Clinical trial NCT03713294
Conditions: Refractory Plasma Cell Myeloma
Sponsor: Mayo Clinic
Start date: 2019-01-14; Completion date: 2024-11-14
Enrollment: 37 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This phase II trial studies how well dexamethasone, elotuzumab, pomalidomide work in treating patients with multiple myeloma that has not responded to previous treatment. Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as elotuzumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Pomalidomide may stop the growth of multiple myeloma by blocking the growth of new blood vessels necessary for tumor growth. Giving dexamethasone, elotuzumab, pomalidomide may work better in treating patients with multiple myeloma.

Detailed description:
PRIMARY OBJECTIVE:

I. To determine the overall response rate (ORR) of utilizing elotuzumab, pomalidomide and dexamethasone in patients with disease refractory to daratumumab.

SECONDARY OBJECTIVES:

I. To determine percentage of patients achieving complete response (CR) with the elotuzumab combination.

II. To determine progression-free survival (PFS) for treatment with the elotuzumab combination.

III. To determine safety profile for treatment with the elotuzumab combination. IV. To determine the overall survival (OS) for patients receiving treatment with the elotuzumab combination.

OUTLINE:

Patients receive dexamethasone intravenously (IV) on days 1, 8, 15, and 22 of cycles 1-2 and IV on day 1 and orally (PO) on days 8, 15, and 22 of subsequent cycles and elotuzumab IV on days 1, 8, 15, and 22 of cycles 1-2 and day 1 of subsequent cycles. Patients also receive pomalidomide PO on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months until progressive disease, then every 6 months thereafter.

Arms: arm 1: Patients receive dexamethasone IV on days 1, 8, 15, and 22 of cycles 1-2 and IV on day 1 and PO on days 8, 15, and 22 of subsequent cycles and elotuzumab IV on days 1, 8, 15, and 22 of cycles 1-2 and day 1 of subsequent cycles. Patients also receive pomalidomide PO on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Interventions: intervention 1: Dexamethasone intervention 2: Elotuzumab intervention 3: Pomalidomide
Intervention descriptions: intervention 1: Given IV and PO intervention 2: Given IV intervention 3: Given PO

Protocol documents:
Prot_SAP_000.pdf: 
 
 
 
 
 
MC1884 / 18-003574 
 
 
Phase II Trial of Sequential Treatment of Multiple Myeloma with 
Antibody Therapy 
 
 
NCT03713294 
 
 
Document Date: 01/13/2022 


MC1884 
Protocol Version Date: 13Jan2022 
 
 
Mayo Clinic Cancer Center 
Phase II Trial of Sequential Treatment of Multiple Myeloma with Antibody Therapy 
Principal Investigator: 
Sikander Ailawadhi, MD  
Mayo Clinic 
4500 San Pablo Rd 
Jacksonville, FL 32224 
904/953-6468 
 
Co-Principal Investigators: 
Vivek Roy, MD  
Mayo Clinic 
4500 San Pablo Rd 
Jacksonville, FL 32224 
 
904/953-2000 
 
Co-Investigators: 
Asher Chanan-Khan, MD 
 
Taimur Sher, MD 
Statistician: 
Betsy LaPlant, MS √ 
FDA IND #: 140595 (Exempt) 
Drug Availability:  
Commercial Agents: Dexamethasone, Elotuzumab, Pomalidomide 
√Study contributor(s) not responsible for patient care 
 
Document History 
(Effective Date) 
Activation 
Amendment 1 
Amendment 2 
December 19, 2018 
September 18, 2019 
Pending Approvals 
 
 
 
 
 
 
 
 


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Protocol Version Date: 13Jan2022 
 
 
Protocol Resources 
 
Questions: 
Contact Name: 
Patient eligibility*, test schedule, 
treatment delays/interruptions/adjustments, 
dose modifications, adverse events, 
forms completion and submission 
Heidi Ganz, Data Manager Specialist 
Phone: 507/266-6117 
E-mail: Hervey.Katie@mayo.edu   
Forms completion and submission  
 
Dustin Chapin, CRC 
Phone: 904/953-3768 
Email: Chapin.Dustin@mayo.edu   
 
Protocol document, consent form, 
regulatory issues 
Nichole Plouffe, Protocol Development Coordinator  
Phone:  904/953-0314 
Email: Sanders.Jessica1@mayo.edu 
 
Serious Adverse Event Reporting 
Patricia G McNamara, SAE Coordinator 
Phone: 507/266-3028 
E-mail: RSTP2CSAES@mayo.edu  
*No waivers of eligibility allowed 
 
 


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Protocol Version Date: 13Jan2022 
 
 
Table of Contents 
Phase II Trial of Sequential Treatment of Multiple Myeloma with Antibody Therapy ............................... 1 
Protocol Resources ........................................................................................................................................ 2 
Table of Contents .......................................................................................................................................... 3 
Schema .......................................................................................................................................................... 4 
1.0 
Background ................................................................................................................................... 5 
2.0 
Goals ............................................................................................................................................. 8 
3.0 
Registration Patient Eligibility ...................................................................................................... 9 
4.0  
Test Schedule .............................................................................................................................. 12 
5.0 
Stratification Factors OR Grouping Factor: ................................................................................ 15 
6.0 
Registration ................................................................................................................................. 15 
7.0 
Protocol Treatment ...................................................................................................................... 17 
8.0 
Dosage Modification Based on Adverse Events ......................................................................... 19 
9.0 
Ancillary Treatment/Supportive Care ......................................................................................... 27 
10.0 
Adverse Event (AE) Monitoring and Reporting ......................................................................... 29 
11.0 
Treatment Evaluation .................................................................................................................. 39 
12.0 
Descriptive Factors ..................................................................................................................... 43 
13.0 
Treatment/Follow–up Decision at Evaluation of Patient ............................................................ 44 
14.0 
Body Fluid Biospecimens ........................................................................................................... 46 
15.0 
Drug Information ........................................................................................................................ 46 
16.0 
Statistical Considerations and Methodology ............................................................................... 55 
17.0  
Pathology Considerations/Tissue Biospecimens......................................................................... 60 
18.0 
Records and Data Collection Procedures .................................................................................... 60 
19.0  
Budget ......................................................................................................................................... 61 
20.0 
References ................................................................................................................................... 62 
Appendix I 
ECOG Performance Status ............................................................................................... 64 
Appendix II 
Creatinine Clearance (CrCl) Calculation .......................................................................... 65 
Appendix III 
New York Heart Association Classification of Congestive Heart Failure ........................ 66 
Appendix IV 
Mayo Risk Stratification ................................................................................................... 67 
Appendix V 
Patient Medication Diary .................................................................................................. 68 
Appendix VI 
 Child Pugh Classification ................................................................................................ 70 
 


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Schema 
 
Registration 
 
 
↓ 
 
 
Treatment 
Treatment Cycles 1-2* 
Elotuzumab: IV 10 mg/Kg Days 1, 
8, 15, 22 
Pomalidomide: 4 mg PO Days 1-21 
Dexamethasone**: 40 mg IV Days 
1, 8, 15, 22 
 
 
↓ 
 
 
Treatment2 
Treatment Cycles 3 Onwards* 
Elotuzumab: IV 20 mg/Kg Day 1 
Pomalidomide: 4 mg PO Days 1-21 
Dexamethasone**: 40 mg IV on 
Day 1 and 40 mg PO on Days 8, 15, 
22  
 
 
↓ 
 
 
Events at any time: 
Disease Progression*** 
Intolerable adverse effects 
Patient refusal 
Subsequent Therapy 
 
 
↓ 
 
 
Survival Follow-up 
 
*Every Cycle = 28 days  
**If patient age ≥75 years, dexamethasone dosing will be 20 mg with same administration as shown in the schema 
***Confirmation of PD is not required. However, treatment may be discontinued for progressive disease that is 
unconfirmed per physician discretion. In this case, an objective status of PD should be entered on the measurement 
form and progressive disease should be reported on the event monitoring form. 
 
Generic name: Elotuzumab  
Brand name(s): Empliciti® 
Mayo Abbreviation: 
ELOTUZUMAB 
Availability: Commercial 
Generic name: Pomalidomide 
Brand name(s): Pomalyst®  
Mayo Abbreviation: 
POMALIDOMIDE 
Availability: Commercial 
Generic name: Dexamethasone 
Brand name (s): Decadron® 
Mayo Abbreviation: DXM 
Availability: Commercial 


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1.0 
Background  
 
Multiple myeloma (MM) is a malignant disorder of the plasma cells, characterized by 
uncontrolled and progressive proliferation of a plasma cell clone. The disease leads to progressive 
morbidity and eventual mortality by lowering resistance to infection and causing significant 
skeletal destruction (with bone pain, pathological fractures, and hypercalcemia), anemia, renal 
failure, neurological complications and hyper viscosity syndrome. 
 
The majority of patients with MM produce a monoclonal protein, also called paraprotein, M-
protein or M-component, which is an immunoglobulin (Ig) or a fragment of one that has lost its 
function.(Kyle & Rajkumar, 2009; Palumbo et al., 2009, ) Normal immunoglobulin levels are 
compromised, leading to susceptibility of infections. The proliferating MM cells displace the 
normal bone marrow leading to dysfunction in normal hematopoietic tissue and destruction of the 
normal bone marrow architecture, which is reflected by clinical findings such as anemia, 
paraprotein in serum or urine, and bone resorption seen as diffuse osteoporosis or lytic lesions 
shown in radiographs.(Kyle et al., 2003) Furthermore, hypercalcemia, renal insufficiency or 
failure, and neurological complications are frequently seen.(Palumbo & Anderson, 2011) A small 
minority of patients with MM are non-secretory. 
 
At the time of diagnosis, multiple myeloma is a heterogeneous disease, with a course that varies 
on the basis of both disease- and host-related factors (e.g., age, renal function, stage, 
chromosomal abnormalities). Multiple myeloma causes significant morbidity and mortality. It 
accounts for approximately 1% of all malignancies and 13% of hematologic cancers. 
Approximately 50,000 patients per year are diagnosed with multiple myeloma in the EU and US, 
and 30,000 patients per year die due to multiple myeloma. 
 
1.1 
Treatment 
 
1.11 
Treatment choices for MM vary with age, performance status, comorbidity, the 
aggressiveness of the disease, and related prognostic factors.(Dingli et al., 2017) 
Despite great improvements in response rates and outcomes, nearly all patients 
have disease relapse and remain incurable. Furthermore, while several drugs and 
regimens are available for the treatment of MM, there are still questions 
regarding how the various regimens need to be sequenced.(Dingli et al., 2017) 
This becomes even more important as more complex combination regimens are 
being used earlier on in the treatment, making it necessary to utlize the available 
agents optimally for patients with relapsed/refractory MM (RRMM). 
 
1.12 
Role of Monoclonal Antibodies in Multiple Myeloma 
So far two monoclonal antibodies are approved by the FDA for treatment of 
patients with RRMM – Daratumumab and Elotuzumab.(Dimopoulos et al, 2017; 
Palumbo et al., 2016; Lonial et al., 2016; Dimopoulos et al., 2016) Daratumumab 
is an immunoglobulin G1 kappa (IgG1k) human monoclonal antibody (mAb) that 
binds to a unique CD38 epitope on CD38-expressing cells with high affinity. It 
was developed by the immunization of human immunoglobulin transgenic mice 
with recombinant CD38 protein.(Sanchez et al., 2016) CD38 is a 46-kDa type II 
transmembrane glycoprotein that is highly expressed on MM cells.(McEllistrim 
et al., 2017) CD38 has various mechanisms including ectoenzymatic activity, 
receptor-mediated regulation of cell adhesion and signal transduction.(Malavasi 
et al., 2006) Preclinical studies have shown that daratumumab induces MM cell 
death through several mechanisms, including complement-dependent 


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cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), 
antibody-dependent cellular phagocytosis (ADCP), and FcR mediated-
crosslinking inducing apoptosis.(Sanchez et al., 2016) In a combined analysis of 
GEN501 and SIRIUS studies including 148 patients, the Overall Response Rate 
(ORR) was 31 %, and at a median follow-up of 14.8 months, the estimated 
Overall Survival (OS) was 19.9 months.(Usmani et al., 2015) These trials 
demonstrated that daratumumab is active as monotherapy in patients with heavily 
pre-treated and relapsed/refractory myeloma (RRMM) alongside maintaining its 
anti-myeloma activity in previously treatment refractory patients as evident by 
ORR 33 and 29.7 % in GEN501and SIRIUS, respectively.(Usmani et al., 2015) 
Preclinical studies have shown that Daratumumab in combination with other 
agents enhances the antimyeloma activity and now there are reported multiple 
phase II /III trials to study the same. These include data from the CASTOR and 
POLLUX trials of the combination of daratumumab and dexamethasone with 
bortezomib and lenalidomide, respectively, showing enhanced efficacy of these 
regimens in patients with early relapsed MM (2nd or 3rd line) and low minimal 
residual disease (MRD) states leading to the FDA approval of these regimens. 
Palumbo et al., 2016; Lonial et al., 2016; Dimopoulos et al., 2016) 
 
Elotuzumab is a first-in-class humanized immunoglobulin G1 
immunostimulatory monoclonal antibody targeted against signaling lymphocytic 
activation molecule F7 (SLAMF7, also called CS1 [cell-surface glycoprotein 
CD2 subset 1]), a glycoprotein expressed on myeloma and natural killer cells but 
not on normal tissues that enables selective killing of myeloma cells with 
minimal effects on healthy tissue.(His et al., 2008) The SLAM family is a 
subgroup of the immunoglobulin superfamily of receptors and consists of six 
members (SLAM, 2B4, Ly-9, NTB-A, CD94, and SLAMF7), all located on 
chromosome 1q23.(15) More than 95% of bone marrow myeloma cells express 
SLAMF7 in a manner that is independent of cytogenetic abnormalities.Hsi et al., 
2008; Tai et al, 2008) Elotuzumab exerts a dual effect by directly activating 
natural killer cells and mediating antibody-dependent cell-mediated cytotoxicity 
through the CD16 pathway.(Collins et al., 2013) SLAMF7 mediates activating 
signals in natural killer cells by coupling with its adapter protein EAT-2. In 
myeloma cells, SLAMF7 signaling is compromised owing in part to the lack of 
EAT-2 expression; therefore, elotuzumab does not induce the proliferation of 
myeloma cells.(Guo et al., 2015; Perez-Quintero et al., 2014) In a single-group, 
phase 2 trial of elotuzumab in combination with lenalidomide and 
dexamethasone, this immunostimulatory activity translated into an improvement 
in progression-free survival in patients with relapsed or refractory multiple 
myeloma and followed by this randomized phase 3 trials were done leading to 
the FDA approval of Elotuzumab with lenalidomide and dexamethasone in 
patients with RRMM.(Dimopoulos et al., 2017) 
 
1.13 
Rationale of Elotuzumab after Daratumumab Treatment in MM 
Daratumumab has emerged as a highly effective anti-MM agent as well as a 
partner to other already available anti-MM drugs including proteasome inhibitors 
and immunomodulatory drugs (IMiDs). This has lead to utilization of 
daratumumab earlier in the treatment paradigm of MM patients.(Dingli et al., 
2017) On the other hand, there have been some questions regarding the optimal 
positioning of Elouzumab, which  has a distinct mechanism of action than 
Daratumumab, and did not show any efficacy by itself. Furthermore, it was not 


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studied in patients who had been previously exposed significantly to IMiDs, 
which are used routinely early on in MM care and majority of patients that may 
become eligible for treatment with Elotuzumab may already have disease 
refractory to lenalidomide (full dose or maintenance dose). Thus, combining 
elotuzumab with another agent, pomalidomide in this case, and utilizing in 
patients who have had disease progression on daratumumab previously is a 
strategy that is warranted to understand how this FDA-approved agent will be 
optimally utilized as the therapeutic landscape of MM advances. 
 
1.14 
Trial Design 
This will be a phase II, open label, prospective clinical trial in MM patients with 
disease previously treated utilizing any daratumumab-based regimen and disease 
progression noted while on the daratumumab-based regimen or within 60 days of 
discontinuation of daratumumab (daratumumab refractory). Such patients will be 
treated with a combination of elotuzumab, pomalidomide and dexamethasone, as 
previously presented.(San Miguel et al., 2016) The efficacy of elotuzumab in 
previously daratumumab-treated patients will help determine its appropriate role 
in treatment of patients with RRMM. 
 
The dose schedule of Elotuzumab selected for the current trial is in accordance of 
several combination clinical trials that have been published with this agent since 
its FDA approval. Based on those trials, Elotuzumab is dosed weekly for the first 
8 weeks and then is given as 20 mg/Kg dose every 4 weeks till disease 
progression or intolerable adverse events. (ref: Elo-pom-dex currently ongoing 
trial NCT#02654132) 
 
 


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2.0 
Goals  
2.1 
Primary Goal 
To determine the overall response rate (ORR) of utilizing elotuzumab, pomalidomide and 
dexamethasone in patients with disease refractory to daratumumab. 
2.2 
Secondary Goals 
2.21 
To determine percentage of patients achieving complete response (CR) with the 
elotuzumab combination. 
2.22 
To determine progression-free survival (PFS) for treatment with the elotuzumab 
combination. 
2.23  
To determine safety profile for treatment with the elotuzumab combination. 
2.24 
To determine the overall survival (OS) for patients receiving treatment with the 
elotuzumab combination. 


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3.0 
Registration Patient Eligibility 
  
3.1 
Registration - Inclusion Criteria 
3.11 
Age ≥18 years 
3.12 
Diagnosis: Pathologically confirmed diagnosis of multiple myeloma and noted to 
have progressive disease (IMWG criteria as per Section 11.5) 
3.13 
At least one prior line of therapy. 
3.14 
Disease refractory to daratumumab as defined by disease progression while on or 
≤ 60 days of completing treatment with a daratumumab-containing regimen as 
part of any prior line of therapy. 
3.15 
Measurable disease ≤ 14 days prior to registration (As per criteria in Section 
11.1). 
3.16 
ECOG Performance Status (PS) 0, 1 or 2 (Appendix I).  
3.17 
The following laboratory values obtained ≤14 days prior to registration:  
• 
Absolute neutrophil count (ANC) ≥1,000 cell/mm3 without growth factor 
support 
• 
Platelet ≥50,000 cells/mm3 for patients who have bone marrow 
plasmacytosis <50% or ≥30,000 cells/mm3 for patients who have bone 
marrow plasmacytosis of ≥50% 
• 
Total bilirubin ≤1.5 x ULN unless due to Gilbert’s syndrome, in which 
case the direct bilirubin must be ≤1.5 X ULN. 
• 
Alanine aminotransferase (ALT) and Aspartate transaminase (AST) ≤3 x 
ULN  
• 
PT/INR/aPTT ≤1.5 x ULN OR if patient is receiving anticoagulant therapy 
and PT/INR or aPTT is within target range of therapy 
• 
Calculated or measured creatinine clearance ≥30 ml/min (see Appendix II) 
3.18 
Negative urine or serum pregnancy test done ≤14 days prior to registration, 
for persons of childbearing potential only. 
NOTE: If the urine test is positive or cannot be confirmed as negative, a serum 
pregnancy test will be required.  
3.19a 
Provide written informed consent. 
3.19b Willing to return to enrolling institution for follow-up (during the Active 
Monitoring Phase of the study). 
3.19c 
Willing to follow the requirements of the {Revlimid®/Pomalyst®} REMS 
program.  
3.2 
Registration - Exclusion Criteria 
3.21 
Non-secretory MM or known AL amyloidosis 
3.22 
Clinically significant active infection requiring intravenous antibiotics (≤14 days 
prior to registration). 
 


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3.23 
≥Grade 3 neuropathy and/or POEMS syndrome (plasma cell dyscrasia with 
polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin 
changes). 
3.24 
Immunocompromised patients and patients known to be HIV positive and 
currently receiving antiretroviral therapy.  
NOTE: Patients known to be HIV positive, but without clinical evidence of an 
immunocompromised state, are eligible for this trial. 
3.25 
Concurrent therapy considered investigational.  
NOTE: Patients must not be planning to receive any radiation therapy (except 
localized radiation for palliative care that must be completed prior to starting 
Cycle 1, Day 1). 
3.26 
Any of the following because this study involves an investigational agent whose 
genotoxic, mutagenic and teratogenic effects on the developing fetus and 
newborn are unknown:  
• Pregnant women 
• Nursing women (lactating females are eligible provided that they agree not to 
breast feed while taking lenalidomide) 
• Men or women of childbearing potential who are unwilling to employ 
adequate contraception 
3.27 
Other active malignancy ≤3 years prior to registration.  
EXCEPTIONS:  
• 
Adequately treated basal cell or squamous cell skin cancer 
• 
Any in situ cancer 
• 
Adequately treated Stage I or II cancer from which the patient is 
currently in complete remission, or 
NOTE: If there is a history of prior malignancy, they must not be receiving other 
specific treatment for their cancer. 
3.28 
Major surgery ≤4 weeks prior to registration. 
3.29a 
History of stroke/intracranial hemorrhage ≤6 months prior to registration. 
3.29b Clinically significant cardiac illness including New York Heart Association 
(NYHA) Class III or Class IV heart failure (Appendix III), unstable angina 
pectoris, myocardial infarction within the past 6 months, or ≥Grade 3 cardiac 
arrhythmias noted ≤ 14 days prior to registration. 
3.29c 
Currently active, clinically significant hepatic impairment Child-Pugh class B or 
C according to the Child Pugh classification (see Appendix VI). 
3.29d Exhibiting clinical signs of meningeal involvement of multiple myeloma. 
3.29e 
Known severe chronic obstructive pulmonary disease or asthma defined as forced 
expiratory volume (FEV1) in 1 second <60% of expected. 
3.29f 
Prior exposure to elotuzumanb. 
3.29g Prior history of disease refractory to pomalidomide. 
3.29h Co-morbid systemic illnesses or other severe concurrent disease which, in the 
judgment of the investigator, would make the patient inappropriate for entry into 


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this study or interfere significantly with the proper assessment of safety and 
toxicity of the prescribed regimens. 
3.29j 
Uncontrolled intercurrent illness including, but not limited to:  
• 
ongoing or active infection 
• 
symptomatic congestive heart failure 
• 
unstable angina pectoris 
• 
cardiac arrhythmia 
• 
or psychiatric illness/social situations that would limit compliance with study 
requirements. 
 
