Clinical trial NCT01712789
Conditions: Multiple Myeloma
Keywords: Multiple Myeloma Relapsed Multiple Myeloma Relapsed and refractory Multiple Myeloma Pomalidomide Dexamethasone
Sponsor: Celgene
Start date: 2012-11-06; Completion date: 2019-12-11
Enrollment: 682 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The primary purpose of the study is to evaluate the safety and efficacy and to generate PK and biomarker data for the combination of pomalidomide and low-dose dexamethasone in patients with refractory or relapsed and refractory multiple myeloma.

The study consists of a Screening phase within 28 days prior to cycle 1 day 1, a Treatment phase and a Follow-up phase which starts within 28 days of discontinuation from study treatment, every 3 months for up to 5 years.

In addition, the collection of steady-state PK data from a large population will enable robust population PK and assess Pomalidomide exposure response analyses.

The exploratory objectives of the study are to investigate potential markers predictive of POM response or resistance and pharmacodynamic markers.

Detailed description:

Arms: arm 1: Pomalidomide 4mg by mouth (PO) daily days 1 through 21 of a 28 day cycle and dexamethasone 40mg/day PO for those ≤75 years of age or 20mg/day for those greater than 75 years of age on Days 1, 8, 15 and 22 of a 28 day cycle.
Interventions: intervention 1: Pomalidomide intervention 2: Dexamethasone
Intervention descriptions: intervention 1: Oral Pomalidomide at the starting dose of 4 mg on Days 1-21 of a 28-day cycle intervention 2: Oral Low dose Dexamethasone at the starting dose of 40mg/day (≤ 75 years old) or 20 mg/day (\> 75 years old) on Days 1, 8, 15 and 22 of a 28-day cycle.

Protocol documents:
Prot_000.pdf: 
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TITLE PAGE
A MULTICENTER, SINGLE-ARM, OPEN-LABEL 
STUDY WITH POMALIDOMIDE IN COMBINATION 
WITH LOW DOSE DEXAMETHASONE IN SUBJECTS 
WITH REFRACTORY OR RELAPSED AND 
REFRACTORY MULTIPLE MYELOMA
INVESTIGATIONAL PRODUCT (IP):
Pomalidomide (CC-4047)
PROTOCOL NUMBER:
CC-4047-MM-010 
ORIGINAL DATE FINAL:
23 May 2012
AMENDMENT 1 DATE FINAL:
30 May 2013
EudraCT NUMBER:
2012-001888-78
IND NUMBER:
066188
SPONSOR NAME / ADDRESS:
Celgene Corporation
CONFIDENTIAL
This protocol is provided to you as an Investigator, potential Investigator, or consultant for review by 
you, your staff, and ethics committee/institutional review board.  The information contained in this 
document is regarded as confidential and, except to the extent necessary to obtain informed consent, 
may not be disclosed to another party unless such disclosure is required by law or regulations.  
Persons to whom the information is disclosed must be informed that the information is confidential 
and may not be further disclosed by them.


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MEDICAL MONITOR / EMERGENCY CONTACT INFORMATION 
Contact Information:
Name: 
Nicolas Leupin, MD 
Title:
Responsible Clinical Research Physician
 
 
 
  




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SITE PRINCIPAL INVESTIGATOR SIGNATURE PAGE
Signature of Site Principal Investigator
dd mmm yyyy
Printed Name of Site Principal Investigator
Institution Name:_______________________________________
By my signature, I agree to personally supervise the conduct of this study at my study 
site and to ensure its conduct is in compliance with the protocol, informed consent, 
Institutional Review Board (IRB)/Ethics Committee (EC) procedures, instructions from 
Celgene representatives, the Declaration of Helsinki, ICH Good Clinical Practices 
Guidelines, and local regulations governing the conduct of clinical studies.


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COORDINATING PRINCIPAL INVESTIGATOR SIGNATURE PAGE
Signature of Coordinating Principal Investigator
dd mmm yyyy
Printed Name of Coordinating Principal Investigator
Institution Name:_______________________________________
By my signature, I agree the protocol has been written to comply with ICH Good 
Clinical Practices guidelines and agree to offer guidance throughout the study as 
needed.


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PROTOCOL SUMMARY
Study Title
A Multicenter, Single-arm, Open-label Study with Pomalidomide in Combination with Low 
Dose Dexamethasone in Subjects with Refractory or Relapsed and Refractory Multiple 
Myeloma. 
Indication
Refractory multiple myeloma (MM) or relapsed and refractory MM. 
Objectives
Primary Objective 
Evaluate the safety of the combination of pomalidomide (POM) and low dose dexamethasone 
(LD-DEX) in a large cohort of subjects with refractory MM or relapsed and refractory MM. 
Secondary Objectives

Analyze the population pharmacokinetics of POM and assess POM exposure 
response relationships in subjects with refractory MM or relapsed and refractory MM 
administered POM and LD-DEX.

Evaluate efficacy of the combination of POM and LD-DEX in subjects with
refractory MM or relapsed and refractory MM.

Evaluate the relationship between cytogenetic profiles and the combination of POM 
and LD-DEX in terms of response and outcome.
 
 
Study Endpoints
Primary Endpoint
Adverse events (AEs) assessment (type, frequency, seriousness, severity, relationship to POM 
and/or DEX and outcomes), including second primary malignancies (SPM)
Secondary Endpoints

POM exposure 

POM population pharmacokinetics and exposure-response 

Overall response rate (ORR)

Time to response 

Duration of response (DoR)

Progression-free survival (PFS)


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
Time to progression (TTP)

Overall survival (OS)

Analysis of cytogenetic profiles 
Study Design
This is an international, multicenter, single-arm, open-label study of POM in combination with 
LD-DEX in subjects with refractory MM or relapsed and refractory MM. 
This study consists of the following consecutive phases: Screening, Treatment and Follow-up.  
Study visits and evaluations will be performed as outlined in Table 1 (“Table of Events”).
Screening Phase
Study subjects will sign an informed consent document (ICD) prior to undergoing any study-
related procedure. Subjects may have the choice to participate in an optional biomarker study 
conducted at selected clinical sites. If a subject chooses to participate in the biomarker study, 
he/she must give consent for the optional biomarker study. Subjects will undergo screening for 
protocol eligibility within 28 days prior to Cycle 1 Day 1, as outlined in Table 1, Table of 
Events. 
Subjects who meet all eligibility criteria will receive the study treatment and will be maintained 
on the pregnancy prevention program for the duration of the study.
The inclusion procedure will be accomplished by a validated interactive voice/web response 
system (IVRS/IWRS).
Treatment Phase
Study treatment administration should start within 72 hours after enrollment (which is defined as 
enrollment on the IVRS/IWRS) of the subject into the study, provided that the inclusion/
exclusion criteria are still met.  Otherwise, the subject will need to be re-screened.  Each subject 
will receive the following study treatment until progressive disease (PD), or as long as they 
benefit from therapy according to the opinion of the responsible study Investigator and discussed 
with the Sponsor:

POM administered orally at the starting dose of 4 mg on Days 1-21 of a 28-day cycle, 

LD-DEX administered orally at the starting dose of 40 mg/day (≤ 75 years old) or 20 
mg/day (> 75 years old) on Days 1, 8, 15 and 22 of a 28-day cycle.
Pharmacokinetic (PK) blood samples for POM quantification will be collected at specified time-
points during the course of the study from all subjects from selected sites with PK capability. 
 


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In addition, the bone marrow aspirate collected from all subjects during screening will be used 
for cytogenetic analysis (once eligibility has been confirmed), and an additional aspirate will be 
required for those subjects who discontinue the study treatment due to disease progression in 
order to identify any change in their cytogenetic profile.
Follow-up Phase
All study subjects will enter the follow-up phase after study treatment discontinuation.  During 
follow-up the following information will be collected from all subjects every 3 months for up to 
5 years after last subject enrollment or longer if clinically indicated: SPMs, survival, subsequent 
anti-myeloma treatments (type of treatment, start and stop dates, best response whenever 
possible) and date of progression.
Study Population
This is a multicenter, international, single-arm, open label, phase IIIb study of POM and LD-
DEX in subjects with refractory MM or relapsed and refractory MM conducted in Europe and 
Israel. The study is anticipated to enroll approximately 720 subjects with refractory MM or 
relapsed and refractory MM and fulfilling the eligibility criteria outlined below.
Inclusion Criteria
Subjects must satisfy the following criteria to be enrolled in the study:
1. Must be ≥18 years at the time of signing the ICD.
2. The subject must understand and voluntarily sign an ICD prior to any study related 
assessments/procedures being conducted.
3. Must be able to adhere to the study visit schedule and other protocol requirements. 
4. Subjects must have documented diagnosis of MM and have measurable disease (serum 
M-protein ≥ 0.5 g/dL or urine M-protein ≥ 200 mg/24 hours). 
5. Subjects must have undergone prior treatment with ≥ 2 treatment lines of anti-myeloma 
therapy.  Induction therapy followed by autologous stem cell transplant (ASCT) and
consolidation/ maintenance will be considered as one line.  A new treatment line is 
always started after progressive disease.
6. Subjects must have either refractory or relapsed and refractory disease defined as 
documented disease progression during or within 60 days of completing their last 
myeloma therapy. 
Primary Refractory: Subjects who have never achieved any response better than PD to 
any previous line of anti-myeloma therapy.
Relapsed and Refractory: Subjects who have relapsed after having achieved at least
stable disease for at least two cycles of treatment to at least one prior regimen and then 
developed PD on or within 60 days of completing their last myeloma therapy.


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7. All subjects must have received at least 2 consecutive cycles of prior treatment that 
included lenalidomide and bortezomib, either alone or in combination regimens.
All subjects must have failed both lenalidomide and bortezomib and medical records
must be available that provide documentation of the following criteria for refractoriness 
that make the subject eligible for the study.

All subjects must have failed treatment with the last lenalidomide-containing regimen 
in one of the following ways: 

Documented PD during or within 60 days of completing last treatment with 
lenalidomide, regardless of the response achieved, or

In case of prior response (≥ partial response - PR) to lenalidomide and PD 
> 60 days, subjects must have relapsed within 6 months after the last dose of 
treatment with lenalidomide-containing regimens.

All subjects must have failed treatment with the last bortezomib-containing regimen 
in one of the following ways:

Documented PD during or within 60 days of completing treatment with 
bortezomib, regardless of the response achieved, or

In case of prior response (≥ PR) to bortezomib and PD > 60 days, subjects must 
have relapsed within 6 months after the last dose of treatment with bortezomib-
containing regimens,
Or for non-progressive subjects:

Subjects who have less than minor response (MR) and have developed 
intolerance/toxicity after a minimum of two cycles of a bortezomib-containing 
regimen. Toxicity such as > grade 2 peripheral neuropathy or ≥grade 2 painful 
neuropathy. Peripheral neuropathy must resolve to grade 1 prior to study entry. 
8. Subjects must have received adequate prior alkylator therapy in one of the following 
ways:
a.
As part of a stem cell transplant; or
b. A minimum of 4 consecutive cycles of an alkylator based therapy; or
c.
Progression on treatment with an alkylator; provided that the subject received at least 
2 cycles of an alkylator-containing therapy.
9. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2.
10. Females of childbearing potential (FCBP1) must agree to utilize two reliable forms of 
contraception simultaneously or practice complete abstinence from heterosexual contact 
for at least 28 days before starting study drug, while participating in the study (including 
dose interruptions), and for at least 28 days after study treatment discontinuation and 
must agree to regular pregnancy testing during this timeframe. (NOTE: True abstinence: 
                                               
1 A female of childbearing potential is a sexually mature woman 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., who 
has had menses at any time in the preceding 24 consecutive months).


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When this is in line with the preferred and usual lifestyle of the subject. [Periodic abstinence 
(e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not 
acceptable methods of contraception])
11. Females must agree to abstain from breastfeeding during study participation and 28 days 
after study drug discontinuation.
12. Males must agree to use a latex condom during any sexual contact with FCBP while 
participating in the study and for 28 days following discontinuation from this study, even 
if he has undergone a successful vasectomy.
13. Males must also agree to refrain from donating semen or sperm while on POM and for 
28 days after discontinuation from this study treatment.
14. All subjects must agree to refrain from donating blood while on study therapy and for 
28 days after discontinuation from this study treatment.
15. All subjects must agree not to share medication.
Exclusion Criteria 
The presence of any of the following will exclude a subject from study enrollment:
1. Any of the following laboratory abnormalities:

Absolute neutrophil count < 800/μL.

Platelet count < 75,000/µL for subjects in whom < 50% of bone marrow nucleated 
cells are plasma cells; or a platelet count < 30,000/µL for subjects in whom ≥ 50% of 
bone marrow nucleated cells are plasma cells. Platelet transfusion is not allowed 
within the previous 3 days before screening.

