxicity at the start of each cycle according to procedures listed in 
Appendix G.  Toxicity evaluation will be interrupted during the stem cell procedure and will 
resume with the onset of consolidation.  Patients will continue on treatment until progression as 
defined in Appendix A, intolerance to side effects, or completion of 2 years of maintenance 
therapy. 
After 24 months of maintenance therapy, patients who have no recorded disease progression or 
death can continue treatment with FDA approved therapies at the discretion of the treating 
physician.  Patients who discontinue study treatment prior to the occurrence of disease 
progression will be followed for a total of up to 3 years post first study treatment or until they 
progress (see Section 7.5.1).  Patients with documented disease recurrence or progression will be 
followed for survival status only for up to 3 years or until death (see Section 7.5.2). 
5.3 
Concomitant medications 
Concomitant medication is defined as any prescription or over-the-counter preparation, including 
vitamins and supplements.  Patients will be instructed not to take any additional medications 


 
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during the course of the study without prior consultation with the research team.  At each visit, 
the patient will be asked about any new medications he/she is taking or has taken after the start 
of study drug treatment. 
5.3.1 
Permitted concomitant medications 
5.3.1.1 
Required premedication prior to administration of elotuzumab 
Premedication is recommended prior to administration of elotuzumab, according to the following 
guidelines: 
 Dexamethasone 28 mg orally (between 3 to 24 hours prior to the start of elotuzumab 
infusion OR as a split dose 12 to 24 hours and 3 hours prior to elotuzumab).  If a dose of 
dexamethasone tablets is missed, it should be taken as soon as possible.  If it is almost 
time for the next dose, the missed dose should be skipped and the regular dosing schedule 
resumed.  Two doses should not be taken at once. 
AND 
 Dexamethasone 8 mg IV on the day of elotuzumab infusion 45 to 90 minutes prior to the 
start of infusion.  If a dose of oral dexamethasone is missed, it is recommended that the 
IV still be administered. 
 H1 blocker:  diphenhydramine (25 to 50 mg orally or IV), or equivalent, 45 to 90 minutes 
prior to the start of elotuzumab infusion 
 H2 blocker:  ranitidine (50 mg IV), or equivalent, 45 to 90 minutes prior to the start of 
elotuzumab infusion 
 Acetaminophen (650 to 1000 mg PO) 45 to 90 minutes prior to the start of elotuzumab 
infusion. 
5.3.1.2 
Premedication in patients with a prior infusion reaction 
Patients with a prior infusion reaction must receive H1, H2 blockers, and acetaminophen at the 
maximum doses specified in Section 5.3.1.1. 
In addition, dexamethasone premedication should be administered as per Table 1. 
Table 1 
Corticosteroid premedicationa for previous infusion reactions 
Prior infusion reaction 
Corticosteroid premedicationb prior to elotuzumab 
None or only Grade 1 prior 
infusion reactionc 
28 mg PO dexamethasone (3 to 24 hours prior to elotuzumab) AND 
8 mg IV dexamethasone at least 45 to 90 minutes prior to elotuzumab 
Prior Grade 2 infusion reactiond 
28 mg PO dexamethasone (3 to 24 hours prior to elotuzumab) AND 
10 mg IV dexamethasone at least 45 to 90 minutes prior to elotuzumab 
Prior Grade 3 or recurrent Grade 2 
infusion reaction 
8 mg oral dexamethasone (12 to 24 hours prior to elotuzumab) AND 
8 mg oral dexamethasone (at least 3 hours prior to elotuzumab) AND 
18 mg IV dexamethasone at least 45 to 90 minutes prior to elotuzumab 
a 
For prior infusion reactions, use maximum doses of H1, H2 blockers, and acetaminophen (see Section 5.3.1.1) 


 
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b 
At the discretion of the Investigator, the oral dexamethasone component may be given as a split dose 12 to 24 
and 3 hours prior to elotuzumab 
c 
Subjects with a prior Grade 1 infusion reaction may be premedicated as per Grade 2 infusion reactions. 
d 
Subjects with prior Grade 2 infusion reactions may be premedicated as per Grade 3 infusion reactions 
 
At the discretion of the investigator, the 28-mg oral dexamethasone component may be given as 
a split dose:  12 mg orally (12 to 24 hours prior to elotuzumab) AND 16 mg orally (3 hours prior 
to elotuzumab). 
If a patient with a prior Grade 2 or 3 infusion reaction also requires dose reduction of 
dexamethasone, the weekly dexamethasone on the days of elotuzumab infusion should be no 
lower than 8 mg IV on the day of elotuzumab infusion administered 45 to 90 minutes prior to 
elotuzumab. 
Patients with a Grade 4 elotuzumab infusion reaction must have elotuzumab permanently 
discontinued. 
5.3.1.3 
Permitted concomitant medications for the maintenance of pre-existing 
conditions 
Medications may be administered for maintenance of existing conditions prior to study 
enrollment or for a new condition that develops while on study, including but not limited to the 
following: 
 Bisphosphonate use, as recommended according to practice guidelines 
 Patients may receive anti-emetics and antidiarrheal agents, as necessary. 
 Colony-stimulating factors may be used if neutropenia occurs, but should not be given 
prophylactically. 
 Patients may receive red blood cell (RBC) or platelet transfusions, if clinically indicated, 
in accordance with institutional guidelines; however, the screening platelet count must be 
independent of platelet transfusions for at least 2 weeks.  Patients who require repeated 
platelet transfusion support should be discussed with the Study Chair. 
 Allopurinol (for use only in patients at risk for tumor lysis syndrome [TLS] due to high 
tumor burden) is optional and will be prescribed at the discretion of the treating 
Investigator.  These patients may receive allopurinol 300 mg PO twice daily (Cycle 1 
Day -2, Day -1), continuing for 2 days after Cycle 1 Day 1 (total of 4 days), then reduce 
dose to 300 mg PO once daily, continuing through Day 17 of Cycle 1.  Allopurinol dose 
should be adjusted according to the package insert.  Patients who do not tolerate 
allopurinol and are at risk for TLS should be discussed with the Study Chair. 
 Radiation therapy to a localized mass for patients on ERd therapy is acceptable with prior 
approval of the Study Chair. 
 Corticosteroids for non-malignant conditions (e.g., asthma, inflammatory bowel disease) 
equivalent to a dexamethasone dose ≤4 mg/day or prednisone ≤20 mg/day are permitted. 


 
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Other medications considered necessary for the patient’s safety and well-being may be given at 
the discretion of the Investigator with the exception of those listed in Section 5.3.2. 
5.3.2 
Prohibited concomitant medications 
The following treatments are prohibited while in this study: 
 No other investigational therapy should be given to patients.  No anticancer agents other 
than the study medications should be given to patients.  If such agents are required for a 
patient, then the patient must first be withdrawn from the study. 
 Corticosteroids for non-malignant conditions (e.g., asthma, inflammatory bowel disease) 
equivalent to a dexamethasone dose >4 mg/day or prednisone >20 mg/day are not 
permitted. 
 Herbal preparations/medications are not allowed throughout the study.  These herbal 
medications include, but are not limited to: St. John’s wort, kava, ephedra (ma huang), 
gingko biloba, dehydroepiandrosterone, yohimbe, saw palmetto, and ginseng.  Patients 
should stop using these herbal medications 7 days prior to first dose of study drug. 
5.4 
Correlative studies 
Bone marrow aspirates collected as standard of care will be used for MRD analysis and GEP to 
correlate with response. 
Minimal residual disease analysis will be conducted per institutional guidelines at any time bone 
marrow is collected as standard of care. 
Gene expression profiling will be conducted per institutional guidelines on bone marrow 
collected as standard of care at diagnosis. 
6. 
DOSE MODIFICATIONS AND PERMANENT DISCONTINUATION 
6.1 
Discontinuation of study treatments 
Administration of elotuzumab, lenalidomide, and dexamethasone can be discontinued 
permanently in the event of a treatment-related toxicity at the Investigator's discretion. 
If a delay of starting a new cycle is greater than 21 days, the patient should be discontinued from 
treatment, unless continuing treatment is mutually agreed upon by the Investigator and the Study 
Chair. 
If either elotuzumab or lenalidomide requires permanent discontinuation before Cycle 4 of 
induction, the patient’s treatment on study will be discontinued.  If either elotuzumab or 
lenalidomide requires permanent discontinuation during consolidation or maintenance cycles, the 
subject may remain on study with the remaining drug(s). 
Treatment doses of dexamethasone may be discontinued without the subject discontinuing the 
other study treatment(s).  If treatment doses of dexamethasone must be discontinued, it is up to 
treating Investigator’s discretion whether to continue with elotuzumab administration.  If 


 
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dexamethasone prophylaxis is discontinued, however, elotuzumab administration should not be 
continued. 
6.2 
Dose modifications 
The following sections and tables summarize dosing modifications of elotuzumab, lenalidomide, 
and dexamethasone to manage possible toxicity. 
The criteria presented in this section for dose modification are meant as general guidelines, and 
they are based on current US standards of clinical practice.  Local standards may differ and may 
be followed.  Dose modification may occur in the setting of lower grade toxicity if the 
Investigator, in consultation with the Study Chair, believes that it is in the interest of patient 
safety. 
6.2.1 
Elotuzumab 
No dose reduction is allowed for elotuzumab. 
6.2.2 
Lenalidomide 
Dose adjustments, as summarized in Table 2, are recommended for the management of NCI 
CTCAE Grade 3 and 4 toxicities for thrombocytopenia, neutropenia or other toxicities that are 
judged by the Investigator to be related to lenalidomide. 
 
Table 2 
Dose reduction steps for lenalidomide 
Dose reductiona 
Lenalidomide PO 
Starting dose level 
Dose level -1 
Dose level -2 
Cycles 1 through 4 
25 mg on Days 1 through 21 
15 
10 
Cycles 5 through 12 
15 mgb on Days 1 through 21 
10 
5 
Cycles 13 and beyond 
10±5 mg on Days 1 through 21 
5 
Stop lenalidomide 
a 
Dose reduction should be based on the worst toxicity demonstrated. 
b 
Lenalidomide can be escalated as tolerated to the MTD administered during induction. 
 
In addition to dose reductions, administration of elotuzumab and lenalidomide will be held 
temporarily in the event of a treatment-related toxicity at the treating Investigator's discretion.  
Study treatment may be reintroduced if the event resolves to the baseline value or to ≤ Grade 1 
within 21 days; otherwise elotuzumab and lenalidomide will be permanently discontinued, unless 
continued administration is approved by the Study Chair. 
6.2.3 
Dexamethasone 
Dose reduction levels of dexamethasone are presented in Table 3.  Dexamethasone delay should 
be performed as clinically indicated at the discretion of the treating Investigator; however, it is 
recommended that both the dexamethasone oral and IV doses be administered as part of the 
premedication for elotuzumab, as indicated.  Refer to Section 5.3.1.1 and Section 5.3.1.2 for 
further guidance on dexamethasone administration before elotuzumab administration and for 


 
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patients with a prior infusion reaction.  If dexamethasone prophylaxis is discontinued, 
elotuzumab administration should not be continued. 
If treatment doses of dexamethasone must be discontinued, it is up to treating Investigator’s 
discretion whether to continue with elotuzumab administration. 
Table 3 
Dose reduction steps for dexamethasone 
Dose reductiona 
Dexamethasone PO & IV 
Starting dose level 
Dose level -1 
Dose level -2 
Cycles 1 & 2 
28 mg PO Days 1, 8, 15, and 22, AND 
8 mg IV on Days 1, 8, 15, and 22 
12 mg 
No change to IV 
0 mg 
No change to IV 
Cycles 3 & 4 
28 mg PO Days 1 and 15 
40 mg PO Days 8 and 22, AND 
8 mg IV on Days 1 and 15 
12 mg 
20 mg 
No change to IV 
0 mg 
12 mg 
No change to IV 
Cycles 5 through 12 
28 mg PO Days 1 and 15 
40 mg PO Days 8 and 22, AND 
8 mg IV on Days 1 and 15 
12 mg 
20 mg 
No change to IV 
0 mg 
12 mg 
No change to IV 
Cycles 13 and beyond 
28 mg PO on Day 1, AND 
8 mg IV on Day 1 
12 mg 
No change to IV 
0 mg 
No change to IV 
a 
Dose reduction should be based on the worst toxicity demonstrated. 
 
If toxicity occurs, the toxicity will be graded utilizing the NCI CTCAE Version 4.03 
(http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf), and 
appropriate supportive care treatment will be administered to decrease the signs and symptoms 
thereof.  Dose adjustments will be based on the organ system exhibiting the greatest degree of 
toxicity. 
6.2.4 
Dose modifications due to hematologic toxicity 
Guidelines for the management of hematologic toxicities (thrombocytopenia and neutropenia) 
are summarized in Table 4. 
 


 
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Table 4 
Dose modifications due to hematologic toxicities 
Event 
Elotuzumab 
Lenalidomide 
Neutropenia (ANC) 
 
 
ANC falls to <0.5 x 109/L 
or to <1.0 x 109/L with 
fever 
Hold elotuzumaba, add G-CSF if 
Grade 3 with fever or Grade 4, 
follow CBC with diff weekly. 
Hold lenalidomidea, add G-CSF if 
Grade 3 with fever or Grade 4, 
follow CBC with diff weekly. 
ANC returns to 1.0 x 109/L 
(if neutropenia was the only 
toxicity noted) 
Resume elotuzumab at full dose. 
Resume lenalidomide at full dose. 
ANC return to 1.0 x 109/L 
(if other toxicity noted) 
Resume elotuzumab at full dose 
unless marked cyclical 
thrombocytopenia is present 
Resume lenalidomide at 1 dose 
decrement. 
ANC subsequently drops to 
<0.5 x 109/L or to <1.0 x 
109/L with fever 
Hold elotuzumaba treatments. 
Hold lenalidomidea treatments. 
ANC returns to 1.0 x 109/L 
Resume elotuzumab 
Resume lenalidomide at 1 dose 
decrement.  Do not dose below 
5 mg. 
Thrombocytopeniab 
 
 
Platelets drop to 
<30 x 109/L 
Hold elotuzumaba and follow CBC 
with diff weekly. 
Hold lenalidomidea and follow 
CBC with diff weekly.  Hold 
prophylactic ant-coagulation until 
platelets return to 30 x 109/L. 
Platelets return to 
≥30 x 109/L 
Resume elotuzumab 
Resume lenalidomide at 1 dose 
decrement. 
Platelets subsequently drop 
to <30 x 109/L 
Hold elotuzumaba and follow CBC 
with diff weekly. 
Hold lenalidomidea and follow 
CBC with diff weekly. 
Platelets return to 
≥30 x 109/L 
Resume elotuzumab 
Resume lenalidomide at 1 dose 
decrement.  Do not dose below 
5 mg. 
a Any patients who require a treatment delay of more than 3 weeks due to treatment-related toxicity will be 
discontinued from study treatment, unless the treating Investigator and the Study Chair agree that continued 
treatment at lower doses is in the best interest of the patient. 
b Platelet transfusions should also be considered for the management of thrombocytopenia, as clinically indicated. 
ANC = absolute neutrophil count, CBC = complete blood count, diff = differential; G-CSF = granulocyte colony-
stimulating factor. 
 