 


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4.0  
Test Schedule 
4.1 
Test schedule for Multiple Myeloma  
 
 
 
Active Monitoring Phase 
Tests and procedures 
≤ 14 days 
prior to 
registration 
Cycle 1, 
Day 15 
Prior to 
subsequent 
cycle/ treatment  
(≥ cycle 2) Day 
1 
During course of 
treatment 
(Day 15 of Cycle 
2) 
End of treatment 
(≤2 weeks after 
the final dose) 
Window 
 
±3 days 
±3 days 
±3 days 
 
Complete medical and disease 
history 
X 
 
X 
 
X 
Physical examination1 
X 
 
X 
 
X 
Performance status (ECOG scale) 
X 
 
X 
 
X 
Hematology group 
 
CBC w/diff 
X 
X 
X 
X 
X 
Chemistry group  
Sodium  
Chloride 
Potassium 
Magnesium 
Phosphate 
Uric acid 
BUN 
Glucose 
ALT/AST 
ALP 
Total protein 
Total bilirubin 
Direct bilirubin 
Albumin 
Serum creatinine 
Calcium 
LDH 
X 
X 
X 
X 
X 
PT/INR/aPTT 
X 
 
 
 
 


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Active Monitoring Phase 
Tests and procedures 
≤ 14 days 
prior to 
registration 
Cycle 1, 
Day 15 
Prior to 
subsequent 
cycle/ treatment  
(≥ cycle 2) Day 
1 
During course of 
treatment 
(Day 15 of Cycle 
2) 
End of treatment 
(≤2 weeks after 
the final dose) 
Bone marrow aspirate/biopsy with 
standard testing (including but not 
limited to myeloma FISH and flow 
cytometry)2 
X 
 
 
 
X 
Electrophoresis of serum and urine 
(SPEP/UPEP) 
X 
 
X9 
 
X 
Serum immunoglobulins3 
X 
 
X 
 
X 
Immunofixation serum and urine 
(IF) 
X 
 
X 
 
X 
Immunoglobulin free light chain 
(FLC) 
X 
 
X 
 
X 
Serum β2-microglobulin 
X 
 
 
 
X 
PET/CT scan4 
X 
 
 
 
X 
Adverse Event monitoring5 
X 
X 
X 
X 
X 
Pregnancy test6 
X 
 
X 
 
 
Registered in the POMALYST 
REMS™ program7 
X 
 
 
 
 
Pill Diary8 
 
 
X 
 
X 
Cycle = 28 days  
 
1. To include blood pressure, pulse rate, temperature, weight. Height to be documented ≤14 days prior to registration 
2. Standard of care procedure: ≤28 days prior to registration, at the time of disease progression, and if considered clinically indicated at any 
other time during the study. NOTE: Repeat biopsy at Cycle 1, Day 1 if biopsy was not completed ≤ 28 prior to registration. 
3. Serum immunoglobulins to include IgG, IgA and IgM for all patients and IgD or IgE where clinically indicated. 
4. A PET scan should be done≤ 28 days prior to registration, at the time of disease progression, and if considered clinically necessary. 
NOTE: Repeat PET/CT at Cycle 1, Day 1 if PET/CT was not completed ≤ 28 prior to registration prior to registration. 
5. During the course of treatment and at end of treatment visit. The patient should be contacted by a nurse 30 days after the last dose of study 
treatment (or at the time of initiation of subsequent treatment if started before 30 days) to check if the patient has experienced any late 
adverse events. Grade 3 or higher adverse events at least possibly related to study treatment and deaths due to any cause should be 


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reported as a late adverse event on the survival follow-up form if they were not already reported on the Adverse Event form for the last 
cycle and they occurred prior to any subsequent treatment and 30 days post-end of treatment 
6. For females of childbearing potential, a negative pregnancy test (urine or serum) must be documented ≤ 14prior to registration on the 
study and thereafter in accordance with the POMALYST REMSTM program. A female of childbearing potential (FCBP) is a sexually 
mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at 
least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months). 
7. ≤ 14 days prior to registration. 
8. To be collected at the end of every cycle of therapy while the patient is receiving pomalidomide or oral dexamethasone.  
9. UPEP testing required at baseline only. Subsequent testing will be as needed per physician discretion.  
 
 
4.2 
Survival Follow-up 
 
 
Survival Follow-up 
q. 3 months 
until PD or 
subsequent 
treatment 
At PD or 
subsequent 
therapy 
After PD or 
subsequent 
therapy 
q. 6 months 
Death 
New 
Primary 
Survival Follow-up 
X 
X 
X 
X 
At each 
occurrence 
1. If a patient is still alive 3 years after registration, no further follow-up is required. 


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5.0 
Stratification Factors OR Grouping Factor:  
 
None. 
6.0 
Registration 
6.1 
Registration (Step 1):  
6.11 
Registering a patient 
To register a patient, access the Mayo Clinic Cancer Center (MCCC) web page 
and enter the registration/randomization application.  The registration/ 
randomization application is available 24 hours a day, 7 days a week. Back up 
and/or system support contact information is available on the website. If unable 
to access the website, call the MCCC Registration Office at (507) 284-2753 
between the hours of 8 a.m. and 4:30 p.m. Central Time (Monday through 
Friday). 
The instructions for the registration/randomization application are available on 
the MCCC web page (http://ccswww/training/index.html) and detail the 
process for completing and confirming patient registration. Prior to initiation of 
protocol treatment, this process must be completed in its entirety and an MCCC 
subject ID number must be available as noted in the instructions. It is the 
responsibility of the individual registering the patient to confirm the process has 
been successfully completed prior to release of the study agent. Patient 
registration via the registration/randomization application can be confirmed in 
any of the following ways: 
• 
Contact the MCCC Registration Office (507) 284-2753. If the patient 
was fully registered, the MCCC Registration Office staff can access the 
information from the centralized database and confirm the registration. 
• 
Refer to “Instructions for Remote Registration” in section 
“Finding/Displaying Information about A Registered Subject.” 
6.2 
Verification of materials 
Prior to accepting the registration, registration/randomization application will verify the 
following: 
• 
IRB approval at the registering institution 
• 
Patient eligibility 
• 
Existence of a signed consent form 
• 
Existence of a signed authorization for use and disclosure of protected health 
information  
6.3 
Documentation of IRB approval 
Documentation of IRB approval must be on file in the Registration Office before an 
investigator may register any patients.  
In addition to submitting initial IRB approval documents, ongoing IRB approval 
documentation must be on file (no less than annually) at the Registration Office (fax: 
507-284-0885). If the necessary documentation is not submitted in advance of attempting 
patient registration, the registration will not be accepted and the patient may not be 
enrolled in the protocol until the situation is resolved. 
When the study has been permanently closed to patient enrollment, submission of annual 
IRB approvals to the Registration Office is no longer necessary. 


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6.4 
Treatment on protocol 
Treatment on this protocol must commence at Mayo Clinic Florida under the supervision 
of a medical oncologist/hematologist. 
6.5 
Treatment start 
Treatment cannot begin prior to registration and must begin ≤ 28 days after registration. 
6.6 
Pretreatment 
Pretreatment tests/procedures (see Section 4.0) must be completed within the guidelines 
specified on the test schedule. 
6.7 
Baseline symptoms 
All required baseline symptoms (see Section 10.6) must be documented and graded. 
6.8a 
Study drug 
Study drug is available on site.  
6.8b 
Study Conduct 
The clinical trial will be conducted in compliance with regulations (21 CFR 312, 50, and 
56), guidelines for Good Clinical Practice (ICH Guidance E6), and in accordance with 
general ethical principles outlined in the Declaration of Helsinki; informed consent will 
be obtained from all participating patients; the protocol and any amendments will be 
subject to approval by the designated IRB prior to implementation, in accordance with 
21 CFR 56.103(a); and subject records will be stored in a secure location and subject 
confidentiality will be maintained. The investigator will be thoroughly familiar with the 
appropriate use of the study drug as described in the protocol and Investigator’s 
Brochure. Essential clinical documents will be maintained to demonstrate the validity of 
the study and the integrity of the data collected. Master files should be established at the 
beginning of the study, maintained for the duration of the study and retained according to 
the appropriate regulations. 
 
 
 
 


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7.0 
Protocol Treatment 
7.1 
Treatment Schedule 
7.11 
Treatment medication table (Cycles 1-2) 
Agent 
 
Dose Level 
Route 
Day 
Elotuzumab 
10 mg/Kg* 
IV 
1, 8, 15, 22 
Pomalidomide 
4 mg 
PO 
1-21 
Dexamethasone 
40 mg** 
IV 
1, 8, 15, 22 
 
 
 
Cycle length = 28 days, Treatment Window (+/- 3 days) 
 
 
 
Dexamethasone to be administered IV 45-90 mins prior to elotuzumab 
 infusions on the days both are being administered to patients 
*Any dose-adjustments will be made as per the prescriber information. 
Elotuzumab administration as per prescriber information and institutional 
guidelines. 
**If patient age ≥ 75, dexamethasone dose will be 20 mg. 
 
 
7.12 
Treatment medication table (Cycles 3 and onward) 
Agent 
 
Dose Level 
Route 
Day 
Elotuzumab 
20 mg/Kg* 
IV 
1 
Pomalidomide 
4 mg 
PO 
1-21 
Dexamethasone 
40 mg** 
IV 
1 
Dexamethasone 
40 mg** 
PO 
8, 15, 22 
 
 
 
Cycle length = 28 days, Treatment Window (+/- 3 days) 
 
 
 
Dexamethasone to be administered IV 45-90 mins prior to elotuzumab infusions  
            on the days both are being administered to patients 
*Any dose-adjustments will be made as per the prescriber information. 
Elotuzumab administration as per prescriber information and institutional 
guidelines. 
**If patient age ≥ 75, dexamethasone dose will be 20 mg. 
 
7.13 Infusion rate for elotuzumab 
 
Cycle 1, Dose 1 
Cycle 1, Dose 2 
Cycle 1, Dose 
3, 4 and all 
Subsequent 
Cycles 
Time Interval 
Rate 
Time Interval 
Rate 
Rate 
0-30 min 
0.5 ml/min 
0-30 min 
3 ml/min 
5 ml/min 
30-60 min 
1 ml/min 
30 min or 
more 
4 ml/min 
60 min or more 
2 ml/min 
 
 
7.2 
Treatment by local medical doctor (LMD) 
Treatment by a local medical doctor (LMD) is not allowed. 
7.3 
Overdose 
Any dose of study drug in excess of the amount provided in the protocol is considered to 
be an overdose. Signs and symptoms of an overdose that meet any Serious Adverse Event 


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criterion must be reported as a Serious Adverse Event in the appropriate timeframe and 
documented as clinical sequelae to an overdose. 
 
There has been no experience of overdosage with elotuzumab in clinical studies.  There is 
no known specific antidote for elotuzumab overdose.  In the event of an overdose, the 
subject should be monitored for any signs or symptoms of adverse effects and appropriate 
symptomatic treatment be instituted immediately. 
 
Refer to section 10 for further information regarding AE reporting. 
 
 


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8.0 
Dosage Modification Based on Adverse Events  
Any adverse event noted in the study and its resultant dose-modifications should be managed as 
per the prescribing information of elotuzuumab and/or pomalidomide and/or dexamethasone as 
per which of these drugs the adverse event is attributable to. 
→ ALERT: 
ADR reporting may be required for some adverse events (See Section 10.0) ← 
8.1  
Recommended Dose Modifications (Based on Adverse Events in Tables 8.2 and 8.3 and 
treating physician assessment) 
 
8.11  
Dose Modifications (Cycle 1 and 2) 
Dose Level 
Elotuzumab (Cycle 
1 and 2) 
Pomalidomide 
Dexamethasone 
1* 
10 mg/kg 
4 mg  
40 mg** 
-1 
Discontinue 
3 mg 
20 mg 
-2 
 
2 mg 
12 mg 
-3 
 
Discontinue 
8 mg 
-4 
 
 
Discontinue 
*Dose level 1 refers to the starting dose. 
** If patient age ≥ 75, dexamethasone dose will be 20 mg. 
 
8.12 
Dose Modifications (Cycle 3 and beyond) 
Dose Level 
Elotuzumab (Cycle 
3 and beyond) 
Pomalidomide 
Dexamethasone 
1* 
20 mg/kg 
4 mg  
40 mg** 
-1 
10 mg/kg 
3 mg 
20 mg 
-2 
Discontinue 
2 mg 
12 mg 
-3 
 
Discontinue 
8 mg 
-4 
 
 
Discontinue 
 
 
*Dose level 1 refers to the starting dose. 
** If patient age ≥ 75, dexamethasone dose will be 20 mg. 
 
NOTES:  
• 
Missed doses for pomalidomide are to be omitted rather than made up, unless the 
dose was forgotten and remembered on the same day, in which case the dose can be 
taken that day. Any doses missed on a particular day are not to be made up the next 
day. Doses that are considered to be vomited are not to be made up and a mention 
about the time of dose and time of vomiting episode should be made in the pill diary.  
• 
Elotuzumab may be administered within ±1 day of the scheduled dose if there are 
any logistical challenges (holiday, patient transport or other logistics, scheduling 
availability, etc.) 
• 
If multiple toxicities are experienced, dose modifications will be based on the toxicity 
requiring the largest dose reduction. 


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• 
Reductions are based on the dose given in the preceding cycle and are based on 
toxicities with an attribution of possible, probable, or definite that were observed 
since the prior toxicity evaluation. 
• 
Patients may continue on treatment with any two of the study drugs (elotuzumab or 
pomalidomide or dexamethasone) in case one of the agents has to be permanently 
discontinued. If a patient on treatment must discontinue two or all three drugs in the 
combination permanently, they should be removed from the protocol therapy and 
proceed to survival follow-up. 
• 
A dose omit/delay of ≤28 days for any of the drugs is allowed. If a patient cannot be 
administered a dose of two or all three drugs in the study treatment for >28 days due 
to adverse events or any other reason, the patient should be removed from the study 
treatment and go to survival follow-up. 
  Use the NCI Common Terminology Criteria for Adverse Events (CTCAE) current version 5.0* 
unless otherwise specified   
* 
Located at http:/ctep.cancer.gov/protocolDevelopment/electronic_applications.ctc.htm 
 
 


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8.2 
Dose Modifications for pomalidomide based on adverse events 
 
CTCAE 
System/Organ/Class 
(SOC) 
ADVERSE EVENT 
AGENT 
ACTION** 
Blood and lymphatic 
system disorders 
 
Anemia 
pomalidomide 
Omit dose if Grade 4 and follow CBC 
weekly until ≤Grade 2. 
•If anemia resolves to ≤Grade 2, 
resume dose at one level lower 
•If the AE does not return to ≤Grade 1 
within 4 weeks, then the patient may 
continue on elotuzumab and 
dexamathesone. Discontinue 
pomalidomide. 
Febrile Neutropenia  
pomalidomide 
Omit dose if ≥ Grade 3 and follow 
CBC weekly. 
• If neutropenia has resolved to ≤Grade 
2, resume dose at same level with 
GCSF support (See Section 9.2) 
Cardiac disorders 
Sinus Bradycardia/ other 
cardiac arrhythmia 
pomalidomide 
Omit dose if Grade 2 and follow 
weekly until resolution.  
• If AE resolves to ≤Grade 1, reduce 
dose by one dose level and continue 
therapy. 
If AE is ≥ Grade 3, discontinue 
pomalidomide and continue 
elotuzumab and dexamethasone. 
Immune System 
Disorders 
Allergic Reaction 
pomalidomide 
Omit dose if Grade 2-4 and follow 
weekly until resolution. 
• If AE resolves to ≤Grade 1, reduce 
dose by 1 level and continue therapy. 
Anaphylaxis 
pomalidomide Discontinue study treatment if Grade 3-
4 and go to survival follow-up. 
Investigations 
Neutrophil count 
decreased  
pomalidomide 
Omit dose if Grade 4 and follow CBC 
weekly until ≤ Grade 1. 
•If neutropenia has resolved to ≤Grade 
2, resume dose at one level lower  
*If, after pomalidomide has been 
omitted, and the AE does not return to 
≤Grade 1 within 4 weeks, then the 
patient may continue on elotuzumab 
and dexamathesone. Discontinue 
pomalidomide.  
 
 


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CTCAE 
System/Organ/Class 
(SOC) 
ADVERSE EVENT 
AGENT 
ACTION** 
Platelet count decreased pomalidomide 
Omit dose if Grade 4 and follow CBC 
weekly until ≤ Grade 1. 
• If thrombocytopenia ≤30,000/mm3 
occurs, reduce dose by one dose level  
and continue therapy when platelet 
count is ≥30,000/mm3. 
•If after pomalidomide has been 
omitted, and the AE does not return to 
≤Grade 1 within 4 weeks, then the 
patient may continue on elotuzumab 
and dexamathesone. Discontinue 
pomalidomide. 
Skin and subcutaneous 
tissue disorders 
Erythema multiforme 
pomalidomide Discontinue study treatment if ≥Grade 
3 and continue to survival follow-up. 
Skin ulceration 
pomalidomide Discontinue study treatment if ≥Grade 
2 and continue to survival follow-up. 
Other:Non-blistering 
rash 
pomalidomide 
Omit dose if Grade 3 and follow 
weekly until resolution. 
• If AE resolves to ≤Grade 2 continue 
therapy 
•Discontinue study treatment if Grade 4 
and continue to survival follow-up. 
Vascular Disorders 
Thromboembolic event 
 
Omit dose if ≥ Grade 3 and start 
anticoagulation; restart at investigator’s 
discretion (maintain dose level) 
Other AEs 
Non-hematologic AE 
assessed as related to 
lenalidomide 
pomalidomide 
Omit dose if ≥Grade 3 and follow 
weekly until resolution 
• If the AE resolves to ≤Grade 2, 
implement one dose reduction step and 
continue therapy (per Table 8.1) 
**  Use the following to describe actions in the Action column: 
 Omit = The current dose(s) for the specified drug(s) during a cycle is skipped.  The 
patient does not make up the omitted dose(s) at a later time. 
 Hold/Delay = The current dose(s) of all drugs during a cycle is delayed.  The patient 
does make up the delayed dose(s) when the patient meets the protocol criteria to restart 
drugs. 
 Discontinue = The specified drug(s) are totally stopped. 
If pomalidomide has been omitted and the toxicity does not return to ≤Grade 2 within 28 days, 
the patient may discontinue any further treatment with pomalidomide and proceed with the other 
agents on the protocol. 
8.21 
Pomalidomide dose adjustment for renal function 
Pomalidomide dose will be adjusted as per standard of care guidelines in the prescribing 
information of pomalidomide for multiple myeloma patients. Patients with creatinine 
clearance (CrCl) <30 ml/min noted while on treatment and not considered secondary to 


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disease progression will have dose modifications as per the clinical judgement. Patients 
with baseline CrCl <30 ml/minute are not eligible for this study (Appendix II). 