Creatinine Clearance (CrCl) < 45 mL/min according to Cockcroft-Gault formula.  If 
CrCl calculated from the 24-hour urine sample is ≥45 mL/min, subject will qualify 
for the study. 

Corrected serum calcium > 14 mg/dL (> 3.5 mmol/L).

Hemoglobin < 8 g/dL (< 4.9 mmol/L; prior red blood cells transfusion or recombinant 
human erythropoietin use is permitted).

Serum SGOT/AST or SGPT/ALT > 3.0 x upper limit of normal (ULN).

Serum total bilirubin > 2.0 mg/dL (34.2 μmol/L); or > 3.0 x ULN for subjects with 
hereditary benign hyperbilirubinemia.
2. Prior history of malignancies, other than MM, unless the subject has been free of the 
disease for ≥5 years.  Exceptions include the following:

Basal or squamous cell carcinoma of the skin

Carcinoma in situ of the cervix or breast

Incidental histological finding of prostate cancer (TNM stage of T1a or T1b).
3. Previous therapy with POM.


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4. Hypersensitivity to thalidomide, lenalidomide, or DEX (this includes ≥ Grade 3 rash 
during prior thalidomide or lenalidomide therapy).
5. Peripheral neuropathy ≥ Grade 2.
6. Subjects who received an allogeneic bone marrow or allogeneic peripheral blood stem 
cell transplant less than 12 months prior to initiation of study treatment and who have not 
discontinued immunosuppressive treatment for at least 4 weeks prior to initiation of study 
treatment and are currently dependent on such treatment.
7. Subjects who are planning for or who are eligible for stem cell transplant.
8. Subjects with any one of the following:

Congestive heart failure (NY Heart Association Class III or IV)

Myocardial infarction within 12 months prior to starting study treatment

Unstable or poorly controlled angina pectoris, including Prinzmetal variant angina 
pectoris.
9. Subjects who received any of the following within the last 14 days of initiation of study 
treatment:

Major surgery (kyphoplasty is not considered major surgery)

Use of any anti-myeloma drug therapy.
10. Use of any investigational agents within 28 days or five half-lives (whichever is longer) 
of treatment, unless approved by the Sponsor.
11. Incidence of gastrointestinal disease that may significantly alter the absorption of POM.
12. Subjects unable or unwilling to undergo antithrombotic prophylactic treatment.
13. Any serious medical condition, laboratory abnormality, or psychiatric illness that would 
prevent the subjects from signing the ICD.
14. Pregnant or breastfeeding females.
15. Known human immunodeficiency virus (HIV) positivity, active infectious hepatitis A, B 
or C or chronic hepatitis B or C.
Length of Study
This study will remain open to enrollment for an estimated 18-24 months, or until subject 
enrollment numbers are complete, whichever occurs first.  Subjects will be followed for up to 5 
years after last subject enrollment or longer if clinically indicated.
The study will consist of the following consecutive phases: Screening, Treatment and Follow-up.  
The screening period may be up to 28 days prior to start of study treatment.  Subjects may 
remain in the study until study treatment is discontinued for any reason or documented PD or as 
long as they benefit from therapy according to the opinion of the responsible study Investigator 
and discussed with the Sponsor.  Once discontinued from the study treatment, subjects will be 
followed for OS and occurrence of SPM every 3 months for up to 5 years after last subject 
enrollment or longer if clinically indicated.


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Study Treatment
All subjects will be treated with open label POM. POM will be supplied as Investigational 
Product by Celgene Corporation as 1 mg, 2 mg, 3 mg, and 4 mg capsules for oral administration. 
Study drug will be packaged in bottles containing a 21-day supply of POM.  The dosing schedule 
is as follows:

POM is administered orally at the starting dose of 4 mg on Days 1-21 of a 28-day 
cycle, 

LD-DEX is administered orally at the starting dose of 40 mg/day (≤ 75 years old) or 
20 mg/day (> 75 years old) on Days 1, 8, 15 and 22 of a 28-day cycle.
Allowed Medications
Low-dose aspirin, low molecular weight heparin, or other equivalent antithrombotic or anti-
coagulant will be given to all subjects.  Antithrombotic prophylaxis will be recorded in the 
electronic case report (eCRF) form at each visit.  Subjects who develop symptomatic deep vein 
thrombosis will be assessed and diagnosed objectively by Doppler ultrasonography or a 
comparable method.  
Prior to study entry and during the treatment phase, subjects with myeloma-associated bone 
disease may receive bisphosphonate therapy, as well as other agents that may be used for 
myeloma-associated bone disease, such as denosumab and teriparatide, unless such therapy is 
contraindicated. 
Hematopoietic growth factors are allowed as per the recommendations of the European Society 
for Medical Oncology (ESMO) guidelines (Crawford, 2010). Platelet and/or red blood cell
transfusions are permitted throughout the study, including the screening period, at the discretion 
of the investigator. If platelet transfusions are given during the screening period, the screening 
platelet assessment must be done a minimum of 3 days (72 hours) after the completion of the 
transfusion.
An independent Data Monitoring Committee (DMC) will review safety data on an ongoing basis 
throughout the study. 
Prohibited Medications
Concomitant use of other anti-myeloma therapy while the subject is taking study drug is 
prohibited.  Subsequent treatment for MM should not be initiated until the PD is documented.  
The need for radiation therapy is considered to be a treatment failure.  However, an exception 
(i.e., subjects are allowed to remain on the treatment phase of the study) is made for radiation 
therapy to a pathological fracture site to enhance bone healing or to treat post-fracture pain that is 
refractory to narcotic analgesics because pathological bone fractures do not, by themselves, 
fulfill a criterion for disease progression.  Chronic use of steroids other than the study drug 
(dexamethasone) or any other immunosuppressive therapies are prohibited in this study.
Drugs known to prolong QT corrected (QTc) interval should be avoided unless deemed 
medically necessary.  See Appendix F for a comprehensive list of drugs which are known to 
elongate the QTc. 
Guidelines for dose modifications for POM and DEX are further described in Section 8.2. 


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Treatment Discontinuation 
Subjects will continue study treatment until the documentation of confirmed PD, intolerable 
toxicity, death, withdrawal of participation/consent in the study, or loss to follow-up, or as long 
as they benefit from therapy according to the opinion of the responsible study Investigator and 
discussed with the Sponsor.  This study will not use Central Imaging or Central efficacy 
assessment review.  Response will be based on Investigator’s assessment using local laboratory 
results.
Subjects are not expected to start any other anti-myeloma therapy before progression.  A 
discontinuation visit will be required for all subjects who discontinue treatment.
Overview of Safety Assessments

Serum/urine beta-human chorionic gonadotropin (β-HCG) (FCBP only).

Vital signs.

Clinical laboratory evaluations (hematology, serum chemistry, urinalysis).
Laboratory measure for safety and efficacy assessments will utilize local, accredited 
laboratories with agreement that the same laboratory will be used for each site for the 
period of the study. 
An abnormal laboratory value is considered to be an AE if the abnormality results in 
discontinuation from the study; requires treatment, modification/interruption of 
investigational product (IP) dose, or any other therapeutic intervention; or is judged to 
be of significant clinical importance by the Investigator.
Regardless of severity grade, only laboratory abnormalities that fulfill a seriousness 
criterion need to be documented as a serious adverse event (SAE).  

Venous thromboembolism (VTE) monitoring

Electrocardiogram (ECG) 

Concomitant medications and procedures

Adverse events of all grades will be recorded on the eCRF throughout the study from 
signing of the ICD until 28 days after discontinuation from the study treatment 
including AE type, frequency, seriousness, severity, relationship to study drug, and 
outcomes.
Adverse events will be coded according to the Medical Dictionary for Regulatory 
Activities (MedDRA).  The severity of AEs will be graded according to the National 
Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) 
(version 4.0, May 2009).  Summaries will be provided by system organ class, and 
preferred term.

Second primary malignancies will be monitored as events of interest and should be 
included as part of the assessment of AEs throughout the course of the study.  
Investigators must report any SPM as SAE regardless of causal relationship to 
investigational product (IP) (POM with or without LD-DEX), occurring at any time 
from the time of signing the ICD until the end of their follow-up.


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For all subjects who develop SPM, sites will be required to submit all diagnostic 
reports (e.g., pathology, cytogenetics, flow cytometry results) from the MM 
diagnostic confirmation samples submitted at screening and all reports for the tumor 
samples from the SPM diagnosis.  For SPMs diagnosed at another institution, (outside 
of the investigational site) sites will be required to make every effort to obtain these 
reports for second primary malignancy confirmation.
Overview of Pharmacokinetic Assessments

Population PK model describing the sparse plasma PK data of POM and associated 
inter-individual variability, potential inter-occasional variability and residual 
variability.

Influence of covariates of extrinsic factors (body weight, CrCl, etc) on the population 
PK parameters of POM.

Bayesian prediction of individual exposure of POM in subjects following oral 
administration for exposure response analysis, and

Potential models describing the potential exposure - response relationships between 
plasma exposures of POM (Bayesian individual exposure) and response variables 
(clinical efficacy endpoints and/or clinical safety endpoints), as appropriate.
Overview of Efficacy Assessments

Myeloma paraprotein

Serum immunoglobulins

Serum Free Light Chain

Beta-2 Microglobulin

Bone marrow aspiration/biopsy

Radiographic assessments of lytic bone lesions

Extramedullary plasmacytoma (EMP) assessments

ECOG performance status
Investigator’s assessment for ORR, will be provided per International Myeloma 
Working Group (IMWG) criteria, and time to response, DoR, TTP and PFS will be 
calculated based on the Investigator’s response assessment. Subject also will be 
followed-up for OS.  All time-to-event endpoints will be estimated from the time of 
study enrollment, except DoR which will be estimated as the time from response.
Overview of Cytogenetic Assessments

Bone marrow aspirate taken during screening and for those subjects who discontinue 
the study treatment due to disease progression will be used to assess:

cytogenetic profiles

disease course


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
response to treatment
 
 
 
 


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TABLE OF CONTENTS
TITLE PAGE..............................................................................................................................1
PROTOCOL SUMMARY ..........................................................................................................6
2.
STUDY OBJECTIVES...........................................................................................29
2.1.
Primary Objective...................................................................................................29
2.2.
Secondary Objectives .............................................................................................29
3.
STUDY ENDPOINTS............................................................................................30
3.1.
Primary Endpoint....................................................................................................30
3.2.
Secondary Endpoints ..............................................................................................30
4.
OVERALL STUDY DESIGN ................................................................................31
4.1.
Study Design ..........................................................................................................31
4.3.
Study Duration .......................................................................................................34
5.
TABLE OF EVENTS.............................................................................................36
6.
PROCEDURES......................................................................................................41
7.
STUDY POPULATION.........................................................................................49
7.1.
Number of Subjects and Sites .................................................................................49
7.2.
Inclusion Criteria....................................................................................................49
7.3.
Exclusion Criteria...................................................................................................51
8.
DESCRIPTION OF STUDY TREATMENTS........................................................53
8.1.
Description of Investigational Product(s)................................................................53
8.2.
Treatment Administration and Schedule .................................................................53
8.3.
Method of Treatment Assignment...........................................................................56
8.4.
Packaging and Labeling..........................................................................................56
8.5.
Investigational Product Accountability and Disposal ..............................................56
8.6.
Investigational Product Compliance........................................................................56


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10.
STATISTICAL ANALYSES..................................................................................59
10.1.
Overview................................................................................................................59
10.2.
Study Population Definitions ..................................................................................59
10.3.
Sample Size and Power Considerations...................................................................59
10.4.
Background and Demographic Characteristics........................................................60
10.5.
Subject Disposition.................................................................................................60
10.6.
Efficacy Analysis....................................................................................................60
10.7.
Safety Analysis.......................................................................................................61
10.8.
Interim Analysis .....................................................................................................62
10.9.
Pharmacokinetic Analysis.......................................................................................62
10.10.
Exposure-Response Analysis ..................................................................................62
10.12.
Cytogenetic Analysis..............................................................................................63
11.
ADVERSE EVENTS..............................................................................................64
11.1.
Monitoring, Recording and Reporting of Adverse Events .......................................64
11.2.
Evaluation of Adverse Events.................................................................................64
11.2.1.
Seriousness.............................................................................................................64
11.2.2.
Severity / Intensity..................................................................................................66
11.2.3.
Causality ................................................................................................................66
11.2.4.
Duration .................................................................................................................67
11.2.5.
Action Taken..........................................................................................................67
11.2.6.
Outcome.................................................................................................................67
11.3.
Abnormal Laboratory Values..................................................................................67
11.4.
Pregnancy...............................................................................................................67
11.4.1.
Females of Childbearing Potential ..........................................................................67
11.4.2.
Male Subjects.........................................................................................................68
11.5.
Reporting of Serious Adverse Events......................................................................68
11.5.1.
Safety Queries ........................................................................................................69
11.6.
Expedited Reporting of Adverse Events..................................................................69
12.
DISCONTINUATIONS .........................................................................................71
13.
EMERGENCY PROCEDURES.............................................................................72
13.1.
Emergency Contact.................................................................................................72