 
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6.2.5 
Dose modifications/management guidelines due to non-hematologic toxicities 
6.2.5.1 
Guidelines for infusion reactions 
Grade 1 infusion reaction 
Grade 1 elotuzumab infusion-related reactions by definition, require no intervention; however, 
increased monitoring is recommended. 
Grade ≥2 infusion reaction 
For a Grade ≥ 2 elotuzumab infusion-related reaction, the infusion must be interrupted.  The 
subject should be treated as clinically indicated with one or more of the following medications or 
interventions: antiemetics, antihistamines, analgesics, corticosteroids, leukotriene inhibitors, 
oxygen inhalation, epinephrine, bronchodilators, or other supportive measures as indicated. 
Patients with a Grade 4 elotuzumab infusion reaction must have elotuzumab permanently 
discontinued.  These subjects should continue to receive lenalidomide and dexamethasone per 
protocol. 
Once the elotuzumab infusion-related reaction has resolved to Grade ≤1, the infusion can be 
restarted at 0.5 mL/minute.  If symptoms do not recur after 30 minutes, the infusion rate may be 
increased in a stepwise fashion (0.5 mL/minute every 30 minutes) to a maximum of 2 mL/minute 
or the rate at which the infusion reaction occurred.  Patients who experience an infusion reaction 
require vital signs to be monitored every 30 minutes for 2 hours after the end of the elotuzumab 
infusion.  If the elotuzumab infusion reaction recurs, the infusion must be stopped and not 
restarted on that day.  Appropriate therapy should be administered to address the subject’s signs 
and symptoms.  The infusion can be reattempted at the next protocol-defined infusion time point 
at the Investigator’s discretion with additional premedication as described in Table 1. 
If a Grade ≥ 2 infusion reaction occurs following completion of an elotuzumab infusion, the 
subject should be treated as clinically indicated with 1 or more of the following medications or 
interventions: diphenhydramine, acetaminophen, hydrocortisone, H2 inhibitor, leukotriene 
inhibitor, oxygen inhalation, epinephrine, bronchodilators, or other supportive measures as 
indicated. 
Subjects with prior Grade 2 or higher infusion reactions should have the next infusion started at 
0.5 mL/minute and then escalated in a stepwise fashion (0.5 mL/minute every 30 minutes to a 
maximum of 2 mL/minute).  If there is no recurrence of a Grade >2 infusion reaction, the next 
infusion may be initiated at 1.0 mL/minute.  The infusion rate may be escalated by 
1.0 mL/minute to a maximum rate of 2 mL/minute, if the subject does not experience an infusion 
reaction within 30 minutes.  Once a subject has received 3 consecutive infusions initiated at 
1.0 mL/minute without a Grade >2 infusion reaction, subsequent infusions may be initiated at a 
maximum rate of 2.0 mL/minute and maintained at that rate. 
The dose reduction guidelines for other non-hematologic toxicities are shown in Table 5. 
 


 
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Table 5 
Dose reductions for non-hematologic toxicities other than infusion reactions 
Toxicity Grade 
Elotuzumab 
Lenalidomide 
Non-blistering rash 
 
 
 
Grade 3 
Hold (if treating Investigator’s 
opinion is possibly related to 
elotuzumab) until ≤ Grade 1, 
then resume dose. 
Hold and follow weekly. 
If the toxicity resolves to 
≤ Grade 1 prior to Day 28 of the 
current cycle, restart at 1 dose 
decrement, and continue the 
cycle until Day 28 of the current 
cycle. 
 
Grade 4 
Hold until ≤ Grade 1, then 
resume dose. 
Discontinue 
Desquamating (blistering) rash 
– any grade 
Hold until ≤ Grade 1, then 
resume dose. 
Discontinue 
Erythema multiforme 
≥ Grade 3 
Hold until ≤ Grade 1, then 
resume dose. 
Discontinue 
Sinus bradycardia/ other 
cardiac arrhythmia 
 
 
 
Grade 2 
Hold until ≤ Grade 1, then 
resume dose. 
Hold and follow at least weekly. 
If the toxicity resolves to 
≤ Grade 1 prior to Day 28, 
restart at 1 dose decrement and 
continue the cycle until Day 28. 
 
≥ Grade 3 
Hold until ≤ Grade 1, then 
resume dose. 
Discontinue 
Allergic 
reaction/hypersensitivity 
 
 
 
Grades 2 to 3 
Hold until ≤ Grade 1, then 
resume dose. 
Hold lenalidomide dose.  
Follow at least weekly. 
If the toxicity resolves to 
≤ Grade 1 prior to Day 28, 
restart at 1 dose decrement and 
continue the cycle until Day 28. 
 
Grade 4 
Discontinue 
Discontinue 


 
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Table 5 
Dose reductions for non-hematologic toxicities other than infusion reactions 
Toxicity Grade 
Elotuzumab 
Lenalidomide 
Tumor lysis syndrome 
(≥3 of the following:  ≥50% 
increase in creatinine, uric acid, 
or phosphate; ≥30% increase in 
potassium; ≥20% decrease in 
calcium; or ≥2-fold increase in 
LDH 
Hold until all abnormalities 
in serum chemistries have 
resolved.  Reinstitute at full 
dose. 
Hold until all abnormalities in 
serum chemistries have 
resolved.  Reinstitute at full 
doses. 
Infection 
Grades 3 or 4 
Hold until systemic treatment 
for infection is completed.  If 
no neutropenia, restart at full 
dose.  If neutropenic, follow 
neutropenic instructions. 
Hold until systemic treatment 
for infection is completed.  If 
no neutropenia, restart both 
drugs at full dose.  If 
neutropenic, follow 
neutropenic instructions. 
Herpes zoster or simplex 
Any grade 
Hold until lesions are dry.  
Reinstitute at full dose. 
Hold until lesions are dry.   
Reinstitute at full dose. 
Neuropathy 
 
 
 
Grade 2 with pain or 
 
Grade 3 
Hold until ≤ Grade 2, then 
restart at full dose. 
Hold until ≤ Grade 2, then 
restart at 1 dose decrement. 
 
Grade 4 
Discontinue 
Discontinue 
Renal dysfunction 
 
 
Serum creatinine >2 mg/dL 
 
Base dose reduction on 
calculated GFR 
CrCl >50 mL/min 
 
Full dose 
CrCl <50 mL/min and 
>30 mL/min 
 
Reduce to 10 mg every 
24 hours; may reinstate prior 
dose if, after 2 cycles, CrCl 
normalizes. 
CrCl <30 mL/min 
 
Reduce to 15 mg every 
48 hours 
CrCl <30 mL/min 
requiring dialysis 
 
5 mg.  Once daily.  On dialysis 
days, the dose should be 
administered following 
dialysis. 
Venous thrombosis/embolism 
≥ Grade 3 
No adjustment required 
Hold dose and adjust 
anticoagulation regimen; re-
start at treating Investigator’s 
discretion at full dose. 


 
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Table 5 
Dose reductions for non-hematologic toxicities other than infusion reactions 
Toxicity Grade 
Elotuzumab 
Lenalidomide 
Congestive heart failure (CHF) Any subject with symptoms 
of CHF, whether or not 
elotuzumab-related, must 
have the dose held until 
resolution or return to 
baseline.  If no resolution of 
CHF after 2 weeks, the 
subject will be withdrawn 
from the study. 
Any subject with symptoms of 
CHF, whether or not 
lenalidomide-related, must 
have the dose held until 
resolution or return to 
baseline.  If CHF was felt to be 
lenalidomide-related, reinstate 
by 1 dose decrement after 
return to baseline.  If no 
resolution of CHF after 
2 weeks, the subject will be 
withdrawn from the study. 
Other non-hematologic toxicity 
assessed as lenalidomide-related 
≥ Grade 3 
Full dose 
Hold dose, and follow at least 
weekly.  If the toxicity 
decreases to ≤ Grade 1 before 
Day 28 of the current cycle, 
restart at 1 dose decrement, 
and continue until Day 28 of 
the current cycle. 
Other non-hematologic toxicity 
assessed as elotuzumab-related 
≥ Grade 3 
Hold dose until toxicity 
resolves to ≤ Grade 1 or 
baseline and restart at full 
dose. 
Full dose 
Other non-hematologic toxicity 
assessed as drug-related 
≥ Grade 3 
Hold treatment and restart at 
full dose when toxicity has 
resolved to ≤ Grade 1 or 
baseline. 
Hold treatment and restart at 
1 dose decrement when 
toxicity has resolved to 
≤ Grade 1 or baseline. 
CHF = congestive heart failure; GFR = glomerular filtration rate 
 
6.2.6 
Dose modifications due to dexamethasone toxicity 
The dose reduction guidelines for toxicities known to be related to dexamethasone are shown in 
Table 6.  If dexamethasone must be discontinued, it is up to treating Investigator’s discretion 
whether to continue with elotuzumab administration. 


 
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Table 6 
Dose modifications due to dexamethasone toxicity 
Body System 
Symptom 
Recommended Action 
Gastrointestinal 
Dyspepsia, gastric, or duodenal 
ulcer, gastritis Grades 1 or 2 
(requiring medical 
management) 
Treat with H2 blockers, sucralfate, or 
omeprazole.  If symptoms persist despite above 
measures, decrease dexamethasone dose by 
1 dose level. 
 
≥ Grade 3 (requiring 
hospitalization or surgery) 
Hold dexamethasone until symptoms adequately 
controlled.  Restart at 1 dose decrement along 
with concurrent therapy with H2 blockers, 
sucralfate, or omeprazole.  If symptoms persist 
despite above measures, discontinue 
dexamethasone permanently. 
 
Acute pancreatitis 
Discontinue dexamethasone permanently. 
Cardiovascular 
Edema 
≥ Grade 3 (limiting function 
and unresponsive to therapy or 
anasarca) 
Diuretics as needed, and restart dexamethasone 
at 1 dose decrement; if edema persists despite 
above measures, decrease dose another level.  
Discontinue dexamethasone permanently if 
symptoms persist despite second reduction. 
Central nervous 
Confusion or mood alteration 
> Grade 2 (interfering with 
function +/- interfering with 
activities of daily living) 
Hold dexamethasone until symptoms resolve.  
Restart at 1 dose decrement.  If symptoms 
persist despite above measures, discontinue 
dexamethasone permanently. 
Musculoskeletal 
Muscle weakness > Grade 2 
(symptomatic and interfering 
with function +/- interfering 
with activities of daily living) 
Decrease dexamethasone by 1 dose level.  If 
weakness persists, decrease dose by 1 more 
dose level.  Discontinue dexamethasone 
permanently if symptoms persist. 
Metabolic 
Hyperglycemia ≥ Grade 3 
Treatment with insulin or PO hypoglycemic 
agents as needed.  If uncontrolled despite above 
measures, decrease dose by 1 dose level until 
levels are satisfactory. 
 


 
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7. 
STUDY ASSESSMENTS AND EVALUATIONS 
7.1 
Overview 
All patients should visit the study center on the days specified within this protocol.  The 
complete Schedule of Assessments for this study is shown in Appendix G.  The baseline medical 
history, physical examination with vital signs, ECOG performance status, 12-lead 
electrocardiogram (ECG), complete blood count (CBC), including 3-part differential and 
platelets, comprehensive metabolic profile (CMP plus magnesium and phosphorus), prothrombin 
time (PT)/activated partial thromboplastin time (aPTT)/ International Normalized Ratio (INR), 
lactate dehydrogenase (LDH) and uric acid, and C-reactive protein (CRP) should be done 
≤7 days prior to initiation of treatment.  However, if these initial examinations are obtained 
within 72 hours of Cycle 1 Day 1, they do not have to be repeated on that day. 
For women of childbearing potential, pregnancy counseling and 2 serum or urine pregnancy tests 
must be performed; one 10 to 14 days prior to initiation of study treatment and one within 
24 hours of initiation of study treatment. 
Disease assessments should be performed ≤28 days prior to initiation of treatment, with the 
exception of the bone marrow aspirate/biopsy and the skeletal survey, which should preferably 
be performed ≤28 days prior to initiation of treatment, but for which ≤60 days prior to Cycle 1 
Day 1 is acceptable. 
7.2 
Baseline study assessments (screening) 
The following information will be collected and procedures will be performed for each patient at 
screening: 
 Written informed consent prior to any other study-related procedures 
 Register patient into Revlimid REMS® program and prescribe lenalidomide 
 Medical history 
 Physical examination, including a neurological evaluation and assessment for peripheral 
neuropathy (see questionnaire in Appendix F), measurements of height (first visit), 
weight, and vital signs (resting heart rate, systolic and diastolic blood pressure, 
respiratory rate, and oral temperature) 
 ECOG performance status (see Appendix C) 
 12-lead ECG 
 Concomitant medication review 
 CBC, including hemoglobin, hematocrit, white blood cells with 3-part differential and 
platelets 
 CMP to include: glucose, blood urea nitrogen, creatinine, sodium, potassium, chloride, 
calcium, carbon dioxide (CO2), alkaline phosphatase (ALP), AST, ALT, total bilirubin, 
total protein, and albumin plus magnesium and phosphorus. 


 
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 Coagulation analysis: PT/aPTT/INR (not repeated if normal at baseline) 
 LDH and uric acid 
 Two serum or urine pregnancy tests for women of childbearing potential are required, 
one 10 to 14 days prior to starting treatment and another within 24 hours prior to start of 
treatment 
 CRP 
 Disease assessments: 
- Urine protein electrophoresis (UPEP) and immunofixation requiring a 24-hour 
urine sample collection 
- SPEP and immunofixation 
- Serum-free light chain (SFLC) 
- Serum β2-microglobulin 
- Quantitative immunoglobulins (IgG, IgA, IgM) 
- Bone marrow aspirate/biopsy (including flow cytometry, cytogenetics, 
fluorescence in-situ hybridization (FISH) to include 1q amplification, 13 del, 1p 
del, t(4;14), t(11;14), t(14;16) and 17p del, and GEP preferably via the MyPRS 
assay as per institutional guidelines 
- Aspirate should be sent for MRD evaluation according to institutional guidelines.  
Fresh or archival tissue can be used for MRD evaluation only. 
- Plasmacytoma evaluation, ONLY for patients with a known plasmacytoma that 
has been imaged before enrolling on study. 
- Skeletal survey including lateral radiograph of the skull, anteroposterior and 
lateral views of the spine, and anteroposterior views of the pelvis, ribs, femora, 
and humeri.  Low dose CT scans can be substituted for skeletal survey as per 
institutional guidelines. 
7.3 
Study treatment assessments 
7.3.1 
ERd Induction Cycles 1 and 2, Day 1 
The following information will be collected and procedures will be performed: 
 Medical history 
 Physical examination, including a neurological evaluation and assessment of peripheral 
neuropathy (see questionnaire in Appendix F), measurements of weight and vital signs 
 ECOG performance status 
 AE evaluation 
 Concomitant medication review 


 
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 CBC 
 CMP plus magnesium and phosphorus 
 LDH and uric acid 
 Serum or urine pregnancy test, including pregnancy counseling, for women of 
childbearing potential 
 Disease assessments (for Cycle 1 Day 1, only if >14 days from baseline disease 
assessments): 
- UPEP and immunofixation requiring a 24-hour urine sample collection 
- SPEP and immunofixation 
- SFLC 
- Quantitative immunoglobulins 
- Plasmacytoma evaluation, if necessary (Cycle 2 only). 
 Study drug administration (see Section 5.1.1 and Appendix G) 
 Study drug compliance. 
7.3.2 
ERd Induction Cycles 1 and 2, Days 8, 15, and 22 
The following information will be collected and procedures will be performed: 
 Vital signs 
 AE evaluation 
 Concomitant medication review 
 CBC 
 CMP plus magnesium and phosphorus 
 Serum or urine pregnancy test, including pregnancy counseling, for women of 
childbearing potential:  weekly during Cycle 1, then monthly thereafter in women with 
regular menstrual cycles or every 2 weeks in women with irregular menstrual cycles. 
 Study drug administration (see Section 5.1.1 and Appendix G) 
 Study drug compliance. 
7.3.3 
Restaging 
Restage every cycle (4 weeks):  response will be evaluated after completion of 1 treatment cycle 
as per IMWG and European Group for Blood and Marrow Transplantation (EBMT) criteria 
(Appendix A).  Thereafter, restaging must be done within a window of -7 to Day 1 of the next 
cycle. 
7.3.4 
ERd Induction Cycles 3 and 4, Day 1 
The following information will be collected and procedures will be performed: 