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8.3 
Elotuzumab Dose Modifications (NOTE: Only if any of the following criteria are met 
and the event cannot be ascribed to pomalidomide or to any other concurrent medication 
that the patient may be on, the elotuzumab infusion must be held/omitted to allow for 
recovery from toxicity). 
CTCAE 
System/Organ/Class 
(SOC) 
ADVERSE EVENT 
AGENT 
ACTION* 
Blood and lymphatic 
system disorders 
Febrile Neutropenia 
elotuzumab 
If AE is ≥ Grade 3, hold if Day 1. Omit if 
days 8, 15, or 22 during Cycles 1 & 2. 
• Hold/omit elotuzumab ** until recovery  
• May restart at same dose at the next 
planned dosing date.  
Investigations 
Neutrophil count 
decreased 
elotuzumab 
If AE is Grade 4 and lasting >7 days, hold 
if Day 1. Omit if days 8, 15, or 22 during 
Cycles 1 & 2. 
• Hold/omit elotuzumab ** until recovery 
to Grade ≤1 or baseline 
• May restart at same dose at the next 
planned dosing date. 
Investigations 
Platelet count decreased elotuzumab 
If AE is Grade 4 and lasting >7 days, hold 
if Day 1. Omit if days 8, 15, or 22 during 
Cycles 1 & 2. 
• Hold/omit elotuzumab ** until recovery 
to Grade ≤1 or baseline 
• May restart at same dose at the next 
planned dosing date. 
Gastrointestinal 
disorders 
Nausea 
elotuzumab 
If AE is ≥ Grade 3and persistent for  >7 
days despite optimal antiemetic therapy, 
hold if Day 1. Omit if days 8, 15, or 22 
during Cycles 1 & 2. 
• Hold/omit elotuzumab ** until recovery 
to Grade ≤1 or baseline 
• May restart at same dose at the next 
planned dosing date. 
Vomiting 
elotuzumab 
If AE is ≥ Grade 3and persistent >7 days 
despite optimal antiemetic therapy, hold if 
Day 1. Omit if days 8, 15, or 22 during 
Cycles 1 & 2. 
• Hold/omit elotuzumab ** until recovery 
to Grade ≤1 or baseline 
• May restart at same dose at the next 
planned dosing date. 
Diarrhea 
elotuzumab 
If AE is ≥ Grade 3and persistent for >7 
days despite antidiarrheal therapy, hold if 
Day 1. Omit if days 8, 15, or 22 during 
Cycles 1 & 2. 
• Hold/omit elotuzumab ** until recovery 
to Grade ≤1 or baseline 
• May restart at same dose at the next 
planned dosing date. 


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CTCAE 
System/Organ/Class 
(SOC) 
ADVERSE EVENT 
AGENT 
ACTION* 
Other (Non-
hematologic)**** 
Any other Grade 4 AE 
or any recurrent Grade 3 
AE that was present at 
baseline or lasts for >7 
days after the last 
administration of 
elotuzumab 
elotuzumab 
Hold if Day 1. Omit if days 8, 15, or 22 
during Cycles 1 & 2. 
• Hold/omit elotuzumab ** until recovery 
to Grade ≤1 or baseline 
• May restart at same dose at the next 
planned dosing date. 
*  Use the following to describe actions in the Action column: 
 Omit = The current dose(s) for the specified drug(s) during a cycle is skipped.  The 
patient does not make up the omitted dose(s) at a later time. 
 Hold/Delay = The current dose(s) of all drugs during a cycle is delayed.  The patient 
does make up the delayed dose(s) when the patient meets the protocol criteria to restart 
drugs. 
 Discontinue = The specified drug(s) are totally stopped. 
Additional Adverse Events: 
** If elotuzumab is omitted in the middle of the cycle and the toxicity resolves, patient 
can re-start the drug but the days of drug treatment missed do not need to be caught-up 
and can be omitted in order to maintain the cycle schedule. 
• 
Dose omission: elotuzumab may be omitted for adverse event considerations for a 
maximum of 28 consecutive days. Study medication should be discontinued 
permanently in the event of AE lasting more than 28 days. 
 
• 
If multiple adverse events are seen, administer dose based on the greatest 
reduction required by any single adverse event observed.  
• 
Dose modifications are for adverse events attributed to study treatment only.  
Dose modifications are not required for adverse events if they are deemed 
unrelated and/or unlikely related to study treatment. 
• 
Reductions apply to treatment given in the preceding cycle and are based on 
adverse events observed since the prior dose. 
• 
Patients can continue pomalidomide and dexamethasone if elotuzumab is 
held/omitted for AEs on Day 1 or during the cycle. 
**** If cough, dyspnea, and other pulmonary symptoms occur, a chest x-ray and high-
resolution chest CT scan should be obtained. Incentive spirometry studies (to include 
DLCO) should be considered.  Consider Pneumocystis pneumonia or viral pneumonitis. 
Patients who experience a deep vein thrombosis (DVT), pulmonary embolus (PE), or 
other clotting event should have all study drugs temporarily omitted while full-dose 
anticoagulation is initiated (other than warfarin or other Vitamin K antagonist). There 
should not be a delay of more than 28 days in reinitiating the study treatment.  
NOTE: If the patient experiences a significant adverse event requiring a dose reduction at the start of the 
next cycle, then the dose will remain lowered for that entire remaining length of the study treatment. 
8.4 
Dexamethasone Dose Modifications 
CTCAE 
System/Organ/Class 
(SOC) 
ADVERSE EVENT 
AGENT 
ACTION 


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CTCAE 
System/Organ/Class 
(SOC) 
ADVERSE EVENT 
AGENT 
ACTION 
Cardiac Disorders 
Sinus bradycardia Grade 
3 or 4 
dexamethasone 
Omit dose and follow at least weekly  
If the AE resolve to ≤2, implement one 
dose reduction step and continue therapy 
General disorders and 
administration site 
conditions 
Edema ≥Grade 3 
(limiting function and 
unresponsive to therapy 
or anasarca) 
dexamethasone 
Diuretics as needed, and decrease 
dexamethasone dose by 1 dose level 
If edema persists despite above measures, 
decrease dose another dose level 
Discontinue dexamethasone and do not 
resume if symptoms persist despite 
second reduction. Can continue 
elotuzumab and pomalidomide. 
Gastrointestinal 
disorders 
Lower gastrointestinal 
hemorrhage 
OR 
Upper gastrointestinal 
hemorrhage  
dexamethasone 
Discontinue dexamethasone 
Can continue elotuzumab and 
pomalidomide. 
Pancreatitis ≥Grade 3 
dexamethasone Discontinue dexamethasone 
Dypepsia, Gastric ulcer, 
duodenal ulcer, OR 
Gastritis ≥Grade 3 
dexamethasone 
Omit dexamethasone until symptoms 
adequately controlled 
Restart one dose level below along with 
concurrent therapy with H2 blockers, 
sucralfate, or omeprazole 
If symptoms persist despite above 
measures, discontinue dexamethasone 
Can continue elotuzumab and 
pomalidomide. 
Other  
Non-hematologic AE 
assessed ≥Grade 3 
dexamethasone 
Omit dose and follow at least weekly 
If the AE resolves to ≤Grade 2, 
implement one dose reduction step and 
continue therapy 
Psychiatric disorders Confusion≥Grade 3 
dexamethasone 
Omit dexamethasone until symptoms 
resolve 
Restart with one dose level reduction 
If symptoms persist despite above 
measures, discontinue dexamethasone 
Can continue elotuzumab and 
pomalidomide. 
*  Use the following to describe actions in the Action column: 
 Omit = The current dose(s) for the specified drug(s) during a cycle is skipped.  The 
patient does not make up the omitted dose(s) at a later time. 
 Hold/Delay = The current dose(s) of all drugs during a cycle is delayed.  The patient 
does make up the delayed dose(s) when the patient meets the protocol criteria to restart 
drugs. 
 Discontinue = The specified drug(s) are totally stopped. 
 
 


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9.0 
Ancillary Treatment/Supportive Care 
9.1 
Full supportive care  
Patients should receive full supportive care while on this study. This includes blood 
product support, antibiotic treatment, and treatment of other newly diagnosed or 
concurrent medical conditions. All blood products and concomitant medications such as 
antidiarrheals, analgesics, and/or antiemetics received from the first day of study 
treatment administration until 30 days after the final dose will be recorded in the medical 
records. 
9.2 
Blood products and growth factors 
Blood products and growth factors should be utilized as clinically warranted and 
following institutional policies and recommendations. The use of growth factors should 
follow published guidelines of the Journal of Clinical Oncology, Volume 33, No 28 
(October 1), 2015: pp. 3199-3212 (WBC growth factors) AND Journal of Clinical 
Oncology, Volume 28, No 33 (November 20), 2010: pp. 4955-5010 
(darbepoetin/epoetin). 
9.3 
Antiemetics 
Antiemetics may be used at the discretion of the attending physician. 
9.4 
Diarrhea 
Diarrhea could be managed conservatively with loperamide. The recommended dose of 
loperamide is 4 mg at first onset, followed by 2 mg every 2-4 hours until diarrhea free 
(maximum 16 mg/day). 
In the event of Grade 3 or 4 diarrhea, the following supportive measures are allowed: 
hydration, octreotide, and antidiarrheals.  
If diarrhea is severe (requiring intravenous rehydration) and/or associated with fever or 
severe neutropenia (Grade 3 or 4), broad-spectrum antibiotics must be prescribed. 
Patients with severe diarrhea or any diarrhea associated with severe nausea or vomiting 
should be hospitalized for intravenous hydration and correction of electrolyte 
imbalances. 
9.5 
Biosphosphonates 
 
 
Patients may receive concurrent treatment with a bisphosphonate. 
9.6 
Thrombophylaxis 
Due to the increased risk of deep vein thrombosis (DVT) for multiple myeloma patients, 
thromboprophylaxis is to be used as standard of care on this regimen according to the 
International Myeloma Working Group guidelines 
(http://jco.ascopubs.org/content/32/6/587.full).(21) 
 
9.7 
Herpes Zoster Prophylaxis 
Patients may be at an increased risk of infection including reactivation of herpes zoster 
and herpes simplex viruses. Prophylaxis with acyclovir 400 mg PO BID should be used 
while on study therapy and for 3 months beyond the end of therapy. 
9.8 
Prohibited Medications 
 
 
The following medications are not permitted during the trial: 
• 
Any other investigational treatment 
• 
Any cytotoxic chemotherapy 


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• 
Any other systemic anti-neoplastic therapy including, but not limited to, 
immunotherapy, hormonal therapy or monoclonal antibody therapy. 
• 
Any external beam radiotherapy. NOTE: Radiation therapy administered with 
palliative intent to control localized symptoms from MM is permitted provided 
the symptoms are not considered due to disease progression. 
9.9 
Concomitant medications 
Any systemic anti-myeloma therapy or steroids other than those prescribed by the 
protocol are prohibited while on protocol therapy. Guidelines for selection and use of 
other concomitant medications should be derived from the dexamethasone, elotuzumab, 
and pomalidomide prescribing information.  Other than study medications, administration 
of any therapeutic or diagnostic investigational agent (for any indication) is prohibited 
while on study. 
 
9.10  
Guidelines for prevention of infusion reactions 
 
Pre-infusion Medications: On elotuzumab infusion days, subjects will receive the 
following medications 45 to 90 minutes prior to infusion in addition to dexamethasone 
outlined in section 7.0: 
 
- Acetaminophen 650-1000 mg orally 
- Diphenhydramine (or comparable H1 blocker) 25 to 50 mg orally or intravenously 
- Famotidine (or comparable H2 blocker) 20 mg orally or intravenously 
 
9.11  
Guidelines for management of infusion reactions 
 
Subjects should be carefully observed during elotuzumab infusions. Trained study staff at 
the clinic should be prepared to intervene in case of any infusion reactions occurring and 
resources necessary for resuscitation must be available at the bedside. 
 
If a Grade 2 or higher infusion reaction occurs during elotuzumab administration, 
interrupt the infusion and institute appropriate medical and supportive measures 
(antiemetics, antihistamines, analgesics, corticosteroids, leukotriene inhibitors, oxygen, 
epinephrine, bronchodilators, or other supportive measures as indicated). Upon resolution 
to Grade 1 or lower, restart at 0.5 mL per minute and gradually increase at a rate of 0.5 
mL per minute every 30 minutes as tolerated to the rate at which the infusion reaction 
occurred. Resume the escalation regimen if there is no recurrence of the infusion reaction 
(see Table 7.13). 
 
In patients who experience an infusion reaction, monitor vital signs every 30 minutes for 
2 hours after the end of the elotuzumab infusion. If the infusion reaction recurs, stop the 
elotuzumab infusion and do not restart on that day.  
 
Infusion reactions after the completion of elotuzumab infusion: Should a Grade ≥ 2 
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. 
 


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Elotuzumab infusions on subsequent weeks after a prior Grade ≥ 2 infusion reaction: 
Subjects with prior Grade 2 or higher infusion reactions should have future infusions 
started at 0.5 mL/min and then escalated in a stepwise fashion (0.5 mL/minute every 30 
minutes, See section 7.13). 
10.0 
Adverse Event (AE) Monitoring and Reporting  
The site principal investigator is responsible for reporting any/all serious adverse events to the 
sponsor as described within the protocol, regardless of attribution to study agent or treatment 
procedure. 
The sponsor/sponsor-investigator is responsible for notifying FDA and all participating 
investigators in a written safety report of any of the following: 
• 
Any suspected adverse reaction that is both serious and unexpected. 
• 
Any findings from laboratory animal or in vitro testing that suggest a significant risk for 
human subjects, including reports of mutagenicity, teratogenicity, or carcinogenicity. 
• 
Any findings from epidemiological studies, pooled analysis of multiple studies, or 
clinical studies, whether or not conducted under an IND and whether or not conducted by 
the sponsor, that suggest a significant risk in humans exposed to the drug 
• 
Any clinically important increase in the rate of a serious suspected adverse reaction over 
the rate stated in the protocol or Investigator’s Brochure (IB). 
Summary of SAE Reporting for this study  
(please read entire section for specific instructions): 
 
WHO: 
WHAT form: 
WHERE to send: 
All sites 
Pregnancy Reporting 
http://ctep.cancer.gov/protocolDevelopment/electronic_a
pplications/docs/PregnancyReportFormUpdated.pdf 
Mayo Sites – attach to MCCC 
Electronic SAE Reporting Form 
http://livecycle2.mayo.edu/worksp
ace/?startEndpoint=MC4158-
56/Processes/MC4158-56-
Process.MC4158-56 
Will automatically be sent to 
CANCERCROSAFETYIN@mayo
.edu and 
RSTP2CSAES@mayo.edu 
 
Mayo Clinic 
Sites 
Mayo Clinic Cancer Center SAE Reporting 
Form:http://livecycle2.mayo.edu/workspace/?startEnd
point=MC4158-56/Processes/MC4158-56-
Process.MC4158-56  
AND attach 
MedWatch 3500A: 
http://www.fda.gov/downloads/AboutFDA/ReportsMa
nualsForms/Forms/UCM048334.pdf 
Will automatically be sent to 
CANCERCROSAFETYIN@mayo
.edu and 
RSTP2CSAES@mayo.edu 
Definitions 


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Adverse Event 
Any untoward medical occurrence associated with the use of a drug in humans, whether or 
not considered drug related.  
Suspected Adverse Reaction 
Any adverse event for which there is a reasonable possibility that the drug caused the adverse 
event. 
Expedited Reporting 
Events reported to sponsor within 24 hours, 5 days or 10 days of study team becoming aware 
of the event. 
Routine Reporting 
Events reported to sponsor via case report forms 
Events of Interest 
Events that would not typically be considered to meet the criteria for expedited reporting, but 
that for a specific protocol are being reported via expedited means in order to facilitate the 
review of safety data (may be requested by the FDA or the sponsor).  
10.1 
Adverse Event Characteristics 
CTCAE term (AE description) and grade: The descriptions and grading scales found 
in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 
5.0 will be utilized for AE reporting. All appropriate treatment areas should have access 
to a copy of the CTCAE version 5.0. A copy of the CTCAE version 5.0 can be 
downloaded from the CTEP web site: 
(http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm) 
a. Identify the grade and severity of the event using the CTCAE version 5.0. 
b. Determine whether the event is expected or unexpected (see Section 10.2). 
c. Determine if the adverse event is related to the study intervention (agent, treatment or 
procedure) (see Section 10.3). 
d. Determine whether the event must be reported as an expedited report. If yes, 
determine the timeframe/mechanism (see Section 10.4).  
e. Determine if other reporting is required (see Section 10.5). 
f. Note: All AEs reported via expedited mechanisms must also be reported via the 
routine data reporting mechanisms defined by the protocol (see Sections 10.6 and 
18.0). 
NOTE: A severe AE is NOT the same as a serious AE, which is defined in Section 10.4. 
10.2 
Expected vs. Unexpected Events  
Expected events - are those described within the Section 15.0 of the protocol, the study 
specific consent form, package insert (if applicable), and/or the investigator brochure, (if 
an investigator brochure is not required, otherwise described in the general 
investigational plan).  
Unexpected adverse events or suspected adverse reactions are those not listed in Section 
15.0 of the protocol, the study specific consent form, package insert (if applicable), or in 
the investigator brochure (or are not listed at the specificity or severity that has been 
observed); if an investigator brochure is not required or available, is not consistent with 
the risk information described in the general investigational plan. 
Unexpected also refers to adverse events or suspected adverse reactions that are 
mentioned in the investigator brochure as occurring with a class of drugs but have not 


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been observed with the drug under investigation. 
An investigational agent/intervention might exacerbate the expected AEs associated with a 
commercial agent. Therefore, if an expected AE (for the commercial agent) occurs with a 
higher degree of severity or specificity, expedited reporting is required. 
NOTE: *The consent form may contain study specific information at the discretion of the 
Principal Investigator; it is possible that this information may NOT be included in the 
protocol or the investigator brochure. Refer to protocol or IB for reporting needs. 
10.3 
Attribution to agent(s) or procedure 
When assessing whether an adverse event (AE) is related to a medical agent(s) medical or 
procedure, the following attribution categories are utilized: 
Definite - The AE is clearly related to the agent(s)/procedure. 
Probable - The AE is likely related to the agent(s)/procedure. 
Possible - The AE may be related to the agent(s)/procedure. 
Unlikely - The AE is doubtfully related to the agent(s)/procedure. 
Unrelated - The AE is clearly NOT related to the agent(s)/procedure. 
10.31 AEs Experienced Utilizing Investigational Agents and Commercial Agent(s) 
on the SAME (Combination) Arm 
NOTE: When a commercial agent(s) is (are) used on the same treatment arm as 
the investigational agent/intervention (also, investigational drug, biologic, 
cellular product, or other investigational therapy under an IND), the entire 
combination (arm) is then considered an investigational intervention for 
reporting. 
• An AE that occurs on a combination study must be assessed in accordance with the 
guidelines for investigational agents/interventions.  
• An AE that occurs prior to administration of the investigational agent/intervention 
must be assessed as specified in the protocol. In general, only Grade 4 and 5 AEs 
that are unexpected with at least possible attribution to the commercial agent require 
an expedited report, unless hospitalization is required. Refer to Section 10.4 for 
specific AE reporting requirements or exceptions. 
An investigational agent/intervention might exacerbate the expected AEs associated 
with a commercial agent. Therefore, if an expected AE (for the commercial agent) 
occurs with a higher degree of severity or specificity, expedited reporting is 
required. 
• An increased incidence of an expected adverse event (AE) is based on the 
patients treated for this study at their site. A list of known/expected AEs is 
reported in the package insert or the literature, including AEs resulting from a 
drug overdose. 
• Commercial agent expedited reports must be submitted to the FDA via MedWatch 
3500A for Health Professionals (complete all three pages of the form). 
http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM0
48334.pdf 
10.32 EXPECTED Serious Adverse Events: Protocol Specific Exceptions to 
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For this protocol only, the following Adverse Events/Grades are expected to occur 
within this population and do not require Expedited Reporting. These events must still 
be reported via Routine Reporting (see Section 10.6).* 
*Report any clinically important increase in the rate of a serious suspected 
adverse reaction (at your study site) over that which is listed in the protocol or 
investigator brochure as an expedited event.  
*Report an expected event that is greater in severity or specificity than expected 
as an expedited event. 
*Specific protocol exceptions to expedited reporting should be reported 
expeditiously by investigators ONLY if they exceed the expected grade of the 
event. 
 
CTCAE 
System Organ Class 
(SOC) 
Adverse event/ Symptoms 
CTCAE Grade at which the event 
will not be reported in an expedited 
manner1 
Blood and lymphatic 
system disorders 
Anemia  
≤Grade 4 
Gastrointestinal Disorders 
Diarrhea 
≤Grade 3 
Nausea 
≤Grade 3 
Vomiting 
≤Grade 3 
General disorders and 
administration site 
conditions 
Fatigue 
≤Grade 3 
Investigations 
Lymphocyte count decreased 
≤Grade 4 
Neutrophil count decreased 
≤Grade 4 
Platelet count decreased 
≤Grade 4 
White blood cell count 
decreased 
≤Grade 4 
1 These exceptions only apply if the adverse event does not result in hospitalization. If the adverse 
event results in hospitalization, then the standard expedited adverse events reporting 
requirements must be followed.  
The following hospitalizations are not considered to be SAEs because there is no “adverse event” 
(i.e., there is no untoward medical occurrence) associated with the hospitalization: 
● Hospitalizations for respite care 
● Planned hospitalizations required by the protocol 
● Hospitalization planned before informed consent (where the condition requiring the hospitalization 
has not changed post study drug administration) 
● Hospitalization for elective procedures unrelated to the current disease and/or treatment on this trial 
● Hospitalization for administration of study drug or insertion of access for administration of study 
drug 
●Hospitalization for routine maintenance of a device (e.g., battery replacement) that was in place 
before study entry 
● Hospitalization, or other serious outcomes for signs and symptoms of progression of the cancer. 
 