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13.2.
Emergency Identification of Investigational Products .............................................72
14.
REGULATORY CONSIDERATIONS...................................................................73
14.1.
Good Clinical Practice............................................................................................73
14.2.
Investigator Responsibilities ...................................................................................73
14.3.
Subject Information and Informed Consent.............................................................73
14.4.
Confidentiality........................................................................................................74
14.5.
Protocol Amendments.............................................................................................74
14.6.
Institutional Review Board/Independent Ethics Committee Review and 
Approval ................................................................................................................74
14.7.
Ongoing Information for Institutional Review Board / Ethics Committee................75
14.8.
Closure of the Study ...............................................................................................75
15.
DATA HANDLING AND RECORDKEEPING.....................................................76
15.1.
Data/Documents .....................................................................................................76
15.2.
Data Management...................................................................................................76
15.3.
Record Retention....................................................................................................76
16.
QUALITY CONTROL AND QUALITY ASSURANCE........................................78
16.1.
Study Monitoring and Source Data Verification......................................................78
16.2.
Audits and Inspections............................................................................................78
17.
PUBLICATIONS ...................................................................................................79
19.
APPENDICES........................................................................................................85
Appendix A:  Declaration of Helsinki .......................................................................................85
Appendix C:  Skeletal (Bone) Survey........................................................................................90
Appendix D:  Pomalidomide Pregnancy Risk Minimization Plan for Celgene Clinical 
Trials ......................................................................................................................91
Appendix D-1:  Pomalidomide Risks of Fetal Exposure, Pregnancy Testing Guidelines 
and Acceptable Birth Control Methods ...................................................................92
Appendix D-2:  Pomalidomide Education and Counselling Guidance Document.......................96
Appendix D-3:  Pomalidomide Information Sheet .....................................................................99
Appendix E:  National Cancer Institute-Common Terminology Criteria for Adverse 
Events...................................................................................................................101
Appendix G:  Staging Systems for Multiple Myeloma.............................................................107


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Appendix H: ECOG Performance Status Scale........................................................................108
Appendix I:  International Myeloma Working Group Response Criteria..................................109
Appendix J:  Pharmacokinetic Sample Handling Instructions ..................................................111
Appendix K:  List of Abbreviations.........................................................................................113


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LIST OF TABLES
Table 1:
Table of Events.......................................................................................................36
Table 2:
Dose Modification Instructions for Pomalidomide ..................................................54
Table 3:
Pomalidomide Dose Reduction Steps......................................................................55
Table 4:
Dose Reductions for Low-Dose Dexamethasone Related Toxicities........................55
Table 5:
Low-Dose Dexamethasone Dose Reduction Steps ..................................................56
Table 6:
Risk for Torsades de Pointes and/or QT Prolongation...........................................102
Table 7:
Possible Risk for Torsades de Pointes and/or QT Prolongation .............................104
Table 8:
Conditional Risk for Torsades de Pointes and/or QT Prolongation........................106
Table 9:
Staging Systems for Multiple Myeloma ................................................................107
Table 10:
Eastern Cooperative Oncology Group Performance Status Grade .........................108
Table 11:
International Myeloma Working Group Response Criteria....................................109
Table 12:
List of Abbreviations    ........................................................................................113


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LIST OF FIGURES
Figure 1:
Overall Study Design..............................................................................................32
















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2.
STUDY OBJECTIVES
2.1.
Primary Objective
The primary objective of the study is to evaluate the safety of the combination of POM and LD-
DEX in a large cohort of subjects with refractory MM or relapsed and refractory MM.
2.2.
Secondary Objectives
The secondary objectives of the study are to

Analyze the population pharmacokinetics of POM and assess POM exposure 
response relationships in subjects with refractory MM or relapsed and refractory MM 
administered POM and LD-DEX.

Evaluate efficacy of the combination of POM and LD-DEX in subjects with 
refractory MM or relapsed and refractory MM.

Evaluate the relationship between cytogenetic profiles and the combination of POM 
and LD-DEX in terms of response and outcome.
 
 


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3.
STUDY ENDPOINTS
3.1.
Primary Endpoint
The primary study endpoint is the incidence of adverse events (type, frequency, seriousness, 
severity, relationship to POM and/or DEX and outcomes), including second primary 
malignancies (SPM).
3.2.
Secondary Endpoints
The secondary endpoints include:

POM exposure.

POM population pharmacokinetics and exposure-response.

Overall response rate (ORR).

Time to response.

Duration of response (DoR).

Progression-free survival (PFS).

Time to progression (TTP).

Overall survival (OS).

Analysis of cytogenetic profiles
 
 


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4.
OVERALL STUDY DESIGN
4.1.
Study Design
This is an international, multicenter, single-arm, open-label study of POM in combination with 
LD-DEX in subjects with refractory MM or relapsed and refractory MM conducted in Europe
and Israel. 
The study is anticipated to enroll approximately 720 subjects with refractory MM or relapsed and 
refractory MM. 
This study consists of the following consecutive phases: a Screening phase within 28 days prior 
to Cycle 1 Day 1, a Treatment phase and a Follow-up phase which starts following
discontinuation from study treatment, every 3 months for up to 5 years after last subject 
enrollment or longer if clinically indicated. 
Each subject will receive POM administered orally at the starting dose of 4 mg on Days 1-21 of a 
28-day cycle and LD-DEX administered orally at the starting dose of 40 mg/day (≤ 75 years old) 
or 20 mg/day (> 75 years old) on Days 1, 8, 15 and 22 of a 28-day cycle.  Dose modifications 
and interruptions are permitted throughout the study.
Subjects will continue study treatment until the documentation of confirmed PD, intolerable 
toxicity, death, withdrawal of participation in the study, withdrawal of consent, or are lost to 
follow-up, or as long as they benefit from therapy according to the opinion of responsible study 
Investigator and discussed with the Sponsor.
Adverse events (primary endpoint) will be recorded and graded according to the National Cancer 
Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) (Version 4.0, May 
2009).  Second primary malignancies will be monitored every 3 months for up to 5 years after 
last subject enrollment as events of interest throughout the course of the study.  An independent 
Data Monitoring Committee (DMC) will review safety data on an ongoing basis throughout the 
study.  
Tumor response, based on the Investigator’s assessment, will be evaluated according to the 
International Myeloma Working Group (IMWG) response criteria (Durie, 2006).
Population pharmacokinetics and exposure-response analyses will be performed at selected sites
on the PK data obtained from the PK blood samples. 
Analysis of biomarkers will also be explored in subjects at selected clinical sites, who consent to 
participate in the optional exploratory biomarker study. 
All subjects will be maintained on the POM pregnancy prevention program (Appendix D) for the 
duration of the study.
For all subjects who enroll into this study, study visits and serial measurements of safety and 
efficacy will be performed as outlined in Table 1, Table of Events.  The Overall Study Design is 
described in Figure 1.


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Figure 1:
Overall Study Design
Screening Phase                                         Treatment Phase                                                                              Follow Up Period
Day -28 to 0
                                        Treatment start
Treatment discontinuation
Screening 
Eligibility& 
ICD signature
Oral Pomalidomide 
on Days 1-21 of a 28-day cycle 
AND
Oral Low-Dose Dexamethasone 
on Days 1, 8, 15 and 22 of a 28-
day cycle
Follow-up visit 28 days 
after study drug 
discontinuation
Follow-up every 3 months 
(84 ± 14 days) for survival, 
subsequent anti-myeloma 
therapies, second primary 
malignancies until 5 years 
after last subject enrollment
or longer if clinically 
indicated
Subjects seen on 
Days 1 (± 1 day) and 
15 (± 2 days) of each 
cycle for the first 
6 cycles then on Day 1 
of each cycle until 
progressive disease or 
discontinuation of study 
drug for any reason




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4.3.
Study Duration 
This study will consist of the following consecutive phases: Screening, Treatment and Follow-
up.
Screening Phase (Day -28 to Day 0)
Potential study subjects will sign the ICD prior to undergoing any study-related procedure.  
Subjects may have the choice to participate in the optional biomarker study conducted at selected 
sites. If a subject chooses to participate in the exploratory biomarker study, he/she must give 
consent for the optional biomarker analysis.
Subjects will undergo screening for protocol eligibility within 28 days prior to Cycle 1 Day 1, as 
outlined in Table 1, Table of Events. 
Subjects must have discontinued anti-myeloma therapies at least 14 days prior to initiation of 
study treatment (wash-out period).  Hematopoietic growth factors, platelet and/or red blood cell 
(RBC) transfusions are allowed throughout the study, including the screening period, at the 
discretion of the investigator. It is recommended that myeloid and erythroid growth factors be 
utilized as per ESMO guidelines (Crawford, 2010). Primary prophylaxis for the prevention of
neutropenia is highly recommended in subjects who are at high risk based on age, medical 
history and disease characteristics.  If platelet transfusions are given during the screening period, 
the screening platelet assessment must be done a minimum of 3 days (72 hours) after the 
completion of the transfusion. Subjects who meet all eligibility criteria will receive the study 
treatment and will be maintained on the pregnancy prevention program for the duration of the 
study.
The inclusion procedure will be accomplished by a validated interactive voice/web response 
system (IVRS/IWRS).
Treatment Phase
Study treatment administration should start within 72 hours after enrollment of the subject in the 
study (which is defined as enrollment on the IVRS/IWRS), provided that the inclusion/exclusion 
criteria are still met.  Otherwise, the subject will need to be re-screened.  Each subject will
receive the following study treatment: 

POM administered orally at the starting  dose of 4 mg on Days 1-21 of a 28-day 
cycle, 

LD-DEX administered orally at the starting dose of 40 mg/day (≤ 75 years old) or 20 
mg/day (> 75 years old) on Days 1, 8, 15 and 22 of a 28-day cycle.
Subjects will be seen at Day 1 (± 1 day) and Day 15 (± 2 days) of each cycle for the first 6 cycles 
then at Day 1 (± 1 day) of each following cycles and may remain on the study until documented 
PD (according to IMWG criteria) or discontinuation of study drug for any reason or as long as 
they benefit from therapy according to the opinion of responsible study Investigator and 
discussed with the Medical Monitor. 
Sparse PK blood samples for POM quantification will be collected on Day 15 (± 2 days) of 
Cycle 1 through 6 at specified time-points during the course of the study from all subjects at 
selected sites with PK capability.  These PK samples are necessary to characterize the steady-


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state PK and exposure-response characteristics of POM when it is administered with LD-DEX in 
the refractory or relapsed and refractory population.
Bone marrow aspirate, bone marrow biopsy (if available) and blood samples will be collected for 
exploratory biomarker analysis from subjects at selected sites, who consent to participate in the 
optional biomarker study. The bone marrow aspirate and bone marrow biopsy (if available) will 
be collected during screening when the procedure is performed for study entry and at response 
assessment or at disease progression when clinically indicated.
Study visits and evaluations will be performed as outlined in Table 1 (“Table of Events”).
Follow-up Phase
All study subjects will enter the follow-up phase after study treatment discontinuation.  During 
the follow-up the following information will be collected from all subjects every 3 months for up 
to 5 years after last subject enrollment: SAEs including SPM, survival, subsequent anti-myeloma 
treatments (type of treatment, start and stop dates, best response whenever possible) and date of 
progression. 


