A Phase II Study of Elotuzumab, Pomalidomide, & Dexamethasone (Elo-Pom-Dex) With Second Autologous Stem Cell Transplantation for Relapsed Multiple Myeloma
Phase: PHASE2
Conditions: Multiple Myeloma in Relapse
Sponsor: Washington University School of Medicine

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A Phase II Study of Elotuzumab, Pomalidomide, & Dexamethasone (Elo-Pom-Dex) with 
Second Autologous Stem Cell Transplantation for Relapsed Multiple Myeloma 
 
Washington University School of Medicine 
Division of Oncology 
660 South Euclid Avenue, Campus Box 8007 
St. Louis, MO  63110 
 
WUSM Protocol #:  201701084 
Bristol-Myers Squibb Protocol #: CA204-225 
Celgene Protocol #: PO-CL-MM-PI-008341   
 
Version Date: 01/19/2023 
 
 
Principal Investigator: 
Ravi Vij, M.D. 
 
 
 
 
Phone: (314) 454-8323 
 
 
 
 
E-mail: rvij@wustl.edu  
 
Sub-Investigators: 
 
Institution: 
 
 
 
Modality 
Christine Chen, M.D.  
Princess Margaret Cancer Centre 
Medical Oncology 
Jeffrey Matous, M.D.  
Sarah Cannon Research Institute 
Medical Oncology 
Ajay Nooka, M.D. 
 
Emory Winship Cancer Institute 
Medical Oncology 
Feng Gao, Ph.D. 
 
Washington University 
 
Biostatistics 
 
Study Drug(s): 
 
elotuzumab (Empliciti) 
pomalidomide (Pomalyst) 
dexamethasone (Decadron) 
 
Clinical Trials.gov# 
NCT03030261 
 
CONFIDENTIAL 
The information contained in this document is regarded as confidential and, except to the 
extent necessary to obtain informed consent, may not be disclosed to another party unless 
law or regulations require such disclosure.  Persons to whom the information is disclosed 
must be informed that the information is confidential and may not be further disclosed by 
them 
 
 

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A Phase II Study of Elotuzumab, Pomalidomide, & Dexamethasone (Elo-Pom-Dex) with 
Second Autologous Stem Cell Transplantation for Relapsed Multiple Myeloma 
 
Protocol Revision History 
 
Initial Approval Version 
 
 
 
 
 
 
01/26/17 
Amendment #1 Version 
 
 
 
 
 
 
09/25/18 
Amendment #2 Version 
 
 
 
 
 
 
03/18/19 
Amendment #3 Version 
 
 
 
 
 
 
08/07/19 
Amendment #4 Version 
 
 
 
 
 
 
02/13/20 
Amendment #5 Version 
 
 
 
 
 
 
06/16/20 
Amendment #6 Version 
 
 
 
 
 
 
11/12/20 
Amendment #7 Version 
 
 
 
 
 
 
01/19/23 

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A Phase II Study of Elotuzumab, Pomalidomide, & Dexamethasone (Elo-Pom-Dex) with 
Second Autologous Stem Cell Transplantation for Relapsed Multiple Myeloma 
 
Principal Investigator Signature Page 
 
 
Principal Investigator 
(printed): 
      
Name of Institution:       
  
 PI Signature  
 
 
 
 
Date 
 
By my signature, I agree to personally supervise the conduct 
of this study and to ensure its conduct in compliance with the 
protocol, informed consent, IRB/HRPO procedures, the 
Declaration of Helsinki, ICH Good Clinical Practices 
guidelines, and the applicable parts of the United States 
Code of Federal Regulations or local regulations governing 
the conduct of clinical studies. 
 
 
 
 

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A Phase II Study of Elotuzumab, Pomalidomide, & Dexamethasone with Second 
Autologous Stem Cell Transplantation for Relapsed Multiple Myeloma 
 
 
SCHEMA 
 
 
 

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Glossary of Abbreviations 
 
AE 
 
 
Adverse event 
ALT(SGPT)  
Alanine aminotransferase 
ASCT  
 
Autologous stem cell transplant 
AST(SGOT)  
Aspartate aminotransferase 
BMS  
 
Bristol-Myers Squibb 
C 
 
 
Celsius 
CBC  
 
Complete blood count 
CMP  
 
Comprehensive metabolic panel 
CNS  
 
Central nervous system 
CR 
 
 
Complete response 
CRF 
 
 
Case report form 
CRR  
 
Complete remission rates 
CT 
 
 
Computerized tomography 
D5W  
 
Dextrose 5% water 
dL 
 
 
Deciliter 
DOB  
 
Date of birth 
DSMC  
 
Data and safety monitoring committee 
EE 
 
 
Efficacy-evaluable 
EFS 
 
 
Event-free survival 
Elo-Pom-Dex or EPd  Elotuzumab, pomalidomide, and dexamethasone 
EOS 
 
 
End of study 
FCBP  
 
Female of childbearing potential 
FNCBP 
 
 
Female not of childbearing potential 
FDA  
 
Food and Drug Administration 
H&P  
 
History and phsycial  
HRPO  
 
Human Research Protection Office at Washington University 
IB 
 
 
Investigator’s brochure 
IEC 
 
 
Institutional ethics committee 
IMIDs  
 
Immunomodulatory imide drugs 
IRB 
 
 
Institutional review board 
ITT  
 
 
Intent-to-treat 
IV  
 
 
Intravenous 
KG  
 
 
Kilogram 
L  
 
 
Liter 
MG  
 
 
Milligram 
min  
 
 
Minute 
mL  
 
 
Milliliter 
MM   
 
Multiple myeloma 
µmol   
 
Millimole 
MRD   
 
Minimal residual disease 
MRI   
 
Magnetic resonance imaging 
ORR   
 
Overall response rate 
OS  
 
 
Overall survival 
PD  
 
 
Progressive disease 

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PET   
 
Positron emission tomography 
PFS  
 
 
Progression-free survival 
PPP  
 
 
Pregnancy prevention plan 
PR  
 
 
Partial response 
PS  
 
 
Performance status 
QASMC  
 
Quality Assurance and Safety Monitoring Committee 
SAE 
 
 
Serious adverse event 
sCR 
 
 
Stringent complete response 
SD  
 
 
Stable disease 
SPEP  
 
Serum protein electrophoresis 
SWFI  
 
Sterile Water for Injection 
UPEP  
 
Urine protein electrophoresis 
UPN  
 
Unique patient number 
VGPR   
 
Very good partial response 
VTE 
 
 
Venous thromboembolism 
WUSM 
 
Washington University School of Medicine 
 

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Table of Contents 
 
SCHEMA ........................................................................................................................................ 4 
1.0 
BACKGROUND AND RATIONALE ................................................................................ 9 
1.1 
Multiple Myeloma ............................................................................................................ 9 
1.2 
Autologous Stem Cell Transplant .................................................................................... 9 
1.3 
Elotuzumab..................................................................................................................... 10 
1.4 
Pomalidomide................................................................................................................. 10 
1.5 
Study Rationale .............................................................................................................. 10 
1.6 
Correlative Studies Rationale ......................................................................................... 10 
2.0 
OBJECTIVES .................................................................................................................... 11 
2.1 
Primary Objective .......................................................................................................... 11 
2.2 
Secondary Objectives ..................................................................................................... 11 
2.3 
Exploratory Objectives ................................................................................................... 11 
3.0 
PATIENT SELECTION .................................................................................................... 11 
3.1 
Inclusion Criteria ............................................................................................................ 11 
3.2 
Exclusion Criteria ........................................................................................................... 12 
3.3 
Inclusion of Women and Minorities............................................................................... 13 
3.4 
Retrospective Cohort ...................................................................................................... 13 
4.0 
REGISTRATION PROCEDURES ................................................................................... 14 
4.1 
Confirmation of Patient Eligibility ................................................................................. 14 
4.2 
Patient Registration in the Siteman Cancer Center OnCore Database ........................... 14 
4.3 
Assignment of UPN ....................................................................................................... 15 
5.0 
TREATMENT PLAN ........................................................................................................ 15 
5.1 
Overview ........................................................................................................................ 15 
5.2 
Elotuzumab Administration ........................................................................................... 15 
5.3 
Pomalidomide Administration ....................................................................................... 16 
5.4 
Dexamethasone Administration ..................................................................................... 17 
5.5 
Melphalan Conditioning and Stem Cell Transplantation ............................................... 17 
5.6 
General Concomitant Medication and Supportive Care Guidelines .............................. 18 
5.7 
Females of Childbearing Potential ................................................................................. 18 
5.8 
Duration of Therapy ....................................................................................................... 19 
5.9 
Duration of Follow-up .................................................................................................... 20 
6.0 
DOSE MODIFICATIONS ................................................................................................ 20 
6.1 
Dose Levels .................................................................................................................... 20 
6.2 
Dosing Modifications for Hematologic Toxicities......................................................... 21 
6.3 
Dosing Modifications for Non-Hematologic Toxicities ................................................ 23 
7.0 
STUDY CALENDAR ....................................................................................................... 27 
8.0 
CENTRAL LABS .............................................................................................................. 29 
8.1 
Future Research .............................................................................................................. 29 
9.0 
DATA SUBMISSION SCHEDULE ................................................................................. 29 
9.1 
Adverse Event Collection in the Case Report Forms ..................................................... 30 
10.0 MEASUREMENT OF EFFECT........................................................................................ 30 
10.1 Response Criteria ........................................................................................................... 30 
10.2 Event-Free Survival........................................................................................................ 33 
10.3 Progression-Free Survival .............................................................................................. 33 

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10.4 Overall Survival ............................................................................................................. 33 
10.5 Overall Response Rate ................................................................................................... 34 
10.6 Complete Response Rate ................................................................................................ 34 
11.0 REGULATORY AND REPORTING REQUIREMENTS ............................................... 34 
11.1 Reporting to the Human Research Protection Office (HRPO) at Washington University
 
34 
11.2 Reporting to the Quality Assurance and Safety Monitoring Committee (QASMC) at 
Washington University .............................................................................................................. 34 
11.3 Secondary Sites Reporting Requirements ...................................................................... 35 
11.4 Reporting to Secondary Sites ......................................................................................... 36 
11.5 Reporting to the FDA ..................................................................................................... 36 
11.6 Reporting to Bristol-Myers Squibb ................................................................................ 37 
11.7 Reporting to Celgene ...................................................................................................... 37 
11.8 Timeframe for Reporting Required Events .................................................................... 38 
11.9 Record Retention ............................................................................................................ 39 
12.0 DATA AND SAFETY MONITORING ............................................................................ 39 
13.0 STATISTICAL CONSIDERATIONS............................................................................... 40 
13.1 Determination of Sample Size........................................................................................ 40 
13.2 Data Analysis ................................................................................................................. 40 
13.3 Analysis Populations ...................................................................................................... 41 
13.4 Study Termination .......................................................................................................... 41 
14.0 AUDITING ........................................................................................................................ 42 
15.0 MULTICENTER REGULATORY REQUIREMENTS ................................................... 42 
17.0 REFERENCES .................................................................................................................. 44 
APPENDIX A: ECOG Performance Scale ................................................................................... 46 
APPENDIX B: Cockcroft-Gault Equation ................................................................................... 47 
APPENDIX C: Elotuzumab Preparation and Administration Guidelines .................................... 48 
APPENDIX D: Guidelines for Elotuzumab Infusion in Subjects with Infusion Reactions ......... 52 
APPENDIX E: Pomalidomide Pregnancy Prevention Plan for Subjects in Clinical Trials ......... 54 
1. 
Pomalidomide Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable 
Birth Control Methods .................................................................................................................. 55 
1.1. 
Risks Associated with Pregnancy .................................................................................. 55 
1.2. 
Counseling ...................................................................................................................... 55 
1.3. 
Contraception ................................................................................................................. 56 
1.4. 
Pregnancy Testing .......................................................................................................... 57 
1.5. 
Pregnancy Precautions for Pomalidomide Use .............................................................. 58 
2. 
Pomalidomide Education and Counseling Guidance Document for Female Subjects ...... 60 
2.1. 
Female of Childbearing Potential:.................................................................................. 60 
2.2. 
Female Not of Childbearing Potential (Natural Menopause for at Least 24 Consecutive 
Months, a Hysterectomy, or Bilateral Oophorectomy): ............................................................ 61 
3. 
Pomalidomide Education and Counseling Guidance Document for Male Subjects.......... 63 
4. 
Pomalidomide Information Sheet ...................................................................................... 65 
APPENDIX F: Definitions for Adverse Event Reporting ............................................................ 67 
G. 
Product Complaints ........................................................................................................ 68 
H. 
Medication Error ............................................................................................................ 68 
I. 
Pregnancies and Suspected Pregnancies ........................................................................ 68 

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APPENDIX G: Reporting Timelines ............................................................................................ 70 
APPENDIX H: Washington University SAE Reporting Cover Sheet ......................................... 75 
 
1.0 
BACKGROUND AND RATIONALE 
 
1.1 
Multiple Myeloma 
 
Multiple myeloma (MM) is a multifocal plasma cell neoplasm resulting from the clonal 
expansion of terminally differentiated B-cells. The disease is characterized by a serum or 
urine monoclonal protein and skeletal destruction with osteolytic lesions, bone pain, 
pathologic fractures, and hypercalcemia. Recurrent infections from depressed normal 
immunoglobulin production, renal dysfunction from light chain production, and anemia 
from generalized marrow involvement are also common. MM is the second most common 
hematological malignancy in the United States, accounting for more than 22,000 new cases 
and over 10,500 deaths in 2013. [1]  
 
1.2 
Autologous Stem Cell Transplant 
 
Treatment with high-dose chemotherapy and autologous stem cell transplant (ASCT) 
results in improved overall response rates (ORRs), complete remission (CR) rates, and 
progression-free survival (PFS) and overall survival (OS) compared with treatment with 
standard dose chemotherapy. [2] Recent studies have shown that lenalidomide 
maintenance therapy after ASCT further prolongs PFS. [3, 4] Despite the benefits of ASCT 
and lenalidomide maintenance, MM remains incurable, with the median PFS after ASCT 
of 41–46 months. [3, 4] 
 
For patients who relapse after ASCT, a second ASCT was historically a common salvage 
therapy. Second ASCT does improve PFS and OS compared to conventional salvage 
therapy [5, 6]. However, the PFS following second ASCT is limited and is generally less 
than 50% compared with that of the first ASCT. [7-11] In patients who fail ASCT with 
lenalidomide maintenance, the PFS following second ASCT are even more modest. We 
retrospectively reviewed 20 patients treated with second ASCT after initial ASCT with 
lenalidomide maintenance. The estimated median PFS was 13 months following second 
ASCT compared to 36 months following initial ASCT despite nearly all patients receiving 
maintenance therapy following second ASCT (unpublished data).  
 
Recent studies have looked to improve the outcomes following second ASCT using more 
intensive conditioning regimens, but none have yet shown improvement in response rate, 
PFS, or OS. [12-19] It is currently unknown if maintenance/continuation therapy following 
second ASCT will results in similar PFS gains as it does following initial ASCT. At the 
time of second ASCT, most patients have already failed proteasome inhibitors and 
immunomodulatory imide drugs (IMIDs) and thus novel regimens are needed for this 
indication.  
 
 
 

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1.3 
Elotuzumab 
 
Elotuzumab (Empliciti; BMS-901608; HuLuc63) is a humanized recombinant monoclonal 
IgG1 antibody product directed to human SLAMF7 (also known as CRACC and CS1), a 
cell surface glycoprotein highly expressed in myeloma cells. When added to lenalidomide 
and dexamethasone, elotuzumab is well tolerated and has been shown to increase response 
rates, PFS, and OS in patients with relapsed MM. Based on this, elotuzumab received FDA 
approval for this indication. However, the utility of the regimen is somewhat limited as 
many relapsed patients have previously failed lenalidomide, and in such patients, response 
is modest. Numerous clinical trials are currently ongoing utilizing elotuzumab in different 
regimens and different indications, such as continuation therapy.  
 
1.4 
Pomalidomide 
 
Pomalidomide, a second generation thalidomide analog with immunomodulatory 
properties like lenalidomide, was recently approved in combination with dexamethasone 
for use in subjects with refractory or relapsed and refractory MM who have failed 
bortezomib and lenalidomide.   
 
As lenalidomide and pomalidomide are in the same class of drugs and have a similar safety 
and pharmacokinetic profile, elotuzumab is expected to elicit a similar safety profile in 
combination with pomalidomide as it does in combination with lenalidomide. In addition, 
the combination may elicit response in patients later in the disease course as pomalidomide 
is active against lenalidomide resistant MM cells. The combination of elotuzumab, 
pomalidomide, and dexamethasone (Elo-Pom-Dex or EPd) is currently being evaluated by 
a number of clinical trials in the relapsed/refractory setting (clinicaltrials.gov 
NCT02612779, NCT02718833, NCT02654132, and NCT02726581). 
 