10.4 
Expedited Reporting Requirements for Commercial or Commercial Imaging Agents 
(Non-IND) Agent(s) ONLY:  


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10.41 Expedited Reporting Requirements for Adverse Events that Occur in a Non-
IND trial within 30 Days of the Last Administration of a Commercial 
Agent1, 2 
FDA REPORTING REQUIREMENTS FOR SERIOUS ADVERSE EVENTS (21 CFR Part 312) 
NOTE: Investigators MUST immediately report to the sponsor ANY Serious Adverse Events, whether or not they 
are considered related to the investigational agent(s)/intervention (21 CFR 312.64) 
An adverse event is considered serious if it results in ANY of the following outcomes:  
1) 
Death 
2) 
A life-threatening adverse event  
3) 
An adverse event that results in inpatient hospitalization or prolongation of existing hospitalization for ≥ 24 
hours  
4) 
A persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions  
5) 
A congenital anomaly/birth defect.  
6) 
Important Medical Events (IME) that may not result in death, be life threatening, or require hospitalization 
may be considered serious when, based upon medical judgment, they may jeopardize the patient or 
subject and may require medical or surgical intervention to prevent one of the outcomes listed in this 
definition. (FDA, 21 CFR 312.32; ICH E2A and ICH E6). 
ALL SERIOUS adverse events that meet the above criteria MUST be immediately reported to the sponsor within 
the timeframes detailed in the table below. 
Hospitalization 
Grade 1 
Timeframes 
Grade 2 
Timeframes 
Grade 3 Timeframes 
Grade 4 & 5 
Timeframes 
Resulting in 
Hospitalization  
≥24 hrs 
7 Calendar Days 
24-Hour  
3 Calendar 
Days 
Not resulting in 
Hospitalization  
≥24 hrs 
Not required 
7 Calendar Days 
Expedited AE reporting timelines are defined as: 
o “24-Hour; 3 Calendar Days” - The AE must initially be reported within 24 hours of learning of the AE, 
followed by a complete expedited report within 3 calendar days of the initial 24-hour report. 
o “7 Calendar Days” - A complete expedited report on the AE must be submitted within 7 calendar days 
of learning of the AE. 
1Serious adverse events that occur more than 30 days after the last administration of investigational 
agent/intervention and have an attribution of possible, probable, or definite require reporting as follows:  
Expedited 24-hour notification followed by complete report within 3 calendar days for: 
• All Grade 4, and Grade 5 AEs 
Expedited 7 calendar day reports for: 
• Grade 2 adverse events resulting in hospitalization or prolongation of hospitalization  
• Grade 3 adverse events 
2 For studies using PET or SPECT IND agents, the AE reporting period is limited to 10 radioactive half-lives, 
rounded UP to the nearest whole day, after the agent/intervention was last administered. Footnote “1” above 
applies after this reporting period. 
Effective Date: May 5, 2011 
NOTE: Refer to Section 10.32 for exceptions to Expedited Reporting 
 


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10.42 General reporting instructions 
The Mayo IND and/or MCCC Compliance will assist the sponsor-investigator in 
the processing of expedited adverse events and forwarding of suspected 
unexpected serious adverse reactions (SUSARs) to the FDA and IRB. 
Use Mayo Expedited Event Report form 
http://livecycle2.mayo.edu/workspace/?startEndpoint=MC4158-
56/Processes/MC4158-56-Process.MC4158-56 for investigational agents or 
commercial/investigational agents on the same arm.  
10.43 Reporting of re-occurring SAEs 
ALL SERIOUS adverse events that meet the criteria outlined in table10.41 
MUST be immediately reported to the sponsor within the timeframes detailed in 
the corresponding table. This reporting includes, but is not limited to SAEs that 
re-occur again after resolution. 
10.5 
Other Required Reporting 
10.51 Unanticipated Problems Involving Risks to Subjects or Others (UPIRTSOS) 
Unanticipated Problems Involving Risks to Subjects or Others (UPIRTSOS) in 
general, include any incident, experience, or outcome that meets all of the 
following criteria: 
1. Unexpected (in terms of nature, severity, or frequency) given (a) the research 
procedures that are described in the protocol-related documents, such as the 
IRB-approved research protocol and informed consent document; and (b) the 
characteristics of the subject population being studied; 
2. Related or possibly related to participation in the research (in this guidance 
document, possibly related means there is a reasonable possibility that the 
incident, experience, or outcome may have been caused by the procedures 
involved in the research); and 
3. Suggests that the research places subjects or others at a greater risk of harm 
(including physical, psychological, economic, or social harm) than was 
previously known or recognized. 
Some unanticipated problems involve social or economic harm instead of the 
physical or psychological harm associated with adverse events. In other cases, 
unanticipated problems place subjects or others at increased risk of harm, but no 
harm occurs. 
Note: If there is no language in the protocol indicating that pregnancy is not 
considered an adverse experience for this trial, and if the consent form does not 
indicate that subjects should not get pregnant/impregnate others, then any 
pregnancy in a subject/patient or a male patient’s partner (spontaneously 
reported) which occurs during the study or within 120 days of completing the 
study should be reported as a UPIRTSO. 
Mayo Clinic Cancer Center (MCCC) Institutions: 
If the event meets the criteria for IRB submission as a Reportable 
Event/UPIRTSO, provide the appropriate documentation and use the Mayo 
Clinic Cancer Center Expedited Event Report form 
http://livecycle2.mayo.edu/workspace/?startEndpoint=MC4158-


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56/Processes/MC4158-56-Process.MC4158-56, to submit to 
CANCERCROSAFETYIN@mayo.edu. The Mayo Clinic Compliance Unit will 
review and process the submission to the Mayo Clinic IRB and work with the 
IND Coordinator for submission to FDA. 
10.52 Death 
Note: A death on study requires both routine and expedited reporting 
regardless of causality, unless as noted below. Attribution to treatment or 
other cause must be provided. 
Any death occurring within 30 days of the last dose, regardless of attribution to 
an agent/intervention under an IND requires expedited reporting within 24-
hours. 
Any death occurring greater than 30 days with an attribution of possible, 
probable, or definite to an agent/intervention under an IND requires expedited 
reporting within 24-hours. 
Reportable categories of Death  
• 
Death attributable to a CTCAE term. 
• 
Death Neonatal: A disorder characterized by cessation of life during the 
first 28 days of life.  
• 
Death NOS: A cessation of life that cannot be attributed to a CTCAE term 
associated with Grade 5. 
• 
Sudden death NOS: A sudden (defined as instant or within one hour of the 
onset of symptoms) or an unobserved cessation of life that cannot be 
attributed to a CTCAE term associated with Grade 5. 
• 
Death due to progressive disease should be reported as Grade 5 
“Neoplasms benign, malignant and unspecified (including cysts and 
polyps) – Other (Progressive Disease)” under the system organ class 
(SOC) of the same name. Evidence that the death was a manifestation of 
underlying disease (e.g., radiological changes suggesting tumor growth or 
progression: clinical deterioration associated with a disease process) 
should be submitted. 
10.53 Secondary Malignancy 
• 
A secondary malignancy is a cancer caused by treatment for a previous 
malignancy (e.g., treatment with investigational agent/intervention, radiation 
or chemotherapy). A secondary malignancy is not considered a metastasis of 
the initial neoplasm. 
• 
All secondary malignancies that occur following treatment with an agent under 
an IND will be reported. Three options are available to describe the event: 
o Leukemia secondary to oncology chemotherapy (e.g., Acute Myeloctyic 
Leukemia [AML]) 
o Myelodysplastic syndrome (MDS) 
o Treatment-related secondary malignancy 
• 
Any malignancy possibly related to cancer treatment (including AML/MDS) 
should also be reported via the routine reporting mechanisms outlined in each 
protocol. 
10.54 Second Malignancy 


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A second malignancy is one unrelated to the treatment of a prior malignancy (and is 
NOT a metastasis from the initial malignancy). Second malignancies require ONLY 
routine reporting unless otherwise specified. 
10.55 Pregnancy, Fetal Death, and Death Neonatal  
If a female subject (or female partner of a male subject) taking investigational 
product becomes pregnant, the subject taking should notify the Investigator, and 
the pregnant female should be advised to call her healthcare provider 
immediately. The patient should have appropriate follow-up as deemed necessary 
by her physician. If the baby is born with a birth defect or anomaly, a second 
expedited report is required. 
Prior to obtaining private information about a pregnant woman and her infant, the 
investigator must obtain consent from the pregnant woman and the newborn 
infant’s parent or legal guardian before any data collection can occur. A consent 
form will need to be submitted to the IRB for these subjects if a pregnancy 
occurs. If informed consent is not obtained, no information may be collected. 
In cases of fetal death, miscarriage or abortion, the mother is the patient. In cases 
where the child/fetus experiences a serious adverse event other than fetal death, 
the child/fetus is the patient. 
NOTE: When submitting Mayo Expedited Adverse Event Report reports for 
“Pregnancy”, “Pregnancy loss”, or “Neonatal loss”, the potential risk of exposure 
of the fetus to the investigational agent(s) or chemotherapy agent(s) should be 
documented in the “Description of Event” section. Include any available medical 
documentation. Include this form: 
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/Pregna
ncyReportFormUpdated.pdf 
10.551 
Pregnancy 
Pregnancy should be reported in an expedited manner as Grade 3 
“Pregnancy, puerperium and perinatal conditions - Other 
(pregnancy)” under the Pregnancy, puerperium and perinatal 
conditions SOC. Pregnancy should be followed until the outcome is 
known. 
10.552 
Fetal Death 
Fetal death is defined in CTCAE as “A disorder characterized by death 
in utero; failure of the product of conception to show evidence of 
respiration, heartbeat, or definite movement of a voluntary muscle after 
expulsion from the uterus, without possibility of resuscitation.” 
Any fetal death should be reported expeditiously, as Grade 4 
“Pregnancy, puerperium and perinatal conditions - Other 
(pregnancy loss)” under the Pregnancy, puerperium and perinatal 
conditions SOC. 
10.553 
Death Neonatal 
Neonatal death, defined in CTCAE as “A disorder characterized by 
cessation of life occurring during the first 28 days of life” that is felt by 
the investigator to be at least possibly due to the investigational 
agent/intervention, should be reported expeditiously.  


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A neonatal death should be reported expeditiously as Grade 4 
“General disorders and administration - Other (neonatal loss)” 
under the General disorders and administration SOC.  
10.6 
Required Routine Reporting  
10.61 Baseline and Adverse Events Evaluations 
Pretreatment symptoms/conditions to be graded at baseline and adverse events to 
be graded at each evaluation.  
Grading is per CTCAE v5.0 unless alternate grading is indicated in the table 
below: 
CTCAE  
System/Organ/Class (SOC) 
Adverse 
event/Symptoms 
Baseline 
Each evaluation 
Blood and lymphatic 
system disorders 
Anemia 
 
X 
General disorders and 
administration site 
conditions 
Maculopapular Rash 
X 
X 
Infusion related 
reaction 
 
X 
Fatigue 
X 
X 
Investigations 
Neutrophil count 
decreased 
 
X 
Platelet count 
decreased 
 
X 
10.62 All other AEs 
Submit via appropriate MCCC Case Report Forms (i.e., paper or electronic, as 
applicable) the following AEs experienced by a patient and not specified in 
Section 10.6: 
10.621 Grade 2 AEs deemed possibly, probably, or definitely related to the study 
treatment or procedure. 
10.622 Grade 3 and 4 AEs regardless of attribution to the study treatment or 
procedure. 
10.623 Grade 5 AEs (Deaths) 
10.6231 
Any death within 30 days of the patient’s last study 
treatment or procedure regardless of attribution to the study 
treatment or procedure. 
10.6232 
Any death more than 30 days after the patient’s last study 
treatment or procedure that is felt to be at least possibly 
treatment related must also be submitted as a Grade 5 AE, 
with a CTCAE type and attribution assigned. 
10.7 
Late Occurring Adverse Events 
Refer to the instructions in the Forms Packet (or electronic data entry screens, as 
applicable) regarding the submission of late occurring AEs following completion of the 
Active Monitoring Phase (i.e., compliance with Test Schedule in Section 4.0). 
10.8 
Adverse Events of Special Interest (AESI) 


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Specific adverse events, or groups of adverse events, will be followed as part of standard 
safety monitoring activities.  
10.81 Major Hemorrhage 
 
Major hemorrhage is defined as any of the following: 
• 
Any treatment-emergent hemorrhagic adverse events of Grade 3 or 
higher*. Any treatment-emergent serious adverse events of bleeding 
of any grade 
• 
Any treatment-emergent central nervous system 
hemorrhage/hematoma of any grade 
*All hemorrhagic events requiring transfusion of red blood cells should be 
reported as grade 3 or higher AE per CTCAE v5.0. 
Events meeting the definition of major hemorrhage will be captured as an event 
of special interest according to section 10.8 above. 
 
 
 


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11.0 
Treatment Evaluation 
The International Myeloma Working Group (IMWG) uniform response criteria (Kumar et al, 
2016) will be used to assess response to therapy.  
11.1 
Terms and definitions 
• 
M-protein: synonyms include M-spike, monoclonal protein and myeloma 
protein, paraprotein, M-component. 
 
Serum M-protein level is quantitated using densitometry on SPEP except in cases 
where the SPEP is felt to be unreliable. 
o M-proteins migrating in the β-region (usually IgA M-proteins) 
o Cases in which the M-protein is so large and narrow on agarose (some 
specimens >4 g/dL) that they underestimate the actual immunoglobulin 
level (by greater than 1500 mg/dL) due to technical staining properties of 
the agarose gel. 
o Cases in which there are multiple peaks of same M-protein (aggregates 
or dimers) 
If SPEP is not available or felt to be unreliable (above examples) for routine M-
protein quantitation, then quantitative immunoglobulin levels derived from 
nephelometry or turbidometry can be accepted, with the exception that 
quantitative IgG may not be used.  However, this must be explicitly reported at 
baseline, and only nephelometry can be used for that patient to assess response. 
SPEP derived M-protein values and quantitative nephelometric immunoglobulin 
values cannot be used interchangeably.   
 
Urine M-protein measurement is estimated using 24-h UPEP only.  Random or 
24 h urine tests measuring kappa and lambda light chain levels are not reliable 
and are not recommended. 
 
FLC estimation is currently carried out using the serum FLC assay (Freelite, 
The Binding Site Limited, UK).  Patients with kappa/lambda FLC ratio <0.26 are 
defined as having monoclonal lambda FLC and those with ratios >1.65 as having 
a monoclonal kappa FLC.  The monoclonal light chain isotype is considered the 
involved FLC isotype, and the opposite light chain type as the uninvolved FLC 
type. 
 
• 
Response terms: The following response terms will be used: stringent Complete 
Response (sCR), complete response (CR), very good partial response (VGPR), partial 
response (PR), Minimal Response (MR), stable disease (SD), and progressive disease 
(PD).  
 
In addition, for each response category, there will be an “unconfirmed” response 
category, which will be for internal use, for the purpose of guiding decision making 
and test ordering. These designations will be applied at the time of the first 
measurement at which the quantitative aspect of the response category has been 
satisfied without the confirmation step having been satisfied. The designation “u” 
will precede the standard abbreviations, and will include usCR, uCR, uVGPR, uPR, 
uMR, uPD. 
 
• 
Measurable disease: Patients who have a measurable serum or urine M-protein. 


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o Serum M-protein ≥1 g/dl  
NOTE:  Quantitative IgG may not be used for defining 
measurable disease 
o Urine M-protein ≥ 200 mg/24 h 
o Serum FLC assay: Involved FLC level ≥  10 mg/dl provided 
serum FLC ratio is abnormal 
 
The serum free light chain (FLC) assay is of particular use in monitoring response to 
therapy in patients who have oligo-secretory or non-secretory disease and should be 
used in assessing response only if the baseline serum and/or urine M proteins 
are not “measurable” as above, and the baseline level of the involved FLC is 
“measurable.”  When using this assay, it is important to note that the FLC levels 
vary considerably with changes in renal function and in patients with renal 
insufficiency, the levels of both the kappa and lambda may remain elevated, but the 
ratio normalizes with achievement of CR.  Thus, both the level of the involved and 
the uninvolved FLC isotype (i.e., the involved/uninvolved ratio or involved-
uninvolved difference) should be considered in assessing response.  Patients 
included on the study on the basis of FLC alone (i.e., no measurable serum/urine 
M-protein) should be the only ones who are evaluated using FLC response criteria.  
The others should follow usual criteria and ignore FLC results with the exception 
of defining stringent complete response. 
 
• 
Evaluable disease: Patients who do not have a “measurable” serum M-protein, 
serum free light chain, or urine M-protein. 
 
• 
Oligosecretory myeloma: Patient with multiple myeloma who has NEVER had 
“measurable” serum M-protein or urine M-protein, but has had a detectable M-
protein in his/her serum and/or urine and/or measurable serum free light chain.  
 
• 
Non-secretory myeloma: Patient with multiple myeloma who has NEVER had a 
detectable M-protein in his/her serum and/or urine. 
11.2 
Clarification of test indications 
Listed below are the minimal required tests required to assess response based on the 
characteristics of their disease at on study. 
 
Table 11.2 
Tests  Required To Assess Response (Must Be Done At Each Disease Measurement Visit 
except as indicated1,2) 
On Study Baseline Value 
SPEP4  
24 hr 
UPEP2  
Ig 
FLC 
BM Bx 
Serum M-protein ≥1 g/dl, and urine M-protein≥ 
200 mg/24 hrs 
X 
X 
 
 
Serum M-protein ≥ 1 g/dl, but urine M-protein < 
200 mg/24 hrs 
X 
 
 
 
Serum M-protein <1 g/dl, and urine M-protein≥ 
200 mg/24 hrs 
 
X 
 
 
Serum M-protein < 1 g/dl, urine M-protein < 200 
mg/24 hrs, but involved Ig FLC is ≥10 mg/dL 
 
 
X 
 
Serum M-protein < 1 g/dl, urine M-protein< 200 
 
 
 
X3 


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mg/24 hrs, involved Ig FLC is <10 mg/dL, bone 
marrow ≥30% plasma cells 
1  SPEP, UPEP, Immunofixation studies of both serum and urine, and Bone marrow 
biopsy are required to document CR regardless of registration values, and in addition 
FLC measurement and bone marrow immunophenotyping is required to document 
sCR.   
2  For serum measurable patients, 24 hour urine does not need to be confirmed (i.e. 
repeated after documented response) for any response category 
3  At a minimum, a bone marrow biopsy should be repeated every 3 months until 
documented response.  Bone marrow biopsy results do not need to be repeated after 
documented response. 
4    If serum M-protein is being followed by quantitative immunoglobulin levels derived 
from nephelometry or turbidometry, quantitative immunoglobulins are required.  SPEP is 
only required to document CR or VGPR. 
11.3 
Confirmed response 
In order to be classified as a hematologic response, confirmation of serum M- protein, 
serum immunoglobulin free light chain (when primary determinant of response) and 
urine M- protein (when primary determinant of response) results must be made by 
verification on two consecutive determinations. 
• 
Bone marrow aspirate and biopsy are only required to document CR or sCR, 
except for patients with evaluable disease only, where a bone marrow is required 
to document all response categories including progression. However, a second 
confirmatory bone marrow is not required to confirm response in any case. 
• 
Radiographic studies are not required to satisfy these response requirements; 
however, if radiographic studies were performed there should be no evidence of 
progressive or new bone lesions. 
 
Appropriate tests required to document and confirm response are listed in Table 11.2 
11.4  
Bone Progression 
Caution must be exercised to avoid rating progression on the basis of variation of 
radiologic technique alone.  Compression fracture does not exclude continued response 
and may not indicate progression.  When progression is based on skeletal disease alone, it 
should be discussed with the Study Chair before removing the patient from the study. 
11.5 
Response and progression 
Table 11.5 
STANDARD IMWG 
RESPONSE 
CATEGORY 
RESPONSE CRITERIA a 
Stringent Complete 
Response (sCR) b 
CR as defined plus 
Normal FLC ratio and 
• Absence of clonal PCs by immunohistochemistry or 2- to 4- color 
flow cytometry i 
Complete Response 
(CR) b  
• Negative immunofixation of serum and urine c and 
• Disappearance of any soft tissue plasmacytoma and 
• <5% PCs in Bone Marrow and 
• If the only measurable disease is FLC, a normal FLC ratio d  
Very Good Partial 
• Serum and urine M-protein detectable by immunofixation but not 


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Response (VGPR)  
on electrophoresis c or 
• ≥90% reduction in serum M-protein and urine M-protein <100 
mg/24 h c 
• If the only measurable disease is FLC, a >90% reduction in the 
difference between involved and uninvolved FLC levels 
Partial Response (PR) 
• If present at baseline, ≥ 50% reduction of serum M-protein and 
reduction in 24-hour urinary M-protein by ≥90% or to <200 
mg/24hrs c 
• If the only measurable disease is FLC, a ≥50% reduction in the 
difference between involved and uninvolved FLC levels 
• If the only measurable disease is BM, a ≥ 50% reduction in BM 
PCs (provided the baseline PCs was ≥ 30%) 
• If present at baseline, ≥ 50% reduction in the size (SPD) of soft 
tissue plasmacytomas j 
Minimal Response (MR)  
• If present at baseline, ≥25% but ≤ 49% reduction of serum M 
protein and reduction in 24-hour urine M-protein by 50-89% 
which still exceeds 200mg/24 hours c and 
• If present at baseline, ≥50% reduction in the size (SPD) of soft 
tissue plasmacytoma j  
Stable Disease (SD) 
• Not meeting criteria for sCR, CR, VGPR, PR, MR or PD 
Progressive Disease 
(PD) b, h 
 
Increase of 25% from lowest value in any of the following f, g: 
• 
Serum M-protein (absolute increase must be ≥ 0.5 g/dL) and/or 
• 
Urine M-protein (absolute increase must be ≥ 200 mg/24 hrs) 
and/or 
• 
If the only measurable disease is FLC, the difference between 
involved and uninvolved FLC levels (absolute increase must be 
>10 mg/dL)  and/or 
• 
If the only measurable disease is BM, bone marrow PC 
percentage (absolute increase must be ≥ 10%) e  
Or any one or more of the following: 
• 
Development of new bone lesion or soft tissue plasmacytoma or 
≥50% increase from nadir in the size (SPD) of  existing bone 
lesions or soft tissue plasmacytoma or ≥ 50% increase in the 
longest diameter of a previous lesion >1 cm in short axis j 
• 
50% increase in circulating plasma cells (minimum of 200 cells 
per  L) if this is the only measure of disease 
a All response categories require two consecutive assessments (sCR, CR, VGPR, PR, 
MR, PD) made at any time before the institution of any new therapy.  sCR, CR, VGPR, 
PR, MR and SD categories require no known evidence of progressive or new bone 
lesions or extramedullary plasmacytomas if radiographic studies were performed. 
However, radiographic studies are not required to satisfy these response requirements.  
Bone marrow assessments need not be confirmed. Each category, except for stable 
disease, will have a working subcategory of “unconfirmed” [prefix ‘u”] to designate first 
time point at which response category MAY have been achieved if confirmed. The date 
of the initial test is considered as the date of response for evaluation of time dependent 
outcomes such as duration of response. 
 
b CR patient will need to progress at the same level as VGPR and PR patients to be 
considered a PD.  A positive immunofixation alone is not sufficient. 
 