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5.
TABLE OF EVENTS
Table 1:
Table of Events
Proceduresa
Screening
(Days -28 to 0)
Day 1 (± 1 day)
of Every Cycle
Day 15 (± 2 days) 
Cycles 1-6 Only
Treatment 
Discontinuation
Follow-up visit
(28 days post 
treatment 
discontinuation)
Long-term 
Follow-up Every 3 
Months (84 ± 14 
days) for Up to 5 
Years After Last 
Subject 
Enrollment
Entry Assessments
Informed Consent Document (ICD)
X
ICD for exploratory biomarker studies (at 
selected sites)
X
Inclusion/exclusion criteria
X
Demographics (age, gender)
X
Medical History 
X
Cytogenetic data from medical historyc
X
Prior anti-myeloma therapies, radiotherapy, 
surgeries
X
Disease Diagnosisd
X
Safety Assessments
Adverse event querye
After signing ICD and until 28 days after discontinuation from treatment
Second Primary Malignancyf
After signing ICD and up to 5 years after last subject enrollment or longer if clinically indicated
Physical Exam
X
X
X
Vital Signsg
X
X
X
X
Hematologyh
X
X
X
X
Serum Chemistryi
X
X
X
X
Urinalysisj
X
X
X


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Table 1:
Table of Events (Continued)
Proceduresa
Screening
(Days -28 to 0)
Day 1 (± 1 day)
of Every Cycle
Day 15 (± 2 days) 
Cycles 1-6 Only
Treatment 
Discontinuation
Follow-up visit
(28 days post 
treatment 
discontinuation)
Long-term 
Follow-up Every 3 
Months (84 ± 14 
days) for Up to 5 
Years After Last 
Subject 
Enrollment
Estimation of Renal Functionk
X
X
X
X
ECGl
X
X
 
Pregnancy testing for FCBPn
X
X
X
X
Pregnancy Counseling
X
X
X
Efficacy Measurements
ECOG Performance Status
X
X
X
Bone Marrow Aspiration and/or Biopsyo
X
Serum Beta-2 Microglobulin
X
Quantitative Serum Immunoglobulin Levelsp
X
X
X
Serum protein electrophoresis (SPEP) and 24-
hour Urine  electrophoresis (UPEP)q
X
X
X
Serum free light-chain (FLC) assayr
X
X
X
Extramedullary Plasmacytoma (EMP) 
Assessmentss
X
X
X
Skeletal Survey (by x-ray/CT)t
X
Assessment of Response u
X
X
Survival Status
X
Subsequent Anti-myeloma Regimensv
X
X


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Table 1:
Table of Events (Continued)
Proceduresa
Screening
(Days -28 to 0)
Day 1 (± 1 day)
of Every Cycle
Day 15 (± 2 days) 
Cycles 1-6 Only
Treatment 
Discontinuation
Follow-up visit
(28 days post 
treatment 
discontinuation)
Long-term 
Follow-up Every 3 
Months (84 ± 14 
days) for Up to 5 
Years After Last 
Subject 
Enrollment
Other Assessments
PK sampling (cycles 1 to 6 only)w
X
Cytogenetic analysisbb
X
X
 
 
Investigational Product Dispensation
Oral POM dispensation/ accountabilityx
X
X
Oral DEX dispensation/ accountabilityy
X
X
AE = adverse event; ANC = absolute neutrophil count; ALC = Absolute lymphocyte count; CR = complete response; Dex = dexamethasone; ECG = electrocardiogram; ECOG = 
Eastern Cooperative Oncology Group; FCBP = females of childbearing potential; LD = low-dose; PD = progressive disease; PK = pharmacokinetic; Pom = Pomalidomide; PR = 
partial response; RBC = red blood cell; SAE = serious adverse event; SPM = second primary malignancy; VTE = venous thrombotic events; WBC = white blood cell.
a Laboratory tests for hematology and biochemistries, vital signs and ECG are recommended and should be performed according to the current standard of care, unless specified in 
this protocol. If screening visit results are ≤ 7 days prior to enrollment, these laboratory assessments do not have to be repeated at Cycle 1 Day 1.
b Day 15 visit will be performed during Cycle 1 to Cycle 6 only. If medically justified, a 5-day window is allowed at Day 15 
c Results for any local cytogenetic testing, if available as part of medical history, will be collected in the eCRFs.
d Date of initial diagnosis and myeloma stage per the International Staging System and/or the Durie-Salmon Staging System (Appendix G) at initial diagnosis (if available) will be 
collected as part of the disease diagnosis assessment.
e All AEs should be assessed starting after the subject signs the informed consent until 28 days after treatment discontinuation. AEs that lead to study discontinuation should be 
followed until resolution or stabilization. SAEs, regardless of relationship to the investigational product (POM or DEX), that occur from the time the subject signs informed 
consent to at least 28 days after treatment discontinuation and those made known to the investigator at anytime thereafter that are suspected of being related to investigational 
product must be reported to Celgene Drug Safety within 24 hours of the investigator’s knowledge of the event.   
f Second primary malignancies (SPM) will be monitored as events of interest and must be reported as SAEs. This includes any SPM, regardless of causal relationship to IP (POM 
or LD-DEX), occurring at any time from the time of signing the ICD up to and including the long-term follow-up period. Events of SPM are to be reported using the SAE report 
form and must be considered an “Important Medical Event” even if no other serious criteria apply; these events must also be documented in the appropriate page(s) of the eCRF 
and subject’s source documents. Documentation on the diagnosis of the SPM must be provided at the time of reporting as a SAE (e.g., any confirmatory pathology, histology or 
cytology results, cytogenetics, flow cytometry, X-rays, CT scans, etc.). For all subjects who develop SPMs, all corresponding diagnostic reports (e.g., pathology, cytogenetics, 
flow cytometry) from the MM diagnosis confirmation performed at screening and from the diagnostic tumor samples obtained at SPM determination, will be required for SPM 


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confirmation. Tissue from bone marrow aspirates performed on study and tissue from the diagnostic sample obtained at SPM determination will be collected. If the SPM 
determination is made at an institution besides the study institution, every effort will be made to collect these samples and reports.
g Vital signs include blood pressure, temperature, respiratory rate and heart rate. The measurement of height will be performed at screening only. The measurement of weight will 
be performed at screening, at Day 1 of each cycle, and at the treatment discontinuation. 
h Assessment of hematology includes: white blood cell count with differential, ANC, ALC, hemoglobin, hematocrit, platelet count, mean corpuscular volume and reticulocyte 
count. This assessment will be performed by the local laboratory. Reticulocyte count will be not performed on Day 15 of every cycle.
i Assessment of serum chemistry includes: total protein, albumin, calcium, corrected serum calcium, glucose, total bilirubin, direct bilirubin (only when total bilirubin is 
increased), alkaline phosphatase, AST/SGOT, ALT/SGPT, GGT, sodium, potassium, creatinine, lactate dehydrogenase, creatinine kinase, and C-reactive protein.  If PD is noted 
based on corrected serum calcium level, a repeat serum chemistry test should be performed as soon as possible to confirm PD. This assessment will be performed by the local 
laboratory. On Day 15 of every cycle serum biochemistry includes only: total bilirubin, alkaline phosphatase, AST/SGOT, ALT/SGPT, GGT, sodium, potassium, creatinine, 
lactate dehydrogenase.
j Assessment of urinalysis includes: specific gravity, pH, glucose, bilirubin, protein, ketones, and blood. Microscopic analysis [casts, bacteria, RBCs, and WBCs] should be 
performed if clinically indicated. This assessment will be performed by the local laboratory.  
k The assessment will be performed using the Cockcroft-Gault formula for estimation of creatinine clearance (CrCl). CrCl also needs to be determined based on a 24 hour urine 
collection at screening visit. A 24-hour urine sample obtained as a standard of care assessment prior to informed consent can be utilized for this study if it was performed < 7 
days prior to the Screening Visit and meets the protocol requirements for collection and analysis.
l ECGs will be performed at Screening visit and at study discontinuation, and the time as clinically indicated at the discretion of the treating physician during the study. All ECGs 
will be performed and reviewed locally.  
n FCBP must have two negative pregnancy tests (sensitivity of at least 25 mIU/mL) prior to starting study drug. The first pregnancy test must be performed within 10-14 days prior 
to the start of study drug and the second pregnancy test must be performed within 24 hours prior to the start of study drug. The subject may not receive study drug until the study 
doctor has verified that the results of these pregnancy tests are negative. FCBP with regular or no menstrual cycles must agree to have pregnancy tests every 7 days (weekly) for 
the first 28 days of study participation and then every 28 days while on study, at treatment discontinuation, and 28 days following treatment discontinuation. If menstrual cycles 
are irregular, the pregnancy testing must occur weekly for the first 28 days and then every 14 days while on study, at treatment discontinuation, and at days 14 and 28 following 
treatment discontinuation.    
o A bone marrow aspirate (and biopsy if necessary) is mandatory and must be obtained within 28 days prior to enrollment to obtain a current estimate of the % plasma cells in the 
marrow. Analysis for % plasma cells in the marrow will be performed locally. After screening, a bone marrow aspirate (or biopsy if necessary) must be performed to document a 
response ≥ CR, and may otherwise be repeated as clinically indicated at the discretion of the treating physician. In subjects, who consent to participate in the exploratory 
biomarker analysis, bone marrow aspirate, and bone marrow biopsy (if available) material will be collected while the subject is undergoing the procedure mandatory for study 
entry. Bone marrow aspirate and bone marrow biopsy (if available) material will also be collected when those subjects participating in the biomarker analysis undergo additional 
bone marrow procedures while on study when clinically indicated.
p This assessment will be performed by the local laboratory. Quantitative immunoglobin assessment (IgG, IgA, IgM, IgE and IgD) should also be performed at the time of 
response confirmation (≥ CR). All subjects will be evaluated for IgG, IgA and IgM. Testing for IgE and IgD is only required for subjects with the respective (IgE or IgD) 
subtype.
q A 24-hour urine sample obtained as a standard of care assessment prior to informed consent can be utilized for this study if it was performed < 7 days prior to the Screening Visit 
and meets the protocol requirements for collection and analysis. This assessment will be performed by the local laboratory. If a response (≥ PR) or PD is noted based on SPEP 
and/or UPEP results, a repeat test should also be conducted as soon as possible to confirm the response or PD. Also, serum and urine immunofixation (IFE) tests are performed at 
screening to identify the immunoglobulin subtype of MM and thereafter are required to be performed whenever M-protein is undetectable in both serum and urine by protein 
electrophoresis studies. Serum and urine IFE tests should also be performed at the time of response confirmation (≥CR).
r This assessment will be performed by the local laboratory. Serum FLC assay should also be performed at the time of response confirmation (≥ CR).  
s Assessment/measurement at specified time-points only required if EMPs are present. If EMPs are clinically assessable, clinical assessment will be performed at screening, at 
every Cycle Day 1, and at treatment discontinuation. If EMPs are only assessable radiographically (x-ray and/or conventional [spiral] CT/MRI scan), scans are required at 
screening, at Cycle 3 Day 1, every 3 cycles thereafter (Cycle 6 Day 1, Cycle 9 Day 1, etc.) during treatment, at treatment discontinuation, and when clinically indicated to 
confirm response (≥ PR).  All scans will be reviewed locally only.


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t A skeletal survey by x-ray or if clinically indicated, a CT-scan will be performed at screening and when clinically indicated per the investigator’s discretion.  If a skeletal survey 
was performed within 60 days prior to the start of Cycle 1, it may be used for the screening assessment if approved by Sponsor. All skeletal survey films or CT scans will be 
performed and analyzed locally by the site investigator/radiologist. Refer to Appendix C for detailed requirements.
 
v Subsequent anti-myeloma regimens: type of treatment, start and stop dates, date of progression and best response whenever possible. 
w PK samples: Cycles 1, 2 and 3. Day 15: pre-dose and Cycles 4,5 and 6 Day 15: one sample per visit.
It is encouraged that the PK sample at each of these 3 visits at Cycles 4, 5 and 6 be at a different time post administration of POM.
x Subject will take oral dose of POM on Days 1 to 21 of each 28-day cycle.  
y Subject will take oral LD-DEX on Days 1, 8, 15, and 22 of each 28-day cycle.
 
 
bb Cytogenetic analysis will be performed using FISH (at local laboratory) at study entry using the bone marrow aspirate that needs to be performed to estimate the % of the plasma 
cells. In addition, cytogenetic analysis will be performed for those subjects who discontinue treatment due to disease progression. If study treatment is discontinued due to 
toxicity, then cytogenetic analysis should be postponed until disease progression. If possible subsequent relapse should also be documented by FISH. The same technique and the 
same approach should be used for a subject thoughout the study.


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6.
PROCEDURES
Study Entry
Prior to screening, subjects must sign an ICD for the main study and have the choice of also 
signing the ICD for the exploratory biomarker study (at selected sites only).  All screening 
assessments must be completed within 28 days prior to start of Cycle 1, with the exception of the 
skeletal survey, which may be performed within 60 days prior to initiation of study treatment.  
Subjects may have the choice to participate in the optional biomarker study conducted at selected 
sites. If a subject chooses to participate in the exploratory biomarker study, he/she must give 
consent for the optional biomarker analysis. Confirmation of diagnosis (including date of 
confirmed initial diagnosis and, if available, myeloma stage at time of initial diagnosis per the 
Salmon-Durie Criteria and/or the International Staging System [Appendix G]) medical, prior
cancer and surgical history, and review of concomitant medications should be documented 
during the screening period.  All prior radiotherapy, surgeries, and anti-myeloma therapies must 
be recorded in the electronic case report form (eCRF), including approximate dates for each 
therapy and the date of progression for each regimen.  Results for any local cytogenetic testing 
(preferably fluorescence in situ hybridization - FISH - results), as part of medical history, will be 
collected in the eCRF.  For all eligible subjects, cytogenetic analysis is also required upon study 
entry based on the bone aspirate sample taken during screening. See Table 1 “Table of Events” 
for all the required assessments during screening.
If the subject’s safety and efficacy laboratory assessments performed at screening are within 
7 days of enrollment into the study, they do not need to be repeated at Cycle 1 Day 1 and can be 
used as baseline results.  The start of study drug dosing is designated as Cycle 1 Day 1.  A 
14-day wash-out period is required for any prior anti-myeloma therapy before study treatment is 
initiated.  Assessments should be performed on Day 1 (± 1 day) and on Day 15 (± 2 days) of 
every cycle for the first 6 cycles then on Day 1 (± 1 day) for the following cycles during the 
treatment and at treatment discontinuation.  In exceptional cases and if medically justified, a 5-
day window at Day 15 of every cycle will be acceptable (for Cycles 1 to 6). Long term follow-up 
will be performed every 84 days (± 14 days).
Safety Assessments
Adverse Events 
All AEs should be assessed starting after the subject signs the ICD until 28 days after treatment 
discontinuation.  Adverse events that lead to study discontinuation should be followed until 
resolution or stabilization. 
Serious Adverse Events 
Serious adverse events, regardless of relationship to the IP (POM or DEX), that occur from the 
time the subject signs the ICD to at least 28 days after treatment discontinuation and those made 
known to the investigator at anytime thereafter that are suspected of being related to the IP (POM 
or DEX) must be reported to Celgene Drug Safety within 24 hours of the investigator’s 
knowledge of the event.    