1.5 
Study Rationale 
 
Based on the need to improve outcomes post second ASCT for MM and the benefits seen 
of maintenance treatment following initial ASCT, the natural next step is to evaluate 
maintenance/continuation therapy following second ASCT.  
 
Pomalidomide is active against MM cells refractory to both bortezomib and lenalidomide, 
making it an ideal choice for continuation therapy following second ASCT. Adding 
elotuzumab may increase efficacy and also the durability of responses which is essential to 
improving outcomes following second ASCT.     
 
1.6 
Correlative Studies Rationale 
 
Samples will be collected for currently undefined future analyses.  
 

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2.0 
OBJECTIVES 
 
2.1 
Primary Objective 
 
To evaluate the one-year event-free survival (EFS) rate of patients with relapsed/refractory 
multiple myeloma following second ASCT with Elo-Pom-Dex continuation therapy.  
 
2.2 
Secondary Objectives 
 
1. To evaluate the overall response rate (ORR) of patients with relapsed/refractory 
multiple myeloma following second ASCT with Elo-Pom-Dex continuation therapy 
2. To evaluate the complete response rate (CRR) of patients with relapsed/refractory 
multiple myeloma following second ASCT with Elo-Pom-Dex continuation therapy 
3. To evaluate the event-free survival (EFS) of patients with relapsed/refractory multiple 
myeloma following second ASCT with Elo-Pom-Dex continuation therapy 
4. To evaluate the progression-free survival (PFS) of patients with relapsed/refractory 
multiple myeloma following second ASCT with Elo-Pom-Dex continuation therapy 
5. To evaluate the overall survival (OS) of patients with relapsed/refractory multiple 
myeloma following second ASCT with Elo-Pom-Dex continuation therapy. 
6. To evaluate the toxicity of second ASCT with Elo-Pom-Dex continuation therapy. 
 
2.3 
Exploratory Objectives 
 
1. To evaluate the minimal residual disease negative (MRD-negative) rate of patients with 
relapsed/refractory multiple myeloma following second ASCT with Elo-Pom-Dex 
continuation therapy 
2. To compare the outcomes of patients with relapsed/refractory multiple myeloma 
following second ASCT with Elo-Pom-Dex continuation therapy with a similar cohort 
of patients treated with alternative therapies off-study. 
 
 
3.0 
PATIENT SELECTION 
 
3.1 
Inclusion Criteria 
 
1. Histologically confirmed diagnosis of multiple myeloma. 
 
2. Received prior autologous stem cell transplantation as first line therapy for multiple 
myeloma with subsequent disease relapse/progression. 
 
3. Failed 1 or 2 prior lines of treatment for multiple myeloma. A line of treatment 
includes all therapy including induction, transplant, and maintenance administered in 
a sequence in the absence of relapse/progression. Once relapse/progression occurs 
and subsequently the anti-myeloma treatment is changed, a new line of treatment has 
begun. Local radiation or corticosteroids will not be considered treatment for multiple 
myeloma. 

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4. Received 2 to 6 cycles of induction therapy per standard of care prior to 2nd 
autologous stem cell transplantation.  
 
5. Received standard of care melphalan conditioning for 2nd autologous stem cell 
transplantation, is currently Day +80 to +120 following transplant, and is responding 
to therapy (partial response or better as compared to pre-induction assessment; see 
section 10.0 for response definitions). 
 
6. All US study participants must be registered into the mandatory POMALYST REMS® 
program and be willing and able to comply with the requirements of the POMALYST 
REMS® program. For Canadian sites, patients will followed according to the 
Pomalidomide pregnancy prevention program (Appendix E).  
 
7. Females of reproductive potential within the US must agree to adhere to the scheduled 
pregnancy testing as required in the POMALYST REMS® program. For Canadian 
sites, patients will followed according to the Pomalidomide pregnancy prevention 
program (Appendix E). 
  
8. At least 18 and no more than 75 years of age at enrollment. 
 
9. ECOG performance status ≤ 2 (Appendix A). 
 
10. Normal bone marrow and organ function as defined as ALL of the following: 
a. Absolute neutrophil count ≥ 1000/mm3 
b. Platelets ≥ 75,000/mm3 (transfusions not permitted within 7 days of screening) 
c. Total bilirubin ≤ 2.0 x IULN 
d. AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN 
e. Creatinine clearance (Appendix B) ≥ 15 mL/min 
 
11. Females of childbearing potential and men must agree to use adequate contraception 
(hormonal or barrier method of birth control, abstinence) prior to study entry through 
Day +100 visit. Should a woman become pregnant or suspect she is pregnant while 
participating in this study, she must inform her treating physician immediately. 
 
12. Able to understand and willing to sign an IRB approved written informed consent 
document. 
 
3.2 
Exclusion Criteria 
 
1. Refractory to elotuzumab and/or pomalidomide, defined as progressive disease or 
clinical relapse on therapy or within 60 days following completion of therapy (see 
section 10.0 for response definitions). Prior exposure to elotuzumab and/or 
pomalidomide is allowed as long as patient is not refractory to these agents. 
 
2. More than one prior transplant prior to study entry with the exception of tandem 

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transplantation. Tandem transplantation is defined as two autologous stem cell 
transplants that occur within 9 months of one another, and the patient did not have 
disease progression in the period between the two transplants. 
 
3. Presence of peripheral neuropathy ≥ grade 3 based on NCI CTCAE v 4.0  
 
4. History of plasma cell leukemia or MM CNS involvement. 
 
5. Receiving renal replacement therapy, hemodialysis, or peritoneal dialysis. 
 
6. Diagnosed with another concurrent malignancy requiring treatment. 
 
7. Known HIV or active hepatitis A, B, or C. Antibody testing not required for screening.   
 
8. Known hypersensitivity to pomalidomide, dexamethasone, or any excipients in 
elotuzumab, formulation, or recombinant protein  
 
9. Receiving any other investigational agents within 14 days prior to enrollment.  
 
10. Uncontrolled intercurrent illness including, but not limited to, ongoing or active 
infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac 
arrhythmia. 
 
11. Pregnant and/or breastfeeding.  Females of childbearing potential must have two 
negative pregnancy tests.  The first test should be performed within 10-14 days of study 
entry, and the second test within 24 hours prior to prescribing pomalidomide. 
 
3.3 
Inclusion of Women and Minorities 
 
Both men and women and members of all races and ethnic groups are eligible for this trial.  
 
3.4 
Retrospective Cohort 
 
As the data on second ASCT is scant in the modern therapy era, a cohort of patients 
meeting the eligibility criteria above who underwent second ASCT at the institution 
11/22/2017-10/01/2021 (to mirror enrollment period for the prospective trial) and did not 
enroll on the prospective trial of Elo-Pom-Dex continuation will be recruited. The 
retrospective data is being used to provide context to the clinical trial data. Based on the 
number of second ASCTs performed among patients not enrolled on this trial, we 
estimate ~30-40 records will be reviewed and ~20 will be eligible for the analysis. 
 
For those meeting eligibility, similar data will be collected as outlined in section 9.0, with 
the exception of adverse events and continuation forms. Adverse events will not be 
collected. Granular data on continuation treatment will not be collected each cycle, rather 
the start and stop dates and response data will be collected for the regimen(s) 
administered.  

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4.0 
REGISTRATION PROCEDURES 
 
In general, patients will sign informed consent prior to 2nd autologous transplantation. 
However, patients may be allowed to consent following 2nd autologous transplantation with 
permission from the principal investigator.  Patients will undergo screening and registration 
following 2nd autologous stem cell transplantation. Patients must not start any protocol 
intervention prior to registration through the Siteman Cancer Center. Patients on the 
retrospective arm of the study will not be formally registered.  
 
The following steps must be taken before registering patients to this study: 
 
1. Confirmation of patient eligibility by Washington University 
2. Registration of patient in the Siteman Cancer Center database 
3. Assignment of unique patient number (UPN) 
 
Once the patient has been entered in the Siteman Cancer Center OnCore database, the WUSM 
coordinator will forward verification of enrollment and the UPN via email. 
 
4.1 
Confirmation of Patient Eligibility 
 
Confirm patient eligibility by collecting the information listed below and scanning and 
emailing it to the research coordinator listed in the Siteman Cancer Center Clinical Trials 
Core Protocol Procedures for Secondary Sites packet at least one business day prior to 
registering patient: 
 
1. Your name and contact information (telephone number, fax number, and email 
address) 
2. Your site PI’s name, the registering MD’s name, and your institution name 
3. Patient’s race, sex, and DOB 
4. Three letters (or two letters and a dash) for the patient’s initials 
5. Currently approved protocol version date 
6. Copy of signed consent form (patient name may be blacked out) 
7. Planned date of enrollment 
8. Completed eligibility checklist, signed and dated by a member of the study team 
9. Copy of appropriate source documentation confirming patient eligibility 
 
4.2 
Patient Registration in the Siteman Cancer Center OnCore Database 
 
Registrations may be submitted Monday through Friday between 8am and 5pm CT. Urgent 
late afternoon or early morning enrollments should be planned in advance and coordinated 
with the Washington University research coordinator.  Registration will be confirmed by 
the research coordinator or his/her delegate by email within one business day. Verification 
of eligibility and registration should be kept in the patient chart. 
 

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All patients at all sites must be registered through the Siteman Cancer Center OnCore 
database at Washington University. 
 
4.3 
Assignment of UPN 
 
Each patient will be identified with a unique patient number (UPN) for this study.  Patients 
will also be identified by first, middle, and last initials.  If the patient has no middle initial, 
a dash will be used on the case report forms (CRFs).  All data will be recorded with this 
identification number on the appropriate CRFs. 
 
 
5.0 
TREATMENT PLAN 
 
5.1 
Overview 
 
Patients will have received 2 to 6 cycle of salvage/induction per standard of care. Following 
induction, patients will undergo standard of care ASCT melphalan conditioning. 
Administration of melphalan and the second ASCT will be done as part of routine care and 
procedures are not dictated by this protocol. 
 
Continuation therapy with Elo-Pom-Dex will begin between Days 80 and 120 following 
the second ASCT for patients meeting protocol eligibility.  Barring dose modifications, 
Elo-Pom-Dex continuation therapy will consist of 
• 10 mg/kg of elotuzumab on Days 1 and 15 for Cycles 1-6 followed by 20 mg/kg on 
Day 1 for Cycles 7+ 
• 2 mg of pomalidomide daily on Days 1-21 of all cycles 
• 40 mg of dexamethasone on Days 1 and 15 for Cycles 1-6 followed by 40 mg on 
Day 1 for Cycles 7+ 
 
Continuation therapy may continue until relapse or progression. 
 
5.2 
Elotuzumab Administration 
 
During continuation therapy, elotuzumab will be administered on a 28-day cycle as 
follows: on Days 1 and 15 for Cycles 1-6 and on Day 1 for Cycles 7+. For Cycles 1-6 
elotuzumab will be administered intravenously at a dose of 10 mg/kg. For Cycles 7+ 
elotuzumab will be administered at a dose of 20 mg/kg. 
 
As per standard elotuzumab treatment guidelines, patients must be premedicated 45-90 
minutes prior with the following: 
• H1 blocker: diphenhydramine (25-50 mg PO or IV) or equivalent 
• H2 blocker: ranitidine (50 mg PO or IV) or equivalent 
• Acetaminophen (650-1000 mg PO) 
• Dexamethasone (8 mg IV) (PO dosing will be reduced to accommodate IV 
premedication for elotuzumab) 
 

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During the first cycle of continuation and escalation to 20mg/kg (Cycle 7 of continuation) 
the elotuzumab infusion rate will be increased gradually to a maximum of 5mL/min. See 
Appendix C for elotuzumab preparation and administration guidelines.  
 
On each day of elotuzumab, vital signs monitoring should be performed at the following 
time points: 
• prior to the start of the elotuzumab infusion 
• 30 minutes after the start of infusion 
• at the end of the infusion 
• 30 minutes post completion of infusion 
 
Patients should be monitored for toxicity and doses of elotuzumab should be modified as 
needed to accommodate patient tolerance to treatment; this may include symptomatic 
treatment or dose interruptions (see Section 6.0). No elotuzumab dose reductions are 
allowed. 
 
5.3 
Pomalidomide Administration 
 
During continuation therapy, pomalidomide will be taken by mouth daily on Days 1-21 of 
each 28-day cycle at a starting dose of 2 mg. During continuation, pomalidomide may be 
dose escalated to 4 mg at the discretion of the treating physician.  
 
Pomalidomide (POMALYST®) will be provided to research subjects for the duration of 
their participation in this trial at no charge to them or their insurance providers. For US 
patients, pomalidomide will be provided in accordance with the Celgene Corporation’s 
POMALYST REMS® program. Per the standard POMALYST REMS® program 
requirements, all physicians who prescribe pomalidomide for research subjects enrolled 
into this trial, and all research subjects enrolled into this trial, must be registered in and 
must comply with all requirements of the POMALYST REMS® program.  
For Canadian sites, pomalidomide will be supplied as Investigational Product by Celgene 
Corporation.  
Only enough pomalidomide for one cycle of therapy will be supplied to the patient each 
cycle.  This is in accordance with the POMALYST REMS® program. 
 
VTE prophylaxis with aspirin 81 mg daily should be administered unless the patient is 
being treated with alternate prophylaxis (Coumadin, low molecular weight heparin, etc) or 
VTE prophylaxis is contraindicated.  
 
Females must follow pregnancy testing requirements as outlined in the POMALYST 
REMS® program (US) or Appendix E (Canada). 
Patients should be monitored for toxicity and doses of pomalidomide should be modified 
as needed to accommodate patient tolerance to treatment; this may include symptomatic 
treatment, dose interruptions, and adjustments of pomalidomide dose (see Section 6.0). 
Once pomalidomide is reduced for toxicity, no dose re-escalation is permitted. 
 

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Pomalidomide capsules should be swallowed whole, and should not be broken, chewed or 
opened.  Pomalidomide should be taken without food, at least 2 hours before or 2 hours 
after a meal. 
 
Pomalidomide should be taken at the same time each day. On days when both 
pomalidomide and elotuzumab are being administered, pomalidomide should be taken at 
least 2 hours following the end of the elotuzumab infusion. If a dose of pomalidomide is 
missed, it should be taken as soon as possible on the same day.  If it is missed for the entire 
day, it should not be made up, rather it should be taken at the next scheduled time point. 
Patients who vomit a dose after ingestion will not receive an additional dose, but should 
resume dosing at the time of the next scheduled dose. Patients who take more than the 
prescribed dose of pomalidomide should be instructed to seek emergency medical care if 
needed and contact study staff immediately.   
5.4 
Dexamethasone Administration 
 
During continuation therapy, dexamethasone will be taken by mouth at a starting dose of 
40 mg.  It will be given on a 28-day cycle as follows: on Days 1 and 15 for Cycles 1-6 and 
on Day 1 only for Cycles 7+. Sufficient quantity of drug for one cycle of therapy will be 
prescribed to the patient at a time.   
 
NOTE: On elotuzumab dosing days, patients will receive IV premedication with 
dexamethasone 8 mg prior to administration of elotuzumab, so the PO dosing will be 
reduced to 28 mg, to be taken 3-24 hours prior to elotuzumab infusion. 
 
Patients should be monitored for toxicity and doses of dexamethasone should be modified 
as needed to accommodate patient tolerance to treatment; this may include symptomatic 
treatment, dose interruptions, and adjustments of dexamethasone dose (see Section 6.0). 
Once dexamethasone is reduced for toxicity, no dose re-escalation is permitted. 
 
Dexamethasone should be taken with food or milk. Patients should be instructed to swallow 
dexamethasone tablets whole and not to break, chew, or open the tablets. Each tablet should 
be swallowed separately with a sip of water.  
 
Missed doses can be taken as soon as the patient remembers if the next scheduled dose is 
8 hours or more away. A double dose should not be taken to make up for a missed dose. 
Patients who vomit a dose after ingestion will not receive an additional dose, but should 
resume dosing at the time of the next scheduled dose.  
 
5.5 
Melphalan Conditioning and Stem Cell Transplantation 
 
Melphalan conditioning prior to ASCT will be administered according to institutional 
guidelines.  Recommendations for melphalan dosing are that it be given 200mg/m2 on Day 
-2 pre-ASCT, with possible dose reduction to 140mg/m2 due to advanced age or other 
contraindication. 
 

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Autologous peripheral blood stem cells (at least 2x106 CD34+ cells/kg recommended) will 
be given on Day 0 to all patients according to institutional guidelines.  
  
5.6 
General Concomitant Medication and Supportive Care Guidelines 
 
5.6.1 Prohibited Concomitant Medications and Procedures  
 
The following procedures are prohibited during the study. 
• 
Any antineoplastic treatment with activity against MM other than study drugs 
• 
Radiation therapy (note that, in general, the requirement for local radiation 
therapy indicates disease progression) 
• 
Co-administration of strong inhibitors of CYP1A2 (unless medically 
necessary). Co-administration of pomalidomide with drugs that are strong 
inhibitors of CYP1A2 (e.g. ciprofloxacin, enoxacin, and fluvoxamine) and 
CYP3A4/5 (e.g. ketoconazole) or P-gp could increase pomalidomide exposure 
and should be avoided, unless medically necessary. 
 