 
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 Medical history 
 Physical examination, including a neurological evaluation and assessment of peripheral 
neuropathy (see questionnaire in Appendix F), measurements of weight and vital signs 
 ECOG performance status 
 AE evaluation 
 Concomitant medication review 
 CBC 
 CMP plus magnesium and phosphorus 
 LDH and uric acid 
 Serum or urine pregnancy test, including pregnancy counseling, for women of 
childbearing potential. 
 Disease assessments: 
- UPEP and immunofixation requiring a 24-hour urine sample collection 
- SPEP and immunofixation 
- SFLC 
- Quantitative immunoglobulins 
- Plasmacytoma evaluation, if necessary (Cycle 4 only) 
 Study drug administration (see Section 5.1.1 and Appendix G) 
 Study drug compliance. 
7.3.5 
ERd Induction Cycles 3 and 4, Day 15 
The following information will be collected and procedures will be performed: 
 Vital signs 
 AE evaluation 
 Concomitant medication review 
 CBC 
 CMP plus magnesium and phosphorus 
 Serum or urine pregnancy test for women of childbearing potential who have irregular 
menstrual cycles.  Pregnancy counseling for all women of child-bearing potential. 
 Study drug administration (see Section 5.1.1 and Appendix G). 
7.3.6 
End of Cycle 4 through start of mobilization 
The following information will be collected and procedures will be performed: 


 
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 Vital signs 
 AE evaluation 
 Concomitant medication review 
 Disease assessments: 
- UPEP and immunofixation requiring a 24-hour urine sample collection 
- SPEP and immunofixation 
- SFLC 
- Quantitative immunoglobulins 
- Bone marrow aspirate/biopsy including flow cytometry, cytogenetics, FISH, and 
MRD, per institutional guidelines 
- Plasmacytoma evaluation, if necessary (every other cycle). 
 Women of child-bearing potential should be reminded to follow approved birth control 
practices while off study treatment. 
 Study drug compliance. 
7.3.7 
Post ASCT evaluation (at 70 to 120 days following transplant) – preference would 
be to perform evaluation on the earlier side (Day 70) and initiate consolidation 
shortly thereafter. 
The following information will be collected and procedures will be performed: 
 Physical examination, including a neurological evaluation and assessment of peripheral 
neuropathy (see questionnaire in Appendix F), measurements of weight and vital signs 
 ECOG performance status 
 CBC 
 CMP plus magnesium and phosphorus 
 LDH and uric acid 
 Serum or urine pregnancy test, including pregnancy counseling, for women of 
childbearing potential.  Note:  women of child-bearing potential were to continue to use 
appropriate birth control methods while off study treatment. 
 Disease assessments: 
- UPEP and immunofixation requiring a 24-hour urine sample collection 
- SPEP and immunofixation 
- SFLC 
- Quantitative immunoglobulins 


 
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- Bone marrow aspirate/biopsy including flow cytometry, cytogenetics, FISH, and 
MRD, per institutional guidelines 
- Plasmacytoma evaluation, if necessary (every other cycle) 
- Skeletal survey or alternate imaging as per institutional guidelines. 
7.3.8 
ERd Consolidation Cycles 6 through 8, Day 1 
Cycle 5 Day 1 assessments are not necessary unless there has been >21 day delay from the 
Day 70-120 evaluation and the start of consolidation. 
The following information will be collected and procedures will be performed: 
 Medical history 
 Physical examination, including a neurological evaluation and assessment of peripheral 
neuropathy (see questionnaire in Appendix F), measurements of weight and vital signs 
 ECOG performance status 
 AE evaluation 
 Concomitant medication review 
 CBC 
 CMP plus magnesium and phosphorus 
 LDH and uric acid 
 Serum or urine pregnancy test, including pregnancy counseling, for women of 
childbearing potential 
 Disease assessments: 
- UPEP and immunofixation requiring a 24-hour urine sample collection 
- SPEP and immunofixation 
- SFLC 
- Quantitative immunoglobulins 
- Bone marrow aspirate/biopsy including flow cytometry and MRD only to confirm 
nCR or CR as per standard of care  
- Plasmacytoma evaluation, if necessary (every other cycle). 
 Study drug administration (see Section 5.1.3 and Appendix G) 
 Study drug compliance. 
7.3.9 
ERd Consolidation Cycles 5 through 8, Day 15 
The following information will be collected and procedures will be performed: 
 Vital signs 


 
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 AE evaluation 
 Concomitant medication review 
 CBC 
 CMP plus magnesium and phosphorus 
 Serum or urine pregnancy test, including pregnancy counseling, for women of 
childbearing potential who have irregular menstrual cycles 
 Study drug administration (see Section 5.1.3 and Appendix G) 
 Study drug compliance. 
7.3.10 
End of Cycle 8 
The following information will be collected and procedures will be performed: 
 Vital signs 
 AE evaluation 
 Concomitant medication review 
 Disease assessments: 
- UPEP and immunofixation requiring a 24-hour urine sample collection 
- SPEP and immunofixation 
- SFLC 
- Quantitative immunoglobulins 
- Bone marrow aspirate/biopsy including flow cytometry, cytogenetics, FISH, and 
MRD, per standard of care as clinically indicated 
- Plasmacytoma evaluation, if necessary 
- Skeletal survey or alternate imaging as per institutional guidelines, per standard of 
care as clinically indicated. 
 Serum or urine pregnancy test, including pregnancy counseling, for women of 
childbearing potential 
 Study drug compliance. 
7.3.11 
Maintenance Cycles 9+, Day 1 
The following information will be collected and procedures will be performed: 
 Medical history 
 Physical examination, including a neurological evaluation and assessment of peripheral 
neuropathy (see questionnaire in Appendix F), measurements of weight and vital signs 
 ECOG performance status 


 
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 AE evaluation 
 Concomitant medication review 
 CBC 
 CMP plus magnesium and phosphorus 
 LDH and uric acid 
 Serum or urine pregnancy test, including pregnancy counseling, for women of 
childbearing potential 
 Disease assessments (every 3 months: Cycles 12, 15, 18, 21, 24, etc.): 
- UPEP and immunofixation requiring a 24-hour urine sample collection 
- SPEP and immunofixation 
- SFLC 
- Quantitative immunoglobulins 
- Plasmacytoma evaluation, if necessary (every other cycle). 
- An evaluation for MRD should be sent to the laboratory for any bone marrow 
aspirate performed as standard of care outside of study assessments, such as at 
1 year and 2 years post-transplant. 
 Study drug administration (see Section 5.1.4 and Appendix G) 
 Study drug compliance (beginning with Cycle 14). 
7.3.12 
Maintenance Cycles 9+, Day 15 
 Serum or urine pregnancy test, including pregnancy counseling, for women of 
childbearing potential who have irregular menstrual cycles. 
7.4 
End-of-treatment visit 
After patients are discontinued from the study, they will visit the study center ≤30 days from the 
date of last dose of study drug for end-of-treatment assessments.  Patients must be followed for 
AEs for 30 calendar days and for SAEs for 60 calendar days after the last dose of study drug. 
The following information will be collected and procedures will be performed: 
 Medical history 
 Physical examination, including a neurological evaluation and assessment of peripheral 
neuropathy (see questionnaire in Appendix F), measurements of weight and vital signs 
 ECOG performance status 
 AE evaluation 
 Concomitant medication review 
 CBC 


 
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 CMP plus magnesium and phosphorus 
 LDH and uric acid 
 Serum or urine pregnancy tests, including pregnancy counseling, for women of 
childbearing potential.  For those with irregular menses, pregnancy tests are required at 
14 and 28 days after treatment discontinuation of lenalidomide. 
 Disease assessments: 
- UPEP and immunofixation requiring a 24-hour urine sample collection 
- SPEP and immunofixation 
- SFLC 
- Quantitative immunoglobulins 
- Bone marrow aspirate/biopsy including flow cytometry, cytogenetics, FISH, and 
MRD, per standard of care as clinically indicated 
- Plasmacytoma evaluation, if necessary 
- Skeletal survey or alternate imaging as per institutional guidelines, per standard of 
care as clinically indicated. 
 Survival status 
 Study drug compliance. 
7.5 
Follow-up visits 
7.5.1 
Off-study follow-up before disease progression 
Patients who discontinue study treatment prior to the occurrence of disease progression will be 
followed every 3 months (±1 month) for a total of up to 3 years from initiation of treatment on 
the protocol or until they progress, whichever comes first. 
The following information will be collected and procedures will be performed during outpatient 
visits: 
 Physical examination, including a neurological evaluation and assessment of peripheral 
neuropathy (see questionnaire in Appendix F), measurements of vital signs 
 CBC 
 CMP plus magnesium and phosphorus 
 Disease assessments: 
- UPEP and immunofixation requiring a 24-hour urine sample collection 
- SPEP and immunofixation 
- SFLC 
- Quantitative immunoglobulins 


 
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- Plasmacytoma evaluation, if necessary 
 Survival status. 
7.5.2 
Off-study follow-up after disease progression 
Patients with documented disease recurrence or progression will be followed every 3 months 
(±1 month) for survival status only (e.g., date and cause of death) for up to 3 years from 
initiation of treatment on the protocol or until death, whichever comes first.  Patients may be 
contacted during outpatient visits or by telephone. 
8. 
DRUG FORMULATION, AVAILABILITY, ADMINISTRATION, AND 
TOXICITY INFORMATION 
8.1 
Elotuzumab 
Elotuzumab (BMS-901608, also known as HuLuc63) is a humanized recombinant monoclonal 
antibody targeted against SLAMF7, a cell surface glycoprotein expressed on myeloma and 
natural killer cells. 
 
Investigational Product 
Dosage Form and Strength 
Manufacturer 
Elotuzumab 
400 and 300 mg/vial 
Bristol-Myers Squibb 
 
8.1.1 
Labeling, packaging, and supply 
Elotuzumab for injection has been developed to be used as an IV infusion for clinical studies and 
will be provided by BMS to the Sarah Cannon Central Pharmacy, which will dispense it to the 
sites.  The drug product is a nonpyrogenic lyophilized powder that is a white to off-white, whole 
or fragmented cake contained in 20 mL Type I glass vials, closed with 20 mm stoppers and 
sealed with aluminum seals.  Each vial of drug product contains the labelled amount of 
elotuzumab drug substance, sucrose, sodium citrate dihydrate, citric acid monohydrate, and 
polysorbate 80.  The drug product will be reconstituted prior to administration. 
The immediate packaging will contain a statement to conform with FDA Investigational New 
Drug (IND) requirements as follows: Caution New Drug - Limited by United States law to 
investigational use. 
8.1.2 
Preparation and administration of elotuzumab 
Each vial of elotuzumab should be reconstituted with sterile water for injection at the clinical 
site.  Prior to IV administration, the reconstituted solution is diluted with 0.9% sodium chloride 
for injection to result in an elotuzumab concentration from 0.9 mg/mL to no higher than 
6.6 mg/mL in a polyvinyl chloride or polyolefin infusion bag.  Alternatively, 5% dextrose 
injection may be used as a diluent in place of 0.9% sodium chloride injection. 


 
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The infusion is to be administered through a sterile, non-pyrogenic, low-protein-binding in-line 
filter using an automated infusion pump.  Care must be taken to ensure the sterility of the 
prepared solution, as the drug product does not contain anti-microbial preservatives or 
bacteriostatic agents.  A sufficient excess of drug product is included in each vial to account for 
withdrawal losses. 
The infusion should be started at 0.5 mL/minute and increased according to Table 7.  Please note 
that infusion rate increases to the next higher level are permitted only if no infusion reactions are 
encountered. 
 
Table 7 
Elotuzumab infusion rates 
Infusion rate 
Duration of infusion 
Volume delivered 
Volume remaininga 
Cycle 1 Dose 1 
Approximate Total Duration: 2 hours 50 minutes 
262 mL 
0.5 mL/min 
30 minutes 
15 mL 
247 mL 
1.0 mL/min 
30 minutes 
30 mL 
217 mL 
2.0 mL/min 
110 minutes 
217 mL 
0 mL 
Cycle 1 Dose 2 
Approximate Total Duration: 1 hour 13 minutes 
262 mL 
3.0 mL/min 
30 minutes 
90 mL 
172 mL 
4.0 mL/min 
43 minutes 
172 mL 
0 mL 
Cycle 1 Doses 3 & 4 
Approximate Total Duration: 53 minutes 
262 mL 
5 mL/min 
53 minutes 
262 mL 
0 mL 
Cycle 2+ 
Approximate Total Duration: 53 minutes 
262 mL 
5 mL/min 
53 minutes 
262 mL 
0 mL 
a 
Volume for an 80 kg patient.  Total volume varies according to patient weight. 
 
8.1.3 
Storage and use of elotuzumab 
All study drugs must be kept in a secure place under appropriate storage conditions. 
Elotuzumab for injection should be stored refrigerated at 2°C to 8°C (36°F to 46°F). 
The reconstituted and diluted solution of elotuzumab for injection is stable for up to 24 hours, 
under refrigerated conditions, 2°C to 8°C (36°F to 46°F).  The drug solution should be 
equilibrated to room temperature (process takes 2 to 2.5 hours) and the container must be gently 
inverted to mix well before administration.  Do not use the accelerated warming method.  If 
administration is delayed beyond the specified time, the prepared dose solution must be 
discarded, and the reason documented. 
The dose of elotuzumab to be administered to a patient will be calculated by multiplying the 
patient’s weight (kg) by 10 mg/kg or 20 mg/kg.  After the dose is diluted in 0.9% sodium 


 
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chloride injection, or 5% dextrose injection, it must be fully administered within 8 hours, if 
stored at room temperature. 
8.1.4 
Precautions and risks associated with elotuzumab 
8.1.4.1 
Infusion reactions 
Elotuzumab can cause infusion reactions.  Infusion reactions were reported in approximately 
10% of patients treated with ERd in the randomized trial in patients with MM.  All reports of 
infusion reaction were Grade 3 or lower.  Grade 3 infusion reactions occurred in 1% of patients.  
The most common symptoms of an infusion reaction included fever, chills, and hypertension.  
Bradycardia and hypotension also developed during infusions. 
In the trial, 5% of patients required interruption of the administration of elotuzumab for a median 
of 25 minutes due to infusion reactions, and 1% of patients discontinued due to infusion 
reactions.  Of the patients who experienced an infusion reaction, 70% (23/33) had them during 
the first dose. 
Administer premedication consisting of dexamethasone, antihistamines (H1 and H2 blockers), 
and acetaminophen prior to elotuzumab infusion. 
Interrupt elotuzumab infusion for Grade 2 or higher infusion reactions and institute appropriate 
medical management. 
8.1.4.2 
Infections 
In a clinical trial of patients with MM (N=635), infections were reported in 81.4% of patients in 
the ERd arm and 74.4% in the lenalidomide and dexamethasone (Ld) arm.  Grade 3 to 4 
infections were noted in 28% and 24.3% of ERd- and Ld-treated patients, respectively.  
Discontinuations due to infections occurred in 3.5% of ERd-treated and 4.1% of Ld-treated 
patients.  Fatal infections were reported in 2.5% and 2.2% of ERd- and Ld-treated patients. 
Opportunistic infections were reported in 22% of patients in the ERd arm and 12.9% of patients 
in the Ld arm.  Fungal infections occurred in 9.7% of patients in the ERd arm and 5.4% of 
patients in the Ld arm.  Herpes zoster was reported in 13.5% of patients treated with ERd and 
6.9% of patients treated with Ld.  Monitor patients for development of infections and treat 
promptly. 
8.1.4.3 
Second primary malignancies 
In a clinical trial of patients with MM (N=635), invasive second primary malignancies have been 
observed in 9.1% of patients treated with ERd and 5.7% of patients treated with Ld.  The rate of 
hematologic malignancies were the same between the ERd and Ld treatment arms (1.6%).  Solid 
tumors were reported in 3.5% and 2.2% of ERd- and Ld-treated patients, respectively.  Skin 
cancer was reported in 4.4% and 2.8% of patients treated with ERd and Ld, respectively.  
Monitor patients for the development of second primary malignancies. 
8.1.4.4 
Hepatoxicity 
Elevations in liver enzymes (AST/ALT greater than 3 times the ULN, total bilirubin greater than 
2 times the ULN, and ALP less than 2 times the ULN) consistent with hepatotoxicity were 
reported in 2.5% and 0.6% of ERd- and Ld-treated patients, respectively, in a clinical trial of 


 
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patients with MM (N=635).  Two patients experiencing hepatotoxicity were not able to continue 
treatment; however, 6 out of 8 patients had resolution and were able to continue treatment.  
Monitor liver enzymes periodically.  Stop elotuzumab upon Grade 3 or higher elevation of liver 
enzymes.  After return to baseline values, continuation of treatment may be considered. 
8.1.4.5 
Interference with determination of complete response 
Elotuzumab is a humanized IgG kappa monoclonal antibody that can be detected on both the 
serum protein electrophoresis (SPEP) and immunofixation (IFE) assays used for the clinical 
monitoring of endogenous M-protein.  This interference can impact the determination of CR and 
possibly relapse from CR in patients with IgG kappa myeloma protein. 
 