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Second Primary Malignancies 
Second primary malignancies will be monitored every 3 months for up to 5 years after the last 
subject is enrolled as events of interest and must be reported as SAEs. This includes any SPM, 
regardless of causal relationship to the IP (POM with or without DEX), occurring at any time 
from the time of signing the ICD up to and including the long-term follow-up period.  Events of 
SPM are to be reported using the SAE report form and must be considered an “Important 
Medical Event” even if no other serious criteria apply; these events must also be documented in 
the appropriate page(s) of the eCRF and subject’s source documents.  Documentation on the 
diagnosis of the SPM must be provided at the time of reporting as a SAE (e.g., any confirmatory 
pathology, histology or cytology results, cytogenetics, flow cytometry, X-rays, CT scans, etc.).  
For all subjects who develop SPMs, all corresponding diagnostic reports (e.g., pathology, 
cytogenetics, flow cytometry) from the MM diagnosis confirmation performed at screening and 
from the diagnostic tumor samples obtained at SPM determination, will be required for SPM 
confirmation. 
For SPMs diagnosed at another institution, (outside of the investigational site) sites will be 
required to make every effort to obtain these reports for SPM confirmation.
 
 
 
 
 
 
 
Complete Physical Exam and Measurement of Vital Signs, Height, and Weight
A complete physical exam will be performed at screening, at Day 1 of every cycle starting at 
Cycle 1, and at treatment discontinuation.  Any on study abnormal and clinically significant 
findings are to be reported as adverse events.
Measurement of vital signs (blood pressure, temperature, heart rate and respiration rate) will be 
performed at screening, at Day 1 of each Cycle, at treatment discontinuation, and at the 28 days 
post treatment discontinuation visit.
Measurement of height will be performed at screening only.  Measurement of weight will be 
performed at screening, at Day 1 of each Cycle, and at treatment discontinuation.  
Electrocardiogram
Electrocardiogram (ECG, 12-lead) monitoring will be performed at Screening visit, 
discontinuation visit and as clinically indicated at the discretion of the treating physician during 
the study.  All ECGs will be performed and reviewed locally.  


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Laboratory Assessments for Safety Parameters 
All laboratory assessments for safety parameters will be performed locally.  
If screening visit results are ≤ 7 days prior to enrollment, these laboratory assessments are not 
required to be repeated at Cycle 1 Day 1.  

Hematology Laboratory Tests. Hematology includes: white blood cell (WBC) 
count with differential, absolute neutrophil count (ANC), absolute lymphocyte count 
(ALC), hemoglobin, hematocrit, platelet count, mean corpuscular volume and 
reticulocyte count.  Hematology will be performed at screening, on Day 1 (± 1 day) 
and Day 15 (± 2 days) of every cycle for the first 6 cycles then on Day 1 (± 1 day) for 
the following cycles, and at treatment discontinuation.  Reticulocyte count will be not 
performed on Day 15 of each cycle. 

Serum Chemistry Laboratory Tests. Serum chemistry includes: total protein, 
albumin, calcium, corrected serum calcium, glucose, total bilirubin, direct bilirubin 
(only when total bilirubin is increased), alkaline phosphatase, aspartate 
aminotransferase (AST/SGOT), alanine aminotransferase (ALT/SGPT), gamma-
glutamyl tranpeptidase (GGT), sodium, potassium, creatinine, lactate dehydrogenase, 
creatinine kinase, and C-reactive protein.  Serum chemistry labs will be performed at 
screening, on Day 1 (± 1 day) of every cycle, and at treatment discontinuation.  If PD 
is noted based on corrected serum calcium level, a repeat serum chemistry test should 
be performed as soon as possible to confirm PD.  Serum biochemistry will also be 
performed on Day 15 (± 2 days) of every cycle during the first 6 cycles and includes 
only: total bilirubin, alkaline phosphatase, AST/SGOT, ALT/SGPT, GGT, sodium, 
potassium, creatinine, lactate dehydrogenase.

Urinalysis. Urinalysis includes: specific gravity, pH, glucose, bilirubin, protein, 
ketones, and blood.  Microscopic analysis (casts, bacteria, RBCs, and WBCs) should 
be performed if clinically indicated.  Urinalysis will be performed at screening, on
Day 1 (± 2 days) of every cycle, and at treatment discontinuation. 

Estimation of Renal Function. The assessment will be performed using the 
Cockcroft-Gault estimation of CrCl.
Cockcroft-Gault Formula (Cockcroft, 1976; Luke, 1990)
CrCl (mL/min) = (140 – age) (weight [kg]) / 72 (serum creatinine [mg/dL]); for 
females, the formula is multiplied by 0.85.
CrCl also needs to be determined based on a 24-hour urine collection at screening 
visit. Estimation of renal function will be performed at screening, on Day 1 (± 1 day) 
and Day 15 (± 2 days) of every cycle for the first 6 cycles then on Day 1 (± 1 day) for 
the following cycles, and at treatment discontinuation. A 24-hour urine sample 
obtained as a standard of care assessment prior to informed consent can be utilized for 
this study if it was performed < 7 days prior to the Screening Visit and meets the 
protocol requirements for collection and analysis.


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If a major discrepancy is observed between Cockcroft-Gault estimation and urine 
measurement, the further management of the subject will be discussed with the 
Sponsor. 
Pregnancy Counseling (Males and Females)
Counseling about pregnancy precautions and the potential risks of fetal exposure must be 
conducted for all subjects at screening, Day 1 of every cycle during treatment and at treatment 
discontinuation visit for all subjects.  Please refer to Pomalidomide Pregnancy Risk 
Minimization Plan in Section 11.4 and Appendix D.
Pregnancy Testing for Females of Child Bearing Potential (FCBP) 
All FCBP must have two medically supervised negative serum or urine pregnancy tests
(sensitivity of at least 25 mIU/mL) prior to starting the study.  The first pregnancy test must be 
performed within 10-14 days prior to the start of study treatment and the second pregnancy test 
must be performed within 24 hours prior to the start of study treatment.  The subject may not 
receive study drug until the study doctor has verified that the results of these pregnancy tests are 
negative.  Females of Child Bearing Potential with regular or no menstrual cycles must agree to 
have pregnancy tests every 7 days (weekly) for the first 28 days of study participation and then 
every 28 days while on study, at treatment discontinuation, and 28 days following treatment 
discontinuation.  If menstrual cycles are irregular, the pregnancy testing must occur weekly for 
the first 28 days and then every 14 days while on study, at treatment discontinuation, and at Days 
14 and 28 following treatment discontinuation).
Efficacy Assessments 
Disease progression status will be assessed by the investigator at each treatment cycle and at 
treatment discontinuation.  Tumor response including progressive disease will be assessed 
according to the IMWG uniform response criteria (Durie, 2006).  All treatment decisions will be 
made by the treating physician based on response as assessed using the IMWG criteria.
Survival status will be collected for all subjects during the treatment phase and the long-term 
follow-up phase.
All efficacy assessments will be performed and reviewed locally.  These efficacy assessments 
include labs used as part of standard care: Eastern Cooperative Oncology Group (ECOG) 
performance status, serum beta-2 microglobulin, myeloma paraprotein protein electrophoresis 
and immunofixation, serum immunoglobulins, serum free light chain assay, and if applicable, 
clinical and/or radiological extramedullary plasmacytoma assessment, skeletal survey, and bone 
marrow aspirate/biopsy.
If a new cycle is delayed greater than seven days (> 7 days, but less than 28 days) from the 
protocol-defined 28-day dosing cycle, an unscheduled visit should be performed for efficacy 
assessments prior to initiation of the next cycle.  If the delay is greater than 28 days, these 
efficacy assessments should be performed every 28 days (± 3 days) until a new cycle can begin.  
For subsequent cycles following a delayed cycle, efficacy assessments should be performed at 
the start of each new cycle.  
The efficacy assessment will be documented in the source documents and recorded on the eCRF.
ECOG Performance Status 


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ECOG Performance Status will be performed at screening, at Day 1 of every Cycle, and at 
treatment discontinuation.  See Appendix H for the ECOG Performance Status Scale.
Laboratory Assessments for Efficacy Parameters  
All laboratory assessments for efficacy parameters will be performed locally.  
If screening visit results are ≤ 7 days prior to enrollment, these laboratory assessments are not 
required to be repeated at Cycle 1 Day 1.  

Serum beta-2 microglobulin: The serum beta-2 microglobulin sample will be 
collected at screening only.

Myeloma Paraprotein (M-Proteins) Protein Electrophoresis.  Serum protein 
electrophoresis (quantified from the serum protein electrophoresis SPEPtest) and 
urine protein electrophoresis (quantified from the urine protein electrophoresis 
UPEPtest performed on 24-hour urine collection or any other validated method, 
will be performed at screening, at every cycle on Day 1 and at treatment 
discontinuation.  A 24-hour urine sample obtained as a standard of care assessment 
prior to informed consent can be utilized for this study if it was performed < 7 days 
prior to the Screening Visit and meets the protocol requirements for collection and 
analysis.  If a response or PD is noted based on SPEP and/or UPEP results, SPEP and 
UPEP tests should be repeated as soon as possible to confirm the response (≥ PR) or 
PD.  

Myeloma Paraprotein (M-Proteins) Immunofixation.  Serum and urine 
immunofixation (IFE) tests are performed at screening to identify the 
immunoglobulin subtype of MM and thereafter are required to be performed 
whenever M-protein is undetectable in both serum and urine by protein 
electrophoresis studies.  Serum and urine IFE tests should also be performed at the 
time of response confirmation for ≥ CR.

Serum Immunoglobulins assessment will be performed at screening and at every 
cycle on Day 1, at treatment discontinuation, and at the time of response confirmation 
for ≥ CR. All subjects will be evaluated for IgG, IgA and IgM. Testing for IgE and 
IgD is only required for subjects with the respective (IgE or IgD) subtype.