5.6.2 Permitted Concomitant Medications and Procedures  
 
The following medications and procedures are permitted during the study: 
• 
Antiemetics, including 5-HT3 serotonin receptor antagonists, may be used at 
the discretion of the investigator. 
• 
Loperamide or other antidiarrheal should be used for symptomatic diarrhea at 
discretion of the investigator. The dose and regimen will be according to 
institutional guidelines. IVF should be given to prevent volume depletion. 
• 
Growth factors (e.g., granulocyte colony stimulating factor [G-CSF], 
granulocyte macrophage-colony stimulating factor [GM-CSF], recombinant 
erythropoietin) are permitted, but should not be given prophylactically. Their 
use should follow published guidelines and/or institutional practice; however, 
alternative usage may be reviewed with the principal investigator.  
• 
Patients should be transfused with red cells and platelets as clinically indicated 
and according to institutional guidelines. 
• 
Antiviral therapy such as acyclovir may be administered if medically 
appropriate. 
• 
Concomitant treatment with bisphosphonates will be permitted, as appropriate. 
• 
Patients who experience worsening neuropathy from baseline may be observed 
for recovery, have dose reductions/delays as indicated in the protocol, and any 
supportive therapy or intervention may be initiated as appropriate at the 
discretion of the investigator. 
• 
Supportive measures consistent with optimal patient care may be given 
throughout the study. 
 
5.7 
Females of Childbearing Potential 
 
Female of childbearing potential (FCBP) is defined as a female who: 1) has achieved 
menarche (first menstrual cycle) at some point, 2) has not undergone a hysterectomy (the 

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surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of both 
ovaries) or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy 
does not rule out childbearing potential) for at least 24 consecutive months (ie, has had 
menses at any time during the preceding 24 consecutive months).  FBCP are required to 
have two negative serum pregnancy tests prior to the first dose of continuation therapy 
because pomalidomide is a thalidomide analogue and is contraindicated for use during 
pregnancy, as thalidomide is a known human teratogen that causes severe birth defects or 
embryo-fetal death.  Of the two negative pregnancy tests required prior to initiating 
therapy, the first should be performed within 10-14 days and the second within 24 hours 
prior to prescribing pomalidomide. 
 
In addition, FCBP should undergo weekly pregnancy tests during the first cycle of 
continuation and on Day 1 of each cycle thereafter for women with regular menstrual cycles 
or on Days 1 and 15 of each cycle thereafter for women with irregular menstrual cycles.   
 
Female patients are required either to abstain continuously from heterosexual sexual 
intercourse or to use acceptable contraception, beginning 4 weeks prior to initiating 
treatment with pomalidomide, during therapy, during dose interruptions (including the 
post-ASCT period), and continuing for 4 weeks following discontinuation of 
pomalidomide.  Acceptable contraception is defined as two methods of reliable birth 
control simultaneously: one highly effective form of contraception (tubal ligation, IUD, 
hormonal [pills, injections, hormonal patches, vaginal rings, or implants], or partner’s 
vasectomy) and one additional effective form of contraception (male latex or synthetic 
condom, diaphragm, or cervical cap). 
 
Male patients must always use a latex or synthetic condom during any sexual contact with 
females of reproductive potential while taking pomalidomide and for 4 weeks following 
discontinuation of pomalidomide, even if they have undergone a successful vasectomy.  
Male patients taking pomalidomide must not donate sperm. 
 
5.8 
Duration of Therapy 
 
If at any time the constraints of this protocol are considered to be detrimental to the 
patient’s health and/or the patient no longer wishes to continue protocol therapy, the 
protocol therapy should be discontinued and the reason(s) for discontinuation documented 
in the case report forms.  Otherwise, therapy may continue for an indefinite number of 
cycles of continuation therapy. 
 
Patients will be removed from the study for any of the following reasons: 
• Disease progression or relapse 
• Death 
• Adverse event(s) that, in the judgment of the investigator, may cause severe or 
permanent harm or which rule out continuation of study drug 
• General or specific changes in the patient’s condition render the patient 
unacceptable for further treatment in the judgment of the investigator 
• Suspected pregnancy 

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• Serious noncompliance with the study protocol 
• Lost to follow-up 
• Patient withdraws consent 
• Investigator removes the patient from study 
• The Siteman Cancer Center decides to close the study 
 
If a patient is withdrawn from study, the sponsor should be notified as soon as possible. 
Patients who are removed from study will undergo an end of study visit (see section 7.0) 
then will enter into the follow-up phase of the trial. Patients who withdraw will not be 
replaced.  
 
5.9 
Duration of Follow-up 
 
Participants will be followed annually for progression-free and overall survival for up to 5 
years after removal from study or until death, whichever occurs first. Follow-up can include 
an office visit and a physical exam, or a phone call from a study coordinator or research 
nurse to the patient.  
 
 
6.0 
DOSE MODIFICATIONS 
 
Elotuzumab, pomalidomide, and dexamethasone dosing is independent. If a patient discontinues 
either elotuzumab or pomalidomide, the patient may continue on study receiving the other 
treatments. Toxicities should be attributed to a specific study drug if possible so that dose 
modifications can be made rationally. If multiple toxicities are noted, the dose adjustments and 
or/delays should made once per cycle according to the guidelines for the most severe toxicity. The 
maximum delay allowed before treatment must be discontinued will be 3 weeks unless permission 
to resume treatment is granted by the principal investigator. Alternative dose modifications than 
those listed below may be recommended after discussion with the principal investigator in order 
to maximize exposure to study treatment while protecting patient safety.   
 
6.1 
Dose Levels 
      
 
 
       Elotuzumab Dose Levels 
 
Dose Level 
Dose (mg) 
 Starting Dose 
10 mg/kg 
-1 
Discontinue (no 
dose modifications 
allowed) 
 
 
 
 
 

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Pomalidomide Dose Levels 
 
Dose Level 
Dose (mg) 
Starting Dose 
4 mg 
-1 
3 mg 
-2 
2 mg 
-3 
1 mg 
-4 
Discontinue 
                                                       
 
 
     
         Dexamethasone Dose Levels 
 
Dose Level 
Dose (mg) 
Starting Dose 
40 mg1  
-1 
20 mg2 
-2 
12 mg3 
-3 
Discontinue 
 
1- 28 mg orally and 8 mg intravenously on elotuzumab dosing days 
2- 8 mg orally and 8 mg intravenously on elotuzumab dosing days 
3- 0 mg orally and 8 mg intravenously on elotuzumab dosing days 
 
 
 
6.2 
Dosing Modifications for Hematologic Toxicities 
 
6.2.1 Thrombocytopenia 
 
Only thrombocytopenia determined to be related to one or more study drugs 
requires dose reductions or adjustments as described in this section. Platelet 
transfusion support is permissible at the discretion of the treating physician.  
Participants who have treatment delayed for greater than three weeks should 
discontinue protocol therapy.   
 
Dose modifications for thrombocytopenia should be instituted as follows: 
 
Platelet 
Count 
Grade 
Modification 
Elotuzumab 
Pomalidomide 
Dexamethasone 
< 25,000/mm3 
4 
No changes. 
Each episode: 
Hold until platelets 
resolve to grade ≤ 
1, then reduce by 
one dose level 
No changes. 
 
 
 
 

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6.2.2 Neutropenia or Febrile Neutropenia 
 
Only neutropenia/febrile neutropenia determined to be related to one or more study 
drugs requires dose reductions or adjustments as described in this section. Colony-
stimulating factor support (such as G-CSF or GM-CSF) for neutropenia is 
permissible at the discretion of the treating physician, but should not be given 
prophylactically. Participants who have treatment delayed for greater than three 
weeks should discontinue protocol therapy.  
 
 
Dose modifications for neutropenia should be instituted as follows: 
 
Neutrophil 
Count 
Grade 
Modification 
Elotuzumab 
Pomalidomide 
Dexamethasone 
< 500/mm3 
4 
No changes. 
Each episode: 
Hold until 
neutrophils resolve 
to grade ≤ 1, then 
reduce by one dose 
level 
No changes. 
 
 
 

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6.3 
Dosing Modifications for Non-Hematologic Toxicities 
 
Dose modification guidelines for treatment related non-hematologic toxicities are as follows: 
Toxicity 
Grade 
Modification 
Elotuzumab 
Pomalidomide 
Dexamethasone 
Confusion or 
Mood Alteration 
2 or 3 
No changes 
First episode: Hold until symptoms 
resolve to baseline, then reduce by one 
dose level.   
 
Second episode: Discontinue 
dexamethasone 
4 
First episode: Discontinue 
dexamethasone 
Diarrhea 
3 
Each episode: Only if the event occurred despite optimal supportive therapy, hold suspected 
study drug(s) until toxicity resolves to ≤ grade 1 or baseline, then reduce suspected drug(s) by one 
dose level. 
4 
Each episode: Discontinue suspected study drug(s). 
Dyspepsia, Gastric 
or duodenal ulcer, 
or Gastritis 
2 
No changes. 
Each episode: Treat with histamine-2 
blockers, sucralfate, or omeprazole as 
needed. If symptoms persist despite these 
measures, decrease dexamethasone by 1 
dose level. 
3 
First episode: Hold until toxicity 
resolves to ≤ grade 1 or baseline, then 
decrease dexamethasone by 1 dose level. 
Prophylactically treat with histamine-2 
blockers, sucralfate, or omeprazole as 
needed.  
 
Second episode: If symptoms persist 
despite these measures, discontinue 
dexamethasone. 

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Toxicity 
Grade 
Modification 
Elotuzumab 
Pomalidomide 
Dexamethasone 
Edema 
3 
No changes. 
First episode: Treat with diuretics as 
needed. Decrease dexamethasone by one 
dose level.  
 
Second episode: If edema persists, 
decrease dexamethasone by one more 
dose level.  
 
Third episode: Discontinue 
dexamethasone 
Elotuzumab 
Infusion Reaction 
1 
No changes. 
No changes. 
2 or 3 
First episode: Interrupt infusion if applicable. See 
Appendix D for instructions. 
 
Second episode: Discontinue elotuzumab. 
 
4 
First episode: Discontinue elotuzumab. 
 
Fatigue 
Any 
No Changes 
Hyperglycemia 
3 
No changes. 
 
Each episode: Treat with insulin or 
hypoglycemic as needed. If uncontrolled 
despite these measures, decrease 
dexamethasone by 1 dose level. 
4 
First episode: Discontinue 
dexamethasone. 
 
 
 

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Toxicity 
Grade 
Modification 
Elotuzumab 
Pomalidomide 
Dexamethasone 
Muscle 
Weakness  
2 or 3 
No changes. 
First episode: Decrease dexamethasone 
by one dose level.  
 
Second episode: If weakness persists, 
decrease dexamethasone by one more 
dose level.  
 
Third episode: Discontinue 
dexamethasone. 
Nausea/Vomiting 
 
3 
Each episode: Only if the event occurred despite optimal anti-emetic prophylaxis, hold 
suspected study drug(s) until toxicity resolves to ≤ grade 1 or baseline, then reduce suspected 
drug(s) by one dose level. 
Pancreatitis 
2 - 4 
No changes. 
First episode: Discontinue 
dexamethasone. 
Peripheral 
Neuropathy 
2 with 
pain 
No changes. 
Each episode: Hold 
until toxicity resolves to 
≤ grade 1 or baseline, 
then reduce by one dose 
level. 
No changes. 
3 or 4 
Each episode: Hold 
until toxicity resolves to 
≤ grade 1 or baseline, 
then reduce by one dose 
level. 
Rash 
 
 
2 or 3 
Each episode: Hold suspected study drug(s) until toxicity resolves to ≤ grade 1 or baseline, then 
restart at previous dose level or reduce by one dose level at the investigator’s discretion  
4 
First episode: Discontinue suspected study drug(s). 
 

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Toxicity 
Grade 
Modification 
Elotuzumab 
Pomalidomide 
Dexamethasone 
Thrombosis or 
Embolism 
2 or 3 
No changes. 
Each episode: Hold 
pomalidomide and 
commence 
anticoagulation therapy, 
then restart at previous 
dose level at the 
investigator’s discretion. 
No changes. 
4 
Each episode: Discontinue suspected study drug(s). 
Tumor Lysis 
Syndrome 
Any 
First episode: Hold all drugs until symptoms resolve to baseline, then restart at previous dose levels 
with appropriate TLS prophylaxis  
 
Second episode: Discontinue protocol treatment.  
Other non-
hematologic 
toxicity  
3 
Each episode: Hold suspected study drug(s) until toxicity resolves to ≤ grade 1 or baseline, then 
reduce suspected drug(s) by one dose level. 
4 
Each episode: Discontinue suspected study drug(s). 

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7.0 
STUDY CALENDAR 
 
 
Pre-ASCT 
Screening1 
ASCT2 
Post-ASCT 
Screening3 
Continuation4 
EOS5 
D1 
D1516 
Informed consent 
X 
 
 
 
 
 
H&P w/ PS & plasmacytoma 
assessment 
X 
 
X 
X14 
 
X 
CBC  
X 
 
X 
X14 
X16 
X 
CMP6 
X 
 
 
X14 
 
 
SPEP  
X 
 
X 
X14 
 
X 
Serum Immunofixation 
X 
 
X 
X15 
 
 
24h urine for total protein,  
and UPEP 7 
X 
 
X 
X14 
 
X 
Urine Immunofixation7 
X 
 
X 
X15 
 
 
Serum-free light chains 
X 
 
X 
X14 
 
X 
Quantitative immunoglobulins 
(IgA, IgG, IgM) 
X 
 
X 
X14 
 
X 
Serum βhCG8 
 
 
X 
X 
X17 
X 
Bone marrow biopsy and 
aspirate9 
X 
 
X 
X15 
 
 
Skeletal imaging10 
As clinically indicated 
Elotuzumab11 
 
 
 
X 
X16 
 
Pomalidomide 
 
 
 
Days 1-21 
 
Dexamethasone 
 
 
 
X 
X16 
 
Melphalan ASCT 
 
X 
 
 
 
 
Blood for future research12 
X 
 
X 
X15 
 
 
Bone marrow aspirate for 
research 
X 
 
X 
X15 
 
 
Adverse event monitoring 
 
 
 
X ------------------ X 
Note- A window of -7 to +7 is allowed during continuation therapy cycles.  
 
 
 

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1. Within 60 days prior to ASCT. For patients who sign consent following ASCT, any missed assessments will not be counted as 
protocol deviations. 
2. As according to institutional guidelines. 
3. Day +80 to Day +120 post-ASCT; to occur within 28 days prior to C1D1 of continuation therapy. 
4. First cycle of continuation therapy must begin between Days +80 to +120 post-ASCT and may continue until disease progression or 
unacceptable toxicity 
5. Within 30 days of last dose of study drugs; following EOS patients will be followed annually for PFS and OS for up to 5 years. 
6. Includes electrolytes, renal function, protein, and liver function tests 
7. Repeat 24h urine only required for patients with ≥ 200 mg/24h of M-protein at screening 
8. Females of childbearing potential only 
9. Bone marrow aspirate and core biopsy – differential required; Cytogenetics, and fluorescent in situ hybridization (FISH) studies 
performed per institutional guidelines. MRD assessment should be performed for patients in VGPR/CR/sCR.  
10. X-rays, CT, MRI, or PET per institutional guidelines 
11. On elotuzumab dosing days, vital signs monitoring should be performed at the following time points: prior to the start of the 
elotuzumab infusion, thirty minutes after the start of infusion, at the end of the infusion, thirty minutes post completion of the elotuzumab 
infusion.  
12. See Section 8.0 for details 
13. Two negative tests are required before initiation of pomalidomide; one within 10-14 days prior and one 24 hours prior to prescribing. 
14. Not required on C1D1 if screening/restaging visit occurred within 28 days prior 
15. Cycle 13 only 
16. Cycles 1-6 only 
17. Required for all females of childbearing potential in Cycle 1; Only required beyond Cycle 1 for women with irregular menstrual 
cycles. 
 

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8.0 
CENTRAL LABS 
 
8.1 
Future Research 
 
Specimens from blood and marrow will be collected and stored for future research 
including, but not limited to, genetic studies.  
 
Approximately 5 ml of bone marrow aspirate and 20 ml of peripheral blood in EDTA (pink 
top) tube(s) will be collected at the following time points: 
 
• 
Pre-ASCT screening 
• 
Post-ASCT screening 
• 
Cycle 13 of continuation 
• 
Time of MRD assessment(s) 
 
Instructions for handling and shipment of central labs will be provided in the study lab 
binder.  
 
 
9.0 
DATA SUBMISSION SCHEDULE 
 
Case report forms with appropriate source documentation will be completed according to the 
schedule listed in this section. 
 