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c If more than one M protein spike meets the criteria for measurable disease at baseline, 
then both need to be followed for response.  Otherwise, only follow the measurable M 
protein spike for response.   
 
d In patients in whom the only measurable disease is by serum FLC levels: CR in such 
patients indicates a normal FLC ratio of 0.26-1.65 in addition to the CR criteria listed 
above. 
 
e Bone marrow criteria for PD are only to be used in patients without measurable disease 
by M protein and by FLC;  
 
f A "25% increase" refers to M protein, FLC and bone marrow results and does not refer 
to bone lesions, soft tissue plasmacytoma or hypercalcemia.  The lowest value does not 
need to be a confirmed value.  If the lowest serum M-protein is ≥ 5 g/dL, an increase in 
serum M-protein of ≥ 1 g/dL is sufficient to define disease progression. 
 
g In the case where a value is felt to be a spurious result per physician discretion (for 
example, a possible lab error), that value will not be considered when determining the 
lowest value. 
 
h Progressive disease should be confirmed on two consecutive evaluations, where the 
timing of confirmation is per the treating physician and can be done immediately within 
the same cycle or on the next cycle.  However, treatment may be discontinued for 
progressive disease that is unconfirmed per physician discretion.  In this case, an 
objective status of PD should be entered on the measurement form and progressive 
disease should be reported on the event monitoring form. 
 
i Presence/absence of clonal cells is based upon the k/l ratio. An abnormal k/l ratio by 
immunohistochemistry requires a minimum of 100 plasma cells for analysis. An 
abnormal ratio reflecting presence of an abnormal clone is k/l of 4:1 or 1:2.  
 
j Plasmacytoma measurements should be taken from the CT portion of the PET/CT, or 
MRI scans, or dedicated CT scans where applicable. For patients with only skin 
involvement, skin lesions should be measured with a ruler. Measurement of tumor size 
will be determined by the sum of the products of the maximal perpendicular diameters of 
measured lesions (SPD). 
 
12.0 
Descriptive Factors  
12.1 
MM risk categories (As per Appendix IV): High vs. standard/intermediate. 
12.2 
Immediately prior treatment was daratumumab-based: yes vs. no 
12.3   Parameters followed for hematologic response: serum monoclonal protein ≥1 g/dL and 
urine monoclonal protein ≥200 mg/24 hours vs. serum monoclonal protein ≥1g/dL only 
vs. urine monoclonal protein ≥200 mg/24 hours only vs. serum immunoglobulin free light 
chain ≥10 mg/dL. Distinguish between SPEP measurements versus quantitative IgA 
measurements versus quantitative IgD measurements for serum monoclonal protein. 
 
 


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13.0 
Treatment/Follow–up Decision at Evaluation of Patient  
Reason Off Treatment (from the Off Treatment Form) 
Go to CFU, SFU, or end 
folder rollout 
1 = Treatment (Intervention) Completed Per Protocol Criteria 
N/A 
2 = Patient Withdrawal/Refusal After Beginning Protocol Therapy 
(Intervention) 
SFU 
3 = Adverse Events/Side Effects/Complications 
SFU 
4 = Disease Progression, Relapse During Active Treatment (Intervention) 
SFU 
5 = Alternative Therapy 
SFU 
6 = Patient Off-Treatment (Intervention) For Other Complicating Disease 
SFU 
7 = Death On Study 
No follow-up 
8 = Other 
SFU 
10 = Disease Progression Before Active Treatment (Intervention) 
No follow-up 
24 = Patient Withdrawal/Refusal Prior To Beginning Protocol Therapy 
(Intervention) 
No follow-up 
 
13.1 
Continuation of treatment 
Patients who are sCR, CR, VGPR, PR, MR, or SD (or usCR, uCR, uVGPR, uPR, uMR 
will continue treatment per protocol. 
13.2 
Progressive disease (PD) 
Patients who develop PD while receiving therapy will go to the survival follow-up phase. 
13.3 
Off protocol treatment 
Patients who go off protocol treatment for reasons other than PD will go to the survival 
follow-up phase per Section 4.0. 
13.9b Ineligible 
A patient is deemed ineligible if after registration, it is determined that at the time of 
registration, the patient did not satisfy each and every eligibility criteria for study entry. If 
the patient received treatment, the patient may continue treatment at the discretion of the 
physician as long as there are not safety concerns.  The patient will continue in the Active 
Monitoring/Treatment phase of the study, as per section 4.0 of the protocol.  
• 
If the patient never received treatment, on-study and the End of Active 
Treatment/Cancel Notification Form must be submitted. No further data submission 
is necessary. 
13.9c 
Major violation 
A patient is deemed a major violation, if protocol requirements regarding treatment in 
cycle 1 of the initial therapy are severely violated that evaluability for primary end point 
is questionable. If the patient received treatment, the patient may continue treatment at 
the discretion of the physician as long as there are not safety concerns.  The patient will 
continue in the Active Monitoring/Treatment phase of the study, as per section 4.0 of the 
protocol. 
13.9d Cancel 
A patient is deemed a cancel if he/she is removed from the study for any reason before 
any study treatment is given. On-study material and the End of Active Treatment/Cancel 
Notification Form must be submitted. No further data submission is necessary. 
 


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14.0 
Body Fluid Biospecimens 
None. 
15.0 
Drug Information 
15.1  Dexamethasone commercial supply (Decadron, Hexadrol, and various) 
 
 
15.11  Formulation and storage (injection):  Dexamethasone sodium phosphate is 
supplied as 4mg/ml IV solution in 5ml vials.  Store intact vials at controlled room 
temperature, do not refrigerate. Protect from heat and light. 
 
 
 
 
 
 
 
Formulation and storage (tablets):  Dexamethasone tablets should be stored at 
room temperature and are stable for at least 2 years.  Dexamethasone should be 
given as a single daily dose in the a.m. after breakfast. 
 
15.12  Preparation:  The sterile solution from the vial may be further diluted in D5W 
or NS (refer to the treatment section of the protocol). 
 
15.13   Stability:  Refer to expiration date on the vial. 
 
15.14   Administration:  IV push or infusion (see treatment section of the protocol). 
 
 
 
15.15   Known potential toxicities: Fluid and electrolyte disturbances, congestive heart 
failure in susceptible persons, hypertension, euphoria, personality changes, 
insomnia, exacerbation of infection, exacerbation or symptoms of diabetes, 
psychosis, muscle weakness, osteoporosis, vertebral compression fractures, 
pancreatitis, esophagitis, peptic ulcer, dermatologic disturbances, convulsions, 
vertigo and headache, endocrine abnormalities, ophthalmic changes, and 
metabolic changes.  Some patients have experienced itching and other allergic, 
anaphylactic or hypersensitivity reactions.  Withdrawal from prolonged therapy 
may result in symptoms including fever, myalgia and arthralgia. 
 
15.16   Drug procurement:  Drug will be procured from the commercial supply of 
Dexamethasone. 
 
15.17 Nursing guidelines: 
15.171  Monitor regularly for hypertension, CHF, and other evidence of fluid 
retention. 
 
15.172  Advise patient of possible mood or behavioral changes, i.e., depression, 
euphoria, insomnia, even psychosis.  Instruct patient to report any 
suspected changes to healthcare team. 
 
15.173  Assess for symptoms of gastric ulcer, heartburn, or gastritis.  Suggest 
antacids.  Instruct patient to report symptoms to healthcare team if unable 
to control. 
 
15.174  Evaluate signs of infection, particularly local candidal infections and 
treat appropriately. 
 
15.175  Monitor blood glucose frequently. 


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15.176 Instruct patient to report frequent unrelenting headaches or visual changes 
to healthcare team. 
 
15.177  Advise patient that easy bruising is a side effect. 
15.2 
Elotuzumab (Empliciti™) 
15.21 Background: Elotuzumab is an antineoplastic agent that is an antibody against 
the SLAMF7 antigen expression on cells including multiple myeloma. 
15.22 Formulation: Elotuzumab drug product is a 300 mg or 400 mg lyophilized 
powder in a single-dose vial for reconstitution. 
15.23 Preparation and storage: Once the dose is calculated (mg), determine the 
number of vials needed for the 10 mg/kg dosage based on patient weight. The 
volume of sterile water for injection (SWFI) needed for reconstitution should be 
calculated as follows: 
 
 
Reconstitution Instructions for EMPLICITI 
Strength 
Amount of Sterile Water 
for Injection, USP 
Required for 
Reconstitution 
Deliverable Volume of 
Reconstituted 
EMPLICITI in the 
Vial 
Postreconstitution 
Concentration 
300 mg vial 
13 ml 
12 ml* 
25 mg/ml 
400 mg vial 
17 ml 
16 ml* 
25 mg/ml 
*After reconstitution, each vial contains overfill to allow for withdrawal of 12 mL (300 mg) 
and 16 mL (400 mg), respectively. 
 
Reconstitution: Aseptically reconstitute each EMPLICITI vial with a syringe of 
adequate size and a less than or equal to 18-gauge needle (e.g., 17-gauge). A 
slight back pressure may be experienced during administration of the Sterile 
Water for Injection, USP, which is considered normal. Hold the vial upright and 
swirl the solution by rotating the vial to dissolve the lyophilized cake. Invert the 
vial a few times in order to dissolve any powder that may be present on top of the 
vial or the stopper. Avoid vigorous agitation. DO NOT SHAKE. The lyophilized 
powder should dissolve in less than 10 minutes. After the remaining solids are 
completely dissolved, allow the reconstituted solution to stand for 5 to 10 
minutes. The reconstituted preparation results in a colorless to slightly yellow, 
clear to slightly opalescent solution. Parenteral drug products should be inspected 
visually for particulate matter and discoloration prior to administration, whenever 
solution and container permit. Discard the solution if any particulate matter or 
discoloration is observed. 
 
Dilution: Once the reconstitution is completed, withdraw the necessary volume 
for the calculated dose from each vial, up to a maximum of 16 mL from 400 mg 
vial and 12 mL from 300 mg vial. Further dilute with 230 mL of either 0.9% 
Sodium Chloride Injection, USP or 5% Dextrose Injection, USP, into an infusion 
bag made of polyvinyl chloride or polyolefin. The volume of 0.9% Sodium 
Chloride Injection, USP or 5% Dextrose Injection, USP can be adjusted so as not 
to exceed 5 mL/kg of patient weight at any given dose of EMPLICITI. Complete 
the EMPLICITI infusion within 24 hours of reconstitution of the EMPLICITI 
lyophilized powder. If not used immediately, the infusion solution may be stored 
under refrigeration conditions: 2°C to 8°C (36°F-46°F) and protected from light. 
15.24 Administration: Intravenous (IV) infusion 


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Administer the entire EMPLICITI infusion with an infusion set and a sterile, 
nonpyrogenic, low-protein-binding filter (with a pore size of 0.2 to 1.2 
micrometer) using an automated infusion pump. Initiate EMPLICITI infusion at 
a rate of 0.5 mL per minute. The infusion rate may be increased in a stepwise 
fashion as described in Table below if no infusion reactions develop. The 
maximum infusion rate should not exceed 5 mL per minute. 
 
Infusion Rate for EMPLICITI 
Cycle 1, Dose 1 
Cycle 1, Dose 2 
Cycle 1, Dose 
3, 4 and all 
Subsequent 
Cycles 
Time Interval 
Rate 
Time Interval 
Rate 
Rate 
0-30 min 
0.5 ml/min 
0-30 min 
3 ml/min 
5 ml/min 
30-60 min 
1 ml/min 
30 min or 
more 
4 ml/min 
60 min or more 
2 ml/min 
 
Adjust the infusion rate following a Grade 2 or higher infusion reaction (as per 
the package insert). Do not mix EMPLICITI with, or administer as an infusion 
with, other medicinal products. No physical or biochemical compatibility studies 
have been conducted to evaluate the coadministration of EMPLICITI with other 
agents. 
15.25 Pharmacokinetic Information: 
Elotuzumab exhibits nonlinear pharmacokinetics (PK), indicative of target 
mediated clearance. The administration of the recommended 10 mg/kg of 
Elotuzumab regimen with Lenalidomide and Dexamethasone is predicted to 
result in geometric mean (CV%) steady-state trough concentrations of 194 
μg/mL (52%).  
 
The clearance of Elotuzumab decreased from a geometric mean (CV%) of 17.5 
(21.2%) to 5.8 (31%) mL/day/kg with an increase in dose from 0.5 (i.e., 0.05 
times the recommended dosage) to 20 mg/kg (i.e., 2 times the recommended 
dosage). When Elotuzumab is administered with lenalidomide and 
dexamethasone, approximately 97% of the maximum steady-state concentration 
is predicted to be eliminated with a geometric mean (CV%) of 82.4 (48%) days. 
 
Clinically significant differences were not observed in the PK of Elotuzumab 
based on age (37 to 88 years) sex, race, baseline lactate dehydrogenase, albumin, 
renal imapairment(creatinine clearance (CLcr) 15 to 89 mL/min), end-stage renal 
disease (CLcr <15mL/min) with or without hemodialysis, and mild heptic 
impairment(total bilirubin ≤ upper limit of normal (ULN) and aspartate 
transaminase (AST)>ULN OR total bilirubin 1 to 1.5 times the ULN and AST 
any value) to severe (total bilirubin > 3 times the ULN and AST any value) 
hepatic impairment is unknown. 
 
The clearance of Elotuzumab increased with increasing body weight supporting a 
weight based dose. 
 
Half-life elimination ~97% of the maximum steady-state concentration is 
expected to be eliminated with a geometric mean (CV%) of 82.4 days. 
15.26 Known Potential Toxicities: 


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• 
Very Common (≥10%) 
Cardiovascular: Decreased heart rate, increased heart rate, altered 
blood pressure  
Central nervous system: Fatigue, peripheral neuropathy, headache  
Endocrine & metabolic: Hyperglycemia, hypocalcemia, 
hypoalbuminemia, decreased serum bicarbonate, hyperkalemia, weight 
loss 
Gastrointestinal: Diarrhea, constipation, decreased appetite, vomiting  
Hematologic & oncologic: Lymphocytopenia, leukopenia, 
thrombocytopenia  
Hepatic: Increased serum alkaline phosphatase  
Immunologic: Immunogenicity  
Infection- Infection, opportunistic infection, herpes zoster, fungal 
infection  
Neuromuscular & skeletal: Limb pain  
Ophthalmic: Cataract  
Respiratory: Cough, nasopharyngitis, upper respiratory tract infection, 
pneumonia, oropharyngeal pain  
Miscellaneous: Fever, infusion related reaction  
• 
Common (1 to <10%) 
Cardiovascular: Chest pain, pulmonary embolism  
Central nervous system: Hypoesthesia, mood changes  
Dermatologic: Night sweats  
Hematologic & oncologic: Second primary malignant neoplasm, 
malignant neoplasm of skin, solid tumor, anemia, malignant neoplasm  
Hepatic: Hepatotoxicity 
Hypersensitivity: Hypersensitivity  
Renal: Acute renal failure 
Respiratory: Respiratory tract infection  
• 
Infusion-related reactions (IRR): IRRS were reported in 
approximately 10% of patients treated with Elotuzumab with 
Lenalidomide and Dexamethasone. All reports of infusion rection 
were Grade 3 or lower. Grade 3 infusion reactions occurred in 1 % of 
patients. The most common symptoms of IRRs included fever, chills 
and hypertension. Bradycardia and hypotension also developed during 
infusions.  
In the trial, 5% of patients required interruption of the administration 
of Elotuzumab for a median of 25 minutes due to infusion reactions, 
and 1% of patients discontinued due to infusion reactions. Of the 
patients who experienced an infusion reaction, 70% (23/33) had them 
during the first dose. 
Administer premedication consisting of dexamethasone, 
antihistamines (H1 and H2 blockers) and acetaminophen prior to 
Elotuzumab infusion. Interrupt Elotuzumab for Grade 2 or higher 
infusion reactions and institute appropriate medical management 
15.27 Drug Procurement: Drug will be procured from the commercial supply of 
elotuzumab.  
15.28 Special Populations: 
• 
Geriatric use: Of the 646 patients across treatment groups in the 
randomized trial in multiple mmyeloma, 57% were 65 years of age or 


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older. No overall differences in efficacy or safety were observed 
between patients 65 years or older and younger patients (less than 65 
years of age) 
• 
Renal impairment: CrCl ≤89 mL/minute. There are no dosage 
adjuments provided in the manufacturer’s labelling; however, based on 
pharmacokinetics, dosage adjustment is not likely necessary. 
• 
Hepatic Impairment: 
Mild (total bilirubin ≤ULN and AST >ULN or total bilirubin 1 to 1.5 times 
ULN and any AST) impairment: There are no dosage adjustments provided 
in the manufacturer's labeling; however, based on pharmacokinetics, dosage 
adjustment is not likely necessary.  
 
Moderate (total bilirubin >1.5 to 3 times ULN and any AST) to severe (total 
bilirubin >3 times ULN and any AST) impairment: There are no dosage 
adjustments provided in the manufacturer's labeling (has not been studied). 
 
Hepatotoxicity during treatment: Grade 3 or higher transaminase elevations: 
Withhold treatment; may consider continuing treatment after liver enzymes 
return to baseline 
15.29 Nursing Guidelines 
15.291 See section 15.24 for specific administration times and rates based on 
cycle/dose#. 
15.292 While no formal drug to drug interactions have been done, in theory 
elotuzumab may enhance the effects of other immunosuppressants agents 
and decreased the effectiveness of immune stimulant (see section 15.26 
for more detail) 
15.293 Agent may cause changes in heartrate, including bradycardia or 
tachycardia. Instruct patient to report any palpitations/fast heartrate or 
symptoms of bradycardia (fatigue/syncope) to the study team 
immediately. 
15.294 Gastrointestinal side effects can be seen, including diarrhea, constipation 
and vomiting. Treat symptomatically and monitor for effectiveness. 
15.295 Monitor CBC w/diff as cytopenias can be seen.  Instruct patient to 
reports any signs or symptoms of infection and/or bleeding to the study 
team. 
15.296 Monitor LFT’s. 
15.297 Monitor for infusion related reactions and have emergency equipment 
available. Administer emegerency medications as ordered and monitor 
for their effectiveness. 
15.298 Monitor creatinine, as rarely renal failure can happen. 
15.3 
Pomalidomide (Pomalyst®) 
15.31 Background: Pomalidomide is a novel drug in the class of immunomodulatory 
agents known as IMiDs compounds.  Pomalidomide binds to its molecular target 
cereblon (CRBN), a protein that is part of an E3 ubiquitin ligase complex, which 
is responsible for the polyubiquitination of substrate proteins, targeting them for 
subcellular redistribution and destruction by the proteasome. The pharmacologic 
properties of pomalidomide are of potential therapeutic benefit in the treatment 
of various hematologic neoplasms (such as multiple myeloma and 
myeloproliferative neoplasm-associated myelofibrosis), non-neoplastic 
hematologic disorders (such as β-thalassemia and sickle cell disease) and non-


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hematologic disorders such as systemic sclerosis, as well as solid tumor 
neoplasms. 
15.32 Formulation:  Pomalidomide capsules can be 0.5-mg gelatin capsules (size 4 
reddish brown), 1-mg hard gelatin capsules (size 4 reddish brown), 2-mg (size 2 
reddish-brown), 3-mg and 4-mg hard gelatin capsules (size 2 reddish-brown), and 
5-mg hard gelatin capsules (size 1 reddish-brown), containing pomalidomide, 
mannitol, pregelatinized starch, and sodium stearyl fumarate. 
15.33 Placebo capsules for pomalidomide are available to use in blinded 
studies. The placebo capsules contain microcrystalline cellulose.  
 