8.2 
Lenalidomide 
Lenalidomide must be prescribed through and in compliance with the Revlimid REMS® 
program of Celgene Corporation.  Prescriptions must be filled within 7 days.  Consideration 
should be given to prescribing lenalidomide 5 to 7 days in advance of Day 1 of each cycle to 
allow time for required patient and prescriber surveys and drug shipment to the patient.   
Lenalidomide is to be administered in accordance with the terms of its marketing authorization 
and in accordance with institutional standard of practice.  Please refer to the US Package Insert 
(http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021880s034lbl.pdf) for detailed 
information about administration. 
Any unused Revlimid® (lenalidomide) should be returned to the patient for disposition in 
accordance with the Revlimid REMS® program. 
8.3 
Dexamethasone 
Dexamethasone is to be administered in accordance with the terms of its marketing authorization 
and in accordance with institutional standard of practice.  In this study, dexamethasone will be 
administered both orally and intravenously.  Commercial supplies will be used.  Please refer to 
the US Package Inserts for detailed information on how to prepare and administer 
dexamethasone for injection (http://www.fda.gov/ohrms/dockets/dockets/07p0167/07p-0167-
cp00001-02-Attachment-A-vol1.pdf) and how to administer dexamethasone tablets 
(http://bidocs.boehringer-
ingelheim.com/BIWebAccess/ViewServlet.ser?docBase=renetnt&folderPath=/Prescribing+Infor
mation/PIs/Roxane/Dexamethasone/Dexamethasone+Tablets+Solution+and+Intensol.pdf). 
8.4 
Accountability for all study drugs 
The Principal Investigator (or designee) is responsible for accountability of all used and unused 
study drug supplies at the site. 
All study drug inventories must be made available for inspection by the Sponsor or its 
representatives and regulatory agency inspectors upon request. 
At the end of the study, all Sarah Cannon Development Innovations Drug Accountability Record 
Form(s) will be completed by the site and sent to the Sarah Cannon Development Innovations 


 
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Regulatory Department.  Study drug supplies must not be destroyed unless prior approval has 
been granted by the Sponsor or its representative.  Please contact Sarah Cannon Development 
Innovations regarding disposal of any study drug. 
9. 
RESPONSE EVALUATIONS AND MEASUREMENTS 
Response and progression will be evaluated in this study as per IMWG and EBMT criteria (see 
Appendix A). 
10. 
STATISTICAL CONSIDERATIONS 
10.1 
Statistical design 
This is a multi-center, open-label, Phase 2 study to assess the feasibility and tolerance of the 
combination of ERd in the induction, consolidation, and maintenance treatment of transplant-
eligible patients newly diagnosed with MM. 
10.2 
Sample size considerations 
In a study looking at a similar population with lenalidomide and dexamethasone as induction 
treatments prior to transplant, only 68% of patients were able to reach the first randomization, 
which occurred after induction and mobilization, but before transplantation (Palumbo et al 2014).  
In this study, the lowest accepted feasibility will be 65% with a target of 80%.  In order to test 
the null hypothesis of an induction feasibility rate of 65% versus an alternative hypothesis with 
an induction feasibility rate of 80%, 48 patients are required in order to have 85% power to test 
the null hypothesis using a one-sided exact binomial test at the 0.1 significance level.  The null 
hypothesis will be rejected if the induction treatment is deemed feasible in at least 36 patients.  
To allow for a possible 10% drop-out rate, the sample size has been inflated to 53 patients. 
10.3 
Analysis population 
The following analysis populations will be used: 
 Response evaluation population is defined as patients who have completed at least 
1 cycle of therapy. 
 Safety population is defined as all patients who provide informed consent and receive at 
least one dose of study treatment. 
10.4 
Data analysis 
A comprehensive description of the statistical analyses and related activities for this study will be 
documented in a statistical analysis plan, which will be finalized prior to database lock. 
10.4.1 
Timing of analyses 
The primary efficacy endpoint, IFR, will be analyzed when 48 patients have completed 4 cycles 
of induction therapy and are able to start ASCT. 
Interim safety analyses are described in Section 10.4.4. 


 
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The final analysis of all study data will occur after all patients have been followed for 3.5 years 
or at death (whichever comes first). 
10.4.2 
Demographics and baseline characteristics 
Demographic and baseline disease characteristics will be summarized.  Data to be tabulated will 
include demographic features such as age, sex and race, as well as disease-specific 
characteristics. 
The number and percentages of patients screened, treated, completed the treatment/study by 
stage, and withdrawn from treatment/study for any reasons will be presented overall. 
10.4.3 
Efficacy analysis 
All efficacy analyses will be performed using the response evaluation population. 
The primary efficacy endpoint is: 
 IFR defined as the percentage of patients successfully completing 4 cycles of induction 
treatment with ERd and able to start ASCT. 
The secondary efficacy endpoints are: 
 Complete response rate (CRR), defined as the percentage of patients who achieve a 
complete response (CR) or near complete response (nCR) to treatment at each stage of 
the study, i.e., induction, ASCT, consolidation, end of study as per IMWG and European 
Group for Blood and Marrow Transplantation (EBMT) criteria 
 Overall response rate (ORR), defined as the percentage of patients who achieve at least a 
partial response (PR) to treatment at each stage of the study, i.e., induction, ASCT, 
consolidation, end of study as per IMWG and EBMT criteria 
 Progression-free survival (PFS), defined as the time from start of induction treatment to 
documented progressive disease (PD) or death from any cause up to 3 years post first 
treatment 
 Overall survival (OS), defined as the time from start of induction treatment to 3 years 
post first treatment or death from any cause, whichever comes first 
 Consolidation feasibility rate (CFR), defined as the percentage of patients starting 
induction treatment with ERd successfully completing treatment to end of consolidation 
 Maintenance feasibility rate (MFR), defined as the percentage of patients starting 
induction treatment with ERd successfully completing treatment to end of maintenance. 
 Safety endpoints including 1) treatment-emergent adverse events (TEAEs), serious 
adverse events (SAEs), and deaths, and 2) clinically significant changes in safety-related 
laboratory parameters according to National Cancer Institute Common Terminology 
Criteria for Adverse Events (NCI CTCAE Version 4.03) and abnormal vital signs. 
 
The exploratory endpoint is: 
 To evaluate MRD defined as the proportion of patients who are MRD positive versus 
those who are MRD negative. 


 
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The IFR will be computed and presented together with the exact 90% confidence interval (CI), 
using the method of Clopper and Pearson 1934.  The null hypothesis of 65% IFR will be rejected 
if at least 36 patients are able to complete 4 cycles of induction treatment and start ASCT. 
The CRR, ORR, CFR, MFR will be computed and presented together with the exact 90% CIs, 
using the method of Clopper and Pearson 1934. 
The Kaplan-Meier product limit method will be used to estimate PFS and OS.  Median values 
and rates at clinically relevant time points will be provided with the 90% CIs.  A Cox 
Proportional Hazards Model may also be utilized to estimate the effects of patient baseline 
characteristics or known prognostic factors on PFS and OS. 
10.4.4 
Safety analysis 
Interim safety analyses 
Significant toxicities for this protocol are based on the most common Grade 3 or greater AEs 
reported in Lonial et al 2015 and include: infusion reactions, fatigue, neutropenia, 
thrombocytopenia, diarrhea, or any unexpected toxicity. 
After 10 patients have completed induction, an interim safety assessment will be performed.  If 
3 or more patients experience unexpected or significant toxicity, further accrual will occur only 
after discussions between the Study Chair and funding partners. 
After 10 patients have completed consolidation, an interim safety assessment will be performed.  
If 3 or more patients experience unexpected or significant toxicity, further accrual will occur 
only after discussions between the Study Chair and funding partners. 
After 10 patients have completed 4 cycles of consolidation, an interim safety assessment will be 
performed.  If 3 or more patients experience unexpected or significant toxicity, further accrual 
will occur only after discussions between the Study Chair and funding partners. 
Final safety analysis 
Safety will be assessed through the analysis of the reported incidence of treatment-emergent 
AEs.  Treatment-emergent AEs are those with an onset on or after the initiation of therapy, and 
will be graded according to NCI CTCAE Version 4.03.  A copy of CTCAE scoring system may 
be downloaded from: http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-
14_QuickReference_5x7.pdf. 
The AEs will be coded using Medical Dictionary for Regulatory Activities (MedDRA), and 
summarized using system organ class and preferred term by stage of treatment for all patients in 
the safety population.  In addition, summaries of SAEs, AEs leading to treatment 
discontinuation, AEs by maximum NCI CTCAE grade, and AEs related to study treatment will 
also be presented by stage of treatment. 
Other safety endpoints including laboratory results, vital signs, and ECG findings will be 
summarized for all patients in the safety population. 
Concomitant medications will be coded using the World Health Organization Drug Dictionary 
and they will be listed and summarized by stage of treatment group. 


 
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11. 
SAFETY REPORTING AND ANALYSES 
Safety assessments will consist of monitoring and recording protocol-defined AEs and SAEs; 
measurement of protocol-specified hematology, clinical chemistry, and urinalysis variables; 
measurement of protocol-specified vital signs; and other protocol-specified tests that are deemed 
critical to the safety evaluation of the study drug. 
The Principal Investigator is responsible for recognizing and reporting AEs and SAEs to the 
Sarah Cannon Development Innovations Safety Department (see Section 11.1.5 and 
Section 11.2, respectively).  It is the Sponsor’s responsibility to report relevant SAEs to the 
applicable local, national, or international regulatory bodies.  In addition, Investigators must 
report SAEs and follow-up information to their responsible IRB according to the policies of that 
IRB. 
The Principal Investigator is also responsible for ensuring that every staff member involved in 
the study is familiar with the content of this section. 
11.1 
Definitions 
11.1.1 
Adverse events 
Adverse event means any untoward medical occurrence associated with the use of a drug in 
humans, whether or not considered drug related.  An AE can be any unfavorable and unintended 
sign (e.g., an abnormal laboratory finding), symptom, or disease temporarily associated with the 
use of a drug, without any judgement about causality.  An AE can arise with any use of the drug 
(e.g., off-label use, use in combination with another drug) and with any route of administration, 
formulation, dose or including overdose. 
11.1.2 
Serious adverse events 
An AE or a suspected adverse reaction (SAR) is considered “serious” if it results in any of 
the following outcomes: 
 Death 
 A life-threatening AE 
 Inpatient hospitalization or prolongation of existing hospitalization 
 A persistent or significant incapacity or substantial disruption of the ability to 
conduct normal life functions 
 A congenital anomaly/birth defect 
 Potential drug-induced liver injury (DILI) is also considered an important medical 
event--see the DILI section below for a definition of a potential DILI event. 
 Suspected transmission of an infectious agent (e.g., pathogenic or non-pathogenic) 
via the study drug is an SAE.1 
Although pregnancy, overdose, cancer, and potential DILIs are not always serious by regulatory 
definition, these events must be handled as SAEs. 


 
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Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered serious when, based upon appropriate medical judgment, they 
may jeopardize the patient or subject and may require medical or surgical intervention to prevent 
one of the outcomes listed in this definition.  Examples of such medical events include allergic 
bronchospasm requiring intensive treatment in an emergency room or at home, blood dyscrasias 
or convulsions that do not result in hospitalization, or development of drug dependency or drug 
abuse. 
It is important to distinguish between “serious” and “severe” AE, as the terms are not 
synonymous.  Severity is a measure of intensity; however, an AE of severe intensity need not 
necessarily be considered serious.  Seriousness serves as the guide for defining regulatory 
reporting obligations.  “Serious” is a regulatory definition and is based on patient/event outcome 
or action usually associated with events that pose a threat to a patient’s life or vital functions.  
For example, nausea which persists for several hours may be considered severe nausea, but may 
not be considered an SAE.  On the other hand, a stroke which results in only a limited degree of 
disability may be considered only a mild stroke, but would be considered an SAE.  Severity and 
seriousness should be independently assessed when recording AEs on the eCRF and SAEs on the 
SAE Report Form. 
11.1.3 
Adverse reaction 
An adverse reaction means any AE caused by a drug.  Adverse reactions are a subset of all 
suspected adverse reactions where there is a reason to conclude that the drug caused the event. 
11.1.4 
Suspected adverse reaction 
Suspected adverse reaction means any AE for which there is a reasonable possibility that the 
drug caused the AE.  Reasonable possibility means that there is evidence to suggest a causal 
relationship between the drug and the AE.  A suspected adverse reaction implies a lesser degree 
of certainty about causality than adverse reaction, which means any AE caused by a drug. 
11.1.5 
Recording and reporting of adverse events 
11.1.5.1 Recording of adverse events 
All AEs of any patient during the course of the research study will be recorded in the eCRF, and 
the investigator will give his or her opinion as to the relationship of the AE to the study drug 
treatment (i.e., whether the event is related or unrelated to study drug administration). 
All AEs should be documented.  A description of the event, including its date of onset and 
resolution, whether it constitutes an SAE or not, any action taken (e.g., changes to study 
treatment), and outcome, should be provided, along with the Investigator’s assessment of 
causality (i.e., the relationship to the study treatments).  For an AE to be a suspected treatment-
related event there should be at least a reasonable possibility of a causal relationship between the 
protocol treatment and the AE.  Adverse events will be graded according to the NCI CTCAE 
Version 4.03, and changes will be documented. 
If the AE is serious, it should be reported immediately to Sarah Cannon Development 
Innovations Safety Department.  Other untoward events occurring in the framework of a clinical 
study are to be recorded as AEs (i.e., AEs that occur prior to assignment of study treatment that 