Case Report Form 
Submission Schedule 
Original Consent Form 
Prior to registration 
Registration Form 
Eligibility Form 
Medical History Form 
Treatment History Form 
MM History 
MM Labs Form 
Extramedullary Disease Form 
At Baseline 
MM Labs Form 
 
Screening and Each Cycle of Treatment  
CBC Form 
 
Screening and Each Cycle of Treatment 
Central Labs Form 
Screening and cycle 13 of continuation 
MRD Form 
Screening and cycle 13 of continuation 
ASCT Form 
At Baseline 
Bone Marrow Form 
 
Screening and cycle 13 of continuation 

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Continuation Form 
Completion of each cycle of treatment 
IMWG Response Form 
Screening and cycle 13 of continuation 
Adverse Events 
Continuous from baseline through safety follow-up 
visit  
MedWatch Form 
See Section 11.0 for reporting requirements 
SAE / CIOMS Form 
See section 11.0 for reporting requirements for 
Canada 
End of Treatment Form 
At the completion of treatment 
PD/Clinical Relapse Form 
At the time of disease progression/clinical relapse 
Follow-Up Form 
Per protocol requirements 
Death Form 
At time of death 
 
Any queries generated by Washington University must be responded to within 28 days of receipt 
by the participating site.  The Washington University research team will conduct a regular review 
of data status at all secondary sites, with appropriate corrective action to be requested as needed. 
 
 
9.1 
Adverse Event Collection in the Case Report Forms 
All adverse events that occur beginning with start of treatment (minus exceptions defined 
in Section 11.0) must be captured in the Toxicity Form.  Baseline AEs should be captured 
on the Medical History Form. 
 
Participant death due to disease progression should be reported on the Toxicity Form as 
grade 5 disease progression.  If death is due to an AE (e.g. cardiac disorders: cardiac arrest), 
report as a grade 5 event under that AE.  Participant death must also be recorded on the 
Death Form. 
 
 
10.0 
MEASUREMENT OF EFFECT 
 
10.1 
Response Criteria  
 
Elotuzumab, a humanized IgG Kappa monoclonal antibody, can be detected in the serum 
by electrophoresis and/or immunofixation. Thus, its administration can interfere with the 
standard International Myeloma Working Group (IMWG) Uniform Response Criteria 
guidelines. Therefore, we will use a modified response criteria utilizing minimal residual 
disease detection by next-generation sequencing. [20-21]  
 
10.1.1 Minimal Residual Disease 
 
For patients in VGPR, CR, or sCR as defined below, minimal residual disease 
(MRD) testing should be performed using clonoSEQ next-generation sequencing 
technology [22]. Patients will be classified as MRD-negative or MRD-positive 
based on the current detection limits of the test (1 MM cell per 1x106 cells).  

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Note: Anytime MRD assessment is performed, correlative studies should also be 
performed. See Section 9.0 for details. 
 
10.1.2 Stringent Complete Response  
 
Stringent complete response (sCR) requires all of the following:  
• CR as defined below 
• Normal free light chain ratio (0.26-1.65) 
• Absence of clonal cells in the bone marrow by immunohistochemistry or 
immunofluorescence  
 
10.1.3 Complete Response  
 
Complete response (CR) requires all of the following:  
• Disappearance of monoclonal protein by both protein electrophoresis and 
immunofixation studies from the blood and urine 
• If serum and urine monoclonal protein are unmeasurable, Normal free light 
chain ratio (0.26-1.65) 
• <5% plasma cells in the bone marrow  
• Disappearance of soft tissue plasmacytoma 
 
Patients who do not meet the definition of CR based solely on residual monoclonal 
protein on serum electrophoresis and/or immunofixation, but are MRD-negative as 
described above, will also be considered CR.        
 
10.1.4 Very Good Partial Response  
 
Very good partial response (VGPR) requires all of the following:  
• Serum and urine monoclonal protein detectable by immunofixation but not 
on electrophoresis  
OR  
≥ 90% reduction in serum monoclonal protein with urine monoclonal 
protein < 100 mg per 24 hours 
• If serum and urine monoclonal protein are unmeasurable, a > 90% decrease 
in difference between the involved and uninvolved free light chain levels is 
required in place of monoclonal protein criteria (The absolute decrease must 
be > 10 mg/dl) 
• If present, > 50% reduction in the size of soft tissue plasmacytomas (by 
clinical or radiographic examinations) 
 
10.1.5 Partial Response  
 
Partial response (PR) requires all of the following:  
• > 50% reduction in the level of the serum monoclonal protein  
• Reduction in urine monoclonal protein by either > 90% or to < 200 mg  

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• If serum and urine monoclonal protein are unmeasurable, a >50% decrease 
in difference between the involved and uninvolved free light chain levels is 
required in place of monoclonal protein criteria (The absolute decrease must 
be > 10 mg/dl)  
• If serum and urine monoclonal protein are unmeasurable and serum free 
light chain is unmeasurable, a > 50% reduction in plasma cells is required 
in place of monoclonal protein, provided that baseline bone marrow plasma 
cell percentage was > 30%  
• If present, > 50% reduction in the size of soft tissue plasmacytomas (by 
clinical or radiographic examinations). 
 
10.1.6 Stable Disease  
 
Stable disease (SD) is defined as not meeting criteria for any other response as 
defined in this section. 
 
10.1.7 Progressive Disease or Clinical Relapse 
 
Progressive disease (PD) requires one or more of the following:  
• > 25% increase in the level of serum monoclonal protein, which must also 
be an absolute increase of at least 0.5 g/dL and confirmed on a repeat 
investigation 
• > 25% increase in 24-hour urine monoclonal protein, which must also be an 
absolute increase of at least 200 mg/24hr and confirmed on a repeat 
investigation.  
• If serum and urine monoclonal protein are unmeasurable, > 25% increase 
in the difference between involved and uninvolved free light chain levels, 
which must also be an absolute increase of at least 10 mg/dL and confirmed 
on a repeat investigation 
• > 25% increase in plasma cells in a bone marrow aspirate or on trephine 
biopsy, which must also be an absolute increase of at least 10%. As results 
may be inconsistent due to the heterogeneity of the bone marrow or 
sampling issues, patients with > 25% increase in plasma cells may be 
allowed to continue on study at the discretion of the treating physician if the 
patient does not meet any of the other definitions of progressive disease. For 
response assessment, the marrow results will be disregarded in these cases.  
• Definite increase in the size of existing lytic bone lesions or soft tissue 
plasmacytomas. A definite increase is defined as at least 50% (and at least 
1 cm) increase as measured serially as the sum of the products of the cross-
diameters of the lesions.  
• Development of new bone lesions or soft tissue plasmacytomas (not 
including compression fracture).  
• Development of hypercalcemia (corrected serum calcium > 11.5 mg/dL or 
2.8 mmol/L not attributable to any cause other than progressive multiple 
myeloma).  
• Decrease in hemoglobin > 2 g/dl not attributable to any cause other than 

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progressive multiple myeloma  
• Increase in creatinine by > 2 mg/dl not attributable to any cause other than 
progressive multiple myeloma  
• Other worsening laboratory result, or clinical condition that the treating 
physician determines is not attributable to any cause other than progressive 
multiple myeloma  
 
Note: A response of progressive disease/clinical relapse nullifies any other 
concurrent response. For example, at a given time point that a participant meets 
criteria for VGPR but has development of new bone lesions, the response is PD not 
VGPR. 
 
10.1.8  Relapse from Complete Response  
 
Relapse from a complete response requires a prior CR or sCR as described above 
and subsequently developing one or more of the following:  
• Reappearance of serum or urinary paraprotein on immunofixation or routine 
electrophoresis excluding oligoclonal immune reconstitution, and 
confirmed on a repeat investigation 
• Development of > 5% plasma cells in the bone marrow aspirate or biopsy. 
• Appearance of any sign of progressive disease or clinical relapse as stated 
above.  
 
10.2 
Event-Free Survival 
 
Event-free survival (EFS) will be defined as time from ASCT to disease progression, 
relapse, or death, whichever occurs first. Patients who are removed from study therapy 
prior to any of these events occurring will be censored at the time of initiation of subsequent 
anti-myeloma treatment.  
 
10.3 
Progression-Free Survival 
 
Progression-free survival (PFS) will be defined as time from ASCT to disease progression 
or relapse. Any patient who expires or withdraws prior to disease progression or relapse 
will be censored at last follow-up. Patients who are removed from study therapy prior to 
progression or relapse will be censored at the time of initiation of subsequent anti-myeloma 
treatment. 
 
10.4 
Overall Survival 
  
Overall survival (OS) will be defined as time from ASCT to death due to any causes. 
Patients who are alive at the time of data analyses will be censored on the last known alive 
date. Patients who are removed from study therapy prior death will be censored at the time 
of initiation of subsequent anti-myeloma treatment.   
 
 

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10.5 
Overall Response Rate 
 
Overall response rate (ORR) will be defined as the proportion of evaluable patients meeting 
the criteria for PR, VGPR, CR, or sCR.   
 
10.6 
Complete Response Rate 
 
Complete response rate (CRR) will be defined as the proportion of evaluable patients 
meeting the criteria CR or sCR. 
 
   
11.0 
REGULATORY AND REPORTING REQUIREMENTS 
 
The entities providing oversight of safety and compliance with the protocol require reporting as 
outline below.  Please refer to Appendix BG for definitions and Appendix HC for a grid of 
reporting timelines. 
 
Adverse events will be collected from first dose of study treatment through the end of study visit.  
All adverse events must be recorded on the toxicity tracking case report form (CRF) with the 
exception of: 
• 
Baseline adverse events, which shall be recorded on the medical history CRF 
• 
planned hospitalizations 
• 
hospitalizations < 24 hours 
• 
respite care 
• 
events related to disease progression 
 
Events that do not require expedited reporting must still be captured in the EDC. 
Refer to the data submission schedule in Section 101 for instructions on the collection of AEs in 
the EDC. 
 
Reporting requirements for Washington University study team may be found in Section 11.01.  
Reporting requirements for secondary site study teams participating in Washington University-
coordinated research may be found in Section 11.32. 
 
11.1 
Reporting to the Human Research Protection Office (HRPO) at Washington 
University 
 
Reporting will be conducted in accordance with Washington University IRB Policies. 
 
Pre-approval of all protocol exceptions must be obtained prior to implementing the change.  
 
11.2 
Reporting to the Quality Assurance and Safety Monitoring Committee 
(QASMC) at Washington University 
 
The Washington University Sponsor Investigator or designee is required to notify the 
QASMC of any unanticipated problems involving risks to participants or others occurring 

Version 01/19/23– Amendment 7 
 
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at WU or any BJH or SLCH institution that has been reported to and acknowledged by 
HRPO as reportable.  (Unanticipated problems reported to HRPO and withdrawn during 
the review process need not be reported to QASMC.) 
 
QASMC must be notified within 10 days of receipt of IRB acknowledgment via email to 
a QASMC auditorqasmc@wustl.edu.  Submission to QASMC must include the myIRB 
form and any supporting documentation sent with the form. 
 
For events that occur at secondary sites, the Washington University Sponsor Investigator 
or designee is required to notify the QASMC within 10 days of Washington University 
notification via email to qasmc@wustl.edu.  Submission to QASMC must include either 
the myIRB form and supporting documentation or (if not submitted to myIRB) the date of 
occurrence, description of the event, whether the event is described in the currently IRB 
approved materials, the event outcome, determination of relatedness, whether currently 
enrolled participants will be notified, and whether the informed consent document and/or 
any study procedures will be modified as a result of this event. 
 
11.3 
Secondary Sites Reporting Requirements 
 
The research team at each secondary site is required to promptly notify the Washington 
University Sponsor-Investigator and designee and research coordinator of all serious 
adverse events (refer to Appendix GB, Section D) reportable events (as described in 
Section 7.6) within 1 working day of the occurrence of the event or notification of the 
secondary site’s PI of the event.  This notification may take place via email if there is not 
yet enough information for a formal written report (using either an FDA For 3500a 
(MedWatch) and Washington University’s cover sheet (Appendix ID) form if required or 
an institutional SAE reporting form if not).  A formal written report must be sent to the 
Washington University Sponsor-Investigator and designee and research coordinator within 
10 working days4 calendar days (for fatal or life-threatening suspected adverse reactions) 
or 11 calendar days (for serious unexpected adverse reactions) of the occurrence of the 
event or notification of the secondary site’s PI of the event.  The death of a research 
participant that qualifies as a reportable event should be reported within 1 working day of 
the occurrence of the event or notification of the secondary site’s PI of the event. 
 
The research team at a secondary site is responsible for following its site’s guidelines for 
reporting applicable events to its site’s IRB according to its own institutional guidelines.  
The research team at Washington University is responsible for reporting all applicable 
events to the FDA, and Millennium as needed. 
 
Washington University pre-approval of all protocol exceptions must be obtained prior to 
implementing the change.  Local IRB approval must be obtained as per local guidelines.  
Washington University IRB approval is not required for protocol exceptions occurring at 
secondary sites. 
 
 
 

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11.4 
Reporting to Secondary Sites 
 
The Washington University Sponsor-Investigator (or designee) will notify the research 
team at each secondary site of all unanticipated problems involving risks to participants or 
others that have occurred at other sites within 10 working days of the occurrence of the 
event or notification of the Sponsor-Investigator(or designee) of the event.  This includes 
events that take place both at Washington University and at other secondary sites, if 
applicable. Refer to Section 16.0 (Multicenter Management) for more information. 
 
11.5 
Reporting to the FDA 
 
The conduct of the study will comply with all FDA safety reporting requirements.  
PLEASE NOTE THAT REPORTING REQUIREMENTS FOR THE FDA DIFFER 
FROM REPORTING REQUIREMENTS FOR HRPO/QASMC.  It is the 
responsibility of the Washington University principal investigator to report to the FDA as 
follows: 
 
• Report any unexpected fatal or life-threatening suspected adverse reaction 
(refer to Appendix H for definitions) no later than 7 calendar days after 
initial receipt of the information.   
• Report a suspected adverse reaction that is both serious and unexpected 
(SUSAR, refer to Appendix H) no later than 15 calendar days after it is 
determined that the information qualifies for reporting.  Report an adverse 
event (refer to Appendix G) as a suspected adverse reaction only if there is 
evidence to suggest a causal relationship between the drug and the adverse 
event, such as: 
o A single occurrence of an event that is uncommon and known to be 
strongly associated with drug exposure 
o One or more occurrences of an event that is not commonly associated 
with drug exposure but is otherwise uncommon in the population 
exposed to the drug 
o An aggregate analysis of specific events observed in a clinical trial that 
indicates those events occur more frequently in the drug treatment 
group than in a concurrent or historical control group 
• Report any findings from epidemiological studies, pooled analysis of 
multiple studies, or clinical studies that suggest a significant risk in humans 
exposed to the drug no later than 15 calendar days after it is determined 
that the information qualifies for reporting. 
• Report any findings from animal or in vitro testing that suggest significant 
risk in humans exposed to the drug no later than 15 calendar days after it 
is determined that the information qualifies for reporting.  
• Report any clinically important increase in the rate of a serious suspected 
adverse reaction of that listed in the protocol or IB within 15 calendar days 
after it is determined that the information qualifies for reporting. 
 

Version 01/19/23– Amendment 7 
 
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Submit each report as an IND safety report in a narrative format or on FDA Form 
3500A or in an electronic format that FDA can process, review, and archive.  Study 
teams must notify the Siteman Cancer Center Protocol Development team of each 
potentially reportable event within 1 business day after initial receipt of the 
information, and must bring the signed 1571 and FDA Form 3500A to the Siteman 
Cancer Center Protocol Development team no later than 1 business day prior to the 
due date for reporting to the FDA. 
 
Each notification to FDA must bear prominent identification of its contents (“IND 
Safety Report”) and must be transmitted to the review division in the Center for 
Drug Evaluation and Research (CDER) or in the Center for Biologics Evaluation 
and Research (CBER) that has responsibility for review of the IND.  Relevant 
follow-up information to an IND safety report must be submitted as soon as the 
information is available and must be identified as such (“Follow-up IND Safety 
Report”). 
 
11.6 
Reporting to Bristol-Myers Squibb 
 
All serious adverse events (SAEs, defined in Section 11.1.2), unexpected adverse 
experiences (defined in Section 11.1.3), and life-threatening adverse events (defined in 
Section 11.1.4) that occur following study treatment commencement through 30 days of 
discontinuation of dosing must be reported to BMS Worldwide Safety regardless of 
relationship to study drug. Pregnancies must also be reported as an SAE.  
 
Report within 24 hours to Worldwide.Safety@BMS.com or via facsimile at (609) 818-
3804. If only limited information is initially available, follow-up reports are required. 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 to BMS using the same 
procedure used for the initial SAE report. All SAEs should be followed to resolution or 
stabilization. 
 
11.7 
Reporting to Celgene 
 
All serious adverse events (SAEs, defined in Section 11.1.2), unexpected adverse 
experiences (defined in Section 11.1.3), and life-threatening adverse events (defined in 
Section 11.1.4) that occur following study treatment commencement through 30 days of 
discontinuation of dosing must be reported to Celgene regardless of relationship to study 
drug. Pregnancies must also be reported as an SAE. 
 