Serum Free Light Chain assay will be performed at screening, at every cycle on 
Day 1, at treatment discontinuation, and at the time of response confirmation for ≥ 
CR.  
Bone Marrow Aspiration and/or Biopsy 
A bone marrow aspirate (and biopsy if necessary) is mandatory and must be obtained within 
28 days prior to enrollment to obtain a current estimate of the % plasma cells in the marrow.  
After screening, a bone marrow aspirate (or biopsy if necessary) must be performed to document 
a ≥CR, and may otherwise be repeated as clinically indicated at the discretion of the treating 
physician. Analysis of bone marrow will be performed locally.
Subjects who signed the additional consent may undergo optional biomarker assessments at a 
selected number of sites. For those subjects who consent to participate in the optional biomarker 
analysis, bone marrow aspirate and bone marrow biopsy (if available) material will be collected 


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during the mandatory bone marrow assessment at screening and during other bone marrow 
assessments that are clinically indicated. No additional intervention will be required at screening, 
only additional volume of aspirate will be withdrawn, or excess material from the biopsy will be 
utilized for the biomarker study.  
Extramedullary Plasmacytoma Assessments 
Extramedullary plasmacytoma assessments/measurements at specified time-points are only 
required if EMPs are present.  
If EMPs are clinically assessable, clinical assessment will be performed at screening, at every 
Cycle Day 1, and at treatment discontinuation. 
If EMPs are only assessable radiographically (x-ray and/or conventional [spiral] CT/MRI scan), 
scans are required at screening, at Cycle 3 Day 1, every 3 cycles thereafter (Cycle 6 Day 1, 
Cycle 9 Day 1, etc.) during treatment, at treatment discontinuation, and when clinically indicated 
to confirm a response ≥ PR.  All scans will be reviewed locally only.
Skeletal Survey 
A skeletal survey by x-ray or if clinically indicated, a CT scan will be performed at screening 
and when clinically indicated per the investigator’s discretion.  If a skeletal survey was 
performed within 60 days prior to the start of Cycle 1, it may be used for the screening 
assessment if approved by the Sponsor.  All skeletal survey films or scans will be performed and 
analyzed locally by the site investigator/radiologist.  Refer to Appendix C for detailed 
requirements.  
Assessment of Response 
Response, including PD, will be assessed using the IMWG criteria (Appendix I) at Day 1of each 
Cycle and at the treatment discontinuation visit. 
Overall Survival and Subsequent Anti-MM Therapies 
During the follow-up period, survival status and subsequent therapies for MM must be collected 
and entered into the eCRF.  All subjects will be assessed 4 times a year (every 3 months) to 
determine survival status for up to 5 years after last subject enrollment.  Primary cause of death 
(medical condition) is to be recorded in the eCRF and the subject’s medical record. All 
subsequent therapies given for MM must be collected and entered into the eCRF.  
Other Assessments 
Cytogenetic analysis
Previous results from cytogenetic analyses performed on subjects at their time of diagnosis are 
required to be recorded in the eCRF. The bone marrow aspirate taken during screening for 
disease staging and characterization will also be used to undertake the cytogenetic analysis at 
study entry for all eligible subjects. In addition, a further bone marrow aspirate is required for 
cytogenetic analysis for those subjects who discontinue study treatment due to disease 
progression. The sites should apply standard, consistent FISH methodology for these analyses, 
with all samples analyzed at their local laboratory.
Pharmacokinetic Study 


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Pharmacokinetic samples for POM quantification will be collected from all subjects at selected 
sites with PK capability from Cycle 1 to Cycle 6 inclusive.  Dosing information and sample 
collection information including dose (mg), dosing date, dosing time (24 hour clock), and actual 
PK sampling time (24 hour clock) should be accurately documented on the appropriate source 
documentation and eCRF pages.
Detailed instructions for sample collection, processing, storage, shipping and handling can be 
found in Appendix J.
Pharmacokinetic blood samples will be collected from subjects at the following time-points: 

Cycles 1, 2, and 3 Day 15: pre-dose 

Cycles 4, 5 and 6 Day 15: one sample per visit. It is encouraged that the PK sample 
at each of these 3 visits be at a different time post administration of POM.
Subjects should take POM at approximately the same time in the morning during Cycles 1, 2, 
and 3.  On Day 15 (± 2 days) of Cycles 1, 2, and 3, POM will be administered to subjects in the 
morning at the study site after the collection of the pre-dose PK blood sample.  Dexamethasone 
should be administered after completion of the PK sample collection.  Starting with Cycle 4, 
subjects may take POM at any time during the day, but are encouraged to take POM at a similar 
time every day.  On Day 15 (± 2 days) of Cycles 4, 5 and 6, subjects will be asked to report the 
actual dosing time of their last dose of POM (i.e. if visit is on Day 15, last dose could be either 
their Day 14 or Day 15 dose) to the study staff during their visit at the study site. A PK blood 
sample will be collected during their visit. 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 


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7.
STUDY POPULATION
7.1.
Number of Subjects and Sites
This is a multicenter, single-arm, open label, phase IIIb study of POM and LD-DEX in adult 
subjects with refractory MM or relapsed and refractory MM. 
This study is anticipated to enroll approximately 720 subjects with refractory MM or relapsed 
and refractory MM in European countries and Israel.
7.2.
Inclusion Criteria
Subjects must satisfy the following criteria to be enrolled in the study:
1. Must be ≥ 18 years at the time of signing the informed consent document (ICD).
2. The subject must understand and voluntarily sign an ICD prior to any study related 
assessments/procedures being conducted. 
3. Must be able to adhere to the study visit schedule and other protocol requirements. 
4. Subjects must have documented diagnosis of multiple myeloma and have measurable 
disease (serum M-protein ≥ 0.5 g/dL or urine M-protein ≥ 200 mg/24 hours). 
5. Subjects must have undergone prior treatment with ≥ 2 treatment lines of anti-myeloma 
therapy.  Induction therapy followed by ASCT and consolidation/maintenance will be 
considered as one line.  A new treatment line is always started after progressive disease.
6. Subjects must have either refractory or relapsed and refractory disease defined as 
documented disease progression during or within 60 days of completing their last 
myeloma therapy. 
Primary Refractory: Subjects who have never achieved any response better than PD to 
any previous line of anti-myeloma therapy.
Relapsed and Refractory: Subjects who have relapsed after having achieved at least 
stable disease for at least two cycles of treatment to at least one prior regimen and then 
developed PD on or within 60 days of completing their last myeloma therapy.
7. All subjects must have received at least 2 consecutive cycles of prior treatment that 
included lenalidomide and bortezomib, either alone or in combination regimens.
All subjects must have failed both lenalidomide and bortezomib and medical records 
must be available that provide documentation of the following criteria for refractoriness 
that make the subject eligible for the study.

All subjects must have failed treatment with the last lenalidomide-containing regimen 
in one of the following ways: 

Documented PD during or within 60 days of completing last treatment with 
lenalidomide, regardless of the response achieved, or


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
In case of prior response (≥ partial response - PR) to lenalidomide and PD > 60 
days, subjects must have relapsed within 6 months after the last dose of treatment 
with lenalidomide-containing regimens.

All subjects must have failed treatment with the last bortezomib-containing regimen 
in one of the following ways:

Documented PD during or within 60 days of completing treatment with 
bortezomib, regardless of the response achieved, or

In case of prior response (≥ PR) to bortezomib and PD > 60 days, subjects must 
have relapsed within 6 months after the last dose of treatment with bortezomib-
containing regimens,
Or for non-progressive subjects:

Subjects who have less than MR response and have developed intolerance/toxicity 
after a minimum of two cycles of a bortezomib-containing regimen. Toxicity such 
as > grade 2 peripheral neuropathy or ≥grade 2 painful neuropathy. Peripheral 
neuropathy must resolve to grade 1 prior to study entry. 
8. Subjects must have received adequate prior alkylator therapy in one of the following 
ways:

As part of a stem cell transplant; or

A minimum of 4 consecutive cycles of an alkylator based therapy; or

Progression on treatment with an alkylator; provided that the subject received at least 
2 cycles of an alkylator-containing therapy.
9. ECOG performance status score of 0, 1, or 2.
10. Females of childbearing potential (FCBP2) must agree to utilize two reliable forms of 
contraception simultaneously or practice complete abstinence from heterosexual contact 
for at least 28 days before starting study drug, while participating in the study (including 
dose interruptions), and for at least 28 days after study treatment discontinuation and 
must agree to regular pregnancy testing during this timeframe. (NOTE: True abstinence: 
When this is in line with the preferred and usual lifestyle of the subject. [Periodic abstinence 
(e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not 
acceptable methods of contraception]).
11. Females must agree to abstain from breastfeeding during study participation and 28 days 
after study drug discontinuation.
12. Males must agree to use a latex condom during any sexual contact with FCBP while 
participating in the study and for 28 days following discontinuation from this study, even 
if he has undergone a successful vasectomy.
                                               
2 A female of childbearing potential is a sexually mature woman 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., who 
has had menses at any time in the preceding 24 consecutive months).


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13. Males must also agree to refrain from donating semen or sperm while on POM and for 
28 days after discontinuation from this study treatment.
14. All subjects must agree to refrain from donating blood while on study therapy and for 
28 days after discontinuation from this study treatment.
15. All subjects must agree not to share medication.
7.3.
Exclusion Criteria
The presence of any of the following will exclude a subject from study enrollment:
1. Any of the following laboratory abnormalities:

Absolute neutrophil count < 800/μL.

Platelet count < 75,000/µL for subjects in whom < 50% of bone marrow nucleated 
cells are plasma cells; or a platelet count < 30,000/µL for subjects in whom ≥ 50% of 
bone marrow nucleated cells are plasma cells. Platelet transfusion is not allowed 
within the previous 3 days before screening.

Creatinine Clearance < 45 mL/min according to Cockcroft-Gault formula.  If 
creatinine clearance calculated from the 24-hour urine sample is ≥45 mL/min, 
subject will qualify for the study.

Corrected serum calcium > 14 mg/dL (> 3.5 mmol/L).

Hemoglobin < 8 g/dL (< 4.9 mmol/L; prior RBC transfusion or recombinant human 
erythropoietin use is permitted).

Serum SGOT/AST or SGPT/ALT > 3.0 x upper limit of normal (ULN).

Serum total bilirubin > 2.0 mg/dL (34.2 μmol/L); or > 3.0 x ULN for subjects with 
hereditary benign hyperbilirubinemia.
2. Prior history of malignancies, other than MM, unless the subject has been free of the 
disease for ≥5 years.  Exceptions include the following:

Basal or squamous cell carcinoma of the skin

Carcinoma in situ of the cervix or breast

Incidental histological finding of prostate cancer (TNM stage of T1a or T1b).
3. Previous therapy with POM.
4. Hypersensitivity to thalidomide, lenalidomide, or DEX (this includes ≥ Grade 3 rash 
during prior thalidomide or lenalidomide therapy).
5. Peripheral neuropathy ≥ Grade 2.
6. Subjects who received an allogeneic bone marrow or allogeneic peripheral blood stem 
cell transplant less than 12 months prior to initiation of study treatment and who have not 
discontinued immunosuppressive treatment for at least 4 weeks prior to initiation of study 
treatment and are currently dependent on such treatment.
7. Subjects who are planning for or who are eligible for stem cell transplant.


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8. Subjects with any one of the following:

Congestive heart failure (NY Heart Association Class III or IV)

Myocardial infarction within 12 months prior to starting study treatment

Unstable or poorly controlled angina pectoris, including Prinzmetal variant angina 
pectoris.
9. Subjects who received any of the following within the last 14 days of initiation of study 
treatment:

Major surgery (kyphoplasty is not considered major surgery)

Use of any anti-myeloma drug therapy.
10. Use of any investigational agents within 28 days or five half-lives (whichever is longer) 
of treatment, unless approved by the Sponsor.
11. Incidence of gastrointestinal disease that may significantly alter the absorption of POM.
12. Subjects unable or unwilling to undergo antithrombotic prophylactic treatment.
13. Any serious medical condition, laboratory abnormality, or psychiatric illness that would 
prevent the subjects from signing the ICD or participating in the study.
14. Pregnant or breastfeeding females.
15. Known human immunodeficiency virus (HIV) positivity, active infectious hepatitis A, B 
or C or chronic hepatitis B or C.


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8.
DESCRIPTION OF STUDY TREATMENTS
8.1.
Description of Investigational Product(s)
Pomalidomide will be supplied as Investigational Product by Celgene Corporation as 1 mg, 2 
mg, 3 mg, and 4 mg capsules for oral administration.  Investigational product will be packaged in 
bottles containing a 21 day supply of POM.
Celgene will provide commercial supplies of DEX 2 mg and 4 mg tablets for oral administration, 
labeled appropriately for investigational use as per the regulations of the relevant country health 
authority.
Other recommended/required concomitant medications per the protocol such as aspirin (or other 
antithrombotic or anti-coagulants) and growth factors are commercially available, and will be 
provided at the site by investigator(s) prescription.  Celgene will not provide these medications.
8.2.
Treatment Administration and Schedule
All study drug doses will be administered orally and subjects will be instructed about the dosing 
schedules for the study.  Subjects enrolled in this study will receive:

Oral POM at the starting dose of 4 mg on Days 1-21 of a 28-day cycle, 

Oral LD-DEX at the starting dose of 40 mg/day (≤ 75 years old) or 20 mg/day (> 75 
years old) on Days 1, 8, 15 and 22 of a 28-day cycle. 
Subjects will also be instructed to return the study drug bottles (and any remaining study drug) at 
the next visit for drug accountability purposes.  For FCBP, study drug may not be dispensed until 
the investigator has verified that the results of the pregnancy test are negative.  Females of 
childbearing potential other than the subject should not handle study drug unless wearing gloves.
All subjects enrolled into the study will continue study treatment until progressive disease or 
unacceptable toxicity.
Dose Modification and Interruption
In the event of any dose reduction for POM, site staff must contact IVRS to record the new dose 
level and obtain the new study treatment assignment.  
If the treatment has been interrupted and the next cycle is delayed beyond 28 days after Day 1 of 
the prior cycle, then Day 1 of the next cycle will be defined as the first day that treatment is 
resumed.
Subjects will be evaluated for AEs at each visit with the NCI-CTCAE (version 4.0) as a guide for 
the grading of severity.  Dosing interruptions and reductions are permitted throughout the study.
Dose Modification Instructions for Pomalidomide
Detailed instructions for POM dose interruptions and reductions are provided in Table 2 and 
Table 3 outlines the dose reduction steps for POM.  
If POM administration is withheld, LD-DEX should also be withheld.  If POM is discontinued 
permanently, then the subject must be permanently discontinued from all study treatments.  