 
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are related to a protocol-mandated intervention, including invasive procedures such as biopsies, 
medication washout, or no treatment run-in). 
Any clinically significant signs and symptoms, abnormal test findings, changes in physical 
examination, hypersensitivity, and other measurements that occur will be reported as AEs and 
collected on the relevant eCRF screen. 
Test findings will be reported as an AE if: the test result requires an adjustment in the study 
drug(s) or discontinuation of treatment, and/or test findings require additional testing or surgical 
intervention, a test result or finding is associated with accompanying symptoms, or a test result is 
considered to be an AE by the Investigator. 
11.1.5.2 Reporting period for adverse events 
All non-serious AEs considered unrelated to study treatments by the treating Investigator, 
spanning from the start of study treatment until 30 calendar days after discontinuation or 
completion of study treatment as defined by the clinical study for that patient, are to be recorded 
on the corresponding screen(s) included in the eCRF. 
All non-serious AEs considered related to study treatments by the treating Investigator, spanning 
from the start of study treatment until 60 calendar days after discontinuation or completion of 
study treatment as defined by the clinical study for that patient, are to be recorded on the 
corresponding screen(s) included in the eCRF. 
All AEs resulting in discontinuation from the study should be followed until resolution or 
stabilization.  All new AEs occurring during this period must be reported and followed until 
resolution unless, in the opinion of the investigator, the AE or laboratory abnormality/ies are not 
likely to improve because of the underlying disease.  In this case, the investigators must record 
his or her reasoning for this decision in the patient’s medical record and as a comment on the 
eCRF screen. 
After 30 days of completion of protocol-specific treatment or discontinuation, only AEs assessed 
by the Investigator as treatment-related are to be reported.  All SAEs, including deaths, will be 
reported from the start of study treatment through 60 days after completion of protocol-specific 
treatment. 
11.1.6 
Assessment of adverse events 
All AEs and SAEs, whether volunteered by the patient, discovered by study personnel during 
questioning, or detected through physical examination, laboratory test, or other means, will be 
reported appropriately.  Each reported AE or SAE will be described by its duration (i.e., start and 
end dates), regulatory seriousness criteria (if applicable), suspected relationship to the study drug 
(see following guidance), and actions taken. 
To ensure consistency of AE and SAE causality assessments, investigators should apply the 
following general guideline: 
YES:  There is a plausible temporal relationship between the onset of the AE and 
administration of the study medication, and the AE cannot be readily explained by the 
patient’s clinical state, intercurrent illness, or concomitant therapies, and/or the AE 
follows a known pattern of response to the study drug, and/or the AE abates or resolves 


 
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upon discontinuation of the study drug or dose reduction and, if applicable, reappears 
upon re-challenge. 
NO:  Evidence exists that the AE has an etiology other than the study drug (e.g., pre-
existing medical condition, underlying disease, intercurrent illness, or concomitant 
medication), and/or the AE has no plausible temporal relationship to study drug 
administration (e.g., cancer diagnosed 2 days after first dose of study drug). 
11.2 
Serious adverse event reporting by Investigators 
Adverse events classified by the treating investigator as serious require expeditious handling and 
reporting to Sarah Cannon Development Innovations Safety Department in order to comply with 
regulatory requirements.  Determination of life-threatening or serious is based on the opinion of 
either the Sponsor or the Investigator. 
Following the start of study treatment, all SAEs, whether related or not related to study drug, 
must be collected, including those thought to be associated with protocol-specified procedures, 
until 60 days after discontinuing study treatment.  The Sarah Cannon Development 
Innovations Safety Department must be notified of all SAEs, regardless of causality, within 
24 hours of the first knowledge of the event by the treating physician or research personnel. 
To report an SAE, the SAE Report Form should be completed with the necessary information. 
The SAE report should be sent to Sarah Cannon Development Innovations Safety Department 
via fax or e-mail using the using the following contact information (during both business and 
non-business hours): 
Sarah Cannon Development Innovations Safety Department 
Safety Dept. Fax #:      1-866-807-4325 
Safety Dept. Email:     CANN.SAE@SCRI-Innovations.com 
Transmission of the SAE report should be confirmed by the site personnel submitting the report. 
Follow-up information for SAEs and information on non-serious AEs that become serious should 
also be reported to Sarah Cannon Development Innovations Safety Department as soon as it is 
available; these reports should be submitted using the Sarah Cannon Development Innovations 
SAE Report Form. 
Investigators must report SAEs and follow-up information to their responsible IRBs according to 
the policies of the responsible IRB. 
11.3 
Recording of adverse events and serious adverse events 
11.3.1 
Diagnosis versus signs and symptoms 
All AEs should be recorded individually in the patient’s own words (verbatim) unless, in the 
opinion of the Principal Investigator or designated physician, the AEs constitute components of a 
recognized condition, disease, or syndrome.  In the latter case, the condition, disease, or 
syndrome should be named rather than each individual sign or symptom.  If a constellation of 
signs and/or symptoms cannot be medically characterized as a single diagnosis or syndrome at 
the time of reporting, each individual event should be recorded as an AE or SAE as appropriate 


 
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on the relevant form(s) (SAE Report Form and/or AE eCRF screen).  If a diagnosis is 
subsequently established, it should be reported as follow-up information is available.  If a 
diagnosis is determined subsequent to the reporting of the constellation of symptoms, the 
signs/symptoms should be updated to reflect the diagnosis. 
Progression of malignancy (including fatal outcomes), if documented by use of appropriate 
method (for example, as per IMWG Uniform Response Criteria), should not be reported as an 
SAE. 
11.3.2 
Persistent or recurrent adverse events 
A persistent AE is one that extends continuously, without resolution, between patient evaluation 
time points.  Such events should only be recorded once on the SAE Report Form and/or the AE 
eCRF screen.  If a persistent AE becomes more severe or lessens in severity, it should be 
recorded on a separate SAE Report Form and/or AE eCRF screen. 
A recurrent AE is one that occurs and resolves between patient evaluation time points, and 
subsequently recurs.  All recurrent AEs should be recorded on an SAE Report Form and/or AE 
eCRF screen. 
11.3.3 
Abnormal laboratory values 
If an abnormal laboratory value or vital sign is associated with clinical signs and/or symptoms, 
the sign or symptom should be reported as an AE or SAE, and the associated laboratory value or 
vital sign should be considered additional information that must be collected on the relevant 
eCRF screen.  If the laboratory abnormality is a sign of a disease or syndrome, only the diagnosis 
needs to be recorded on the SAE Report Form or AE eCRF screen. 
Abnormal laboratory values will be reported as an AE if: the laboratory result requires an 
adjustment in the study drug(s) or discontinuation of treatment, and/or laboratory findings 
require additional testing or surgical intervention, a laboratory result or finding is associated with 
accompanying symptoms, or a laboratory result is considered to be an AE by the Investigator. 
11.3.4 
Deaths 
Deaths that occur during the protocol-specified AE reporting period that are attributed by the 
Investigator solely to progression of disease will be recorded on the “Study Discontinuation” 
eCRF screen.  All other on-study deaths, regardless of attribution, will be recorded on an SAE 
Report Form and expeditiously reported to the Sarah Cannon Development Innovations Safety 
Department. 
When recording a SAE with an outcome of death, the event or condition that caused or 
contributed to the fatal outcome should be recorded as the single medical concept on the SAE 
Report Form and Adverse Event screen of the eCRF.  If the cause of death is unknown and 
cannot be ascertained at the time of reporting, record “Death NOS” on the eCRF Adverse Event 
screen.  During post-study survival follow-up, deaths attributed to progression of disease will be 
recorded only on the “After Progressive Disease Follow-Up” eCRF screen. 


 
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11.3.5 
Hospitalization, prolonged hospitalization, or surgery 
Any AE that results in hospitalization of >24 hours or prolongation of pre-existing 
hospitalization should be documented and reported as an SAE unless specifically instructed 
otherwise in this protocol.  There are some hospitalizations that do not require reporting as an 
SAE. 
Treatment within or admission to the following facilities is not considered to meet the criteria of 
“inpatient hospitalization” (although if any other SAE criteria are met, the event must still be 
treated as an SAE and immediately reported): 
 Emergency department or emergency room 
 Outpatient or same-day surgery units 
 Observation or short-stay unit 
 Rehabilitation facility 
 Hospice or skilled nursing facility 
 Nursing homes, custodial care or respite care facility 
Hospitalization during the study for a pre-planned surgical or medical procedure (one which was 
planned prior to entry in the study) does not require reporting as an SAE to the Sarah Cannon 
Development Innovations Safety Department. 
11.3.6 
Pre-existing medical conditions 
A pre-existing medical condition is one that is present at the start of the study.  Such conditions 
should be recorded on the General Medical History eCRF screen.  A pre-existing medical 
condition should be recorded as an AE or SAE only if the frequency, severity, or character of the 
condition worsens during the study.  When recording such events on an SAE Report Form and/or 
AE eCRF screen, it is important to convey the concept that the pre-existing condition has 
changed by including applicable descriptors. 
11.3.7 
New cancers 
The development of a new primary cancer should be regarded as an AE and will generally meet 
at least one of the seriousness criteria (see Section 11.1.2).  New primary cancers are those that 
are not the primary reason for the administration of the study treatment and have developed after 
the inclusion of the patient into the study.  They do not include metastases of the original cancer.  
Symptoms of metastasis or the metastasis itself should not be reported as an AE/SAE, as they are 
considered to be disease progression. 
11.3.8 
Pregnancy, abortion, birth defects/congenital anomalies 
If a patient becomes pregnant while enrolled in the study, a Pregnancy Form (see Appendix E) 
should be completed and faxed to the Sarah Cannon Development Innovations Safety 
Department.  Sarah Cannon Development Innovations Safety Department should be notified 
expeditiously, irrespective of whether or not it meets the criteria for expedited reporting.  
Abortions (spontaneous, accidental, or therapeutic) must also be reported to Sarah Cannon 
Development Innovations Safety Department. 


 
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If a female partner of a male patient becomes pregnant during the male patient’s participation in 
this study, this must be reported to the Sarah Cannon Development Innovations Safety 
Department immediately.  Every effort should be made to follow the pregnancy for the final 
pregnancy outcome. 
Congenital anomalies/birth defects always meet SAE criteria, and should therefore be 
expeditiously reported as an SAE, using the previously described process for SAE reporting.  A 
Pregnancy Form (see Appendix E) should also have been previously completed, and will need to 
be updated to reflect the outcome of the pregnancy. 
11.3.9 
Elotuzumab overdose 
Symptomatic and non-symptomatic overdose must be reported in the eCRF.  Any accidental or 
intentional overdose with the study treatment that is symptomatic, even if not fulfilling a 
seriousness criterion, is to be reported to the Sarah Cannon Development Innovations Safety 
Department no greater than 24 hours from first knowledge of the event using the corresponding 
screens in the eCRF and following the same process described for SAE reporting (see 
Section 11.2). 
11.4 
Protocol-defined events of special interest 
The following are events of special interest, and will need to be reported expeditiously (see 
Section 11.1.5).  These events include the following: 
Elotuzumab - 
Hypersensitivity, Infusion reactions 
 
11.5 
Serious adverse event reporting requirements to BMS 
Sarah Cannon Development Innovations Safety Department will forward SAE information to: 
SAE Email Address: Worldwide.Safety@BMS.com 
SAE Fax Number: 609-818-3804 
within 1 business day of Sarah Cannon Development Innovations Safety Department personnel 
becoming aware of the SAE. 
Sarah Cannon Development Innovations is responsible for reporting relevant SAEs to the 
competent authority, other applicable regulatory authorities, and participating investigators, in 
accordance with International Conference on Harmonisation guidelines, FDA regulations, and/or 
local regulatory requirements. 
11.5.1 
Bristol-Myers Squibb-specific requirements for adverse event reporting 
Following the start of study treatment, all SAEs, whether related or not related to study drug, 
must be collected, including those thought to be associated with protocol-specified procedures, 
until 60 days after discontinuing dosing.  If applicable, SAEs must be collected that relate to any 
later protocol-specific procedure (such as follow-up skin biopsies). 
The Investigator should report any SAE occurring after these time periods that is believed to be 
related to study drug or protocol-specified procedure. 


 
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An SAE report should be completed for any event where doubt exists regarding its status of 
seriousness. 
If the Investigator believes that an SAE is not related to study drug, but is potentially related to 
the conditions of the study (such as withdrawal of previous therapy, or a complication of a study 
procedure), the relationship should be specified in the narrative section of the SAE Report Form. 
If an ongoing SAE changes in its intensity or relationship to study drug or if new information 
becomes available, a follow-up SAE report should be sent within 24 hours to the BMS (or 
designee) using the same procedure used for transmitting the initial SAE report. 
All SAEs should be followed to resolution or stabilization. 
11.5.2 
Sponsor assessment of unexpected 
The Sponsor is responsible for assessing an AE or SAR as “unexpected.” 
An AE or SAR is considered “unexpected” when the following conditions occur: 
 Event(s) is not mentioned in the Investigator’s Brochure 
 Event(s) is not listed at the specificity or severity that has been observed 
 Event(s) is not consistent with the General Investigative Plan or in the current application 
 Includes AEs or SARs that may be anticipated from the pharmacological properties of the 
study drug, or that occur with members of the drug class, or that have previously been 
observed under investigation 
When applicable, an unexpected AE may also apply to an event that is not listed in the current 
US Package Insert, or an event that may be mentioned in the package insert, but differs from the 
event because of greater severity or specificity. 
Known as Suspected Unexpected Serious Adverse Reactions (SUSAR), these events are 
suspected (by the Investigator or Sponsor) to be related to the study drug, are unexpected (not 
listed in the Investigator’s Brochure or package insert), and are serious (as defined by the 
protocol) and require expedient submission to relevant health authorities within 7 days (fatal or 
life-threatening event) or 15 days (all serious events), or as defined by law.  The term SUSAR is 
used primarily in the reporting of events to regulatory authorities. 
Expected AEs are those events that are listed or characterized in the package insert or current 
Investigator’s Brochure (Elotuzumab 2014). 
11.5.3 
Sponsor reporting for clinical studies under an Investigational New Drug 
Application 
All written IND Safety Reports submitted to the FDA by the Sarah Cannon Development 
Innovations Safety Department must also be faxed to pharmaceutical company that is supporting 
the study with either funding or drug supply: 
SAE Email Address: Worldwide.Safety@BMS.com 
SAE Fax Number: 609-818-3804 


 
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12. 
QUALITY ASSURANCE AND QUALITY CONTROL 
12.1 
Study monitoring, auditing, and inspecting 
The Investigator will permit study-related monitoring, quality audits, and inspections by the 
Sponsor or its representative(s), government regulatory authorities, and the IRB/EC of all study-
related documents (e.g., source documents, regulatory documents, data collection instruments, 
case report forms).  The Investigator will ensure the capability for inspections of applicable 
study-related facilities.  The Investigator will ensure that the study monitor or any other 
compliance or Quality Assurance reviewer is given access to all study-related documents and 
study-related facilities. 
At the Sponsor’s discretion, Source Document Verification may be performed on all data items 
or a percentage thereof. 
Participation as an investigator in this study implies the acceptance of potential inspection by 
government regulatory authorities, the Sponsor or its representative(s). 
13. 
ETHICAL, FINANCIAL, AND REGULATORY CONSIDERATIONS 
This research study will be conducted according to the standards of Good Clinical Practice 
outlined in the ICH E6 Tripartite Guideline and CFR Title 21 part 312, applicable government 
regulations, institutional research policies and procedures and any other local applicable 
regulatory requirement(s). 
13.1 
Institutional Review Board approval 
The clinical study protocol, informed consent form, Investigator’s Brochure, available safety 
information, patient documents (e.g., study diary), patient recruitment procedures (e.g., 
advertisements), information about payments (i.e., Principal Investigator payments) and 
compensation available to the patients, and documentation evidencing the Principal 
Investigator’s qualifications should be submitted to the IRB/EC for ethical review and approval 
if required by local regulations, prior to the study start. 
The Principal Investigator/Sponsor and/or designee will follow all necessary regulations to 
ensure appropriate, initial, and on-going IRB study review.  The Principal Investigator/Sponsor 
(as appropriate) must submit and, where necessary, obtain approval from the IRB for all 
subsequent protocol amendments and changes to the informed consent document.  Investigators 
will be advised by the Sponsor or designee whether an amendment is considered substantial or 
non-substantial and whether it requires submission for approval or notification only to an 
IRB/EC. 
Safety updates for elotuzumab will be prepared by the Sponsor or its representative as required 
for distribution to the Investigators and submission to the relevant IRB. 
13.2 
Regulatory approval 
As required by local regulations, the Sponsor will ensure all legal aspects are covered, and 
approval of the appropriate regulatory bodies obtained, prior to study initiation.  If required, the 