Report within 24 hours to drugsafety@celgene.com or via facsimile at (908) 673-9115 for 
US and (289)-291-4820 for Canada. The initial report must be as complete as possible, 
including an assessment of the causal relationship between the event and the investigational 
product(s). Information not available at the time of the initial report (e.g., an end date for 
the adverse event or laboratory values received after the report) must be documented on a 
follow-up report. A final report to document resolution of the SAE is required. The Celgene 
tracking number (PO-CL-MM-PI-008341) and the institutional protocol number should be 

Version 01/19/23– Amendment 7 
 
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included on SAE reports (or on the fax cover letter) sent to Celgene. A copy of the fax 
transmission confirmation of the SAE report to Celgene should be attached to the SAE and 
retained with the patient records. 
 
All reports must include the patient number, age, sex, weight, severity of reaction (e.g. 
mild, moderate, severe), relationship to drug (e.g. probably related, unknown relationship, 
definitely not related), date and time of administration of test medications and all 
concomitant medications, and medical treatment provided. The investigator is responsible 
for evaluating all adverse events to determine whether criteria for “serious” and as defined 
above are present.  
 
For the purpose of regulatory reporting, Celgene Drug Safety will determine the 
expectedness of events of being related to pomalidomide based on the Investigator 
Brochure. In the United States, all suspected unexpected serious adverse reactions 
(SUSARs) will be reported in an expedited manner in accordance with 21 CFR 312.3 and 
Health Canada/ICH Guidance Document E2A: "Clinical Safety Data Management: 
Definitions and Standards for Expedited Reporting" and Canadian Foods and Drugs Act 
C.05.014. 
 
Participating study sites must report SAEs to Celgene as described and within 24 hours of 
awareness.  Participating sites should also report SAEs to the primary study site. 
 
Celgene Drug Safety Contact Information: 
For US Study Sites: 
Celgene Corporation      
Global Drug Safety and Risk Management    
86 Morris Avenue, Summit, NJ 07901      
Fax: 
 
(908) 673-9115 
E-mail:  
drugsafety@celgene.com 
 
For Canadian Study Sites: 
Celgene Inc. 
6755 Mississauga Road, 
Mississauga, ON 
L5N 7Y2 
Fax:   
(289) 291-4820 
Email:       
 drugsafety-canada@celgene.com 
 
11.8 
Timeframe for Reporting Required Events  
 
Adverse events will be reported from study treatment commencement through 30 days of 
discontinuation of dosing or the start of next anti-myeloma therapy, whichever comes first.  
 
 
 
 

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page 39 of 75 
11.9 
Record Retention  
 
As the sponsor, Washington University, will retain all source data and documentation 
pertaining to this clinical trial for a period of 25 years.  
 
 
12.0 
DATA AND SAFETY MONITORING 
 
Board (DSMB) will be specifically convened for this trial to review toxicity data.  A DSMB will 
consist of no fewer than 3 members including 2 clinical investigators and a biostatistician.  DSMB 
members must be employed by Washington University, Barnes-Jewish Hospital, or St. Louis 
Children’s Hospital.  Like investigators, DSMB members are subject to the Washington University 
School of Medicine policies regarding standards of conduct. Individuals invited to serve on the 
DSMB will disclose any potential conflicts of interest to the trial principal investigator and/or 
appropriate university officials, in accordance with institution policies. Potential conflicts that 
develop during a trial or a member’s tenure on a DSMB must also be disclosed.  
 
Until such a time as the first secondary site enrolls its first patient, a semi-annual DSM report to 
be prepared by the study team will be submitted to the Quality Assurance and Safety Monitoring 
Committee (QASMC) semi-annually beginning six months after study activation at Washington 
University (if at least one patient has been enrolled) or one year after study activation (if no patients 
have been enrolled at the six-month mark). 
 
The DSM report for the DSMB will be prepared by the study team with assistance from the study 
statistician, will be reviewed by the DSMB, and will be submitted to the QASM Committee.  The 
DSMB must meet at least every six months beginning six months after study activation at 
Washington beginning six months after enrollment of the first patient at a secondary site, no more 
than one month prior to the due date of the DSM report to QASMC.   
• HRPO protocol number, protocol title, Principal Investigator name, data coordinator name, 
regulatory coordinator name, and statistician 
• Date of initial HRPO approval, date of most recent consent HRPO approval/revision, date 
of HRPO expiration, date of most recent QA audit, study status, and phase of study 
• History of study including summary of substantive amendments; summary of accrual 
suspensions including start/stop dates and reason; and summary of protocol exceptions, 
error, or breach of confidentiality including start/stop dates and reason 
• Study-wide target accrual and study-wide actual accrual including numbers from 
participating sites 
• Protocol activation date at each participating site 
• Average rate of accrual observed in year 1, year 2, and subsequent years at each 
participating site 
• Expected accrual end date and accrual by site 
• Objectives of protocol with supporting data and list the number of participants who have 
met each objective 
• Measures of efficacy 
• Early stopping rules with supporting data and list the number of participants who have met 
the early stopping rules 

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• Summary of toxicities at all participating sites 
• Abstract submissions/publications 
• Summary of any recent literature that may affect the safety or ethics of the study 
 
Further DSMC responsibilities are described in the DSMC charter. 
 
The study principal investigator and coordinator will monitor for serious toxicities on an ongoing 
basis. Once the principal investigator or coordinator becomes aware of an adverse event, the AE 
will be reported to the HRPO and QASMC according to institutional guidelines (please refer to 
Section 11.0). 
 
Refer to the Washington University Quality Assurance and Data Safety Monitoring Committee 
Policies and Procedures for full details on the responsibilities of the DSMB. This is located on the 
QASMC website at https://siteman.wustl.edu/research/clinical-research-resources/protocol-
office-prmcqasmc/.   
 
 
13.0 
STATISTICAL CONSIDERATIONS 
 
This is an open-label, single arm phase II study that will accrue at 5-6 centers within the United 
States. The total accrual goal is 40 patients evaluable for the primary objective. The estimated 
accrual is 1-2 patients per month, with a projected enrollment time frame of 24 months.  
 
13.1 
Determination of Sample Size 
 
A power analysis was performed using one-sample log-rank test for the primary objective. 
The smallest increase in 1-year EFS rate with Elo-Pom-Dex continuation therapy is 20%, 
with a result of < 19% being considered ineffective. Based on the literature, we estimate 
that the 1-year EFS following second melphalan ASCT is ~40%. Assuming EFS times 
follow an exponential distribution and a minimal 1-year follow-up period, forty evaluable 
patients will detect a 20% improvement (40% vs. 60%) in 1-year EFS with 80% power at 
1-sided 0.05 alpha. 
 
13.2 
Data Analysis 
 
Demographic and clinical characteristics of the sample, as well as adverse events, will be 
summarized using descriptive statistics. For continuous variables, the number of patients, 
mean, standard deviation, median, minimum and maximum will be provided.  For 
categorical 
variables, 
the 
number 
and 
percent 
of 
patients 
in 
each 
demographic/characteristic category will be summarized. 
 
All time-to-event variables (EFS, PFS, and OS) will be described using Kaplan-Meier 
product limit estimator. The 1 year EFS rate and its 90% confidence interval (CI) will be 
estimated using Kaplan-Meier product limit estimator.  Kaplan-Meier curves will also be 
used to describe the association between response (both prior to and after continuation 
therapy) and EFS, PFS, and OS, and proportional hazards Cox models will be used to 

Version 01/19/23– Amendment 7 
 
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control the potential confounding effects of other patient and clinical characteristics.  
 
Response rates (MRD, ORR, CRR) will be described using descriptive statics with the 
corresponding 90% confidence intervals.  
 
The final primary analysis will be performed once enrollment has been concluded and all 
treated patients have completed 1 year of follow-up post-ASCT and/or have been 
withdrawn from study treatment.    
 
An interim analysis will be performed at the 2-year mark (where approximately one-half 
of patients will have at least 1-year follow-up if assuming uniform accrual) and the 
conditional power will be calculated for futility analysis based on the accumulated data. 
Conditional power is defined as the projected power to reject the null hypothesis at the end 
of the study given the data accrued up to the interim analysis. Therefore, a small value of 
conditional power indicates a highly likely, if not inevitable, conclusion of negative finding 
given the current data. If conditional power of 0.3 or less is obtained at the interim analysis, 
an early termination due to futility will be recommended. 
 
Parallel analyses will be performed on the data of patients in retrospective cohort. As the 
data on second ASCT is scant in the modern therapy era, the retrospective data is being 
used to provide context to the clinical trial data. There will be no direct statistical 
comparisons between the prospective and retrospective cohorts. 
 
13.3 
Analysis Populations 
 
13.3.1 Intent-to-Treat 
 
The intent-to-treat (ITT) population will be defined as all patients who receive at 
least one dose of Elo-Pom-Dex continuation.  
 
13.3.2 Safety 
 
The safety population will be defined as all patients with at least one dose of Elo-
Pom-Dex continuation. 
 
13.4 
Study Termination 
 
There are no planned early stopping rules. However, at any time the study may be 
discontinued by the sponsor due to excessive toxicity, enrollment issues, etc. In this 
event, all participating sites, physicians, and patients will be notified and alternative 
treatment plans will be arranged.  
 
 
 
 
 

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14.0 
AUDITING 
 
As coordinating center of this trial, Washington University (via the Quality Assurance and Safety 
Monitoring Committee (QASMC) will monitor each participating site to ensure that all protocol 
requirements are being met; that applicable federal regulations are being followed; and that best 
practices for patient safety and data collection are being followed per protocol.  Participating sites 
will be asked to send copies of all audit materials, including source documentation.  The audit 
notification will be sent to the Washington University Research Patient Coordinator, who will 
obtain the audit materials from the participating institution. 
 
Notification of an upcoming audit will be sent to the research team one month ahead of the audit. 
Once accrual numbers are confirmed, and approximately 30 days prior to the audit, a list of the 
cases selected for review (up to 10 for each site) will be sent to the research team. However, if 
during the audit the need arises to review cases not initially selected, the research team will be 
asked to provide the additional charts within two working days. 
 
Items to be evaluated include: 
• Subject screening and enrollment 
• Reporting of adverse events 
• Maintenance of HIPAA compliance 
• Completeness of regulatory documentation 
• Completeness of participant documentation 
• Acquisition of informed consent 
• IRB documentation 
• Issues of protocol adherence 
 
Additional details regarding the auditing policies and procedures can be found at 
https://siteman.wustl.edu/wp-content/uploads/2015/10/QASMC-Policies-and-Procedures-
03.31.2015.pdf 
 
15.0 
MULTICENTER REGULATORY REQUIREMENTS 
 
Washington University requires that each participating site sends its informed consent document 
to be reviewed and approved by the Washington University Regulatory Coordinator (or designee) 
prior to IRB/IEC submission.    
 
Site activation is defined as when the secondary site has received official written documentation 
from the coordinating center that the site has been approved to begin enrollment.  At a minimum, 
each participating institution must have the following documents on file at Washington University 
prior to study activation: 
• Documentation of IRB approval of the study in the form of a letter or other official 
document from the participating institution’s IRB.  This documentation must show which 
version of the protocol was approved by the IRB. 
• Documentation of IRB approval of an informed consent form. The consent must include a 
statement that data will be shared with Washington University, including the Quality 

Version 01/19/23– Amendment 7 
 
page 43 of 75 
Assurance and Safety Monitoring Committee (QASMC), the DSMC (if applicable), and 
the Washington University study team. 
• Documentation of FWA, signed FDA Form 1572 (if applicable), and the CVs of all 
participating investigators. 
• Protocol signature page signed and dated by the investigator at each participating site. 
 
The coordinating center Principal Investigator (or designee) is responsible for disseminating to the 
participating sites all study updates, amendments, reportable adverse events, etc.  Protocol/consent 
modifications and IB updates will be forwarded electronically to the secondary sites within 4 
weeks of obtaining Washington University IRB approval.  Activated secondary sites are expected 
to submit protocol/consent/IB modifications to their local IRBs within 4 weeks of receipt unless 
otherwise noted.  Upon the secondary sites obtaining local IRB approval, documentation of such 
shall be sent to the Washington University study team within 2 weeks of receipt of approval. 
 
Documentation of participating sites’ IRB approval of annual continuing reviews, protocol 
amendments or revisions, all SAE reports, and all protocol violations/deviations/exceptions must 
be kept on file at Washington University. 
 
The investigator or a designee from each institution must participate in a regular conference call 
to update and inform regarding the progress of the trial. 
 
 

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17.0 
REFERENCES 
 
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randomized trial of autologous bone marrow transplantation and chemotherapy in multiple 
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3. Attal M, Lauwers-Cances V, Marit G, Caillot D, Moreau P, Facon T et al. Lenalidomide 
maintenance after stem-cell transplantation for multiple myeloma. New Engl J Med 2012; 366: 
1782–1791.  
4. McCarthy PL, Owzar K, Hofmeister CC, Hurd DD, Hassoun H, Richardson PG et al. 
Lenalidomide after stem-cell transplantation for multiple myeloma. New Engl J Med 2012; 
366: 1770–1781.  
5. Cook G, Williams C, Cairns DA, Hockaday A, Cavenagh JD, Snowden JA, et al. A Salvage 
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from the UK MRA Myeloma X (Intensive) Trial. Presented at 2015 UK Myeloma Forum.   
6. Singh Abbi KK, Zheng J, Devlin SM, Giralt S, Landau H. Second Autologous Stem Cell 
Transplant: An Effective Therapy for Relapsed Multiple Myeloma. Biol Blood Marrow 
Transplant 2015; 21: 468–472.  
7. Blimark C, Veskovski L, Westin J, Rodjer S, Brune M, Hjorth M et al. Melphalan 100 mg/m2 
with stem cell support as first relapse treatment is safe and effective for myeloma patients with 
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9. Jimenez-Zepeda VH, Mikhael J, Winter A, Franke N, Masih-Khan E, Trudel S et al. Second 
autologous stem cell transplantation as salvage therapy for multiple myeloma: impact on 
progression-free and overall survival. Biol Blood Marrow Transplant 2012; 18: 773–779.  
10. Olin RL, Vogl DT, Porter DL, Luger SM, Schuster SJ, Tsai DE et al. Second auto-SCT is safe 
and effective salvage therapy for relapsed multiple myeloma. Bone Marrow Transplant 2009; 
43: 417–422.  
11. Sellner L, Heiss C, Benner A, Raab MS, Hillengass J, Hose D et al. Autologous 
retransplantation for patients with recurrent multiple myeloma: a single-center experience with 
200 patients. Cancer 2013; 119: 2438–2446.  
12. Anagnostopoulos A, Aleman A, Ayers G, Donato M, Champlin R, Weber D et al. Comparison 
of high-dose melphalan with a more intensive regimen of thiotepa, busulfan, and 
cyclophosphamide for patients with multiple myeloma. Cancer 2004; 100: 2607–2612.  
13. Benson DM Jr., Elder PJ, Lin TS, Blum W, Penza S, Avalos B et al. High-dose melphalan 
versus busulfan, cyclophosphamide, and etoposide as preparative regimens for autologous 
stem cell transplantation in patients with multiple myeloma. Leuk Res 2007; 31: 1069–1075.  
14. Kazmi SM, Saliba RM, Donato M, Wang M, Hosing C, Qureshi S et al. Phase II trial of high-
dose topotecan, melphalan and CY with autologous stem cell support for multiple myeloma. 
Bone Marrow Transplant 2011; 46: 510–515.  
15. Roussel M, Moreau P, Huynh A, Mary JY, Danho C, Caillot D et al. Bortezomib and high-
dose melphalan as conditioning regimen before autologous stem cell transplantation in patients 

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with de novo multiple myeloma: a phase 2 study of the Intergroupe Francophone du Myelome 
(IFM). Blood 2010; 115: 32–37.  
16. Lonial S, Kaufman J, Tighiouart M, Nooka A, Langston AA, Heffner LT et al. A phase I/II 
trial combining high-dose melphalan and autologous transplant with bortezomib for multiple 
myeloma: a dose- and schedule-finding study. Clin Cancer Res 2010; 16: 5079–5086.  
17. Gimsing P, Hjertner O, Abildgaard N, Andersen NF, Dahl TG, Gregersen H et al. A phase II 
study of bortezomib-dexamethason followed by high-dose melphalan combined with 
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18. Thompson PA, Prince HM, Seymour JF, Ritchie D, Stokes K, Burbury K et al. Bortezomib 
added to high-dose melphalan as pre-transplant conditioning is safe in patients with heavily 
pre-treated multiple myeloma. Bone Marrow Transplant 2011; 46: 764–765. 
19. Wang TF, Fiala MA, Cashen AF, Uy GL, Abboud CN, Fletcher T et al. A phase II study of V-
BEAM as conditioning regimen before second auto-SCT for multiple myeloma. Bone Marrow 
Transplant 2014; 49: 1366–1370. 
20. Durie BGM, et al. International uniform response criteria for multiple myeloma. Leukemia 
2006; 1-7.  
21. Kumar, S, et al. International Myeloma Working Group consensus criteria for response and 
minimal residual disease assessment in multiple myeloma. Lancet Oncology 2016; 17(8): 
e328-e346. 
22. Martinez-Lopez, et al. Prognostic Value of Deep Sequencing Method for Minimal Residual 
Disease Detection in Multiple Myeloma. Blood 2014; 123(20): 3073-3079. 
 