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Table 2:
Dose Modification Instructions for Pomalidomide
Toxicity
Dose Modification
Neutropenia
Grade 4 neutropenia (ANC < 500/μL) or
Febrile neutropenia (ANC < 1,000/μL 
with a single temperature of > 38.3 °C or 
a sustained temperature of ≥ 38 °C for 
more than one hour)
Hold the dose for remainder of cycle.  If the subject was not receiving 
GCSF therapy, GCSF therapy may be started at the discretion of the 
treating physician.  On Day 1 of the next cycle, the dose of POM may 
be maintained if neutropenia was the only POM-related toxicity 
requiring a dose modification and GCSF treatments are continued.  
Otherwise, decrease by one dose level at start of next cycle.
Note, ANC must be ≥ 800/ μL to re-start dosing
Thrombocytopenia
Grade 4 Thrombocytopenia (Platelets 
<25,000/μL)
Hold the dose for remainder of cycle.  Dosing may resume at one dose 
level lower once the platelet count has recovered to ≥ 30,000/μL.
Rash = Grade 3
Hold dose for remainder of cycle.  Decrease by one dose level when 
dosing restarted at next cycle (rash must resolve to ≤ Grade 1 before 
restarting dosing).
Rash = Grade 4 or Blistering
Discontinue subject from POM treatment regimen.
Constipation ≥ Grade 3
Hold dose for remainder of cycle.  Initiate bowel regimen.  Decrease 
by one dose level when dosing restarted at next cycle (constipation 
must resolve to ≤ Grade 2 before restarting dosing).
VTE ≥ Grade 3
Hold dose for remainder of cycle.  Initiate anticoagulation treatment.  
Maintain dose level when dosing restarted at next cycle at discretion of 
treating physician.
Hypo/hyperthyroidism ≥ Grade 2
Hold dose for remainder of cycle.  Initiate appropriate medical therapy.  
Maintain dose level when dosing restarted at next cycle at discretion of 
treating physician.
Other ≥ Grade 3 POM-related
a adverse 
events
Hold dose for remainder of cycle.  Decrease by one dose level when 
dosing restarted at next cycle (adverse event must resolve to ≤ Grade 2 
before restarting dosing).
GCSF = granulocyte-colony stimulating factor; POM = pomalidomide; VTE = venous thrombotic event.
a For Grade 3 or 4 AEs that are not considered to be related to study drug, the treating physician should consult with the Sponsor 
for dose interruptions and reductions.
To initiate a new cycle of POM following a dose interruption, the neutrophil count must be 
≥800/μL with or without GCSF, the platelet count must be ≥ 30,000/μL, and non-hematologic 
AEs must have recovered as outlined in Table 2.
If recovery from toxicities is prolonged beyond 14 days, then the dose of POM will be decreased 
by one dose level when dosing is restarted.


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Table 3:
Pomalidomide Dose Reduction Steps 
Dose Level
Oral POM
Dose (Days 1-21 of 
28-day Cycle)
Oral POM
Dose (Days 1-21 of 
28-day Cycle)
Oral POM
Dose (Days 1-21 of 
28-day Cycle)
Oral POM
Dose (Days 1-21 of 
28-day Cycle)
Starting Dose
4.0 mga
3.0 mg
2.0 mg
1.0 mg
Dose Level -1
3.0 mg
2.0 mg
1.0 mg
Not applicable
Dose Level -2
2.0 mg
1.0 mg
Not applicable
Not applicable
Dose Level -3
1.0 mg
Not applicable
Not applicable
Not applicable
a Planned starting dose in the present study.
The minimum permitted dose level for POM is 1.0 mg.  No dose re-escalation is permitted for 
POM.
Dose Modification Instructions for Low-Dose Dexamethasone
Table 4 details instructions for LD-DEX dose interruptions and reductions and Table 5 outlines 
the dose reduction steps for LD-DEX; however, the full product information and labeling 
contained in the current DEX Package Insert should also be reviewed.  
If LD-DEX is held or permanently discontinued due to toxicity, POM may be continued.   
Table 4:
Dose Reductions for Low-Dose Dexamethasone Related Toxicities
Toxicity
Low-Dose Dexamethasone Dose Modification
Dyspepsia = Grade 1-2
Maintain dose and treat with histamine (H2) blockers or equivalent.  
Decrease by one dose level if symptoms persist.
Dyspepsia ≥ Grade 3
Hold dose until symptoms are controlled.  Add H2 blocker or 
equivalent and decrease one dose level when dose restarted.
Edema ≥ Grade 3
Use diuretics as needed and decrease dose by one dose level.
Confusion or mood alteration ≥ Grade 2
Hold dose until symptoms resolve.  When dose restarted decrease 
dose by one dose level.
Muscle weakness (steroid myopathy) 
≥ Grade 2
Hold dose until muscle weakness ≤ Grade 1.  When dose restarted 
decrease dose by one dose level.
Hyperglycemia ≥ Grade 3
Decrease dose by one dose level.  Treat with insulin or oral 
hypoglycemic agents as needed.
Acute pancreatitis
Discontinue subject from dexamethasone treatment regimen.
Other ≥ Grade 3 dexamethasone-related 
adverse events
Stop DEX dosing until the adverse event resolves to ≤ Grade 2.  
Decrease by one dose level when DEX dosing is resumed.
If recovery from toxicities is prolonged beyond 14 days, then the dose of DEX will be decreased 
by one dose level when dose is restarted.


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Table 5:
Low-Dose Dexamethasone Dose Reduction Steps 
Dose Level
≤75 Years Old
Dose (Days 1, 8, 15, 22 of a
28-day Cycle)
>75 Years Old
Dose (Days 1, 8, 15, 22 of a
28-day Cycle)
Starting Dose
40 mg
20 mg
Dose Level -1
20 mg
12 mg
Dose Level -2 
10 mg
8 mg
Dexamethasone should be discontinued if subject is unable to tolerate 10 mg if ≤75 years old or 
8 mg if >75 years old.
8.3.
Method of Treatment Assignment
This study will utilize the IVRS for enrollment.  Designated research personnel at each 
investigational site will be assigned password protected, coded identification numbers which 
gives them the authorization to call into IVRS to enroll subjects.  For drug assignment at each 
cycle start and in the event of any dose reduction, site staff must contact IVRS to record the new 
dose level and obtain the new study treatment assignment.
8.4.
Packaging and Labeling
The label(s) for the IP POM will include sponsor name, address and telephone number, the 
protocol number, IP name, dosage form and strength (where applicable), amount of IP per 
container, lot number, expiry date (where applicable), medication identification/kit number, 
dosing instructions, storage conditions, and required caution statements and/or regulatory 
statements as applicable. 
Celgene will provide commercial supplies of DEX labeled appropriately for investigational use 
as per the regulations of the relevant country health authority.
Additional information may be included on the label as applicable per local regulations.
8.5.
Investigational Product Accountability and Disposal 
Celgene will instruct the Investigator on the return, disposal and/or destruction of IP and/or 
medical device materials if applicable. 
8.6.
Investigational Product Compliance
The investigator will document the number of capsules of POM and DEX issued to and returned 
by each subject at each study visit. 






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10.
STATISTICAL ANALYSES
10.1.
Overview
The final statistical analyses will be performed when all subjects have completed/discontinued 
the study including the follow-up phase.
10.2.
Study Population Definitions
The safety population is the primary population for this study
Safety Population
The safety population is defined as all enrolled subjects who receive at least one dose of the 
study treatment. The safety population shall be used for all safety analyses.
Intention-to-Treat (ITT) Population
The ITT population is defined as all enrolled subjects (which is defined as enrollment on the 
IVRS/IWRS) regardless of whether they received any of the of the study treatment or not. The 
ITT population shall be used for all efficacy analyses.
Per-protocol (PP)
The PP population is defined as all enrolled subjects who receive at least one dose of the study 
treatment and do not have any known protocol deviations. The PP population shall be used for 
analysis of both safety and efficacy based endpoints.
Subject screening shall continue up to approximately 720 evaluable subjects for the primary 
endpoint have been enrolled. Subjects are defined as evaluable if they have received at least one 
dose of POM with or without LD-DEX. Subjects retrospectively found to be non-eligible for the 
study or not receiving any study medication will not be replaced.
10.3.
Sample Size and Power Considerations
The profile of AEs considered related to POM is well defined based on studies of the IP in this 
indication [MM-002 (Richardson, 2013a), IFM 2009-02 (Leleu, 2013) and the recently published 
data from the MM-003 study (Dimopoulos 2012)].
The current study will support a more detailed evaluation of the safety profile of POM plus LD-
DEX. The sample size in this study has been determined to enable the characterization of 
uncommon adverse events. The initial sample size of 500 subjects permitted the evaluation of 
previously undocumented adverse drug reactions with an incidence of 3/500 (0.6%) assuming a 
power of 95%. Increasing the initial sample size of the study will increase the chances of 
detecting uncommon adverse events (defined as events with a frequency of <1% and > 0.1%).
Two hundred and twenty additional subjects will be enrolled, bringing the total sample size to 
720 subjects. This increase has been made to help detect adverse drug reactions with an 
incidence of 0.4%, assuming a power of 95%. This rate of incidence will therefore be confirmed 
if at least 1 such AE is observed in the treated 720 subjects.


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A sample size of 720 subjects will, in addition to allowing identification of infrequent AEs, 
allow confirmation of the percentage of subjects observed as having a Grade 3 or 4 AE as 
indicated in the MM-002 study (N = 112) at the time of the interim analysis (88.40%). With a 
99% confidence level, we expect the percentage of subjects observed with a Grade 3 or 4 AE to 
lie within the range 85.32% to 91.48% (i.e. 88.4 ± 3.08).
At least 320 subjects with complete PK samples should enable informative population PK and 
exposure-response analyses.  This is based on an assumption of a 2-fold improvement in 
exposure-response analysis over dose-response analysis.  
10.4.
Background and Demographic Characteristics
Subject demographic and medical continuous data including age, height, weight, and baseline 
characteristics will be summarized using descriptive statistics (median, minimum and maximum 
value), while gender and other categorical demographic and medical history variables will be 
provided using frequency tabulations showing frequency of occurrence and corresponding 
percentage. Medical history data will be summarized using frequency tabulations by system 
organ class and preferred term.
10.5.
Subject Disposition
Subject disposition (analysis population allocation, entered, discontinued, along with primary 
reason for discontinuation) will be summarized using frequency and percent.  A summary of 
subjects enrolled by site will be provided.  Protocol violations will be summarized using 
frequency tabulations.
10.6.
Efficacy Analysis
Overall Response Rate
The overall response rate (ORR; as defined as the rate of at least PR) will be calculated as the 
percentage of confirmed responders, as well as being summarized by each response category 
(i.e., stringent complete response (SCR), CR, VGPR, PR, SD, and PD) in the ORR using the 
IMWG criteria.  A response that is documented after the initiation of another anti-myeloma 
treatment will not be counted as a response.  However, these subjects will be included in the 
denominator for the ORR calculation. Subjects without an assessment shall be considered a non-
responder.
Time to Response 
Time to response is calculated as the time from study enrollment to the first documented 
response (PR or better) based on IMWG criteria.  Subjects without a documented response will 
be censored at the time of their last tumor assessment (or at the time of trial enrollment if no 
assessment was conducted).
Duration of Response 
Duration of response, calculated for responders only, is defined as time from the initial 
documented response (PR or better) to the first confirmed PD.  Subjects without a documented 
progression will be censored at the time of their last tumor assessment.


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Time to Progression
Time to progression will be calculated as the time from study enrollment until PD (as determined 
by the site investigator based on the IMWG criteria).  Subjects not experiencing a documented 
progression will be censored at the time of their last tumor assessment (or at the time of trial 
enrollment if no assessment was conducted).
Progression-free Survival
Progression-free survival will be calculated as the time from study enrollment until the time of 
PD (as determined by the site investigator based on the IMWG criteria) or death from any cause 
on study treatment.  Subjects not experiencing a documented progression will be censored at the 
time of their last tumor assessment (or at the time of trial enrollment if no assessment was 
conducted).
Overall Survival
Overall survival will be calculated as the time from study enrollment until the time of death from 
any cause. If no death is recorded the subject will be censored at the time the subject was last 
known to be alive. 
All time-to-event type endpoints will be assessed using the Kaplan-Meier method to calculate the 
median time along with the corresponding 95% confidence interval.
10.7.
Safety Analysis
Data from all subjects receiving any of the study treatment will be included in the safety 
analyses. 
Adverse Events
Adverse events will be coded according to the most recent version of Medical Dictionary for 
Regulatory Activities (MedDRA).  The severity of AEs will be graded according to the NCI-
CTCAE (version 4.0, May 2009). 
Treatment-emergent adverse events (TEAEs) are defined as any AE occurring or worsening on 
or after the first treatment of the study medication and within 28 days after the last dose.  All 
TEAEs, AEs leading to study medication discontinuation, AEs leading to dose reduction/
interruption, AEs related to the IP, SAEs and AE leading to death will be summarized by cycle 
and 28 day period after last cycle as well as by subject (worse recorded grade) per event type 
(organ class and preferred tern) and grade.  A summary of AEs with NCI-CTCAE grade 3 or 
higher, as well as the most frequent preferred terms, will also be provided. 
Additional analyses of the primary endpoint shall include subgroup analyses including AEs by 
selected demographic characteristics such as gender and age grouping in addition to amount of 
therapy administered such as time on treatment (1 complete cycle, 2 complete cycles etc.).
Deaths
Deaths during treatment (defined as deaths from the first dose and within 30 days after the last 
dose of study medication) and during the long-term follow-up phase shall be summarized by 
frequency of occurrence and corresponding percentage by cause of death per period (during 
treatment or follow-up) as well as overall. 