 
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Sponsor will also ensure that the implementation of substantial amendments to the protocol and 
other relevant study documents happen only after approval by the relevant regulatory authorities. 
13.3 
Informed consent 
Informed consent is a process by which a patient voluntarily confirms his or her willingness to 
participate in a particular study after having been informed of all aspects of the study that are 
relevant to the patient's decision to participate.  Informed consent is documented by means of a 
written, signed, and dated ICF. 
The ICF will be submitted for approval to the IRB that is responsible for review and approval of 
the study.  Each consent form must include all of the relevant elements currently required by the 
FDA, as well as local county authority or state regulations and national requirements. 
Before recruitment and enrollment into the study, each prospective candidate will be given a full 
explanation of the research study.  Once the essential information has been provided to the 
prospective candidate, and the Investigator is sure that the individual candidate understands the 
implications of participating in this research study, the candidate will be asked to give consent to 
participate in the study by signing an ICF.  A notation that written informed consent has been 
obtained will be made in the patient’s medical record.  A copy of the ICF, to include the patient’s 
signature, will be provided by the investigator to the patient. 
If an amendment to the protocol substantially alters the study design or the potential risks to the 
patients, the patient’s consent to continue participation in the study should be obtained. 
13.3.1 
Confidentiality 
13.3.1.1 Patient confidentiality 
Confidentiality of patients’ personal data will be protected in accordance with the Health 
Insurance Portability and Accountability Act of 1996 (HIPAA).  HIPAA regulations require that, 
in order to participate in the study, a patient must sign an authorization form for the study that he 
or she has been informed of following: 
 What protected health information (PHI) will be collected from patients in this study 
 Who will have access to that information and why 
 Who will use or disclose that information 
 That health information may be further disclosed by the recipients of the information, and 
that if the information is disclosed the information may no longer be protected by federal 
or state privacy laws 
 The information collected about the research study will be kept separate from the 
patient’s medical records, but the patient will be able to obtain the research records after 
the conclusion of the study 
 Whether the authorization contains an expiration date 
 The rights of a research patient to revoke his or her authorization 


 
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In the event that a patient revokes authorization to collect or use his or her PHI, the investigator, 
by regulation, retains the ability to use all information collected prior to the revocation of patient 
authorization.  For patients that have revoked authorization to collect or use PHI, attempts should 
be made to obtain permission to collect at least vital status (i.e., that the patient is alive) at the 
end of their scheduled study period. 
In compliance with ICH GCP guidelines and applicable parts of 21 CFR it is a requirement that 
the investigator and institution permit authorized representatives of the Sponsor, the regulatory 
authorities and the IRB direct access to review the patient’s original medical records at the site 
for verification of study-related procedures and data. 
Measures to protect confidentiality include: only a unique study number and initials will identify 
patients in the eCRF or other documents submitted to the Sponsor.  This information, together 
with the patient’s date of birth, will be used in the database for patient identification.  Patient 
names or addresses will not be entered in the eCRF.  No material bearing a patient’s name will 
be kept on file by Sponsor.  Patients will be informed of their rights within the ICF. 
13.3.1.2 Investigator and staff information 
Personal data of the Investigators and sub-Investigators may be included in the Sarah Cannon 
Development Innovations database, and shall be treated in compliance with all applicable laws 
and regulations.  When archiving or processing personal data pertaining to the investigator or 
sub-Investigator, Sarah Cannon Development Innovations shall take all appropriate measures to 
safeguard and prevent access to this data by any unauthorized party. 
13.4 
Financial information 
The finances for this clinical study will be subject to a separate written agreement between Sarah 
Cannon Development Innovations, LLC and applicable parties.  Any Investigator financial 
disclosures as applicable to 21CFR Part 54 shall be appropriately provided. 
14. 
RESEARCH RETENTION AND DOCUMENTATION OF THE STUDY 
14.1 
Amendments to the protocol 
Amendments to the protocol shall be planned, documented, and signature authorized prior to 
implementation. 
If an amendment to the protocol is required, the amendment will be originated and documented 
by the Sponsor, or its representatives.  All amendments require review and approval of Bristol-
Myers Squibb and the Study Chair supporting the study.  The written amendment must be 
reviewed and approved by the Sponsor, and submitted to the IRB at the Investigator’s facility for 
the board’s approval. 
Amendments specifically involving change to study design, risk to patient, increase to dosing or 
exposure, patient number increase, or addition or removal of new tests or procedures shall be 
reviewed and approved by the IRB of record for the Investigator’s facility. 
The amendment will be submitted formally to the FDA or other regulatory authorities by the 
Sponsor, as applicable, and IRB approval obtained, specifically when an increase to dosing or 


 
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patient exposure and/or patient number has been proposed; or, when the addition or removal of 
an Investigator is necessitated. 
Items requiring a protocol amendment approval from the IRB and/or FDA or other regulatory 
authorities include, but are not limited to, the following: 
 Change to study design 
 Risk to patient 
 Increase to dose or patient exposure to drug 
 Patient number increase 
 Addition or removal of tests and/or procedures 
 Addition/removal of a new Investigator 
It should be further noted that, if an amendment to the protocol substantially alters the study 
design or the potential risks to the patients, their consent to continue participation in the study 
should be obtained. 
14.2 
Documentation required to initiate the study 
Before the study may begin certain documentation required by FDA regulations and ICH GCP 
must be provided by the Investigator.  The required documentation should be submitted to: 
Sarah Cannon Development Innovations 
Regulatory Department 
1100 Charlotte Avenue, Suite 800 
Nashville, TN  37203 
Documents at a minimum required to begin a study in the US include, but are not limited to, the 
following: 
 A signature-authorized protocol and contract 
 A copy of the official IRB/EC approval of the study and the IRB/EC members list 
 Current Curricula Vitae for the Principal Investigator and any associate Investigator(s) 
who will be involved in the study 
 Indication of appropriate accreditation for any laboratories to be used in the study and a 
copy of the normal ranges for tests to be performed by that laboratory 
 Original Form FDA 1572 (Statement of Investigator), appropriately completed and 
signed 
 A copy of the IRB-approved consent form (and patient information sheet, if applicable) 
containing permission for audit by representatives of  Sarah Cannon Development 
Innovations, the IRB, and the FDA and other regulatory agencies (as applicable) 
 Financial disclosure forms for all Investigators listed on Form FDA 1572 (if applicable) 


 
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 Site qualification reports, where applicable 
 Verification of Principal Investigator acceptability from local and/or national debarment 
list(s). 
14.3 
Study documentation and storage 
The Principal Investigator must maintain a list of appropriately qualified persons to whom he/she 
has delegated study duties and should ensure that all persons assisting in the conduct of the study 
are informed of their obligations.  All persons authorized to make entries and/or corrections on 
the eCRFs are to be included on this document.  All entries in the patient’s eCRF are to be 
supported by source documentation where appropriate. 
Source documents are the original documents, data, records, and certified copies of original 
records of clinical findings, observations, and activities from which the patient’s eCRF data are 
obtained.  These can include, but are not limited to, hospital records, clinical and office charts, 
laboratory, medico-technical department and pharmacy records, diaries, microfiches, ECG 
traces, copies or transcriptions certified after verification as being accurate and complete, 
photographic negatives, microfilm or magnetic media, X-rays, and correspondence. 
The Principal Investigator and each study staff member are responsible for maintaining a 
comprehensive and centralized filing system (e.g., regulatory binder or investigator study file 
[ISF]) of all study-related (essential) documentation, suitable for inspection at any time by 
representatives from the Sponsor and/or applicable regulatory authorities.  The ISF must consist 
of those documents that individually or collectively permit evaluation of the conduct of the study 
and the quality of the data produced.  The ISF should contain as a minimum all relevant 
documents and correspondence as outlined in ICH GCP Section 8 and 21 CFR Part 312.57, 
including key documents such as the Investigator’s Brochure and any amendments, protocol and 
any amendments, signed ICFs, copies of completed eCRFs, IRB approval documents, Financial 
Disclosure forms, patient identification lists, enrollment logs, delegation of authority log, staff 
qualification documents, laboratory normal ranges, and records relating to the study drug 
including accountability records.  Drug accountability records should, at a minimum, contain 
information regarding receipt, shipment, and disposition.  Each form of drug accountability 
record, at a minimum, should contain Principal Investigator name, date drug shipped/received, 
date, quantity, and batch/code or lot number for identity of each shipment.  In addition, all 
original source documents supporting entries in the eCRF must be maintained and be readily 
available. 
The Sponsor shall maintain adequate investigational product records and financial interest 
records as per 21CFR Part 54.6 and Part 312.57 for no less than 2 years after the last marketing 
application has been approved by the FDA; or, in the event that the marketing application has not 
been approved by the FDA, for no less than 2 years after the last shipment/delivery of the drug 
for investigational use is discontinued and the FDA has been notified of the discontinuation. 
The IRB shall maintain adequate documentation/records of IRB activities as per 21CFR Part 
56.115 for at least 3 years after completion of the research. 
The Investigator shall maintain adequate records of drug disposition, case histories, and any 
other study-related records as per 21 CFR Part 312.62 for no less than 2 years after the last 


 
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marketing application has been approved by the FDA; or, in the event that the marketing 
application has not been approved by the FDA, for no less than 2 years after the last 
shipment/delivery of the drug for investigational use is discontinued and the FDA has been 
notified of the discontinuation. 
To enable evaluations and/or audits from regulatory authorities or from the Sponsor or its 
representative, the investigator additionally agrees to keep records, including the identity of all 
participating patients (sufficient information to link records e.g., eCRFs, medical records); all 
original, signed ICFs; and copies of all eCRFs, SAE Reporting forms, source documents, 
detailed records of treatment disposition, and related essential regulatory documents.  The 
documents listed above must be retained by the investigator for as long as needed to comply with 
national and international regulations (generally 2 years after discontinuing clinical development 
or after the last marketing approval).  Sponsor will notify the investigator(s)/institutions(s) when 
the study-related records are no longer required. 
If the investigator relocates, retires, or for any reason withdraws from the study, both the Sponsor 
and its representative should be prospectively notified.  The study records must be transferred to 
an acceptable designee, such as another investigator, another institution, or to the Sponsor.  The 
investigator must obtain the Sponsor’s written permission before disposing of any records, even 
if retention requirements have been met.  All study files will be maintained by the Sponsor 
(Sarah Cannon Development Innovations) throughout the study, and will be held by the Sponsor 
at the conclusion of the study. 
14.4 
Data collection 
The study eCRF is the primary data collection instrument for the study.  Case report forms will 
be completed using the English language and should be kept current to enable the Sponsor to 
review the patients’ statuses throughout the course of the study. 
In order to maintain confidentiality, only study number, patient number, initials and date of birth 
will identify the patient in the eCRF.  If the patient’s name appears on any other document (e.g., 
laboratory report), it must be obliterated on the copy of the document to be supplied to Sarah 
Cannon Development Innovations and replaced instead with the patient number and patient’s 
initials.  The investigator will maintain a personal patient identification list (patient numbers with 
corresponding patient identifiers) to enable records to be identified and verified as authentic.  
Patient data/information will be kept confidential, and will be managed according to applicable 
local, state, and federal regulations. 
All data requested in the eCRF must be supported by and be consistent with the patient’s source 
documentation.  All missing data must be explained.  When a required laboratory test, 
assessment, or evaluation has not been done or an “Unknown” box is not an option on the eCRF, 
a note should be created verifying that the field was “Not Done” or “Unknown.”  For any entry 
errors made, the error(s) must be corrected, and a note explaining the reason for change should 
be provided. 
The investigator will electronically sign and date the patient eCRF casebook indicating that the 
data in the eCRF has been assessed.  Each completed eCRF will be signed and dated by the 
Principal Investigator, once all data for that patient is final. 


 
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14.5 
Disclosure and publication policy 
All information provided regarding the study, as well as all information collected/documented 
during the course of the study, will be regarded as confidential.  The Sponsor reserves the right 
to release literature publications based on the results of the study.  Results from the study will be 
published/presented as per the Sponsor’s publication process. 


 
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15. 
REFERENCES 
Arastu-Kapur et al 2008 
Arastu-Kapur S, Shenk K, Parlati F, et al. Non-proteasomal targets of proteasome inhibitors 
bortezomib and carfilzomib. Blood (ASH Annual Meeting Abstracts), Nov 2008;112: 2657. 
Clopper and Pearson 1934 
Clopper C and Pearson E S. The use of confidence or fiducial limits illustrated in the case of the 
binomial. Biometrika 1934;26:404–13. doi:10.1093/biomet/26.4.404. 
Dimopoulos et al 2007 
Dimopoulos M, Spencer A, Attal M, et al. Lenalidomide plus dexamethasone for relapsed or 
refractory multiple myeloma. N Engl J Med 2007; 357(21):2123-32. 
Elotuzumab 2014 
Elotuzumab (BMS-901608) Investigator Brochure, Edition 10, 28 July 2014, Bristol-Myers 
Squibb Research and Development, Lawrenceville, NJ. 
EMPLICITI 
EMPLICITI Prescribing Information.  http://packageinserts.bms.com/pi/pi_empliciti.pdf 
Howlader et al 2014 
Howlader N, Noone AM, Krapcho M, et al (eds). SEER Cancer Statistics Review, 1975-2011, 
National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2011/, based on 
November 2013 SEER data submission, posted to the SEER web site, April 2014. 
Hsi et al 2008 
Hsi ED, Steinle R, Balasa B, et al. CS1, a potential new therapeutic antibody target for the 
treatment of multiple myeloma. Clin Cancer Res 2008;14(9):2775-84. 
Kirk et al 2008 
Kirk CJ, Jiang J, Muchamuel T, et al. The selective proteasome inhibitor carfilzomib is well 
tolerated in experimental animals with dose intensive administration. Blood (ASH Annual 
Meeting Abstracts), Nov 2008;112: 2765. 
Kumar et al 2008 
Kumar SK, Rajkumar SV, Dispenzieri A, et al. Improved survival in multiple myeloma and the 
impact of novel therapies. Blood. 2008;111(5):2516-20. 
Lonial et al 2012 
Lonial S, Vij R, Harousseau JL, Facon T, Moreau P, Mazumder A, et al. Elotuzumab in 
Combination With Lenalidomide and Low-Dose Dexamethasone in Relapsed or Refractory 
Multiple Myeloma. J Clin Oncology. 2012;30(16):1953-9. 
Lonial et al 2015 
Lonial S, Dimopoulos M, Palumbo A, White D, Grosicki S, Spicka I, et al. Elotuzumab Therapy 
for Relapsed or Refractory Multiple Myeloma. N Engl J Med. 2015;373:621-31. 
Palumbo and Anderson 2011 
Palumbo A and Anderson K. Multiple myeloma. N Engl J Med 2011;364:1046-60. 