 
Pomalidomide capsules and pomalidomide placebo capsules are supplied in high 
density polyethylene (HDPE) containers fitted with induction seals and child-
resistant plastic closures or PVC/PCTFE blister with push-through foil. 
15.33   Preparation and storage:  Store drug at controlled room temperature, 
between 68-77 ºF (20-25ºC) or as indicated on the manufacturer’s label.  
The expiration date is indicated on the label.  
 
 
Only enough drug for one month of therapy may be dispensed. 
15.34 Administration:  Pomalidomide is administered by mouth at 
approximately the same time each day.  Pomalidomide should be taken 
without food (at least 2 hours before or 2 hours after a meal).  Capsules 
should be swallowed whole, and should not be broken, chewed or opened. 
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.  
Patients should be instructed never to give this medicinal product to 
another person and to return any unused capsules to the study doctor at the 
end of treatment.  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. 
15.35 Pharmacokinetic information:  
a)  Absorption – oral absorption has been moderately rapid with first dose Cmax 
occurring in 1.5 to 4 hrs. More than 70% of the pomalidomide dose is absorbed 
in humans.  A high fat meal decreased the rate of absorption but had minimal 
effect on overall extent of absorption; therefore drug may be administered 
without regard to food intake. 
b)  Distribution – Apparent volume of distribution in healthy subjects 
ranged from 74-138 L across a dose range of 1 to 10 mg daily.  
Pomalidomide protein binding in human plasma is low to moderate 
(15.8% for R-enantiomer, 42.2% for S-enantiomer) and the binding is 
concentration independent in the concentration range of 30 and 1000 
ng/mL.  Drug distributes into semen. 
 
c)  Metabolism – Eight metabolites were detected in plasma, each at 
exposures < 10% of the plasma pomalidomide.  CYP-dependent 
metabolites accounted for approximately 43% of the excreted 
radioactivity, while non-CYP dependent hydrolytic metabolites accounted 
for 25%, and excretion of unchanged pomalidomide accounted for 10%. 
d)  Excretion – In healthy patients, 72.8% of the dose was recovered in 
urine and 15.5% was recovered in feces. Less than 3% of the dose is 
excreted as unchanged pomalidomide in the urine.  The geometric mean 


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terminal elimination half-life (t1/2) of pomalidomide was approximately 7.5 
hours. 
Pomalidomide is metabolized primarily by the liver. Following single dose 
administration, the AUC of pomalidomide increased 51%, 58%, and 72% 
in subjects with mild (Child-Pugh class A), moderate (Child-Pugh class 
B), and severe (Child-Pugh class C) hepatic impairment compared to 
subjects with normal liver function. Dose adjustment is recommended in 
patients with hepatic impairment. 
For patients with mild or moderate hepatic impairment (Child-Pugh 
classes A or B), the recommended starting dose is 3 mg daily (25% dose 
reduction). For patients with severe hepatic impairment (Child-Pugh class 
C), the recommended dose is 2 mg (50% dose reduction) 
15.36 Potential Drug Interactions:  Pomalidomide is partially metabolized by 
CYP1A2 and CYP3A4/5.  Pomalidomide is also a substrate for P-
glycoprotein (P-gp). Coadministration of pomalidomide with the strong 
CYP3A4/5 and P-gp inhibitor ketoconazole, or the strong CYP3A4/5 
inducer carbamazepine, had no clinically relevant effect on exposure to 
pomalidomide.  Coadministration of the strong CYP1A2 inhibitor 
fluvoxamine with pomalidomide increased mean exposure to 
pomalidomide by 125% compared to pomalidomide alone. If strong 
inhibitors of CYP1A2 are coadministered with pomalidomide, the 
pomalidomide dose by should be reduced 50%. 
Smoking: Administration of pomalidomide in smokers, with smoking 
tobacco known to induce the CYP1A2 isoform, had no clinically relevant 
effect on exposure to pomalidomide relative to that exposure to 
pomalidomide observed in non-smokers. 
Dexamethasone: Co-administration of multiple doses of 4 mg 
pomalidomide with 20 mg to 40 mg dexamethasone (a weak inducer of 
CYP3A) to patients with multiple myeloma had no effect on the 
pharmacokinetics of pomalidomide compared with pomalidomide 
administered alone. 
 
15.37  Known potential toxicities: 
Very common known potential toxicities, ≥ 10%:   
Anemia, leukopenia, neutropenia, thrombocytopenia, constipation, diarrhea, 
nausea, fatigue, peripheral edema, pyrexia, bronchitis, pneumonia, upper 
respiratory tract infection, decreased appetite, bone pain, muscle spasm, 
dizziness, peripheral neuropathy, blood creatinine increased, acute renal failure, 
cough, dyspnea, pruritis 
 
Common known potential toxicities, ≥1% - <10%:  
Febrile neutropenia, pancytopenia, vertigo, vomiting, gastrointestinal 
hemorrhage, hemorrhoidal hemorrhage, rectal hemorrhage, hematochezia, 
gingival bleeding, bronchopneumonia, herpes zoster, nasopharyngitis, 
neutropenic sepsis, respiratory tract infection, alanine aminotransferase 
increased, increased liver function test, aspartate aminotransferase increased, 
gamma-glutamyltransferase increased, neutrophil count decreased, platelet count 
decreased, white blood cell count decreased, hyperkalemia, hyponatremia, 
depressed level of consciousness, peripheral sensory neuropathy, paresthesia, gait 
disturbance, polyneuropathy, hypoesthesia, neuralgia, peripheral motor 


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neuropathy, tremor, confusional state, renal failure, renal impairment, 
hypercreatininemia, urinary retention, pelvic pain, pulmonary embolism, pruritus 
generalized, rash, swelling face, face edema, deep vein thrombosis 
 
Uncommon and rare known potential toxicities, <1%:  
Melena, Mallory-Weiss syndrome, upper gastrointestinal hemorrhage, mucosal 
hemorrhage, hyperbilirubinemia, blood bilirubin increased, transaminases 
increased, blood alkaline phosphates increased, liver function test abnormal, basil 
cell carcinoma, dysesthesia, areflexia, motor dysfunction, sensory disturbance, 
burning sensation, muscle atrophy, blood urea increased, creatinine renal 
clearance decreased, oliguria, glomerular filtration rate decreased, renal tubular 
necrosis, acute prerenal failure, azotemia, pneumonitis, interstitial lung disease, 
pruritis generalized, angioedema, urticarial, eyelid edema,  
 
Frequency not defined:  
Hepatitis, hepatitis B viral reactivation, tumor lysis syndrome, squamous cell 
carcinoma of skin, eye swelling, periorbital edema, lip swelling, swollen tongue, 
mouth edema, pharyngeal edema, Stevens-Johnson syndrome, toxic epidermal 
necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS) 
 
All 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.  Females of 
reproductive potential must adhere to the scheduled pregnancy testing.  
Females of childbearing potential should not handle or administer 
pomalidomide unless they are wearing gloves. 
 
15.38 Drug procurement: 
Drug will be procured from the commercial supply of pomalidomide. 
15.39 Nursing Guidelines 
15.191 Agent is known to be teratogenic in rabbits.  Therefore, all women 
who are pregnant or who could become pregnant should not 
handle the agent outside of the original packaging. Chemotherapy 
gloves should be worn if contact is necessary. 
15.192 Because of the similarity of this agent to thalidomide certain 
precautions MUST be employed by all subjects on protocol and 
for 4 weeks after discontinuation of agent. Instruct patients the 
following must be adhered to: No donation of 
tissue/blood/semen/sperm; sexually active males/ females must 
use protocol-specific contraception (regardless of fertility status-
i.e. history of vasectomy). 
15.193 Cytopenias are common (neutropenia most common). Monitor 
CBC closely and instruct patient to report any signs/symptoms of 
infection or unusual bruising or bleeding to the study team. 
15.194 Thrombotic events have been reported. Anticoagulation 
prophylaxis may be recommended. Instruct patients to report any 
problems with bleeding, extremity pain or swelling, or shortness 
of breath to the study team immediately. 


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15.195 Patients may experience cough, URI, pneumonia, or sinusitis. 
Instruct patients to report respiratory symptoms to the study team. 
15.196 Gastrointestinal side effects consisting of diarrhea, constipation, 
stomatitis, nausea, decreased appetite, and abdominal pain have 
been seen. Treat symptomatically and monitor for effectiveness. 
15.197 Drug should be taken without food (at least 2 hours before or 2 
hours after a meal). Do not open or crush capsules. 
15.198 Patients may experience myalgias and muscle spasms. Treat 
symptomatically and monitor for effectiveness. 
15.199 Fatigue is common. Instruct patient in energy conserving lifestyle. 
15.199b Warn patients about the possibility of peripheral neuropathy, 
headache, confusion, and dizziness. 
15.199c Patients may experience URI, pneumonia, dyspnea, and cough. 
Instruct patients to report respiratory symptoms to the study team.  
15.199d Severe dermatologic reactions have been seen (including 
urticaria). Instruct patient to report and rash or skin changes to the 
study team. 
15.199e All patients must be registered in the POMALYST REMS 
program. See protocol for more details. 
15.99f Monitor creatinine, as patients may experience elevated creatinine 
levels, with rare reports of renal failure. 
15.199g Rare reports of GI bleeding have been seen. Instruct patient to 
report any hematochezia, or melena to the study team 
immediately. 
 
 


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16.0 
Statistical Considerations and Methodology  
16.1 
Overview 
This is a phase II study of elotuzumab, pomalidomide and dexamethasone in patients 
with multiple myeloma refractory to daratumumab.  This study is designed to assess the 
overall response rate using a one stage phase II study design with an interim analysis. 
 
16.11 Primary Endpoint: The primary endpoint of this study is the overall response 
rate.  A response is defined as a PR,VGPR, CR, or sCR noted as the objective 
status on two consecutive evaluations.   All patients meeting the eligibility 
criteria, who have signed a consent form and have begun treatment will be 
evaluable for response, unless they are determined to be a major violation. 
 
16.12 Sample Size: The one stage study design with an interim analysis to be used is 
fully described below. A minimum of 17 and a maximum of 37 evaluable 
patients will be accrued total onto this phase II study unless undue toxicity is 
encountered. We anticipate accruing an additional 4 patients to account for 
ineligibility, cancellation, major treatment violation, or other reasons for a total 
of 41 patients overall. 
 
16.13 Accrual Rate and Study Duration:  The anticipated accrual rate is 2 evaluable 
multiple myeloma patients per month. Therefore, the accrual period for this 
phase II study is expected to be about 2 years. The maximum total study duration 
is expected to be approximately 5 years, or until the last patient accrued has been 
observed for at least 3 years after registration. 
16.2 
Statistical Design: 
 
 
16.21 Decision Rule: 
The largest success proportion where the proposed treatment regimen would be 
considered ineffective in this population is 20% (based on data from quad- and 
penta-refractory disease data in recent clinical trials), and the smallest success 
proportion that would warrant subsequent studies with the proposed regimen in 
this patient population is 40%. The following one–stage design with an interim 
analysis is based on a two-stage Simon optimum design(23) and requires 37 
evaluable patients to test the null hypothesis that the true success proportion in 
this patient population is at most 20%. 
 
 
 
16.211 Interim Analysis: Enter 17 evaluable patients into the study. If 3 or fewer 
successes are observed in the first 17 evaluable patients, we will consider 
this regimen ineffective in this patient population and terminate the 
study.  Otherwise, if the number of successes is at least 4, we will 
continue accrual. 
16.212 Final Decision Rule:  Enter an additional 20 evaluable patients into the 
study.  If 10 or fewer successes are observed in the first 37 evaluable 
patients, we will consider this regimen ineffective in this patient 
population and terminate this study. Otherwise, if the number of 
successes is at least 11, this will be considered evidence of promising 
activity and the treatment may be recommended for further testing in 
subsequent studies in this population. 


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16.213 Over Accrual: If more than the target number of patients are accrued, the 
additional patients will not be used to evaluate the stopping rule or used 
in any decision making process. 
16.214 NOTE:  We will not suspend accrual at the interim analysis to allow the 
first 17 patients to become evaluable, unless undue toxicity is observed. 
Given the limited overall sample size and the inclusion of an adverse 
events stopping rule, we feel it is ethical to not halt accrual for the 
interim analysis. However, if accrual is extremely rapid, we may 
temporarily suspend accrual in order to obtain safety data on these 
patients before re-opening accrual to further patients. 
 
16.22 Power and Significance Level: Assuming that the number of successes is 
binomially distributed, the significance level is .09, i.e. there is a 9% chance of 
finding the drug to be effective when it truly is not.  The probability of declaring 
that this regimen warrants further study (i.e. statistical power) and the probability 
of stopping at the interim analysis under various success proportions can be 
tabulated as a function of the true success proportion as shown in the following 
table. 
 
 
If the true success proportion is... 
0.20 
0.25 
0.30 
0.35 
0.40 
Then the probability of declaring 
that the regimen warrants further 
study is… 
0.09 
0.28 
0.54 
0.76 
0.90 
And the probability of stopping at 
the interim analysis is… 
0.55 
0.35 
0.20 
0.10 
0.05 
 
16.23 Other considerations:  Adverse events, quality/duration of response, and patterns 
of treatment failure observed in this study, as well as scientific discoveries or 
changes in standard care will be taken into account in any decision to terminate 
the study. 
 
16.3 
Analysis Plan 
The analysis for this trial will commence at planned time points (see 16.2) and at the time 
the patients have become evaluable for the primary endpoint. The Statistician and Study 
Chair will make the decision, in accord with CCS Standard Operating Procedures, 
availability of data for secondary endpoints (e.g., laboratory correlates), and the level of 
data maturity. It is anticipated that the earliest date in which the results will be made 
available via manuscript, abstract, or presentation format is when all patients have been 
followed for at least 6 cycles or have discontinued study treatment prior to completing 6 
cycles. 
 
16.31 Primary Outcome Analysis: 
16.311 Definition: The primary endpoint of this trial is the overall response rate. 
A response is defined as a PR,VGPR, CR, or sCR noted as the objective 
status on two consecutive evaluations.   All patients meeting the 
eligibility criteria who have signed a consent form and have begun 
treatment will be evaluable for response, unless they are determined to be 
a major violation. 
16.312 Estimation:  The proportion of successes will be estimated by the number 
of successes divided by the total number of evaluable patients. Ninety-


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five percent confidence intervals for the true success proportion will be 
calculated according to the approach of Duffy and Santner.(24) 
16.313 Over Accrual:  If more than the target number of patients are accrued, the 
additional patients will not be used to evaluate the stopping rule or used 
in any decision making processes; however, they will be included in final 
point estimates and confidence intervals. 
 
 
 
16.32 Secondary Outcome Analyses 
16.321 The complete response rate will be estimated by the number of patients 
who achieve a sCR or CR divided by the total number of evaluable 
patients. Exact binomial 95% confidence intervals for the true complete 
response rate will be calculated. 
16.322 Progression-free survival time is defined as the time from registration to 
the time of progression or death due to any cause. Patients who are alive 
and progression-free will be censored on the date of their last disease 
assessment. Patients who receive subsequent treatment for myeloma 
before disease progression will be censored on the date of their last 
disease assessment prior to initiation of the subsequent treatment. The 
distribution of progression-free survival will be estimated using the 
method of Kaplan-Meier.(25) 
16.323 Survival time is defined as the time from registration to death due to any 
cause. The distribution of survival time will be estimated using the 
method of Kaplan-Meier. 
16.324 Adverse Events: All eligible patients that have initiated treatment will be 
considered evaluable for assessing adverse event rate(s).  The maximum 
grade for each type of adverse event will be recorded for each patient, 
and frequency tables will be reviewed to determine patterns.  
Additionally, the relationship of the adverse event(s) to the study 
treatment will be taken into consideration. 
16.4 
Data & Safety Monitoring 
16.41 Safety review 
The principal investigator(s) and the study statistician will review the study 
monthly to identify accrual, adverse event, and any endpoint problems that might 
be developing. The Mayo Clinic Cancer Center (MCCC) Data Safety Monitoring 
Board (DSMB) is responsible for reviewing accrual and safety data for this trial 
at least biannually, based on reports provided by the MCCC Statistical Office. 
16.42 Adverse Event Stopping Rules  
The stopping rules specified below are based on the knowledge available at study 
development.  We note that the Adverse Event Stopping Rule may be adjusted in 
the event of either (1) the study re-opening to accrual or (2) at any time during 
the conduct of the trial and in consideration of newly acquired information 
regarding the adverse event profile of the treatment(s) under investigation.  The 
study team may choose to suspend accrual because of unexpected adverse event 
profiles that have not crossed the specified rule below. 
 
Accrual will be temporarily suspended to this study if at any time we observe 
events considered at least possibly related to study treatment (i.e. an adverse 


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event with attribute specified as  “possible,” “probable,” or “definite”) that 
satisfy one of the following: 
o If 5 or more patients in the first 15 treated patients experience a grade 4 or 
higher non-hematologic adverse event at least possibly related to treatment. 
o If after the first 15 patients have been treated, 30% of all patients experience 
a grade 4 or higher non-hematologic adverse event at least possibly related to 
treatment. 
 
We note that we will review grade 4 and 5 adverse events deemed “unrelated” or 
“unlikely to be related”, to verify their attribution and to monitor the emergence 
of a previously unrecognized treatment-related adverse event. 
 
 
16.5 
Results Reporting on ClinicalTrials.gov 
At study activation, this study will have been registered within the “ClincialTrails.gov” 
website. The Primary and Secondary Endpoints along with other required information for 
this study will be reported on www.ClinicalTrials.gov. For purposes of timing of the 
Results Reporting, the initial estimated completion date for the Primary Endpoint of this 
study is 3 years after the study opens to accrual. The definition of “Primary Endpoint 
Completion Date” (PECD) for this study is at the time all patients registered have either 
achieved a response (PR or better noted as the objective status on two consecutive 
evaluations) or have discontinued study treatment without achieving a response. 
 
16.6 
Subset Analyses for Minorities 
16.61 Study availability 
This study will be available to all eligible patients, regardless of gender, race or 
ethnic origin.  
16.62 Statistical analysis by subset 
There is no information currently available regarding differential effects of this 
regimen in subsets defined by race, gender, or ethnicity, and there is no reason to 
expect such differences to exist. Therefore, although the planned analyses will 
look for differences in treatment effect based on racial groupings, the sample size 
is not increased in order to provide additional power for subset analyses.  
16.63 Regional population 
The geographical region served by MCCC has a population which includes 
approximately 3% minorities. Expected sizes of racial by gender subsets are 
shown in the following table: 
 
Accrual Targets 
Ethnic Category 
Sex/Gender 
Females 
Males 
Total 
Hispanic or Latino 
0 
1 
1 
Not Hispanic or Latino 
16 
24 
40 
Ethnic Category: Total of all subjects 
16 
25 
41 
Racial Category 
American Indian or Alaskan Native 
0 
0 
0 
Asian 
0 
0 
0 


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Accrual Targets 
Ethnic Category 
Sex/Gender 
Females 
Males 
Total 
Black or African American 
1 
1 
2 
Native Hawaiian or other Pacific Islander 
0 
0 
0 
White 
15 
24 
39 
Racial Category: Total of all subjects 
16 
25 
41 
 
 
Ethnic 
Categories: 
Hispanic or Latino – a person of Cuban, Mexican, Puerto Rican, South or Central 
American, or other Spanish culture or origin, regardless of race. The term “Spanish 
origin” can also be used in addition to “Hispanic or Latino.” 
Not Hispanic or Latino 
Racial 
Categories: 
American Indian or Alaskan Native – a person having origins in any of the original 
peoples of North, Central, or South America, and who maintains tribal affiliations or 
community attachment. 
Asian – a person having origins in any of the original peoples of the Far East, 
Southeast Asia, or the Indian subcontinent including, for example, Cambodia, China, 
India, Japan, Korea, Malaysia, Pakistan, the Philippine Islands, Thailand, and 
Vietnam. (Note: Individuals from the Philippine Islands have been recorded as Pacific 
Islanders in previous data collection strategies.)  
Black or African American – a person having origins in any of the black racial 
groups of Africa. Terms such as “Haitian” or “Negro” can be used in addition to 
“Black or African American.” 
Native Hawaiian or other Pacific Islander – a person having origins in any of the 
original peoples of Hawaii, Guam, Samoa, or other Pacific Islands. 
White – a person having origins in any of the original peoples of Europe, the Middle 
East, or North Africa. 


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17.0  
Pathology Considerations/Tissue Biospecimens 
None. 
 