 

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APPENDIX A: ECOG Performance Scale 
 
 
Grade 
 
 
Description 
0 
Normal activity.  Fully active, able to carry on all pre-disease 
performance without restriction. 
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). 
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. 
3 
 
In bed >50% of the time.  Capable of only limited self-care, confined 
to bed or chair more than 50% of waking hours. 
 
4 
100% bedridden.  Completely disabled.  Cannot carry on any self-care.  
Totally confined to bed or chair. 
5 
 
Dead. 
 
 
 
 

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APPENDIX B: Cockcroft-Gault Equation 
 
For males: 
Creatinine Clearance = (140-age[years] × weight [kg]) 
OR 
(140–age[years] × weight 
[kg]) 
72 × (serum creatinine[mg/dL]) 
 
0.81 × (serum 
creatinine[µmol/L]) 
 
For females: 
Creatinine Clearance = 0.85 (140-age[years] × weight [kg]) OR  0.85 (140-age[years] × weight 
[kg]) 
72 × (serum creatinine[mg/dL]) 
 
0.81 × (serum 
creatinine[µmol/L]) 
 
Source:  Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. 
Nephron 1976;16(1):31-41. 
 
 

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APPENDIX C: Elotuzumab Preparation and Administration Guidelines  
 
Product 
Description / 
Class and 
Dosage Form 
Potency 
IMP/Non-
IMP 
Blinded or 
Open Label 
Packaging/ 
Appearance 
Storage 
Conditions 
(per label) 
Elotuzumab 
Powder for 
Solution for 
Infusion 
400 mg or 
300mg/vial 
IMP 
Open Label 
20 mL Vial/ Sterile, 
white to off-white, 
preservative-free, 
lyophilized cake 
Store at 
2°C - 8°C 
 
Dose Preparation Instructions 
 
After dilution in normal saline, elotuzumab infusion must be completed within 8 hours if kept at 
room temperature (25C). In the United States and Puerto Rico, where a shortage of normal saline 
has been reported, dextrose 5% water (D5W) may be used. Normal saline is the preferred diluent 
and D5W should only be used if normal saline is not available. If a delay is anticipated after the 
dose has been diluted in normal saline, the prepared dose (properly identified) may be 
refrigerated at 2C to 8C for up to 24 hours. If stored under refrigerated conditions, the study drug 
solution should be equilibrated to room temperature (takes about 2 to 2.5 hours), and the 
container must be gently inverted to thoroughly mix the contents before administration. If the 
storage time limit is exceeded, the prepared dose solution must be discarded and the reason 
documented by the pharmacist in the study drug accountability records. 
 
Elotuzumab will be administered to each subject as an IV infusion, using an automated infusion 
pump set at the appropriate rate according to the dose administration section (see Administration 
Instruction section below). The dose of elotuzumab will be calculated using the subject’s predose 
weight on Day 1 of each cycle (the screening weight can be used for Cycle 1 dose calculation), 
and then added to 0.9% saline for infusion. 
 
Reconstitute elotuzumab lyophilized study drug, as described in steps 1 to 5. 
 
Step 1: For a 440 mg vial of lyophilized elotuzumab, draw 17 mL of Sterile Water for Injection 
(SWFI), USP into a syringe equipped with an 18-gauge or smaller needle. 
 
Step 2: Remove the flip-top from the elotuzumab vial. 
 
Step 3: Place the vial upright on a flat surface and, using standard aseptic techniques, insert the 
syringe needle into the vial through the center of the rubber stopper and deliver 17 mL (into the 
20-mL vial containing 440 mg elotuzumab) SWFI, USP, into the vial. Slowly remove the syringe 
needle out of the vial. The final volume of the reconstituted solution is approximately 17.6 mL, 
which includes the volume displaced by the solid cake. The concentration of elotuzumab in the 
reconstituted solution is approximately 25 mg/mL. 
 
Step 4: DO NOT SHAKE. Hold the vial upright and gently swirl the solution by rotating the vial 

Version 01/19/23– Amendment 7 
 
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to dissolve the lyophilized cake. Then gently invert the vial a few times in order to dissolve any 
powder that may be present on top of the vial or the stopper. Finally, hold the vial upright again 
and gently swirl the solution a few more times to dissolve any remaining particles. Avoid 
prolonged or vigorous agitation. DO NOT SHAKE. 
 
Step 5: After the remaining solids are completely dissolved, allow the reconstituted solution to 
stand for 5 to 10 minutes. It is acceptable to have small bubbles and/or foam around the edge of 
the vial. The reconstituted 
preparation results in a colorless to slightly yellow, clear to slightly opalescent solution 
containing approximately 25 mg/mL of elotuzumab. 
 
Step 6: Once the reconstitution is completed, withdraw the calculated drug volume and further 
dilute with 100-500 ml of normal saline into an infusion bag (see Pharmacy Manual for 
additional details). The volume of saline or D5W can be adjusted so as not to exceed 5 mL/kg of 
patient weight at any given dose of elotuzumab. The resulting elotuzumab concentration must be 
from 1.0 mg/mL to 6.0 mg/mL. Elotuzumab solutions are compatible with polyvinyl chloride 
and polyolefin bags. Examples of such bags include Viaflo, MacoPharma Easyflex N, Macoflex 
N, B Braun Excel, and Braun Ecobag. 
 
Drug volume will be calculated based on subject weight: For example, a subject receiving 
10 mg/kg elotuzumab who weighs 80 kg on Day 1 [predose] will require 800 mg of study drug 
for infusion. Withdraw 32 mL of elotuzumab (25 mg/mL) from 2 vials and add to an infusion 
bag already containing 230 mL saline, for a total of 262 mL to be infused. 
Similarly, an 80 kg subject receiving 20 mg/kg elotuzumab [predose] will require 1600 mg of 
study drug for infusion. Withdraw 64 mL of elotuzumab (25 mg/mL) from 4 vials and add to an 
infusion bag already containing 340 mL saline, for a total of 404 mL to be infused. 
 
Use a new sterile needle for withdrawing solution from each vial. 
 
The same vial must not be used to prepare elotuzumab for more than one subject. Used 
elotuzumab vials will be stored until study drug accountability has been completed by the BMS 
designee, and destruction or return is authorized. Used vials do not need to be refrigerated. 
 
Note: Subjects must be premedicated as described in Section 5.2 prior to elotuzumab infusion. 
 
Administration Instructions 
 
The first dose of elotuzumab will be administered following premedications (described in 
Section 5.2) to each subject as an IV infusion, using an automated infusion pump set at an 
initial rate of 0.5 mL per minute (30 mL/hour). If the subject does not have an infusion reaction 
within 30 minutes, escalate the infusion rate by 0.5 mL per minute. If the subject still does not 
have an infusion reaction within 30 minutes, escalate the infusion rate to a maximum of 2 mL 
per minute (120 mL/hour). If a subject experiences a Grade > 2 infusion reaction, the infusion 
must be interrupted. Please  see below for detailed information on the management of infusion 
reaction and re-initiation of infusion. 
 

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The second dose of elotuzumab must be initiated at an infusion rate of 3 mL per minute if no 
infusion reactions were observed with the first elotuzumab infusion. If the subject does not 
experience an infusion reaction during the first 30 minutes of the second dose of elotuzumab, 
escalate the infusion rate to 4 mL per minute. 
 
The third dose of elotuzumab must be initiated at an infusion rate of 5 mL per minute if no 
infusion reactions were reported with the second elotuzumab infusion. 
 
The fourth and subsequent doses of elotuzumab must be initiated at an infusion rate of 5 mL 
per minute if no infusion reactions were reported. 
 
On the first dose of escalation to 20mg/kg (Cycle 7 of continuation), patient who have escalated 
to 5ml/min at 10 mg/kg dose must decrease the rate to 3 mL/min at the first infusion at 20 mg/kg 
(see Table 2 below). 
 
Elotuzumab Infusion Rate 
 
The elotuzumab infusion rate will be increased gradually to a maximum of 5 mL/min as 
presented in Table 1. Table 1 represents an example for an 80 kg subject receiving 10mg/kg 
dose. The total volume varies according to the subject weigh and the elotuzumab administered 
dose. 
 
Table 1 Elotuzumab Infusion Rate Plan     
 
 
 
 
 
 
 
Infusion Rate   
Duration of infusion   
    Volume delivered    Volume remaining 
Cycle 1 Dose 1  
Approximate Total Duration:  2hrs 50min  
 
 
262 mL* 
0.5 mL/min   
 
30 min  
 
 
15 mL   
 
247 mL 
1 mL/min  
 
 
30 min  
 
 
30 mL   
 
217 mL 
2 mL/min  
 
 
110 min  
 
 
217 mL  
 
0 mL 
Cycle 1 Dose 2  
Approximate Total Duration: 1hrs 13min  
 
 
262 mL 
3 mL/min  
 
 
30 min  
 
 
90 mL   
 
172 mL 
4 mL/min  
 
 
43 min  
 
 
172 mL  
 
0 mL 
Cycle 1 Dose 3 and 4  Approximate Total Duration: 53min   
 
 
262 mL 
5 mL/min  
 
 
53 min  
 
 
262 mL  
 
0 mL 
Cycle 2 +  
 
 
Approximate Total Duration: 53min   
 
262 mL 
5 mL/min  
 
 
53 min  
 
 
262 mL  
 
0 mL 
 
* Volume for 80 kg subject. Total volume varies according to the subject weight. 
Please note that infusion rate increase to the next higher level only if no infusion reactions 
encountered. 
 
Table 2 Elotuzumab Infusion Rate Plan for 20 mg/kg 
 
 
 
 
 
 
Dose 1 
Dose 2 and all subsequent doses 
Time Interval 
Rate 
Rate 
0-30 min 
3 mL/min 
5 ml/min 
30 min or more 
4 mL/min 
 

Versi o n 0 1/ 1 9/ 2 3 – A me n d me nt 7  
 
pa ge 5 1  of 7 5  
 
 
I nf usi o n Re acti o ns 
 
If a s u bject e x perie nces a Gra de 2 i nf usi o n reacti o n, t he i nf usi o n m ust be i nterr u pte d. 
P lease ref er t o A p p e n di x D f or detaile d i nf or mati o n o n t he ma na ge me nt of i nf usi o n reacti o n 
an d re-i nitiati o n of i nf usi o n. If a s u bject e x perie nces a Gra de 3 e l ot uz u ma b i nf usi o n reacti o n 
that has res ol ve d t o Gr a d e 1, s u bse q ue nt i nf usi o n rate of el ot uz u ma b s h o ul d be escalat e d i n a 
ste p wise fas hi o n ( 0. 5 m L e ver y 3 0 mi n utes as per a b o ve). 
 
1. A d mi nister t hr o u g h a l o w- pr otei n- bi n di n g 0. 2 2 - micr o meter or s maller i n -li ne filter ( place d 
as pr o xi mal t o t he s u bject as is practical). Pri me t h e i nf usi o n li ne wit h st u d y dr u g b ef ore  
starti n g t he i nf usi o n. 
 
2. Set t he I V p u m p t o deli ver t he i nf usi o n at t he rate of 0. 5 m L p er mi n ute (i ncl u di n g t he dr u g 
i n t he li ne). T he t otal ti me of i nf usi o n will var y de pe n di n g u p o n t he m a xi m u m t olerate d 
m L/ mi n i nf usi o n rate as disc usse d a b o ve. 
 
3. Rec or d e v er y ti me t he i nf usi o n is starte d a n d st o p pe d a n d t he reas o n w h y t he start a n d st o p 
occ urr e d.  
 
4. M o nit or t he I V set u p a n d t he s u bject’s I V site fre q ue ntl y d uri n g i nf usi o n, c hec ki n g f or t he  
c orrect i nf usi o n rate a n d I V site i nfiltrati o n.  
 
5. E ns ure t hat t he f ull v ol u me of el ot uz u ma b is i nf use d. 
 
After el ot uz u ma b has bee n i nf use d fr o m t he li ne, disc o nti n ue t he i nf usi o n, disc o n nect t he 
I V t u bi n g, a n d dis p ose of materials a p pr o priatel y acc or di n g t o t he facilit y’s sta n dar d pr oce d ure. 
 
N ote: S u bjects m ust be pre me dicat e d as des cri be d i n Secti o n 5. 2  pri or t o el ot uz u ma b i nf usi o n. 
 
 
 

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APPENDIX D: Guidelines for Elotuzumab Infusion in Subjects with Infusion Reactions 
 
Grade 1 Infusion Reaction 
Grade 1 elotuzumab infusion-related reactions by definition do not require intervention; 
however, increased monitoring is recommended. 
 
Grade 2 or 3 Infusion Reaction 
Infusion reactions during the elotuzumab infusion: For a Grade 2 or 3 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. 
 
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 the rate at which the 
infusion reaction occurred. If no recurrence of the infusion reaction, the escalation regimen can be 
resumed. Subjects who experience an infusion reaction require vital signs to be monitored every 
30 minutes for 1 or 2 hours after the end of the elotuzumab infusion (as clinically indicated). 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 throughout Section 4.5.4 
 
Infusion reactions after the completion of elotuzumab infusion: Should a Grade 2 or 
3 infusion reaction occur 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. 
 
Elotuzumab infusion on subsequent infusions after a Grade 2 or 3 infusion reaction: 
Subjects with a Grade 2 or 3 infusion reactions should have the next infusion started at 0.5 
mL/min and then escalated in a stepwise fashion (0.5 mL/minute every 30 minutes) to the rate at 
which the infusion reaction occurred.  
 
If no Grade > 2 infusion reaction occurs, at the next infusion, the escalation regimen will be 
resumed starting at the maximum rate achieved during the prior infusion and then escalated in a 
stepwise fashion (0.5 mL/minute every 30 minutes). 
   
Grade 4 Infusion Reaction 
Subjects with a Grade 4 elotuzumab infusion reaction must have elotuzumab permanently 
discontinued. 
 
Elotuzumab Premedication Regimen in Subjects With a Prior Infusion Reaction 
To be re-treated with elotuzumab, subjects with a prior infusion reaction must receive H1, H2 
blockers and acetaminophen at maximum doses specified (ie, 50 mg diphenhydramine, 50 mg 

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ranitidine (or equivalent), and 650-1000 mg acetaminophen) 45 to 90 minutes before initiating 
the elotuzumab. 
 
If a subject with a prior Grade 2 to 3 infusion reaction also requires dose reduction of 
dexamethasone, the dexamethasone dose on the days of elotuzumab infusion should be no less 
than 8 mg IV.  
 
Subjects with Grade 4 infusion reaction are not eligible to receive additional elotuzumab. These 
subjects may continue to receive pomalidomide and dexamethasone. 
 
 

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APPENDIX E: Pomalidomide Pregnancy Prevention Plan for Subjects in Clinical Trials  
 
The Pregnancy Prevention Plan (PPP) applies to all subjects receiving pomalidomide within a 
clinical trial. The following PPP documents are included:  
1. The Pomalidomide Risks of Fetal Exposure, Pregnancy Testing Guidelines and 
Acceptable Birth Control Methods document (Section 1) provides the following 
information: 
• Potential risks to the fetus associated with pomalidomide exposure 
• Definition of female of childbearing potential (FCBP)/female not of childbearing 
potential (FNCBP) 
• Requirements for counseling of all subjects receiving pomalidomide about pregnancy 
precautions and the potential risks of fetal exposure to pomalidomide 
• Acceptable birth control methods for both female subjects of childbearing potential 
and male subjects receiving pomalidomide in the study 
• Pregnancy testing requirements for subjects receiving pomalidomide who are FCBP 
2. The Pomalidomide Education and Counseling Guidance Document for each gender 
(female and male; Section 2 and Section 3 respectively) must be completed and signed by 
a trained counselor at the participating clinical center prior to each dispensing of 
pomalidomide. A copy of this document must be maintained in the subject’s records for 
each dispense. 
3. The Pomalidomide Information Sheet (Section 4) will be given to each subject receiving 
pomalidomide. The subject must read this document prior to starting pomalidomide and 
each time the subject receives a new supply of pomalidomide. 