 
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Palumbo et al 2014 
Palumbo A, Cavallo F, Gay F, Di Raimondo F, Yehuda DB, Petrucci MT, et al. Autologous 
transplantation and maintenance therapy in multiple myeloma.  N Engl J Med 2014; 371;895-
905. 
Richardson et al 2015 
Richardson PG, Jagannath S, Moreau P, Jakubowiak AJ, Raab MS, Facon T, et al. Elotuzumab 
in combination with lenalidomide and dexamethasone in patients with relapsed multiple 
myeloma: final phase 2 results from the randomised, open-label, phase 1b-2 dose-escalation 
study. Lancet Haematol. 2015;2(12):e516-27. 
Weber et al 2007 
Weber DM, Chen C, Niesvizky R, et al. Lenalidomide plus dexamethasone for relapsed multiple 
myeloma in North America. N Engl J Med 2007;357(21):2133-42. 
Zonder et al 2012 
Zonder JA, Mohrbacher AF, Singhal S, van Rhee F, Bensinger WI, Ding H, et al. A phase 1, 
multicenter, open-label, dose escalation study of elotuzumab in patients with advanced multiple 
myeloma. BLOOD, 2012;120(3):552-9. 
 


 
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16. 
APPENDICES 
Appendix A: Response Criteria for Multiple Myeloma 
 
International Myeloma Working Group (IMWG) Criteria1,2 
Response Category 
Definition  
sCR 
Stringent Complete 
Response 
CR criteria as defined below AND 
 
Normal free light chain (FLC) ratio AND 
 
Absence of clonal PCs by immunochistochemistry or 2-to 4-color flow 
cytometry 
CR 
Complete Response 
 
Negative immunofixation on the serum and urine AND 
 
Disappearance of any soft tissue plasmacytoma(s)AND 
 
<5% plasma cells in bone marrowb. 
 
In case the only measurable disease in a patient with CR at baseline is the 
serum FLC level, a normal FLC ratio of 0.26 to 1.65 is required 
additionally to qualify for CR. 
VGPR 
Very Good Partial 
Response 
 
Serum and urine M-protein detectable by immunofixation but not by 
electrophoresis (PEP) or ≥90% reduction from baseline serum AND urine 
M-protein level <100 mg/ 24 hours 
AND 
 
In case of presence of soft tissue plasmacytoma(s) at baseline, 
disappearance of any soft tissue plasmacytomas 
In case the only measurable disease in a patient with VGPR at baseline is the 
serum FLC level (i.e. no measurable disease in serum and urine PEP), a 
decrease of > 90% in the difference between involved and uninvolved FLC 
levels from baseline is required. 
PR 
Partial Response 
≥50% reduction from baseline in serum M-protein 
AND 
≥90% reduction from baseline in 24h urinary M-protein OR  
urine M-protein <200 mg/24 hours 
 
If serum and urine M-protein are non-measureable at baseline, a >50% 
reduction form baseline in the difference between involved and uninvolved 
FLC levels is required in place of the M-protein criteria. 
If serum and urine M-protein are non-measurable, and serum free light assay 
is also non-measurable, >50% reduction from baseline in percent plasma cells 
in bone marrow is required instead of M-protein measurement, provided 
baseline plasma cells in bone marrow was >30%.  
AND 
In case of presence of soft tissue plasmacytoma(s) at baseline, a reduction in 


 
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the SPD by >50% is required. 
 


 
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Appendix A: International Myeloma Working Group Uniform Response Criteria: 
Complete Response and Other Response Categories (continuation) 
SD  
Not meeting criteria for sCR, CR, VGPR, PR or PD 
PDc  
Progressive Disease 
Increase of  ≥ 25% from the nadir in at least one of the following 
criteria: 
 
serum M-protein (absolute increase must be ≥0.5 g/dL and absolute 
value must be ≥1 g/dL) 
 
urine M-protein (absolute increase must be ≥200 mg/24h) 
 
only in patients with non-measurable serum and urine M-protein 
levels: difference in involved and uninvolved FLC levels (absolute 
increase must be >10 mg/dL) 
 
only in patients with non-measurable serum and urine M-protein 
levels and non-measurable disease by FLC levels, bone marrow 
plasma cell percentage (absolute % must be ≥10%) 
OR 
 
definite development of new lytic bone lesions or increase from 
baseline in size of lytic bone lesion(s) 
OR 
 
development of new soft tissue plasmacytoma(s) or definite increase 
from nadir in existing soft tissue plasmacytomas 
OR 
 
development of hypercalcemia (corrected serum calcium 
>11.5 mg/dL) for patients without hypercalcemia at baseline. In case 
of preexisting hypercalcemia at baseline, PD will only be assessed 
due to the hypercalcemia criterion in case the corrected serum 
calcium level was ≤11.5 mg/dL post-baseline and increased thereafter 
beyond 11.5 mg/dL. 
 


 
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Additional Response Criteria for Specific Disease States (adopted from the European 
Group for Blood and Marrow Transplantation [EBMT] Criteria)1,2,3,4 
MR 
Minor response in 
patients with 
relapsed and 
refractory myeloma 
 
≥25% but ≤49% reduction of serum M protein and reduction in 24-
hour urine M-protein by 50-89% 
AND 
 
If present at baseline, 25-49% reduction in the size of sort tissue 
plasmacytomas is also required 
 
No increase in size or number of lytic bone lesions (development of 
compression fracture does not exclude response 
nCR 
Near Complete 
Response 
 
The absence of myeloma protein on electrophoresis, with positive 
immunofixation, stable bone disease, and a normal serum calcium 
concentration. 
Immunophenotypic 
CR 
 
Stringent CR 
AND 
 
Absence of phenotypic abarrent PC (clonal) in bone marrow with a 
minimum of one million of total BM cells analyzed by 
multiparametric flow cytometry (with ≥4 colors). 
Molecular CR 
 
Stringent CR 
AND 
 
Negative ASO-PCR (sensitivity 10-5) 
a   All response categories require two consecutive assessments made at any time before the institution of any new therapy; all categories also 
require no known evidence of progressive or new bone lesions if radiographic studies were performed. Radiographic studies are not required 
to satisfy these response requirements. 
b   Confirmation with repeat bone marrow biopsy not needed. 
c    At any point in this treatment, patients suspected of PD will have response assessed again to confirm disease progression (i.e. 2 sets of 
response assessments at least 1 week apart). The outcomes will be reviewed by the study chair before the patient is removed from the study 
 


 
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Appendix B: Diagnostic Criteria and Staging for Multiple Myeloma 
This appendix contains both 2011 IMWG criteria and 2014 IMWG criteria.  Please note the set 
of criteria used in the eCRF. 
International Myeloma Working Group Criteria for Diagnosis (2011) 
The following criteria must be met, except as noted: 
 clonal bone marrow plasma cells ≥10% 
 presence of serum and/or urinary monoclonal protein (except in patients with non-
secretory multiple myeloma*) and  
 evidence of end-organ damage, which can be attributed to the underlying plasma cell 
proliferative disorder, specifically: 
- hypercalcemia: serum calcium ≥11.5 mg/dL 
- renal insufficiency: serum creatinine >2 mg/dL  
- anemia: normochromic, normocytic with a hemoglobin value of >2 g/dL below 
the lower limit of normal or, a hemoglobin value of <10 g/dL 
- bone lesions: lytic lesions, severe osteopenia or pathologic fractures  
*More than 10% clonal plasma cells are required for the diagnosis of nonsecretory myeloma 
Dimopoulos., et al., Consensus recommendations for standard investigative workup:  report of the International 
Myeloma Workshop Consensus Panel 3. 2011 Blood J 117: 4701-4705 


 
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Revised International Myeloma Working Group Criteria for Diagnosis (2014) 
 
Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos MV, et al. International Myeloma 
Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014;15(12):e538-48. 
A: 
Durie and Salmon Staging System 
Stage I 
All of the following: 
 Hemoglobin >10 g/dL 
 Serum calcium <12 mg/dL 
 Normal bone structure or solitary plasmacytoma on radiographs 
 Low M component  
- IgG <5 g/dL 
- IgA <3 g/dL 
- Urine light chains <4 g/24 hours 
Stage II 
Fitting neither Stage I nor Stage III 
Stage III 
One or more of the following: 
 Hemoglobin <8.5 g/dL 
 Serum calcium >12 mg/dL 


 
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 Advanced lytic bone lesions 
 Hyper M component 
- IgG >7 g/dL 
- IgA >5 g/dL 
- Urinary light-chain excretion >12 g/24 hours 
Subclassification 
A:  serum creatinine <2.0 mg/dL 
B:  serum creatinine equal to or >2.0 mg/dL 
 
B: 
International Staging System (ISS) for Myeloma 
Stage I Serum ß2-microglobulin <3.5 mg/L 
 
 
Serum albumin ≥3.5 g/dL 
Stage II 
Fitting neither Stage I nor III* 
Stage III 
Serum ß2-microglobulin ≥5.5 mg/L 
There are two categories for Stage II:  serum ß2-microglobulin <3.5 mg/L but serum albumin 
<3.5 g/dL; or serum ß2-microglobulin ≥3.5 mg/L and <5.5 mg/L irrespective of the serum 
albumin level. 
Greipp P., et al., International staging system for multiple myeloma. 2005. JCO 23:3412-3420 


 
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Appendix C: ECOG and Karnofsky Performance Status Scales 
 
ECOG Performance Status Scale 
 
Karnofsky Performance Scale 
Grade 
Descriptions 
Percent 
Description 
0 
Normal activity. Fully active, able to carry 
on all pre-disease performance without 
restriction. 
 
100 
Normal, no complaints, no evidence of 
disease. 
 
90 
Able to carry on normal activity; minor 
signs or symptoms of disease. 
1 
Symptoms, but ambulatory.  Restricted in 
physically strenuous activity, but 
ambulatory and able to carry out work of a 
light or sedentary nature (e.g., light 
housework, office work). 
 
80 
Normal activity with effort; some signs or 
symptoms of disease. 
 
70 
Cares for self, unable to carry on normal 
activity or to do active work. 
2 
In bed <50% of the time.  Ambulatory and 
capable of all self-care, but unable to carry 
out any work activities.  Up and about more 
than 50% of waking hours. 
 
60 
Requires occasional assistance, but is able 
to care for most of his/her needs. 
 
50 
Requires considerable assistance and 
frequent medical care. 
3 
In bed >50% of the time.  Capable of only 
limited self-care, confined to bed or chair 
more than 50% of waking hours. 
 
40 
Disabled, requires special care and 
assistance 
 
30 
Severely disabled, hospitalization 
indicated.  Death no imminent. 
4 
100% bedridden.  Completely disabled.  
Cannot carry on any self-care.  Totally 
confined to bed or chair. 
 
20 
Very sick, hospitalization indicated.  Death 
not imminent. 
 
10 
Moribund, fatal processes progressing 
rapidly. 
5 
Dead 
0 
Dead 


 
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Appendix D: New York Heart Association (NYHA) Classification of Cardiac Disease 
 
The following table presents the NYHA classification of cardiac disease. 
Class 
Functional Capacity 
Objective Assessment 
I 
Patients with cardiac disease but without resulting limitations of physical 
activity.  Ordinary physical activity does not cause undue fatigue, 
palpitation, dyspnea, or anginal pain. 
No objective evidence of 
cardiovascular disease. 
II 
Patients with cardiac disease resulting in slight limitation of physical 
activity.  They are comfortable at rest.  Ordinary physical activity results in 
fatigue, palpitation, dyspnea, or anginal pain. 
Objective evidence of 
minimal cardiovascular 
disease. 
III 
Patients with cardiac disease resulting in marked limitation of physical 
activity.  They are comfortable at rest.  Less than ordinary activity causes 
fatigue, palpitation, dyspnea, or anginal pain. 
Objective evidence of 
moderately severe 
cardiovascular disease. 
IV 
Patients with cardiac disease resulting in inability to carry on any physical 
activity without discomfort.  Symptoms of heart failure or the anginal 
syndrome may be present even at rest.  If any physical activity is undertaken, 
discomfort is increased. 
Objective evidence of 
severe cardiovascular 
disease. 
Source:  The Criteria Committee of New York Heart Association.  Nomenclature and Criteria for Diagnosis of 
Diseases of the Heart and Great Vessels.  9th Ed. Boston, MA:  Little, Brown & Co; 1994:253-256. 


 
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Appendix E: Guidelines for Female Patients of Childbearing Potential and Fertile Male 
Patients 
Females of reproductive potential must have 2 negative pregnancy tests prior to initiating 
therapy.  The first test should be performed within 10 to 14 days, and the second test within 
24 hours prior to administration of study therapy and then weekly during the first month, then 
monthly thereafter in women with regular menstrual cycles or every 2 weeks in women with 
irregular menstrual cycles. 
Acceptable Contraception Methods: 
Women of childbearing potential, defined as all women physiologically capable of becoming 
pregnant, must use highly effective contraception for at least 4 weeks before beginning study 
therapy, during therapy, during dose interruptions, and for 4 weeks following discontinuation 
of study therapy. 
Highly effective contraception is defined as either: 
True Abstinence 
When this is in line with the preferred and usual lifestyle of the patient. 
Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-
ovulation methods) and withdrawal are not acceptable methods of 
contraception. 
Sterilization  
When a woman of childbearing potential has had surgical bilateral 
oophorectomy (with or without hysterectomy) or tubal ligation at least 
six weeks prior to study entry.  In case of oophorectomy alone, only 
when the reproductive status of the woman has been confirmed by 
follow up hormone level assessment. 
Male Partner Sterilization When the appropriate post-vasectomy documentation of the 
absence of sperm in the ejaculate. 
Use of a combination of any two of the following (one from a + one from b): 
a) Placement of an intrauterine device (IUD) or intrauterine system (IUS) 
b)  Barrier methods of contraception: Condom or Occlusive cap (diaphragm or 
cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository. 
Lenalidomide is present in the semen of patients receiving the drug.  Fertile male patients, 
defined as all males physiologically capable of conceiving offspring, with female partners of 
child-bearing potential must always use a latex or synthetic condom during any sexual contact 
with females of reproductive potential while taking lenalidomide, during dose interruptions, 
and for 4 weeks after discontinuing lenalidomide, even if they have undergone a successful 
vasectomy.  Male patients taking lenalidomide must not donate sperm. 


 
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The following are acceptable forms of barrier contraception: 
 Latex condom, diaphragm or cervical/vault cap when used with spermicidal 
foam/gel/film/cream/suppository 
Unacceptable Contraception Methods: for women of childbearing potential include: 
 IUD progesterone T 
 Female condom 
 Natural family planning (rhythm method) or breastfeeding 
 Fertility awareness 
 Withdrawal 
 Cervical shield 
Pregnancies 
If pregnancy does occur during treatment, lenalidomide must be discontinued immediately. 
To ensure patient safety, each pregnancy in a patient on study treatment must be reported to 
the Sarah Cannon Development Innovations Safety Department within 24 hours of 
learning of its occurrence using the pregnancy form at the end of this appendix.  The 
pregnancy should be followed up for 3 months after the termination of the pregnancy to 
determine outcome, including spontaneous or voluntary termination, details of the birth, and 
the presence or absence of any birth defects, congenital abnormalities, or maternal and/or new-
born complications.  Pregnancy follow-up should be recorded on the same form and should 
include an assessment of the possible relationship to the study drug of any pregnancy outcome.  
Any SAE experienced during pregnancy must be reported on the SAE Report Form. 
Pregnancy outcomes must be collected for the female partners of any males who took study 
treatment in this study.  Consent to report information regarding these pregnancy outcomes 
should be obtained from the mother. 
Women Not of Childbearing Potential are defined as Follows: 
 Women are considered post-menopausal and not of childbearing potential if they have had 
12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., 
age appropriate, history of vasomotor symptoms). 
 Women who are permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral 
salpingectomy, bilateral oophorectomy). 
 Women who are >45 years-of-age, not using hormone-replacement therapy and who have 
experienced total cessation of menses for at least 12 months OR who have a follicle 
stimulating hormone (FSH) value >40 mIU/mL and an estradiol value <40 pg/mL 
(140 pmol/L). 
 Women who are >45 years-of-age, using hormone-replacement therapy and who have 
experienced total cessation of menses for at least 1 year OR who have had documented 


 
CONFIDENTIAL 
STUDY DRUG(S):  ELOTUZUMAB 
  
              SARAH CANNON DEVELOPMENT 
INNOVATIONS  
 
  
 
 
 
STUDY NUMBER:  MM 
61 
AMENDMENT 2 DATE:  07 DECEMBER 2016 
 
 
 
 
VERSION 3.0 
Page 90 of 96 
evidence of menopause based on FSH >40 mIU/mL and estradiol <40 pg/mL prior to 
initiation of hormone-replacement therapy. 