18.0 
Records and Data Collection Procedures  
18.1 
Submission Timetable 
Data submission instructions for this study can be found in the Data Submission 
Schedule. 
18.2 
Survival Follow-up 
See Section 4.  
18.3 
CRF completion 
This study will use Medidata Rave for remote data capture (rdc) of all study data. Data 
collection for this study will be done exclusively through the Medidata Rave clinical data 
management system. Access to the trial in Rave is granted through the iMedidata 
application to all persons with the appropriate roles assigned in Regulatory Support 
System (RSS). To access Rave via iMedidata, the site user must have an active account 
and the appropriate Rave role (Rave CRA, Read-Only, Site Investigator) on either the 
organization roster at the enrolling site. 
18.4 
Site responsibilities 
Each site will be responsible for insuring that all materials contain the patient’s initials, 
MCCC registration number, and MCCC protocol number. Patient’s name must be 
removed. 
18.5 
Supporting documentation  
This study requires supporting documentation for diagnosis prior to study entry as well as 
for evidence of response to study therapy and progression after study therapy. Supporting 
documentation for diagnosis will include either a pathology report or a laboratory report 
demonstrating multiple myeloma (including SPEP, UPEP, FLC, Serum and Urine 
Immunofixation, Bone Marrow Biopsy and Aspirate, skeletal bone survey, PET scan, 
Plasma Cell Proliferation and Assessment and FISH). These reports should be uploaded 
into the Supporting Documentation: Baseline form within 14 days of registration. 
 
For progression of disease prior to study entry, supporting documentation includes the 
evidence needed to determine the patient’s progression prior to enrollment. These 
documents should be uploaded into the Supporting Documentation: Baseline form within 
14 days of registration. 
 
For response to treatment, supporting documentation may include SPEP, UPEP, FLC, 
Serum and Urine Immunofixation, Bone Marrow Biopsy and aspirate, skeletal bone 
survey, and PET scan. These documents should be uploaded into the Supporting 
Documentation form. 
  
For patients who progress after study therapy supporting documentation may include any 
of the following: SPEP, UPEP, FLC, serum and urine immunofixation, bone marrow 
biopsy and aspirate, skeletal bone survey, and PET scan. These documents should be 
uploaded into the Supporting Documentation form. 


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18.6 
Labeling of materials 
Each site will be responsible for insuring that all materials contain the patient’s initials, 
MCCC registration number, and MCCC protocol number. Patient’s name must be 
removed. 
18.7 
Overdue lists 
A list of overdue forms and outstanding queries will be available in Rave through the 
Rave Task Summary. In addition to this, the Overdue Materials report is available on the 
Cancer Center Systems homepage. 
19.0  
Budget 
19.1 
Costs charged to patient: routine clinical care and cost of study drugs 
19.3 
Other budget concerns: 
The Department of Hematology and Oncology at Mayo Clinic Florida will provide 
funding to support the costs of running this study. 
 
 
 


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20.0 
References 
1.  Cannons JL, Tangye SG, Schwartzberg PL. (2011). SLAM family receptors and SAP adaptors in 
immunity. Annual Review Immunolology. 29:665-705. 
2.  Child CG, Turcotte JG. “Surgery and portal hypertension”. In Child CG. The liver and portal 
hypertension. Philadelphia: Saunders. 1964. pp. 50-64. 
3.  Collins SM, Bakan CE, Swartzel GD, Hofmeister CC, Efebera YA, Kwon H, et al. (2013). 
Elotuzumab directly enhances NK cell cytotoxicity against myeloma via CS1 ligation: evidence 
for augmented NK cell function complementing ADCC. Cancer Immunol Immunotherapy. 
62(12):1841-9. 
4.  Dimopoulos MA, Lonial S, White D, Moreau P, Palumbo A, San-Miguel J, et al. (2017). Elotuzumab 
plus lenalidomide/dexamethasone for relapsed or refractory multiple myeloma: ELOQUENT-2 
follow-up and post-hoc analyses on progression-free survival and tumour growth. British 
Journal of Haematology. 178(6):896-905. 
5.  Dimopoulos MA, Oriol A, Nahi H, San-Miguel J, Bahlis NJ, Usmani SZ, et al. (2016) Daratumumab, 
Lenalidomide, and Dexamethasone for Multiple Myeloma. New England Journal of Medicine. 
375(14):1319-1331. 
6.  Dingli D, Ailawadhi S, Bergsagel PL, Buadi FK, Dispenzieri A, Fonseca R, et al. (2017). Therapy for 
Relapsed Multiple Myeloma: Guidelines From the Mayo Stratification for Myeloma and Risk-
Adapted Therapy. Mayo Clinic Proceedings. 92(4):578-98. 
7.  Duffy D, Santner T. (1987) Confidence intervals for a binomial parameter based on multistage tests. 
Biometrics. 43:81-93.  
8.   Guo H, Cruz-Munoz ME, Wu N, Robbins M, Veillette A. (2015) Immune cell inhibition by SLAMF7 
is mediated by a mechanism requiring src kinases, CD45, and SHIP-1 that is defective in 
multiple myeloma cells. Molecular and Cellular Biology. 35(1):41-51. 
9.  Hsi ED, Steinle R, Balasa B, Szmania S, Draksharapu A, Shum BP, et al. (2008) CS1, a potential new 
therapeutic antibody target for the treatment of multiple myeloma. Clinical Cancer Research. 
14(9):2775-84. 
10.  Kaplan EL, Meier P. (1958). Nonparametric Estimation from Incomplete Observations. Journal of 
the American Statistical Association. 53:457-81. 
11. Kyle RA, Gertz MA, Witzig TE, Lust JA, Lacy MQ, Dispenzieri A, et al. (2003). Review of 1027 
patients with newly diagnosed multiple myeloma. Mayo Clinic Proceedings, 78(1):21-33. 
12. Kyle RA and Rajkumar SV. (2009). Criteria for diagnosis, staging, risk stratification and response 
assessment of multiple myeloma. Leukemia, 23(1):3-9. 
13. Lonial S, Weiss BM, Usmani SZ, Singhal S, Chari A, Bahlis NJ, et al. (2016). Daratumumab 
monotherapy in patients with treatment-refractory multiple myeloma (SIRIUS): an open-label, 
randomised, phase 2 trial. Lancet, 387(10027):1551-60. 
14. Malavasi F, Deaglio S, Ferrero E, Funaro A, Sancho J, Ausiello CM, et al. (2006). CD38 and CD157 
as receptors of the immune system: a bridge between innate and adaptive immunity. Molecular 
Medicine,12(11-12):334-41. 
15. McEllistrim C, Krawczyk J, O'Dwyer ME. (2017). New developments in the treatment of multiple 
myeloma - clinical utility of daratumumab. Biologics,11:31-43. 


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16. Oken, M.M., Creech, R.H., Tormey, D.C., Horton, J., Davis, T.E., McFadden, E.T., Carbone, P.P. 
(1982) Toxicity And Response Criteria Of The Eastern Cooperative Oncology Group. American 
Journal of Clinical Oncology, 5:649-655. 
17. Ozer H, Armitage JO, Bennett CL, Crawford J, Demetri GD, Pizzo PA, et al. (2000). Update of 
recommendations for the use of hematopoietic colony-stimulating factors: evidence-based, 
clinical practice guidelines. American Society of Clinical Oncology Growth Factors Expert 
Panel. Journal of Clinical Oncology, 18(20):3558-85. 
18. Palumbo A, Chanan-Khan A, Weisel K, Nooka AK, Masszi T, Beksac M, et al. (2016). 
Daratumumab, Bortezomib, and Dexamethasone for Multiple Myeloma. New England Journal 
of Medicine, 375(8):754-66. 
19. Palumbo A, Anderson K. (2011). Multiple myeloma. New England Journal of Medicine, 
364(11):1046-60. 
20. Palumbo A, Rajkumar SV, Dimopoulos MA, Richardson PG, San Miguel J, Barlogie B, et al. (2008). 
Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma. Leukemia, 
22(2):414-23. 
21. Palumbo A, Sezer O, Kyle R, Miguel JS, Orlowski RZ, Moreau P, et al. (2009). International 
Myeloma Working Group guidelines for the management of multiple myeloma patients 
ineligible for standard high-dose chemotherapy with autologous stem cell transplantation. 
Leukemia, 23(10):1716-30.  
22. Perez-Quintero LA, Roncagalli R, Guo H, Latour S, Davidson D, Veillette A. (2014). EAT-2, a SAP-
like adaptor, controls NK cell activation through phospholipase Cgamma, Ca++, and Erk, 
leading to granule polarization. Journal of Experimental Medicine. 211(4):727-42. 
23. Pugh RN, Murray-Lyon IM, Dawson L, Pietroni MC, Williams R. “Transection of the oesophagus for 
bleeding oesophageal varices”.  The British journal of surgery, 1973; 60: 646-9.  
24. San Miguel J, Raab MS, Goldschmidt H, Lonial S, Richardson P, Shelat S, et al. (2016) A 
Randomized Phase 2 Study of Pomalidomide/Dexamethasone With or Without Elotuzumab in 
Patients With Relapsed/Refractory Multiple Myeloma. Journal of Clinical Oncology, 
34(15):TPS8066 (Abstract). 
25. Sanchez L, Wang Y, Siegel DS, Wang ML. (2016). Daratumumab: a first-in-class CD38 monoclonal 
antibody for the treatment of multiple myeloma. Journal of Hematology and Oncology, 9(1):51. 
26. Simon R. (1989) Optimal two-stage designs for phase II clinical trials. Controlled Clinical Trials, 
10(1):1-10. 
27. Tai YT, Dillon M, Song W, Leiba M, Li XF, Burger P, et al. (2008). Anti-CS1 humanized 
monoclonal antibody HuLuc63 inhibits myeloma cell adhesion and induces antibody-dependent 
cellular cytotoxicity in the bone marrow milieu. Blood, 112(4):1329-37. 
28. Usmani S, Weiss B, Bahlis N, Belch A, Lonial S, Lokhorst H, et al. (2015). Clinical Efficacy of 
Daratumumab Monotherapy in Patients with Heavily Pretreated Relapsed or Refractory Multiple 
Myeloma. Blood, 126:29 (Abstract). 
 


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Appendix I 
ECOG Performance Status 
 
ECOG PERFORMANCE STATUS* 
Grade ECOG 
0 
Fully active, able to carry on all pre-disease performance without restriction 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out 
work of a light or sedentary nature, e.g., light house work, office work 
2 
Ambulatory and capable of all selfcare but unable to carry out any work 
activities. Up and about more than 50% of waking hours 
3 
Capable of only limited selfcare, confined to bed or chair more than 50% of 
waking hours. 
4 
Completely disabled. Cannot carry on any selfcare. Totally confined to bed or 
chair. 
5 
Dead 
*As published in Am. J. Clin. Oncol.: 
Oken, M.M., Creech, R.H., Tormey, D.C., Horton, J., Davis, T.E., McFadden, E.T., Carbone, P.P.: 
Toxicity And Response Criteria Of The Eastern Cooperative Oncology Group. Am J Clin Oncol 5:649-
655, 1982. 
The ECOG Performance Status is in the public domain therefore available for public use. To duplicate the 
scale, please cite the reference above and credit the Eastern Cooperative Oncology Group, Robert Comis 
M.D., Group Chair. 
From http://www.ecog.org/general/perf_stat.html 
 
 


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Appendix II Creatinine Clearance (CrCl) Calculation 
 
Cockcroft-Gault Equation: 
Creatinine clearance for males =  
(140 - age)(weight in kg) 
 
(72)(serum creatinine in mg/dL) 
 
Creatinine clearance for females =  
(140 - age)(weight in kg)(0.85) 
 
(72)(serum creatinine in mg/dL) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Appendix III New York Heart Association Classification of Congestive Heart Failure 
NYHA Class 
Symptoms 
I 
Cardiac disease, but no symptoms and no limitation in ordinary physical activity, e.g. 
no shortness of breath when walking, climbing stairs etc. 
II 
Mild symptoms (mild shortness of breath and/or angina) and slight limitation during 
ordinary activity. 
III 
Marked limitation in activity due to symptoms, even during less-than-ordinary 
activity, e.g. walking short distances (20–100 m). Comfortable only at rest. 
IV 
Severe limitations. Experiences symptoms even while at rest. Mostly bedbound 
patients. 
Adapted from Dolgin M, Association NYH, Fox AC, Gorlin R, Levin RI, New York Heart Association. 
Criteria Committee. Nomenclature and criteria for diagnosis of diseases of the heart and great vessels. 
9th ed. Boston, MA: Lippincott Williams and Wilkins; March 1, 1994. 
Original source: Criteria Committee, New York Heart Association , Inc.  Diseases of the Heart and Blood 
Vessels. Nomenclature and Criteria for diagnosis, 6th edition  Boston, Little, Brown and Co. 1964, p 114. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Appendix IV Mayo Risk Stratification 
High Risk 
FISH deletion 17p 
FISH t(14; 16) 
FISH t(14; 20) 
GEP (if done) High-risk signature 
 
 
Intermediate Risk 
 
FISH t(4:14) 
Metaphase cytogenetic del 13 
Hypodiploidy 
 
 
Standard Risk 
 
All others including: 
 
FISH t(11; 14) 
 
FISH t(6; 14) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Appendix V Patient Medication Diary 
Name _ 
 
Study ID Number  
 
 
Please complete this diary on a daily basis. Write in the amount of the dose of pomalidomide and 
dexamethasone that you took in the appropriate “Day” box. 
 
On the days that you do not take any study drug, please write in “0”. If you forget to take your 
daily dose, please write in “0”, but remember to take your prescribed dose at the next regularly 
scheduled time; unless the dose was forgotten and remembered on the same day, in which case 
the dose can be taken that day.. Pomalidomide should be taken without food (at least 2 hours 
before or 2 hours after a meal). Do not open or crush capsules. Doses that are considered to be 
vomited are not to be made up and a mention about the time of dose and time of vomiting 
episode should be made in the pill diary. 
 
If you experience any health/medical complaints or take any medication other than 
pomalidomide and dexamethasone, please record this information. 
 
Study Drug(s) 
Dose Study Coordinator only: 
Write in the dose assigned by the study doctor in this 
column if different than the dose listed in the previous 
column 
Pomalidomide 
4 mg 
 
Dexamethasone  
40 mg 
 
 
Week of: _________________________ 
 
Day 1 
Day 2 
Day 3 
Day 4 
Day 5 
Day 6 
Day 7 
Date 
 
 
 
 
 
 
 
Pomalidomide 
 
 
 
 
 
 
 
Dexamethasone 
 
 
 
 
 
 
 
 
Week of: _________________________ 
 
Day 8 
Day 9 
Day 10 
Day 11 
Day 12 
Day 13 
Day 14 
Date 
 
 
 
 
 
 
 
Pomalidomide 
 
 
 
 
 
 
 
Dexamethasone 
 
 
 
 
 
 
 
 
Week of: _________________________ 
 
Day 15 
Day 16 
Day 17 
Day 18 
Day 19 
Day 20 
Day 21 
Date 
 
 
 
 
 
 
 
Pomalidomide 
 
 
 
 
 
 
 
Dexamethasone 
 
 
 
 
 
 
 
 
Week of: _________________________ 
 
Day 22 
Day 23 
Day 24 
Day 25 
Day 26 
Day 27 
Day 28 
Date 
 
 
 
 
 
 
 


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Pomalidomide 
 
 
 
 
 
 
 
Dexamethasone 
 
 
 
 
 
 
 
 
Patient signature: ___________________________________________ 
 
Health or medical complaints during this time: 
 
 
 
 
 
 
 
 
 
Other medications or supplements taken during this time:  
 
Name of medication or 
supplement 
How much did you take? 
(example: Two 500mg pills) 
When did you take it 
(examples: Every day 
Or Day 19 and Day 20) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Use a separate sheet of paper if more space is needed. 
 
My next scheduled visit is: _______________________________ 
If you have any questions, please call: ______________________ 
 
 
Study Coordinator Use Only 
Number of pills returned ______ 
Number of vials returned: _______ 
 
Discrepancy Yes____/No____ 
Verified by __________________ 
Date_______________ 
 
 
 


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Appendix VI  Child Pugh Classification 
 
 
Parameter 
1 point 
2 points 
3 points 
Total Bilirubin 
<34 µmol/L 
(<2mg/dL) 
34–50 µmol/L 
(2-3mg/dL) 
>50 µmol/L 
(>3mg/dL) 
Albumin Serum 
>3.5 g/dL 
2.8-3.5 g/dL 
<2.8 g/dL 
Prothrombin Time 
<1.7 (INR) 
1.71-2.30 (INR) 
 
>2.30 (INR) 
 
Ascites 
absent 
Slight (medically 
controlled) 
Moderate to 
Severe (poorly 
controlled) 
Hepatic 
Encephalopathy* 
None 
Grade 1-2 (or 
suppressed with 
medication) 
Grade 3-4 (or 
refractory) 
 
*Grades of Hepatic Encephalopathy 
 
Grade 1 – Inverted sleep pattern; forgetfulness, agitation, irritability, apraxia 
 
Grade 2 – Lethargy; disorientation for time or place, subtle personality change; 
asterixis, ataxia 
 
Grade 3 – Somnolence but rousability; disorientation as regards place; asterixis, 
hyperactive reflexes, Babinski signs, muscle rigidity 
 
Grade 4 – Coma (unresponsive to verbal or noxious stimuli) 
 
 
Points 
Class 
5-6 
A 
7-9 
B 
10-15 
C 
 
Source:  
1. Child CG, Turcotte JG. “Surgery and portal hypertension”. In Child CG. The liver and portal 
hypertension. Philadelphia: Saunders. 1964. pp. 50-64. 
2. Pugh RN, Murray-Lyon IM, Dawson L, Pietroni MC, Williams R. “Transection of the 
oesophagus for bleeding oesophageal varices”.  The British journal of surgery, 1973; 60: 646-9. 

ICF_001.pdf: 
 
 
 
 
 
MC1884 / 18-003574 
 
 
Phase II Trial of Sequential Treatment of Multiple Myeloma with 
Antibody Therapy 
 
 
NCT03713294 
 
 
Document Date: 08/13/2021 


 
 
Approval Date:  
August 13, 2021 
Not to be used after: August 12, 2022 
 
 
IRB#:  18-003574 00           E-sign 
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Name and Clinic Number 
Protocol #: MC1884 
Version #:1.0 
 
RESEARCH PARTICIPANT CONSENT AND PRIVACY 
AUTHORIZATION FORM 
 
 
Study Title: MC1884: Phase II Trial of Sequential Treatment of Multiple Myeloma with 
Antibody Therapy  
 
IRB#:  
18-003574  
 
Principal Investigator: Dr. Sikander Ailawadhi and Colleagues 
 
Please read this information carefully. It tells you important things about this research study. A 
member of our research team will talk to you about taking part in this research study.  If you 
have questions at any time, please ask us. 
 
Take your time to decide.  Feel free to discuss the study with your family, friends, and healthcare 
provider before you make your decision.   
 
To help you decide if you want to take part in this study, you should know: 
• Taking part in this study is completely voluntary.  
• You can choose not to participate.  
• You are free to change your mind at any time if you choose to participate.   
• Your decision won’t cause any penalties or loss of benefits to which you’re otherwise 
entitled. 
• Your decision won’t change the access to medical care you get at Mayo Clinic now or in 
the future if you choose not to participate or discontinue your participation.   
 
For purposes of this form, Mayo Clinic refers to Mayo Clinic in Arizona, Florida and Rochester, 
Minnesota; Mayo Clinic Health System; and all owned and affiliated clinics, hospitals, and 
entities. 
 
If you decide to take part in this research study, you will sign this consent form to show that you 
want to take part. We will give you a copy of this form to keep. A copy of this form will be put 
in your medical record. 
 
 
 
 
 


 
 
Approval Date:  
August 13, 2021 
Not to be used after: August 12, 2022 
 
 
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Name and Clinic Number 
Protocol #: MC1884 
Version #:1.0 
 
CONTACT INFORMATION 
 
 
You can contact … 
At … 
If you have questions about … 
Principal Investigator: 
Sikander Ailawadhi, M.D. 
 
Phone: 
(904) 953-2000 
 
Institution Name and Address: 
Mayo Clinic Florida 
4500 San Pablo Rd, 
Jacksonville, FL 32224 
 
 Study tests and procedures 
 Research-related injuries or 
emergencies 
 Any research-related concerns or 
complaints 
 Withdrawing from the research study 
 Materials you receive 
 Research-related appointments 
Mayo Clinic 
Institutional Review 
Board (IRB) 
Phone: 
(507) 266-4000 
 
Toll-Free: 
(866) 273-4681 
 
 Rights of a research participant 
 
Research Subject 
Advocate 
(The RSA is independent 
of the Study Team) 
Phone: 
(507) 266-9372 
 
Toll-Free: 
(866) 273-4681 
 
E-mail: 
researchsubjectadvocate@mayo.edu 
 
 Rights of a research participant 
 Any research-related concerns or 
complaints 
 Use of your Protected Health 
Information 
 Stopping your authorization to use 
your Protected Health Information 
Patient Account Services 
 
Toll-Free: 
(844) 217-9591 
 
 Billing or insurance related to this 
research study 
 
Other Information:   
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required 
by U.S. Law. This Web site will not include information that can identify you. At most, the Web 
site will include a summary of the results. You can search this Web site at any time. 


 
 
Approval Date:  
August 13, 2021 
Not to be used after: August 12, 2022 
 
 
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Name and Clinic Number 
Protocol #: MC1884 
Version #:1.0 
 
 
1. 
Why are you being asked to take part in this research study? 
 
 
You are being asked to take part in this research study because you have been diagnosed with 
Multiple Myeloma, previously treated with daratumumab as part of their standard of care, and 
are considered eligible to participate.  The plan is to have about 41 people take part in this study 
at Mayo Clinic. 
 