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1. 
POMALIDOMIDE RISKS OF FETAL EXPOSURE, PREGNANCY TESTING 
GUIDELINES AND ACCEPTABLE BIRTH CONTROL METHODS 
1.1. 
Risks Associated with Pregnancy 
Pomalidomide was teratogenic in both rats and rabbits when administered during the period of 
organogenesis. Pomalidomide is an analogue of thalidomide. Thalidomide is a known human 
teratogen that causes severe life-threatening human birth defects. If pomalidomide is taken 
during pregnancy, it can cause birth defects or death to an unborn baby. 
The teratogenic effect of pomalidomide in humans cannot be ruled out. Therefore, a pregnancy 
prevention program must be followed. 
1.1.1. 
Definition of Females of Childbearing Potential 
A FCBP is a female who: 1) has achieved menarche at some point, 2) has not undergone a 
hysterectomy or bilateral oophorectomy or 3) has not been naturally postmenopausal 
(amenorrhea following cancer therapy does not rule out childbearing potential) for at least 
24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months). 
1.1.2. 
Definition of Females Not of Childbearing Potential 
Females who do not meet the above definition of FCBP should be classified as FNCBP. 
1.2. 
Counseling 
1.2.1. 
Females of Childbearing Potential 
For a FCBP, pomalidomide is contraindicated unless all of the following are met (ie, all FCBP 
must be counseled concerning the following risks and requirements prior to the start of 
pomalidomide):  
• She understands the potential teratogenic risk to the unborn child 
• She understands the need for effective contraception, without interruption, 28 days 
before starting pomalidomide, throughout the entire duration of pomalidomide, 
during dose interruptions and for at least 28 days after the last dose of pomalidomide 
• She understands and agrees to inform the Investigator if a change or stop of method 
of contraception is needed 
• She must be capable of complying with effective contraceptive measures 
• She is informed and understands the potential consequences of pregnancy and the 
need to notify her study doctor immediately if there is a risk of pregnancy 
• She understands the need to commence pomalidomide as soon as it is dispensed 
following a negative pregnancy test 
• She understands and accepts the need to undergo pregnancy testing based on the 
frequency outlined in this plan (Section 1.4) and in the Informed Consent 
• She acknowledges that she understands the hazards pomalidomide can cause to an 
unborn fetus and the necessary precautions associated with the use of pomalidomide. 

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The Investigator must ensure that a FCBP: 
• Complies with the conditions of the pregnancy prevention plan, including 
confirmation that she has an adequate level of understanding 
• Acknowledges the aforementioned requirements. 
1.2.2. 
Females Not of Childbearing Potential 
For a FNCBP, pomalidomide is contraindicated unless all of the following are met (ie, all 
FNCBP must be counseled concerning the following risks and requirements prior to the start of 
pomalidomide):  
• She acknowledges she understands the hazards pomalidomide can cause to an unborn 
fetus and the necessary precautions associated with the use of pomalidomide. 
1.2.3. 
Males 
The effect of pomalidomide on sperm development is not known and has not been studied. The 
risk to an unborn baby in females of child bearing potential whose male partner is receiving 
pomalidomide is unknown at this time. Therefore, male subjects taking pomalidomide must meet 
the following conditions (ie, all males must be counseled concerning the following risks and 
requirements prior to the start of pomalidomide): 
• Understand the potential teratogenic risk if engaged in sexual activity with a pregnant 
female or a FCBP 
• Understand the need for the use of a condom even if he has had a vasectomy, if 
engaged in sexual activity with a pregnant female or a FCBP 
• Understand the potential teratogenic risk if the subject donates semen or sperm. 
1.3. 
Contraception 
1.3.1. 
Female Subjects of Childbearing Potential 
Females of childbearing potential enrolled in this protocol must agree to use two reliable forms 
of contraception simultaneously or to practice complete abstinence (True abstinence is 
acceptable when this is in line with the preferred and usual lifestyle of the subject. Periodic 
abstinence [eg calendar, ovulation, symptothermal or post-ovulation methods] and withdrawal 
are not acceptable methods of contraception.) from heterosexual contact during the following 
time periods related to this study: 1) for at least 28 days before starting pomalidomide; 2) while 
taking pomalidomide; 3) during dose interruptions; and 4) for at least 28 days after the last dose 
of pomalidomide.  
The two methods of reliable contraception must include one highly effective method and one 
additional effective (barrier) method. If the below contraception methods are not appropriate for 
the FCBP, she must be referred to a qualified provider of contraception methods to determine the 
medically effective contraception method appropriate to the subject. The following are examples 
of highly effective and additional effective methods of contraception: 
• Examples of highly effective methods: 

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− Intrauterine device (IUD) 
− Hormonal (birth control pills, injections, implants, levonorgestrel-releasing 
intrauterine system [IUS], medroxyprogesterone acetate depot injections, 
ovulation inhibitory progesterone-only pills [e.g. desogestrel]) 
− Tubal ligation 
− Partner’s vasectomy 
• Examples of additional effective methods: 
− Male condom 
− Diaphragm 
− Cervical Cap 
Because of the increased risk of venous thromboembolism in subjects with multiple myeloma 
taking pomalidomide and dexamethasone, combined oral contraceptive pills are not 
recommended. If a subject is currently using combined oral contraception the subject should 
switch to another one of the highly effective methods listed above. The risk of venous 
thromboembolism continues for 4 to 6 weeks after discontinuing combined oral contraception. 
The efficacy of contraceptive steroids may be reduced during co-treatment with dexamethasone.  
Implants and levonorgestrel-releasing intrauterine systems are associated with an increased risk 
of infection at the time of insertion and irregular vaginal bleeding. Prophylactic antibiotics 
should be considered particularly in subjects with neutropenia.  
1.3.2. 
Male Subjects 
Male subjects must practice complete abstinence (True abstinence is acceptable when this is in 
line with the preferred and usual lifestyle of the subject. Periodic abstinence [eg calendar, 
ovulation, symptothermal or post-ovulation methods] and withdrawal are not acceptable methods 
of contraception.) or agree to use a condom during sexual contact with a pregnant female or a 
FCBP while taking pomalidomide, during dose interruptions and for at least 28 days after the last 
dose of pomalidomide, even if he has undergone a successful vasectomy.  
1.4. 
Pregnancy Testing 
Medically supervised pregnancy tests with a minimum sensitivity of 25 mIU/mL must be 
performed for FCBP. 
Females of childbearing potential must have two negative pregnancy tests (sensitivity of at least 
25 mIU/mL) prior to starting pomalidomide. The first pregnancy test must be performed within 
10 to 14 days prior to the start of pomalidomide and the second pregnancy test must be 
performed within 24 hours prior to the start of pomalidomide. The subject may not receive 
pomalidomide until the study doctor has verified that the results of these pregnancy tests are 
negative. 
Females of childbearing potential with regular or no menstrual cycles must agree to have 
pregnancy tests weekly for the first 28 days of study participation and then every 28 days while 

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taking pomalidomide, at study discontinuation, and at Day 28 following the last dose of 
pomalidomide.  
Females of childbearing potential with irregular menstrual cycles must agree to have pregnancy 
tests weekly for the first 28 days of study participation and then every 14 days while taking 
pomalidomide, at study discontinuation, and at Days 14 and 28 following the last dose of 
pomalidomide.  
1.5. 
Pregnancy Precautions for Pomalidomide Use 
1.5.1. 
Before Starting Pomalidomide 
1.5.1.1. 
Female Subjects of Childbearing Potential 
Females of childbearing potential must have two negative pregnancy tests (sensitivity of at least 
25 mIU/mL) prior to starting pomalidomide. The first pregnancy test must be performed within 
10 to 14 days prior to the start of pomalidomide and the second pregnancy test must be 
performed within 24 hours prior to the start of pomalidomide. The subject may not receive 
pomalidomide until the study doctor has verified that the results of these pregnancy tests are 
negative. 
Females of childbearing potential must use two reliable forms of contraception simultaneously, 
or practice complete abstinence (True abstinence is acceptable when this is in line with the 
preferred and usual lifestyle of the subject. Periodic abstinence [eg calendar, ovulation, 
symptothermal or post-ovulation methods] and withdrawal are not acceptable methods of 
contraception.) from heterosexual contact for at least 28 days before starting pomalidomide. 
1.5.1.2. 
Male Subjects 
Male subjects must agree to practice complete abstinence (True abstinence is acceptable when 
this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence [eg 
calendar, ovulation, symptothermal or post-ovulation methods] and withdrawal are not 
acceptable methods of contraception.) or agree to use a condom during sexual contact with a 
pregnant female or a FCBP while taking pomalidomide, during dose interruptions and for at least 
28 days after the last dose of pomalidomide, even if he has undergone a successful vasectomy.  
1.5.2. 
During and After Study Participation 
1.5.2.1. 
Female Subjects 
• Females of childbearing potential with regular or no menstrual cycles must agree to 
have pregnancy tests weekly for the first 28 days of study participation and then every 
28 days while taking pomalidomide, at study discontinuation, and at Day 28 
following the last dose of pomalidomide.  
• Females of childbearing potential with irregular menstrual cycles must agree to have 
pregnancy tests weekly for the first 28 days of study participation and then every 
14 days while taking pomalidomide, at study discontinuation, and at Days 14 and 28 
following the last dose of pomalidomide.  

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• At each visit, the Investigator must confirm with the FCBP that she is continuing to 
use two reliable methods of birth control if not committing to complete abstinence, or 
confirm commitment to complete abstinence. 
• If a FCBP considers the need to change or to stop a method of contraception, the 
Investigator must be notified immediately. 
• Counseling about pregnancy precautions and the potential risks of fetal exposure 
must be conducted at a minimum of every 28 days.  
• If pregnancy or a positive pregnancy test does occur in a subject, pomalidomide must 
be immediately discontinued. 
• Pregnancy testing and counseling must be performed if a subject misses her period or 
if her pregnancy test or her menstrual bleeding is abnormal. Pomalidomide must be 
discontinued during this evaluation. 
• Females must agree to abstain from breastfeeding while taking pomalidomide and for 
at least 28 days after the last dose of pomalidomide. 
1.5.2.2. 
Male Subjects 
• Must practice complete abstinence (True abstinence is acceptable when this is in line 
with the preferred and usual lifestyle of the subject. Periodic abstinence [eg calendar, 
ovulation, symptothermal or post-ovulation methods] and withdrawal are not 
acceptable methods of contraception.) or use a condom during sexual contact with a 
pregnant female or a FCBP while receiving pomalidomide, during dose interruptions 
and for at least 28 days after the last dose of pomalidomide, even if he has undergone 
a successful vasectomy. 
• Must not donate semen or sperm while receiving pomalidomide, during dose 
interruptions or for at least 28 days after the last dose of pomalidomide. 
• Counseling about pregnancy precautions and the potential risks of fetal exposure 
must be conducted at a minimum of every 28 days. 
• If pregnancy or a positive pregnancy test does occur in the partner of a male subject 
while taking pomalidomide, the Investigator must be notified immediately. 
1.5.3. 
Additional Precautions 
• Subjects should be instructed to never give pomalidomide to another person. 
• Subjects should be instructed to return any unused capsules to the study doctor. 
• Subjects should not donate blood while receiving pomalidomide, during dose 
interruptions and for at least 28 days after the last dose of pomalidomide. 
• No more than a 28-day pomalidomide supply may be dispensed with each cycle of 
pomalidomide.  

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2. 
POMALIDOMIDE EDUCATION AND COUNSELING GUIDANCE 
DOCUMENT FOR FEMALE SUBJECTS 
To be completed prior to each dispensing of pomalidomide. 
Protocol Number: ____________________________________________ 
Subject Name (Print): __________________ DOB: _____/_____/_____ (dd/mmm/yyyy) 
Check one risk category: 
 FCBP (Female of childbearing potential): a female who: 1) has achieved menarche 
(first menstrual cycle) at some point, 2) has not undergone a hysterectomy (the 
surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of 
both ovaries) or 3) has not been naturally postmenopausal (amenorrhea following 
cancer therapy does not rule out childbearing potential) for at least 24 consecutive 
months (ie, has had menses at any time during the preceding 24 consecutive months) 
 NOT FCBP 
2.1. 
Female of Childbearing Potential: 
1. I have verified and counseled the subject regarding the following: 
 Potential risk of fetal exposure to pomalidomide: A teratogenic potential of 
pomalidomide in humans cannot be ruled out. If pomalidomide is taken during 
pregnancy, it may cause birth defects or death to any unborn baby. Females are 
advised to avoid pregnancy while taking pomalidomide. Females of childbearing 
potential must agree not to become pregnant while taking pomalidomide.  
 
That the required pregnancy tests performed are negative. 
 The subject confirmed that she is using TWO reliable methods of birth control at the 
same time, or complete abstinence (True abstinence is acceptable when this is in line 
with the preferred and usual lifestyle of the subject. Periodic abstinence [eg calendar, 
ovulation, symptothermal or post-ovulation methods] and withdrawal are not 
acceptable methods of contraception.) from heterosexual contact (at least 28 days 
prior to receiving pomalidomide, while receiving pomalidomide, during dose 
interruptions and for at least 28 days after the last dose of pomalidomide).  
One highly effective method and one additional method of birth control must be used 
AT THE SAME TIME. The following are examples of highly effective and 
additional effective methods of contraception: 
− Examples of highly effective methods: 
o Intrauterine device (IUD) 
o Hormonal (birth control pills, injections, implants, levonorgestrel-releasing 
intrauterine system [IUS], medroxyprogesterone acetate depot injections, 
ovulation inhibitory progesterone-only pills [e.g. desogestrel]) 
o Tubal ligation 
o Partner’s vasectomy 

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− Examples of additional effective methods: 
o Male condom 
o Diaphragm 
o Cervical Cap 
 The subject confirmed that even if she has amenorrhea she must comply with advice 
on contraception. 
 Pregnancy tests before, during administration of pomalidomide and at the last dose of 
pomalidomide, even if the subject agrees not to have reproductive heterosexual 
contact. 
 Frequency of pregnancy tests to be done: 
− Two pregnancy tests will be performed prior to receiving pomalidomide, one 
within 10 to 14 days, and a second within 24 hours of the start of pomalidomide. 
− Every week during the first 28 days of this study and a pregnancy test every 
28 days while the subject is taking pomalidomide if menstrual cycles are regular.  
− Every week during the first 28 days of this study and a pregnancy test every 
14 days while the subject is taking pomalidomide if menstrual cycles are 
irregular. 
− If the subject missed a period or has unusual menstrual bleeding.   
− When the subject is discontinued from the study and at Day 28 after the last dose 
of pomalidomide if menstrual cycles are regular. If menstrual cycles are irregular, 
pregnancy tests will be done at discontinuation from the study and at Days 14 and 
28 after the last dose of pomalidomide. 
 The subject confirmed that she will stop taking pomalidomide immediately in the 
event of becoming pregnant and to call her study doctor as soon as possible.  
 The subject confirmed that she has not and will not breastfeed a baby while taking 
pomalidomide and for at least 28 days after the last dose of pomalidomide. 
 The subject has not and will never share pomalidomide with anyone else. 
 The subject has not and will not donate blood while taking pomalidomide, during 
dose interruptions and for at least 28 days after the last dose of pomalidomide. 
 The subject has not and will not break, chew, or open pomalidomide capsules at any 
point. 
 The subject confirmed that she will return unused pomalidomide capsules to the study 
doctor. 
2. I have provided the Pomalidomide Information Sheet to the subject. 
2.2. 
Female Not of Childbearing Potential (Natural Menopause for at Least 24 
Consecutive Months, a Hysterectomy, or Bilateral Oophorectomy): 
1. I have verified and counseled the subject regarding the following: 

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 Potential risk of fetal exposure to pomalidomide: A teratogenic potential of 
pomalidomide in humans cannot be ruled out. If pomalidomide is taken during 
pregnancy, it may cause birth defects or death to any unborn baby. 
 The subject has not and will never share pomalidomide with anyone else. 
 The subject has not and will not donate blood while taking pomalidomide, during 
dose interruptions and for at least 28 days after the last dose of pomalidomide. 
 The subject has not and will not break, chew, or open pomalidomide capsules at any 
point. 
 The subject confirmed that she will return unused pomalidomide capsules to the study 
doctor. 
2. I have provided the Pomalidomide Information Sheet to the subject. 
Do Not Dispense Pomalidomide if: 
• The subject is pregnant. 
• No pregnancy tests were conducted for a FCBP. 
• The subject states she did not use TWO reliable methods of birth control (unless 
practicing complete abstinence from heterosexual contact) at least 28 days prior 
to receiving pomalidomide, while receiving pomalidomide and during dose 
interruptions. 
• The subject stated that she has or does not want to adhere to pregnancy 
precautions outlined within this PPP. 
 