 
CONFIDENTIAL 
STUDY DRUG(S):  ELOTUZUMAB 
  
              SARAH CANNON DEVELOPMENT 
INNOVATIONS  
 
  
 
 
 
STUDY NUMBER:  MM 
61 
AMENDMENT 2 DATE:  07 DECEMBER 2016 
 
 
 
 
VERSION 3.0 
Page 91 of 96 
 
PREGNANCY FORM 
Date of Report (DD/MMM/YYYY):      
/
/
 
Investigative Site Name/ Number: 
Clinical Study Number/ Protocol: 
Patient Initial:  
    Patient Number:   
   
 
Patient Date of Birth (DD/MMM/YYYY):      
/
/
 
 
PREGNANCY TEST RESULT 
  N/A (Female, post-menopausal/ surgically sterile) 
Result 
Date of Test Result 
(DD/MMM/YYYY) 
 Negative          
 Positive        
 Not Done 
/
/
 
PREGNANCY  OUTCOME 
Date of Outcome (DD/MMM/YYYY):    
/
/
 
RESULT 
 Carried to Term  
 
 Spontaneous Abortion 
 
 Elected Abortion 
 Ectopic Pregnancy 
 
 Congenital Abnormality 
 
 Unknown 
MOTHER COMPLICATIONS 
Did the mother experience any complications during:  (check all that may apply) 
 
     
 Pregnancy         
 Labor/ Delivery        
 Postpartum 
 


 
CONFIDENTIAL 
STUDY DRUG(S):  ELOTUZUMAB 
  
              SARAH CANNON DEVELOPMENT 
INNOVATIONS  
 
  
 
 
 
STUDY NUMBER:  MM 
61 
AMENDMENT 2 DATE:  07 DECEMBER 2016 
 
 
 
 
VERSION 3.0 
Page 92 of 96 
If yes, please explain: 
_________________________________________________________________ 
 
Intervention: 
_________________________________________________________________________ 
 
Continuing:   
 Yes     
 No 
 
PREGNANCY/ FETAL  OUTCOME 
 Live Birth/ Full Term (>37 weeks)     
 
 Live Birth/ Premature (<37 weeks) 
 
 Live Birth and Neonatal Death   
 Spontaneous/ Missed Abortion, Gestational Age: 
____________ 
 
 Fetal Death in Utero/ Stillbirth, Gestational Age: 
_____________ 
 
 Post-Natal Death, Age:___________ 
Were congenital or chromosomal abnormalities detected?   
 Yes     
 No 
 
If yes, please specify: 
____________________________________________________________________ 
 
Completed by: ________________________________________________ Date: 
_____________________ 
Reviewed by: _________________________________________________ Date: 
_____________________ 
 


 
CONFIDENTIAL 
STUDY DRUG(S):  ELOTUZUMAB 
  
              SARAH CANNON DEVELOPMENT 
INNOVATIONS  
 
  
 
 
 
STUDY NUMBER:  MM 
61 
AMENDMENT 2 DATE:  07 DECEMBER 2016 
 
 
 
 
VERSION 3.0 
Page 93 of 96 
Appendix F: Neurotoxicity Questionnaire 
Instructions for Patients: By circling one (1) number per line, please indicate how true each 
statement has been for you during the past 7 days.  
 
Not at all 
A little 
bit 
Somewhat 
Quite a 
bit 
Very 
much 
I have numbness or tingling in my 
hands 
0 
1 
2 
3 
4 
I have numbness or tingling in my 
feet 
0 
1 
2 
3 
4 
I feel discomfort in my hands 
0 
1 
2 
3 
4 
I feel discomfort in my feet 
0 
1 
2 
3 
4 
I have joint pain or muscle cramps 
0 
1 
2 
3 
4 
I feel weak all over 
0 
1 
2 
3 
4 
I have trouble hearing 
0 
1 
2 
3 
4 
I get a ringing or buzzing in my ears 
0 
1 
2 
3 
4 
I have trouble buttoning buttons 
0 
1 
2 
3 
4 
I have trouble feeling the shape of 
small objects when they are in my 
hand 
0 
1 
2 
3 
4 
I have trouble walking 
0 
1 
2 
3 
4 
 
Instructions for Health Care Professionals 
This assessment tool is provided to help you evaluate peripheral neuropathy in patients 
receiving chemotherapy. There is no correlation between assessment scores and toxicity 
grades.  
 


 
 
 
Appendix G: Schedule of assessments MM 61 
ASSESSMENTS 
Screena 
ERd Induction 
Cycles 1 through 4 
End of 
Cycle 4 
thru 
Start of 
Mobili 
zation 
70-120 
Days 
Post 
Trans 
Planth 
 
ERd Consolidationv 
Cycles 6 through 8 
(Start 70 to 120 
days Following 
ASCT) 
End of 
Cycle 8 
1 yr Post 
ASCT FU 
Visit 
ERd 
Mainten 
ance 
2 Years 
C 9+ 
End of 
Treat 
ment 
Visits 
Off Study 
FU 
Before 
PDt 
Off 
Study 
FU 
After 
PDu 
Days 
 
-28 to 1 
C 1&2 
C 3&4 
 
 
1 
 
15 
 
 
1 
 
 
 
1 
8 
15 
22 
1 
15 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Revlimid REMS® 
programb 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical historya 
X 
X 
 
 
 
X 
 
 
 
X 
 
 
X 
X 
 
 
Physical examinationa,c 
X 
X 
 
 
 
X 
 
 
X 
X 
 
 
X 
X 
X 
 
Peripheral neuropathy 
questionnairea 
X 
X 
 
 
 
X 
 
 
X 
X 
 
 
X 
X 
X 
 
Vital signsa,d 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
ECOG performance statusa 
X 
X 
 
 
 
X 
 
 
X 
X 
 
 
X 
X 
 
 
12-lead electrocardiograma 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AE and SAE evaluationse 
 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
 
CBC, 3-part diff and 
plateletsa 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
 
X 
X 
X 
 
CMP plus mag and phosa,f 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
 
X 
X 
X 
 
Coagulation testsa,g 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
LDH and uric acida 
X 
X 
 
 
 
X 
 
 
X 
X 
 
 
X 
X 
 
 
Serum or urine pregnancy 
test and counseling i 
X 
X 
X 
X 
X 
X 
X 
Xi 
X 
X 
X 
X 
X 
X 
 
 
C-reactive proteina 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Disease Assessments:  Restaging at the end of every cyclej 
UPEP and immunofixationj,k 
X 
Xj 
 
 
 
Xj 
 
X 
X 
Xj 
 
X 
Xo 
X 
X 
 
SPEP and immunofixationj,l 
X 
Xj 
 
 
 
Xj 
 
X 
X 
Xj 
 
X 
Xo 
X 
X 
 
Serum-free light chainj 
X 
Xj 
 
 
 
Xj 
 
X 
X 
Xj 
 
X 
Xo 
X 
X 
 
Serum β2-microglobulin 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Quantitative Igsj 
X 
Xj 
 
 
 
Xj 
 
X 
X 
Xj 
 
X 
Xo 
X 
X 
 
BM aspirate/biopsy 
Xm 
 
 
 
 
 
 
Xn 
Xn 
Xn 
 
Xn 
 
Xn 
 
 
Gene expression profilingm 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
MRD evaluationn 
X 
 
 
 
 
 
 
Xn 
Xn 
Xn 
 
Xn 
X 
Xn 
 
 
Plasmacytoma evaluationp 
X 
Xj 
 
 
 
Xj 
 
X 
X 
Xj 
 
X 
Xo 
X 
X 
 
Skeletal surveyq 
X 
 
 
 
 
 
 
 
X 
 
 
X 
 
Xq 
 
 
Survival status 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
X 
Study Drug Administration 
Elotuzumab 
 
X 
X 
X 
X 
X 
X 
 
 
X 
X 
 
X 
 
 
 
Lenalidomide 
 
1 thru 21 
 
1 thru 21 
 
 
1 thru 21 
 
1 thru 21 
 
 
 
Dexamethasone IVr 
 
X 
X 
X 
X 
X 
X 
 
 
X 
X 
 
X 
 
 
 
Dexamethasone Oral 
 
X 
X 
X 
X 
1, 8, 15 & 22 
 
 
X 
X 
 
X 
 
 
 
Study drug compliance 
 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
 


 
 
Appendix G: Schedule of Assessments (continued) 
 
a 
Baseline procedures including medical history, physical examination (including a neurological evaluation and a peripheral neuropathy questionnaire), 
ECOG performance status, 12-lead ECG, CBC, CMP plus magnesium and phosphorus, prothrombin time (PT)/activated partial thromboplastin time 
(aPTT)/and International Normalized Ratio (INR), LDH and uric acid, and c-reactive protein (CRP) should be done ≤7 days prior to initiation of treatment.  
However, if these initial examinations are obtained within 72 hours of Cycle 1 Day 1, they do not have to be repeated. 
b 
Lenalidomide must be prescribed through and in compliance with the Revlimid REMS® program of Celgene Corporation.  Prescriptions must be filled 
within 7 days.  Consideration should be given to prescribing lenalidomide 5 to 7 days in advance of Day 1 of each cycle to allow time for required patient 
and prescriber surveys and drug shipment to patient.  Any unused Revlimid® (lenalidomide) should be returned to the patient for disposition in accordance 
with the Revlimid REMS® program. 
c 
Physical examinations will include the measurement of height at the screening visit only.  Patients should be weighed within 24 hours prior to elotuzumab 
dosing on Day 1 of each cycle, in order to calculate the correct dose.  Measurement of weight is not required for visits occurring after completion of 
treatment.  All physical examinations should include an assessment of peripheral neuropathy (see Appendix F). 
d 
Vital signs will include resting heart rate, systolic and diastolic blood pressure readings, respiratory rate, and temperature. 
e 
All events will be recorded from first study treatment.  Non-serious AEs considered by the Investigator to be unrelated to study treatments will be collected 
for 30 days post last treatment, and non-serious AEs considered by the Investigator to be related to study treatments and all SAEs will be collected for 
60 days post last treatment. 
f 
CMP will include measurements of glucose, blood urea nitrogen, creatinine, sodium, potassium, chloride, calcium, CO2, ALP, AST, ALT, total bilirubin, 
total protein, albumin, magnesium, and phosphorus. 
g 
Coagulation tests:  PT, aPTT, and INR.  If normal at baseline, they do not need to be repeated.  Patients requiring the initiation of an anti-coagulation 
therapy during study treatment should have coagulation tests performed according to standard practice guidelines. 
h 
Standard of care 70 to 120 day post-transplant visit before start of the first consolidation cycle (Cycle 5) 
i 
Serum or urine pregnancy tests and pregnancy counseling are to be conducted in women of childbearing potential.  For definition of childbearing potential, 
see Appendix E.  Two serum or urine pregnancy tests must be performed; one 10 to 14 days prior to initiation of study treatment and one within 24 hours 
of initiation of study treatment.  Serum or urine pregnancy tests, including pregnancy counseling, for women of childbearing potential will continue 
weekly during Cycle 1, then monthly thereafter in women with regular menstrual cycles or every 2 weeks in women with irregular menstrual cycles.  For 
those with irregular menses, pregnancy tests are required at 14 and 28 days after treatment discontinuation of lenalidomide.  From the end of Cycle 4 thru 
the start of mobilization, pregnancy tests are not required, but women of child-bearing potential should be reminded to follow approved birth control 
practices while off study treatment. 
j 
Restage every cycle (4 weeks):  response will be evaluated after completion of 1 treatment cycle.  Thereafter, restaging must be done within a window of -
7 to Day 1 of the next cycle.  Disease assessments need only be done on Cycle 1 Day 1 if >14 days elapsed since baseline disease assessments. 
k 
24-hour urine total protein, urine protein electrophoresis (UPEP), and urine protein immunofixation.  For patients whose disease is being monitored 
through UPEP, additional post baseline 24-hour urine collections are required, as indicated. 
l 
Serum protein electrophoresis (SPEP):  obtain blood for M-protein levels measured by SPEP and quantitative immunoglobulins for those patients in whom 
SPEP are felt to be unreliable (IgA type multiple myeloma), depending upon which studies were positive at baseline. 
m 
Baseline bone marrow aspirate and biopsy are to be sent for flow cytometry, cytogenetics, and FISH for 1q amplification, 13 del, 1p del, t(4;14), t(11;14), 
t(14;16) and 17p del) per institutional guidelines.  Sample should also be used for gene expression profiling (GEP) per institutional guidelines.  Bone 
marrow aspirates/biopsies obtained ≤60 days prior to Cycle 1 Day 1 will be allowed. 
n 
Bone marrow aspirates should be collected as clinically indicated.  Anytime bone marrow is drawn for standard of care, such as 1-year and 2-years post-
transplant, MRD analysis should be conducted per institutional guidelines. 
o 
Beginning with Cycle 12 Day 1, restaging (SPEP, UPEP, plasmacytoma (if applicable), quantitative Igs [IgG, IgA, IgM], and SFLC) is to be conducted 
every 3 months during maintenance. 
p 
Plasmacytoma:  ONLY for patients with a known plasmacytoma that has been imaged before enrolling on study (to be done at baseline and every 2 cycles 
after that) 


 
 
q 
Skeletal survey or alternate imaging as per institutional guidelines:  should preferably be within 28 days of planned treatment start, but ≤60 days prior to 
Cycle 1 Day 1 is acceptable.  This assessment includes lateral radiograph of the skull, anteroposterior and lateral views of the spine, and anteroposterior 
views of the pelvis, ribs, femora, and humeri.    Skeletal survey need only be repeated if clinically indicated (i.e., bone pain). 
r 
Dexamethasone 8 mg IV is pre-medication on the day of elotuzumab infusion 45 to 90 minutes prior to the start of elotuzumab infusion (for all pre-
medications, see Section 5.1. 
s 
After patients are discontinued from the study, they will visit the study center ≤30 days from the date of last dose of study drug for end-of treatment-
assessments.  Patients must be followed for all AEs for 30 calendar days and for related AEs and SAEs for 60 calendar days after the last dose of study 
drug. 
t 
Patients who discontinue study treatment prior to the occurrence of disease progression will be followed every 3 months (±1 month ) for a total of up to 3 
years from initiation of treatment on the protocol or until they progress, whichever comes first. 
u 
Patients with documented disease recurrence or progression will be followed every 3 months (±1 month) for survival status (e.g., date and cause of death) 
for up to 3 years from initiation of treatment on the protocol or death, whichever comes first.  Patients may be contacted during outpatient visits or by 
telephone. 
v 
Cycle 5 Day 1 assessments need to be done only if >21 days elapsed between the Day 70 to 120 evaluation and start of consolidation.