 
2. 
Why is this research study being done? 
 
 
The purpose of this study is to determine the effect of combining the drugs elotuzumab, 
pomalidomide and dexamethasone in patients who do not respond to daratumumab based 
treatment.  Everyone in this study will receive the combination of elotuzumab, pomalidomide, 
and dexamethasone which is still experimental and isn’t approved by the U.S. Food and Drug 
Administration (FDA). However, the FDA has allowed the use of this drug combination in this 
research study.  We hope the information from this study will help us improve treatment for 
patients with Multiple Myeloma. 
 
 
3. 
Information you should know 
 
 
Who is Funding the Study? 
 
This study will be funded by the Mayo Clinic Division of Hematology-Oncology 
 
Information Regarding Conflict of Interest: 
 
Your healthcare provider may be referring you to this research study. If your healthcare provider 
is also an investigator on this study, there is the chance that his or her responsibilities for the 
study could influence his or her recommendation for your participation. If you prefer, your 
healthcare provider will be happy to refer you to another investigator on the research study team 
for you to decide if you want to participate in the study and to see you for the research study 
activities while you are in the study. 
 


 
 
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August 13, 2021 
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Name and Clinic Number 
Protocol #: MC1884 
Version #:1.0 
 
 
4. 
How long will you be in this research study? 
 
 
You will be in the study for up to 3 years. 
 
 
5. 
What will happen to you while you are in this research study? 
 
 
If you agree to be in the study, you will be asked to participate in the following: 
 
Screening Visit  
During these visits, we will do some tests and procedures to see if you are eligible to take part in 
this research study. The Principal Investigator will review the results of these tests and 
procedures. If you aren’t eligible, the Principal Investigator will tell you why. At this visit we 
will: 
• Ask you about your medical history  
• Give you a physical exam, including height, weight, and “vital signs” (blood pressure, 
temperature, heart and breathing rates)  
• Draw a blood sample  
• Ask you for a urine sample  
• Test your blood and/or urine for pregnancy if you are a female able to become pregnant  
• Bone Marrow Aspirate/Biopsy. 
• PET/CT scan  
 
Day 1 of Every Cycle (Each cycle = 28 days) 
• Physical Exam 
• Draw a blood sample  
• Ask you for a urine sample  
• Test your blood and/or urine for pregnancy if you are a female able to become pregnant 
• Bone Marrow Aspirate/Biopsy (if clinically necessary) 
• PET/CT scan (if clinically necessary) 
 
 
 


 
 
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Day 15 for Cycles 1-2 only 
• Draw a blood sample  
• Ask you for a urine sample 
• PET/CT scan (if clinically necessary)  
 
These exams, tests or procedures are part of regular clinical care and may be done even if you do 
not join the study. If you have had some of them recently, they may not need to be repeated. This 
will be up to the Principal Investigator. 
  
During this period, we will also ask you to keep a pill diary for your dexamethasone and 
pomalidomide tablets. Pomalidomide should be taken without food (at least 2 hours before or 2 
hours after a meal). Do not open or crush capsules. Missed doses are to be omitted rather than 
made up, unless the dose was forgotten and remembered on the same day, in which case the dose 
can be taken that day. Any doses missed on a particular day are not to be made up the next day. 
Doses that are considered to be vomited are not to be made up and a mention about the time of 
dose and time of vomiting episode should be made in the pill diary.   
 
End of Treatment 
• Physical Exam  
• Draw a blood sample  
• Ask you for a urine sample  
• Test your blood and/or urine for pregnancy if you are a female able to become pregnant  
• Bone Marrow Aspirate/Biopsy 
• PET/CT Scan  
 
Follow-up 
After you have completed the end of treatment visit, you will be contacted by study staff to 
check if you have experienced any adverse events and to confirm your disease status. The timing 
of contact may vary depending on your disease status and if you report an adverse event. Contact 
is as follows:  
• Every 3 months until your disease progresses 
• At disease progression, if applicable 
• Every 6 months after disease progression 
• New adverse events occurrences 
 
After you have been followed for 3 years from the date you entered the study, no further follow-
up will be required; therefore, the study staff will no longer contact you.  
 
 
 


 
 
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Treatment (Cycles 1-2) 
Elotuzumab and dexamethasone will be administered by IV on Days 1, 8, 15, and 22 of Cycles 1 
and 2. Each infusion may take between 45-90 minutes each. You will also take pomalidomide 
(oral capsule) during days 1-21 of Cycles 1-2.  
 
Treatment (Cycles 3 and beyond) 
Elotuzumab and dexamethasone will be administered by IV on Day 1 during Cycles 3 and 
beyond. Each infusion may take between 45-90 minutes each. In addition to receiving 
dexamethasone infusions, you will take an oral capsule on Days 8, 15, and 22. You will also take 
pomalidomide (oral capsule) during days 1-21 of Cycle 3 and beyond.  
 
You must return to Mayo Clinic for treatment while participating in this study as administration 
of these drugs by any other doctor or medical facility is not allowed. In order to obtain 
pomalidomide, your name, address, phone, date of birth and the fact that you are participating in 
this trial will be disclosed to Celgene and its agents or vendors that supply pomalidomide and 
administer the POMALYST REMS™ program. By signing this consent form you agree to this 
disclosure. 
 
Management of Infusion Reactions 
In order to prevent infusion reactions, you may receive the following medications 45-90 minutes 
prior to your infusion: 
• Acetaminophen 
• Diphenhydramine 
• Famotidine 
 
You will be monitored for infusion reactions by trained study staff after each infusion.  If a 
reaction is suspected, your infusion may be interrupted and appropriate medical measures will be 
taken such as administration of antiemetics, antihistamines, analgesics, corticosteroids, oxygen, 
ephinephrine, or any other measure deemed necessary by the study team. 
 
 
6. 
What are the possible risks or discomforts from being in this research 
study? 
 
 
Risks associated with Dexamethasone 
 
Likely risks of Dexamethasone for Oral and IV Administration (DXM) 
• Fluid and electrolyte disturbances 


 
 
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• Congestive heart failure in susceptible persons 
• High blood pressure (hypertension) 
• Heightened or exaggerated sense of happiness or well-being (euphoria) 
• Personality changes 
• Inability to remain or fall asleep (insomnia) 
• Exacerbation of infection 
• Exacerbation or symptoms of diabetes 
• Experiencing anxiety, become paranoid, hear voices, become agitated or disoriented 
(psychosis) 
• Muscle weakness 
• Thinning of the bones and reducing bone mass (osteoporosis) 
• Vertebral compression fractures 
• Inflammation of the pancreas (pancreatitis) 
• Inflammation of the esophagus (esophagitis) 
• Ulcer in the stomach or esophagus (peptic ulcer) 
• Changes in the skin (dermatologic disturbances) 
• Seizures (convulsions) 
• Feeling of dizziness or spinning (vertigo) 
• Headache 
• Endocrine abnormalities 
• Changes in the eye (ophthalmic changes) 
• Metabolic changes 
• Itching 
• Hypersensitivity reactions (allergic reaction)  
• Life-threatening allergic reaction -such as difficulty breathing, low blood pressure, and/or 
organ failure ( anaphylactic reaction) 
• Withdrawal from prolonged therapy may result in symptoms including fever, myalgia 
and pain in joints (arthralgia). 
 
You may experience easy bruising while using dexamethasone. If you experience frequent, 
unrelenting headaches or visual changes while taking dexamethasone, please let the study doctor 
or know as soon as possible. 
 
Risks associated with Elotuzumab 
 
Likely risks of Elotuzumab (events occurring greater than 20% of the time) 
• Fever associated with dangerously low levels of a type of white blood cell (neutrophils) 
 


 
 
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Less likely risks of Elotuzumab (events occurring less than or equal to 20% of the time) 
• Reaction that can occur during or following the infusion of the drug. The reaction may 
include fever, chills, rash, low blood pressure and difficulty breathing. 
• Taste changes 
• Infection of the air tube from the windpipe to the lungs 
• Infection in the mouth  
• Change in liver or kidney function  
• Lung infection 
• Sinus infection  
• Blood infection 
• Urinary tract infection 
• Skin infection  
• Infection in the stomach or intestines  
• Changes in the amounts of salts and minerals in the blood  
• Uncontrolled trembling or shaking movements in one or more parts of your body 
• Hiccups  
• Feeling of sadness, worthlessness, thoughts of suicide or death (depression)  
• Increased blood sugar level  
• Voice changes  
• Hives 
• Tiredness (fatigue)  
• Inability to sleep 
 
Rare but serious risks of Elotuzumab (events occurring less than 2-3% of the time) 
• Fast or slow heartbeat  
• Chest pain due to heart problems 
• Abnormal heart rhythm 
• Unpleasant sensation of irregular and/or forceful beating of the heart  
• Dry eyes  
• Cloudiness of the eye (cataract)  
• Excess gas or bloating  
• Infection caused by a virus  
• Neck or jaw pain  
• Toothache  
• Sleepiness, the state of feeling drowsy, ready to fall asleep  
• Sudden severe confusion and rapid changes in brain function that occur with physical or 
mental illness  
• Irritability; Agitation or restlessness  


 
 
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• Memory loss 
• Inability to control the flow of urine from the bladder  
• Stuffy nose  
• Inflammation (swelling and redness) of the skin  
• Loss of bladder control 
• Formation of a blood clot that plugs the blood vessel; blood clots may break loose and 
travel to another place, such as the lung 
 
Other Risks 
It is also possible that your immune system could make antibodies against elotuzumab, which 
would limit how well it works against the myeloma.   
 
Risks associated with Pomalidomide 
 
Likely risks pomalidomide (greater than 10% chance this may happen): 
• Decrease in the number of platelets that help your blood to clot (thrombocytopenia) 
• Changes in bowel movement (constipation, diarrhea) 
• Cough 
• Decrease in the cells carrying oxygen to your body (anemia) 
• Decreased appetite 
• Fever (pyrexia) 
• Low number of white blood cells (leukopenia, neutropenia) 
• Muscle cramp (muscle spasms) 
• Nausea 
• Bone pain 
• Pneumonia 
• Shortness of breath (dyspnea) 
• Swelling including arms and legs (edema peripheral) 
• Tiredness (fatigue) 
 
Less likely risks of pomalidomide (between a 1-10% chance that this may happen): 
• Infection (bronchitis, upper respiratory tract infection, respiratory tract infection, 
neutropenic sepsis) 
• Dizziness (vertigo) 
• Vomiting 
• Rash 
• Abnormal shaking (tremor) changes in sensations including decreased sense of touch, 
burning sensation, or tingling (neuropathy peripheral) 


 
 
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• Sore throat (nasopharyngitis) 
• Kidney not working well (renal failure) 
• Confusion (confusional state) 
• Abnormal blood test results (hyperkalemia, hyponatremia) 
• Abnormal liver lab test (alanine aminotransferase increased) 
• Less alert (depressed level of consciousness) 
• Blood clots in legs or lungs (pulmonary embolism, deep vein thrombosis) 
• Difficulty in passing urine (urinary retention) 
• Itching (pruritus) 
• Abnormally low number of red and white blood cells, as well as platelets (pancytopenia) 
• Low number of white blood cells with a fever (febrile neutropenia) 
• Pelvic pain).  
 
Rare but serious risks of pomalidomide (Between 0.1-1% chance that this may happen): 
•  Abnormal blood test results (Hyperbilirubinemia) 
 
Risk with Intravenous (IV) Drug Administration  
Temporary irritation and bruising may occur at the infusion site. There may also be discomfort, pain, 
or bruising from the needle puncture. In rare cases, an infection may also occur at the site of the 
needle stick. 
 
Herpes Zoster Prophylaxis 
You may be at an increased risk of infection including reactivation of herpes zoster and herpes 
simplex viruses.  For this reason, you may receive acyclovir while during study treatment and 3 
months after stopping treatment. 
 
Pregnancy Risk-Fetus or Breast Feeding 
The effect of these drugs on a fetus (developing baby still in the womb), or on a breastfeeding 
infant, is unknown and may be harmful. Because of these risks, women cannot take part in this 
study if they are pregnant or breastfeeding.  
 
If you are a female, you must have a negative pregnancy test in order to participate in this study 
unless you cannot become pregnant. 
 
Birth Control Requirements for Female participants 
If you are sexually active and able to become pregnant, you must agree to use 2 of the birth 
control methods listed below: 
 Hormonal methods, such as birth control pills, patches, injections, vaginal ring, or 
implants 


 
 
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 Barrier methods (such as a condom or diaphragm) used with a spermicide (a foam, 
cream, or gel that kills sperm) 
 Intrauterine device (IUD) 
 Abstinence (no sex) 
 Partner’s vasectomy (2nd method should be one of the barrier methods listed above) 
 
You must use birth control 4 weeks prior to your first treatment, during the entire study, and for 
at least 4 week after your last dose of study drugs. Please do not donate any tissue or blood 
during this time. If you miss a period, or think you might be pregnant during the study, you must 
tell the Principal Investigator immediately. 
 
Birth Control Requirements for Male participants 
If you are sexually active, and able to father a child, you must agree to use the birth control 
method listed below: 
 Barrier methods (such as a condom or diaphragm) used with a spermicide (a foam, 
cream, or gel that kills sperm) 
 
Pomalidomide is known to appear in semen; therefore, only barrier methods (listed above) are 
acceptable and must be used during any sexual contact with females. You must use birth control 
during the entire study and for at least 4 weeks after your last dose of study drugs, even if you 
have undergone a success vasectomy. Please do not donate blood, tissue, or semen during this 
time. 
 
If your partner thinks she might have become pregnant while you are in the study or 4 weeks 
afterwards, you must tell the Principal Investigator immediately.  The Principal Investigator may 
ask for your partner’s permission to collect information about the outcome of her pregnancy and 
her newborn.  You won’t have to stop taking the study drug or stop taking part in the study if 
your partner becomes pregnant. 
 
 
7. 
Are there reasons you might leave this research study early? 
 
 
You may decide to stop at any time. You should tell the Principal Investigator if you decide to stop 
and you will be advised whether any additional tests may need to be done for your safety.  
In addition, the Principal Investigator or Mayo Clinic may stop you from taking part in this study at 
any time:  
• 
If it is in your best interest,  
• 
If you don’t follow the study procedures,  
• 
If the study is stopped.  


 
 
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Version #:1.0 
 
If you leave this research study early, or are withdrawn from the study, no more information about 
you will be collected; however, information already collected about you in the study may continue to 
be used. 
  
We will tell you about any new information that may affect your willingness to stay in the research 
study. 
 
 
8. 
What if you are injured from your participation in this research study? 
 
 
Where to get help: 
 
If you think you have suffered a research-related injury, you should promptly notify the Principal 
Investigator listed in the Contact Information at the beginning of this form. Mayo Clinic will 
offer care for research-related injuries, including first aid, emergency treatment and follow-up 
care as needed. 
 
Who will pay for the treatment of research related injuries? 
 
Care for such research-related injuries will be billed in the ordinary manner, to you or your 
insurance. You will be responsible for all treatment costs not covered by your insurance, 
including deductibles, co-payments and coinsurance. 
 
 
9. 
What are the possible benefits from being in this research study? 
 
 
There are limited standard of care options available for the treatment of your disease. This study 
may not make your health better; however, the combination of pomalidomide, elotuzumab and 
dexamethasone may help to improve your disease and provide better standard of care treatment 
options in the future, if proven effective.   
 
 
 


 
 
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10. 
What alternative do you have if you choose not to participate in this 
research study? 
 
 
You don’t have to be in this study to receive treatment for your condition. Your other choices 
include carfilzomib, ixazomib, panobinistat, or other treatments your doctor may feel is 
appropriate for your disease. Talk to the Principal Investigator or your doctor if you have any 
questions about any of these treatments or procedures. 
 
 
11. 
What tests or procedures will you need to pay for if you take part in this 
research study?  
 
 
You and/or your insurance will need to pay for all tests and procedures that you would have as part 
of your clinical care. These tests and procedures are: 
• Drugs and drug administration 
• Routine Laboratory tests (blood and urine) 
• Pregnancy tests 
• Bone Marrow Aspirate/Biopsy 
• Physical Exams 
• PET/CT scans 
 
If you have billing or insurance questions call Patient Account Services at the telephone 
number provided in the Contact Information section of this form. 
 
 
12. 
Will you be paid for taking part in this research study? 
 
 
You won’t be paid for taking part in this study. 
 
 
 


 
 
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13. 
How will your privacy and the confidentiality of your records be protected? 
 
 
Mayo Clinic is committed to protecting the confidentiality of information obtained about you in 
connection with this research study. To protect the data and confidentiality of subject’s data, a 
code will be used as an identifier. The code will be a registration number assigned specifically to 
the patient by Mayo Clinic. The correlating Mayo Clinic number and the patient's name for 
reference will be maintained in a secure database accessible by Mayo Clinic assigned research 
staff.  
 
During this research, information about your health will be collected. Under Federal law called 
the Privacy Rule, health information is private. However, there are exceptions to this rule, and 
you should know who may be able to see, use and share your health information for research and 
why they may need to do so. Information about you and your health cannot be used in this 
research study without your written permission. If you sign this form, it will provide that 
permission.  
 
Health information may be collected about you from: 
• Past, present and future medical records. 
• Research procedures, including research office visits, tests, interviews and 
questionnaires. 
 
Why will this information be used and/or given to others? 
• To do the research. 
• To report the results. 
• To see if the research was done correctly. 
 
If the results of this study are made public, information that identifies you will not be used. 
 
 
 


 
 
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Who may use or share your health information? 
• Mayo Clinic research staff involved in this study.  
 
With whom may your health information be shared?  
• The Mayo Clinic Institutional Review Board that oversees the research.  
• Other Mayo Clinic physicians involved in your clinical care.  
• Researchers involved in this study at other institutions. 
• Federal and State agencies (such as the Food and Drug Administration, the Department of 
Health and Human Services, the National Institutes of Health and other United States 
agencies) or government agencies in other countries that oversee or review research. 
• The sponsor(s) of this study and the people or groups it hires to help perform this 
research. 
• A group that oversees the data (study information) and safety of this research. 
 
How your information may be shared with others: 
While taking part in this study, you will be assigned a code that is unique to you, but does not 
include information that directly identifies you. This code will be used if your study information 
is sent outside of Mayo Clinic. The groups or individuals who receive your coded information 
will use it only for the purposes described in this consent form. 
 
If the results of this study are made public (for example, through scientific meetings, reports or 
media), information that identifies you will not be used. 
 
In addition, individuals involved in study oversight and not employed by Mayo Clinic may be 
allowed to review your health information included in past, present, and future medical and/or 
research records. This review may be done on-site at Mayo Clinic or remotely (from an off-site 
location). These records contain information that directly identifies you. However, the 
individuals will not be allowed to record, print, or copy (using paper, digital, photographic or 
other methods), or remove your identifying information from Mayo Clinic. 
 
Is your health information protected after it has been shared with others? 
Mayo Clinic asks anyone who receives your health information from us to protect your privacy; 
however, once your information is shared outside Mayo Clinic, we cannot promise that it will 
remain private and it may no longer be protected by the Privacy Rule. 
 
Your Privacy Rights 
You do not have to sign this form, but if you do not, you cannot take part in this research study. 
 


 
 
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IRB Doc. Ctrl # 10013.30 
 
 
 
 
 
 
 
Name and Clinic Number 
Protocol #: MC1884 
Version #:1.0 
If you cancel your permission to use or share your health information, your participation in this 
study will end and no more information about you will be collected; however, information 
already collected about you in the study may continue to be used. 
 
If you choose not to take part or if you withdraw from this study, it will not harm your 
relationship with your own doctors or with Mayo Clinic. 
 
You can cancel your permission to use or share your health information at any time by sending a 
letter to the address below: 
 
Mayo Clinic 
Office for Human Research Protection 
ATTN:  Notice of Revocation of Authorization 
201 Building 4-60 
200 1st Street SW 
Rochester, MN  55905 
 
Alternatively, you may cancel your permission by emailing the Mayo Clinic Research Subject 
Advocate at: researchsubjectadvocate@mayo.edu. 
 
Please be sure to include in your letter or email: 
• The name of the Principal Investigator, 
• The study IRB number and /or study name, and 
• Your contact information. 
 
Your permission lasts until the end of this study, unless you cancel it.  Because research is an 
ongoing process, we cannot give you an exact date when the study will end. 
 
 


 
 
Approval Date:  
August 13, 2021 
Not to be used after: August 12, 2022 
 
 
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Name and Clinic Number 
Protocol #: MC1884 
Version #:1.0 
 
 
ENROLLMENT AND PERMISSION SIGNATURES 
 
 
Your signature documents your permission to take part in this research.  
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
  
Printed Name  
 
 
Date (mm/dd/yyyy) 
 
 
Time (hh:mm am/pm)  
 
 
 
 
 
 
 
 
_______________________________ 
Signature 
 
 
Person Obtaining Consent  
• I have explained the research study to the participant. 
• I have answered all questions about this research study to the best of my ability. 
 
 
 
Printed Name  
 
 
Date (mm/dd/yyyy) 
 
 
Time (hh:mm am/pm) 
 
 
_______________________________ 
Signature 
 
chkEsi
dteParticipantSig
sigParticipant
prtParticipantName
prtPOCName
dtePOCSig
sigPOC
sigWitness