Counselor Name (Print): ____________________  
 
Counselor Signature: _______________________ Date: _____/_____/_____(dd/mmm/yyyy) 
 
**Maintain a copy of the Education and Counseling Guidance Document in the subject’s 
records.** 

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3. 
POMALIDOMIDE EDUCATION AND COUNSELING GUIDANCE 
DOCUMENT FOR MALE SUBJECTS 
To be completed prior to each dispensing of pomalidomide. 
Protocol Number: ____________________________________________ 
Subject Name (Print): __________________ DOB: _____/_____/_____ (dd/mmm/yyyy) 
 
1. I have verified and counseled the subject regarding the following: 
 Potential risk of fetal exposure to pomalidomide: A teratogenic potential of 
pomalidomide in humans cannot be ruled out. If pomalidomide is taken during 
pregnancy, it may cause birth defects or death to any unborn baby. 
 The subject confirmed that he has practiced complete abstinence (True abstinence is 
acceptable when this is in line with the preferred and usual lifestyle of the subject. 
Periodic abstinence [eg calendar, ovulation, symptothermal or post-ovulation 
methods] and withdrawal are not acceptable methods of contraception.) or used a 
condom when engaging in sexual contact (including those who have had a 
vasectomy) with a pregnant female or FCBP, while taking pomalidomide, during 
dose interruptions and for at least 28 days after the last dose of pomalidomide. 
 The subject confirmed that he has not impregnated his female partner while in the 
study. 
 The subject confirmed that he will notify his study doctor if his female partner 
becomes pregnant and the female partner of a male subject taking pomalidomide 
confirmed that she will call her healthcare provider immediately if she becomes 
pregnant. 
 The subject has not and will never share pomalidomide with anyone else. 
 The subject confirmed that he has not donated and will not donate semen or sperm 
while taking pomalidomide or during dose interruptions and that he will not donate 
semen or sperm for at least 28 days after the last dose of pomalidomide. 
 The subject has not and will not donate blood while taking pomalidomide, during 
dose interruptions and for at least 28 days after the last dose of pomalidomide. 
 The subject has not and will not break, chew, or open pomalidomide capsules at any 
point. 
 The subject confirmed that he will return unused pomalidomide capsules to the study 
doctor. 
2. I have provided the Pomalidomide Information Sheet to the subject. 
Do Not Dispense Pomalidomide if: 
• The subject stated that he has or does not want to adhere to pregnancy 
precautions outlined within this PPP. 

Version 01/19/23– Amendment 7 
 
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Counselor Name (Print): ____________________  
 
Counselor Signature: _______________________  Date: _____/_____/_____(dd/mmm/yyyy) 
 
**Maintain a copy of the Education and Counseling Guidance Document in the subject’s 
records.** 

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4. 
POMALIDOMIDE INFORMATION SHEET  
For subjects enrolled in clinical research studies  
Please read this Pomalidomide Information Sheet before you start taking pomalidomide and each 
time you get a new supply. This Pomalidomide Information Sheet does not take the place of an 
informed consent to participate in clinical research or talking to your study doctor or healthcare 
provider about your medical condition or your treatment.   
What is the most important information I should know about pomalidomide? 
1. Pomalidomide may cause birth defects (deformed babies) or death of an unborn 
baby. Pomalidomide is similar to the medicine thalidomide. It is known that thalidomide 
causes life-threatening birth defects. Pomalidomide has not been tested in pregnant 
women but may also cause birth defects. Pomalidomide was found to cause birth defects 
when tested in pregnant rats and rabbits. 
If you are a female who is able to become pregnant: 
• Do not take pomalidomide if you are pregnant or plan to become pregnant 
• You must practice complete abstinence from sexual contact with a male or use 
two reliable, separate forms of effective birth control at the same time:  
− for 28 days before starting pomalidomide 
− while taking pomalidomide  
− during breaks (dose interruptions) of pomalidomide  
− for at least 28 days after the last dose of pomalidomide  
• You must have pregnancy testing done at the following times: 
− within 10 to 14 days prior to the first dose of pomalidomide 
− 24 hours prior to the first dose of pomalidomide  
− weekly for the first 28 days 
− if you have regular menstrual periods: every 28 days after the first month  
− if you have irregular menstrual periods: every 14 days after the first month 
− if you miss your period or have unusual menstrual bleeding 
− 28 days after the last dose of pomalidomide (14 and 28 days after the last dose if 
menstrual periods are irregular) 
• Stop taking pomalidomide if you become pregnant while taking pomalidomide 
− If you suspect you are pregnant at any time during the study, you must stop 
pomalidomide immediately and immediately inform your study doctor. Your 
study doctor will report all cases of pregnancy to Celgene Corporation. 
• Do not breastfeed while taking pomalidomide and for at least 28 days after the 
last dose of pomalidomide 

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• The study doctor will be able to advise you where to get additional advice on 
contraception. 
If you are a female not able to become pregnant: 
In order to ensure that an unborn baby is not exposed to pomalidomide, your study doctor 
will confirm that you are not able to become pregnant. 
If you are a male: 
The effect of pomalidomide on sperm development is not known and has not been 
studied. The risk to an unborn baby in females whose male partner is receiving 
pomalidomide is unknown at this time.  
• Male subjects (including those who have had a vasectomy) must practice complete 
abstinence or must use a condom during sexual contact with a pregnant female or a 
female that can become pregnant: 
− While you are taking pomalidomide  
− During breaks (dose interruptions) of pomalidomide  
− For at least 28 days after the last dose of pomalidomide   
• Male subjects should not donate sperm or semen while taking pomalidomide, 
during breaks (dose interruptions) and for at least 28 days after the last dose of 
pomalidomide.  
• If you suspect that your partner is pregnant any time during the study, you must 
immediately inform your study doctor. The study doctor will report all cases of 
pregnancy to Celgene Corporation. Your partner should call their healthcare 
provider immediately if they become pregnant. 
2. All subjects: 
• Do not share pomalidomide with other people. It must be kept out of the reach of 
children and should never be given to any other person. 
• Do not donate blood while you take pomalidomide, during breaks (dose 
interruptions) and for at least 28 days after the last dose of pomalidomide.  
• Do not break, chew, or open pomalidomide capsules at any point. 
• You will get no more than a 28-day supply of pomalidomide at one time. 
• Return unused pomalidomide capsules to your study doctor. 
Additional information is provided in the informed consent form and you can ask your 
study doctor for more information. 
 
 

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APPENDIX F: Definitions for Adverse Event Reporting 
A. Adverse Events (AEs) 
 
As defined in 21 CFR 312.32: 
 
Definition: any untoward medical occurrence associated with the use of a drug in humans, 
whether or not considered drug-related. 
 
Grading: the descriptions and grading scales found in the revised NCI Common Terminology 
Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting.  A 
copy of the CTCAE version 4.0 can be downloaded from the CTEP website. 
 
Attribution (relatedness), Expectedness, and Seriousness: the definitions for the terms 
listed that should be used are those provided by the Department of Health and Human Services’ 
Office for Human Research Protections (OHRP).  A copy of this guidance can be found on 
OHRP’s website: 
http://www.hhs.gov/ohrp/policy/advevntguid.html 
 
B. Suspected Adverse Reaction (SAR) 
 
As defined in 21 CFR 312.32: 
 
Definition: any adverse event for which there is a reasonable possibility that the drug caused 
the adverse event.  “Reasonable possibility” means there is evidence to suggest a causal 
relationship between the drug and the adverse event.  “Suspected adverse reaction” implies a 
lesser degree of certainty about causality than adverse reaction, which means any adverse event 
caused by a drug. 
 
C. Life-Threatening Adverse Event / Life Threatening Suspected Adverse Reaction  
 
As defined in 21 CFR 312.32: 
 
Definition: any adverse drug event or suspected adverse reaction is considered “life-
threatening” if, in the view of the investigator, its occurrence places the patient at immediate 
risk of death. It does not include an adverse event or suspected adverse reaction that, had it 
occurred in a more severe form, might have caused death. 
 
D.  Serious Adverse Event (SAE) or Serious Suspected Adverse Reaction 
 
As defined in 21 CFR 312.32: 
 
Definition:  an adverse event or suspected adverse reaction is considered “serious” if, in the 
view of the investigator, it results in any of the following outcomes: 
o Death 
o A life-threatening adverse event 
o Inpatient hospitalization or prolongation of existing hospitalization 

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o A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
o A congenital anomaly/birth defect 
o Any other important medical event that does not fit the criteria above but, based upon 
appropriate medical judgment, may jeopardize the subject and may require medical or 
surgical intervention to prevent one of the outcomes listed above 
 
E. Protocol Exceptions 
 
Definition: A planned change in the conduct of the research for one participant. 
 
F. Deviation 
 
Definition: Any alteration or modification to the IRB-approved research without prospective 
IRB approval.  The term “research” encompasses all IRB-approved materials and documents 
including the detailed protocol, IRB application, consent form, recruitment materials, 
questionnaires/data collection forms, and any other information relating to the research study. 
 
A minor or administrative deviation is one that does not have the potential to negatively impact 
the rights, safety, or welfare of participants or others or the scientific validity of the study. 
 
A major deviation is one that does have the potential to negatively impact the rights, safety, or 
welfare of participants or others or the scientific validity of the study. 
 
G. Product Complaints 
 
Definition: A product complaint is a verbal, written, or electronic expression that implies 
dissatisfaction regarding the identity, strength, purity, quality, or stability of a drug product.  
Individuals who identify a potential product complaint situation should immediately contact 
MedComm Solutions (see below) and report the event.  Whenever possible, the associated 
product should be maintained in accordance with the label instructions pending further 
guidance from a Millennium Quality representative. 
 
Product complaints in and of themselves are not AEs.  If a product complaint results in an 
SAE, an SAE form should be completed (refer to Section 8.10).   
 
 
H. Medication Error 
 
A medication error is a preventable event that involves an identifiable patient and that leads 
to inappropriate medication use, which may result in patient harm.  While overdoses and 
underdose constitute medication errors, doses missed inadvertently by a patient do not.  
Individuals who identify a potential medication error situation should immediately contact 
Millennium (see below) and report the event. 
 
I.  Pregnancies and Suspected Pregnancies 
 

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Pregnancies and suspected pregnancies (including elevated βhCG or positive pregnancy test in 
a female subject of reproductive potential, regardless of disease state) occurring while the 
subject is on study treatment, or within 30 days of the subject’s last dose of study treatment, 
are considered immediately reportable events. Study treatment is to be discontinued 
immediately.  
 
The pregnancy, suspected pregnancy, or positive pregnancy test must be reported to Bristol-
Myers Squibb and Celgene Drug Safety within 24 hours of the Investigator’s knowledge of the 
event as described in Sections 11.6-11.7.  
 
The female subject should be referred to an obstetrician-gynecologist, (preferably one with 
reproductive toxicity experience) or another appropriate healthcare professional for further 
evaluation and counseling. The Investigator will follow the female subject until completion of 
the pregnancy outcome and up to 1 year to monitor the baby, and must notify Bristol-Myers 
Squibb and Celgene Drug Safety immediately about the outcome of the pregnancy.   
 
If the outcome of the pregnancy was abnormal (e.g., spontaneous or therapeutic abortion, 
STILLBIRTH, NEONATAL DEATH, OR CONGENITAL ANOMALY) the Investigator 
should report the abnormal outcome as an SAE. All neonatal deaths that occur within 28 days 
of birth should be reported, without regard to causality, as SAEs. In addition, any infant death 
after 28 days that the Investigator suspects is related to the in utero exposure to study treatment 
should also be reported. 
 
If a female partner of a male subject taking investigational product becomes pregnant, the male 
subject taking study treatment should notify the Investigator immediately, and the pregnant 
female partner should be advised to call their healthcare provider immediately. Male patients 
treated with pomalidomide are advised to continue complete abstinence or condom use during 
treatment and 28 days after stopping treatment.  

Version 01/19/23– Amendment 7 
 
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APPENDIX G: Reporting Timelines 
 
Expedited Reporting Timelines 
Event 
HRPO 
QASMC 
FDA 
Celgene 
Bristol Myers-
Squibb 
Serious AND 
unexpected suspected 
adverse reaction 
 
 
Report no later than 15 
calendar days after it is 
determined that the 
information qualifies for 
reporting 
Report within 24 
hours 
Report within 24 
hours 
Unexpected fatal or 
life-threatening 
suspected adverse 
reaction 
 
 
Report no later than 7 
calendar days after initial 
receipt of the information 
Report within 24 
hours 
Report within 24 
hours 
Unanticipated problem 
involving risk to 
participants or others 
Report within 10 
working days.  If the 
event results in the 
death of a participant 
enrolled at 
WU/BJH/SLCH, report 
within 1 working day. 
Report via email after IRB 
acknowledgment 
 
 
 
Major deviation 
Report within 10 
working days.  If the 
event results in the 
death of a participant 
enrolled at 
WU/BJH/SLCH, report 
within 1 working day. 
 
 
 
 
A series of minor 
deviations that are 
being reported as a 
Report within 10 
working days.   
 
 
 
 

Version 01/19/23– Amendment 7 
 
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continuing 
noncompliance 
Protocol exception 
Approval must be 
obtained prior to 
implementing the 
change 
 
 
 
 
Clinically important 
increase in the rate of a 
serious suspected 
adverse reaction of that 
list in the protocol or 
IB 
 
 
Report no later than 15 
calendar days after it is 
determined that the 
information qualifies for 
reporting 
 
 
Complaints 
If the complaint reveals 
an unanticipated 
problem involving 
risks to participants or 
others OR 
noncompliance, report 
within 10 working 
days.  If the event 
results in the death of a 
participant enrolled at 
WU/BJH/SLCH, report 
within 1 working day.  
Otherwise, report at the 
time of continuing 
review. 
 
 
 
 
Breach of 
confidentiality 
Within 10 working 
days. 
 
 
 
 
Incarceration 
If withdrawing the 
participant poses a 
safety issue, report 
 
 
 
 

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Routine Reporting Timelines 
Event 
HRPO 
QASMC 
FDA 
Celgene 
Bristol Myers-
Squibb 
Adverse event or 
SAE that does not 
require expedited 
reporting 
If they do not meet the 
definition of an 
unanticipated problem 
involving risks to 
participants or others, 
report summary 
information at the time of 
continuing review 
Adverse events will be 
reported in the toxicity table in 
the DSM report which is 
typically due every 6 months. 
The most current toxicity 
table from the DSM report 
is provided to the FDA 
with the IND’s annual 
report. 
Report within 24 
hours 
Report within 24 
hours 
Minor deviation 
Report summary 
information at the time of 
continuing review. 
 
 
 
 
Complaints 
If the complaint reveals an 
unanticipated problem 
involving risks to 
participants or others OR 
noncompliance, report 
within 10 working days.  
 
 
 
 
within 10 working 
days.   
 
If withdrawing the 
participant does not 
represent a safety issue 
and the patient will be 
withdrawn, report at 
continuing review. 
Pregnancies 
 
 
 
Report within 24 
hours 
Report within 24 
hours 

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If the event results in the 
death of a participant 
enrolled at 
WU/BJH/SLCH, report 
within 1 working day.  
Otherwise, report at the 
time of continuing review. 
Incarceration 
If withdrawing the 
participant poses a safety 
issue, report within 10 
working days.   
 
If withdrawing the 
participant does not 
represent a safety issue 
and the patient will be 
withdrawn, report at 
continuing review. 
 
 
 
 
 
 
Expedited Reporting Timelines for Secondary Sites 
Event 
WU (Coordinating Center) 
Local IRB 
FDA 
Celgene 
Bristol Myers-
Squibb 
Serious AND unexpected 
suspected adverse reaction 
Report no later than 11 
calendar days after it is 
determined that the 
information qualifies for 
reporting. 
Report all 
applicable events 
to local IRB 
according to 
local 
institutional 
guidelines. 
The research team at 
Washington University is 
responsible for reporting 
all applicable events to the 
FDA as needed. 
The research team at 
Washington 
University is 
responsible for 
reporting all 
applicable events to 
Millennium as 
needed. 
The research team 
at Washington 
University is 
responsible for 
reporting all 
applicable events 
to Millennium as 
needed. 
Unexpected fatal or life-
threatening suspected 
adverse reaction 
Report no later than 4 calendar 
days after initial receipt of the 
information. 

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Expedited Reporting Timelines for Secondary Sites 
Event 
WU (Coordinating Center) 
Local IRB 
FDA 
Celgene 
Bristol Myers-
Squibb 
Unanticipated problem 
involving risk to 
participants or others 
Report no later than 4 calendar 
days after initial receipt of the 
information. 
Adverse event or SAE 
that does not require 
expedited reporting 
As per routine data entry 
expectations 
Protocol exception 
Approval must be obtained 
prior to implementing the 
change. 
 
 

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APPENDIX H: Washington University SAE Reporting Cover Sheet 
 
SAE COVER SHEET- Secondary Site Assessment 
 
Washington University HRPO#:  
Sponsor-Investigator:  
Subject Initials:   
Subject ID:  
Treating MD:  
Treating Site:  
EVENT TERM:  
Event Start Date:  
EVENT GRADE: 
Date of site’s first notification: 
 
Treating MD Event Assessment:  
 
 
Is this event possibly, probably, or definitely related study treatment? 
 
 yes  
 
 no 
 
If yes, please list which drug (if more than one)______________________________ 
 
       
Explain ______________________________________________________________________ 
 
______________________________________________________________________________ 
 
 
 
_________________________           ___________________________      _________________  
Physician’s Name 
 
 
Physician’s Signature 
 
Date