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Clinical Laboratories
Clinical laboratory values will be graded according to NCI-CTCAE (version 4.0, May 2009) for 
applicable tests.  Baseline grade and worst grade during treatment for selected laboratory results 
will be summarized.  Shift from baseline to the worst grade observed during the treatment for 
selected laboratory results will also be provided.
Vital Signs
For vital signs, shift from baseline to worst during the treatment in below, within, and above the 
normal ranges will be displayed in cross–tabulations.  Summary statistics (N, Mean, Standard 
Deviation, Median, Minimum, and Maximum) of observed and change from baseline values will 
be presented.
Electrocardiogram
The overall ECG interpretation will be summarized by presenting the number and percentage of 
subjects with ‘Normal’, ‘Abnormal, not clinically significant’ and ‘Abnormal, clinically 
significant’.  Shift from baseline to worst during the treatment in the overall ECG interpretation 
will be displayed in cross–tabulations.
10.8.
Interim Analysis
No formal interim analysis is planned.
10.9.
Pharmacokinetic Analysis
Pharmacokinetic samples will be collected from subjects to determine POM concentrations in 
plasma.  Population PK analysis will be performed using plasma concentration data of POM.  
Population estimates of PK parameters of POM such as apparent oral plasma clearance (CL/F) 
and apparent volume of distribution (V/F) will be estimated, and intra- and inter-subject 
variability of these parameters will be characterized.  The effect of demographics/covariates 
(e.g., age, body weight, gender, prior treatment and use of concomitant medications, etc.) on the 
PK of POM will be evaluated.
Other PK parameters will be determined and reported as deemed appropriate.  If the data are 
insufficient for population PK analysis, only the concentrations of POM will be reported.
10.10.
Exposure-Response Analysis
An exploratory exposure-response (ER) analysis will be performed to assess whether POM 
exposure improves the PD, safety and efficacy endpoints and estimate the minimal plasma POM
level and/or duration to effect a desired change in the PD/safety/efficacy endpoints.
The key exposure data are serum drug concentration, Cmax, Cmin and AUC derived from the 
population PK analysis. The key efficacy and safety endpoints include AEs, ORR, time to 
response, DoR, PFS, TTP, and OS. Other efficacy and safety endpoints may also be explored, as 
appropriate.
The exploratory ER analysis will include graphical examination of potential relationship of POM 
exposure and efficacy/safety endpoints; PK/PD modeling as appropriate to define the change of 
PD, safety, and efficacy endpoint versus. POM exposure quantitatively. In addition, trial 


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simulation based on appropriate model supported by data may be performed to assess the 
robustness of the exposure-response trend.
 
 
 
 
 
 
 
 
10.12.
Cytogenetic Analysis
Survival rates can vary considerably among MM subgroups 
 
. In particular, subjects with cytogenetic profiles that show a deletion of 17p132,5 
or t(4;14),1,3 as detected by FISH, retain their poor prognosis despite the use of single or tandem 
autologous stem cell transplantation 
 and maintenance with 
thalidomide
. As shown, cytogenetics in relapsed and/or refractory 
MM still has an impact on the outcome. So far only very limited data are available on the role of 
POM in subjects harboring ‘high-risk’ cytogenetic abnormalities 
. To further
investigate the role of POM in high-risk subjects and to understand the cytogenetic changes that 
occur throughout the disease course, cytogenetic profiles will be analyzed at initial diagnosis, at 
study entry, and at relapse.
Subjects will be classified according to their cytogenetic profiles and certain efficacy analyses 
will be performed based on those subgroups.


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11.
ADVERSE EVENTS
11.1.
Monitoring, Recording and Reporting of Adverse Events
An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may 
appear or worsen in a subject during the course of a study.  It may be a new intercurrent illness, a 
worsening concomitant illness, an injury, or any concomitant impairment of the subject’s health, 
including laboratory test values (as specified by the criteria below), regardless of etiology.  Any 
worsening (i.e., any clinically significant adverse change in the frequency or intensity of a pre-
existing condition) should be considered an AE.  A diagnosis or syndrome should be recorded on 
the AE page of the CRF rather than the individual signs or symptoms of the diagnosis or 
syndrome.  
An overdose, accidental or intentional, whether or not it is associated with an AE, or abuse, 
withdrawal, sensitivity or toxicity to an investigational product should be reported as an AE.  If 
an overdose is associated with an AE, the overdose and adverse event should be reported as 
separate terms.
All subjects will be monitored for AEs during the study.  Assessments may include monitoring 
of any or all of the following parameters:  the subject’s clinical symptoms, laboratory, 
pathological, radiological or surgical findings, physical examination findings, or other 
appropriate tests and procedures.
All AEs will be recorded by the investigator from the time the subject signs ICD to at least 
28 days after treatment discontinuation.  AEs that lead to study discontinuation should be 
followed until resolution or stabilization.  AEs and SAEs will be recorded on the AE page of the 
eCRF and in the subject’s source documents.  All SAEs must be reported to Celgene Drug Safety 
immediately (i.e., within 24 hours of the investigator’s knowledge of the event) by facsimile, or 
other appropriate method, using the SAE Report Form, or approved equivalent form.
11.2.
Evaluation of Adverse Events
A qualified investigator will evaluate all AEs as to: 
11.2.1.
Seriousness 
A SAE is any AE occurring at any dose that:

Results in death;

Is life-threatening (i.e., in the opinion of the investigator, the subject is at immediate 
risk of death from the AE);

Requires inpatient hospitalization or prolongation of existing hospitalization 
(hospitalization is defined as an inpatient admission, regardless of length of stay);

Results in persistent or significant disability/incapacity (a substantial disruption of the 
subject’s ability to conduct normal life functions);

Is a congenital anomaly/birth defect;


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
Constitutes an important medical event.
Important medical events are defined as those occurrences that may not be immediately life 
threatening or result in death, hospitalization, or disability, but may jeopardize the subject or 
require medical or surgical intervention to prevent one of the other outcomes listed above.  
Medical and scientific judgment should be exercised in deciding whether such an AE should be 
considered serious.
SPMs will be monitored as events of interest and must be reported as SAEs (see Section 11.5).  
This includes any SPM, regardless of causal relationship to IP (POM with or without DEX), 
occurring at any time from the time of signing the ICD up to and including the long-term follow-
up period.  Events of SPM are to be reported using the SAE report form and must be considered 
an “Important Medical Event” even if no other serious criteria apply; these events must also be 
documented in the appropriate page(s) of  the eCRF and subject’s source documents. 
Documentation on the diagnosis of the SPM must be provided at the time of reporting as a SAE 
(e.g., any confirmatory histology or cytology results, X-rays, CT scans, etc.).
Events not considered to be SAEs are hospitalizations for:

A standard procedure for protocol therapy administration.  However, hospitalization 
or prolonged hospitalization for a complication of therapy administration will be 
reported as an SAE.  

Routine treatment or monitoring of the studied indication not associated with any 
deterioration in condition.

The administration of blood or platelet transfusion as routine treatment of studied 
indication.  However, hospitalization or prolonged hospitalization for a complication 
of such transfusion remains a reportable SAE.

A procedure for protocol/disease-related investigations (e.g., surgery, scans, 
endoscopy, sampling for laboratory tests, bone marrow sampling).  However, 
hospitalization or prolonged hospitalization for a complication of such procedures 
remains a reportable SAE.

Hospitalization or prolongation of hospitalization for technical, practical, or social 
reasons, in absence of an AE.

A procedure that is planned (i.e., planned prior to starting of treatment on study); 
must be documented in the source document and the CRF.  Hospitalization or 
prolonged hospitalization for a complication remains a reportable SAE.

An elective treatment of a pre-existing condition unrelated to the studied indication.  

Emergency outpatient treatment or observation that does not result in admission, 
unless fulfilling other seriousness criteria above.
If an AE is considered serious, both the AE page/screen of the eCRF and the SAE Report Form 
must be completed.
For each SAE, the investigator will provide information on severity, start and stop dates,
relationship to IP, action taken regarding IP, and outcome.


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11.2.2.
Severity / Intensity
For both AEs and SAEs, the investigator must assess the severity of the event.  
The severity of AEs will be graded based upon the subject’s symptoms according to the current 
active minor version of NCI-CTCAE (Version 4.0, May 2009): 
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_40.
AEs that are not defined in the NCI-CTCAE should be evaluated for severity according to the 
following scale:

Grade 1 = Mild – transient or mild discomfort; no limitation in activity; no medical 
intervention/ therapy required.

Grade 2 = Moderate – mild to moderate limitation in activity, some assistance may be 
needed; no or minimal medical intervention/therapy required.

Grade 3 = Severe – marked limitation in activity, some assistance usually required; 
medical intervention/therapy required, hospitalization is possible.

Grade 4 = Life threatening – extreme limitation in activity, significant assistance 
required; significant medical intervention/therapy required, hospitalization or hospice 
care probable.

Grade 5 = Death - the event results in death.
The term “severe” is often used to describe the intensity of a specific event (as in mild, moderate 
or severe myocardial infarction); the event itself, however, may be of relatively minor medical 
significance (such as severe headache).  This criterion is not the same as “serious” which is 
based on subject/event outcome or action criteria associated with events that pose a threat to a 
subject’s life or functioning.  
Seriousness, not severity, serves as a guide for defining regulatory obligations.
11.2.3.
Causality 
The investigator must determine the relationship between the administration of IP and the 
occurrence of an AE/SAE as Not Suspected or Suspected as defined below:
Not suspected:
The temporal relationship of the adverse event to IP 
administration makes a causal relationship unlikely or 
remote, or other medications, therapeutic interventions, or 
underlying conditions provide a sufficient explanation for the 
observed event.
Suspected:
The temporal relationship of the adverse event to IP 
administration makes a causal relationship possible, and other 
medications, therapeutic interventions, or underlying conditions 
do not provide a sufficient explanation for the observed event.


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If an event is assessed as suspected of being related to a comparator, ancillary or additional IP 
that has not been manufactured or provided by Celgene, please provide the name of the 
manufacturer when reporting the event.
11.2.4.
Duration
For both AEs and SAEs, the investigator will provide a record of the start and stop dates of the 
event.
11.2.5.
Action Taken
The investigator will report the action taken with IP as a result of an AE or SAE, as applicable 
(e.g., discontinuation or reduction of IP, as appropriate) and report if concomitant and/or 
additional treatments were given for the event. 
11.2.6.
Outcome
The investigator will report the outcome of the event for both AEs and SAEs.
All SAEs that have not resolved upon discontinuation of the subject’s participation in the study 
must be followed until recovered, recovered with sequelae, not recovered (death due to another 
cause) or death (due to the SAE). 
11.3.
Abnormal Laboratory Values
An abnormal laboratory value is considered to be an AE if the abnormality:

results in discontinuation from the study;

requires treatment, modification/ interruption of IP dose, or any other therapeutic 
intervention; or

is judged to be of significant clinical importance by the Investigator.
Regardless of severity grade, only laboratory abnormalities that fulfill a seriousness criterion 
need to be documented as a serious adverse event. 
If a laboratory abnormality is one component of a diagnosis or syndrome, then only the diagnosis 
or syndrome should be recorded on the AE page/screen of the CRF.  If the abnormality was not a 
part of a diagnosis or syndrome, then the laboratory abnormality should be recorded as the AE. 
11.4.
Pregnancy
11.4.1.
Females of Childbearing Potential
Pregnancies and suspected pregnancies (including a positive pregnancy test regardless of age or 
disease state) of a female subject occurring while the subject is on IP, or within 28 days of the 
subject’s last dose of IP, are considered immediately reportable events.  Investigational product 
is to be discontinued immediately and the subject instructed to return any unused portion of the 
IP to the investigator.  The pregnancy, suspected pregnancy, or positive pregnancy test must be 
reported to Celgene Drug Safety immediately by facsimile, or other appropriate method, using 
the Initial Pregnancy Report Form, or approved equivalent form.  The female should be referred 
to an obstetrician-gynecologist, preferably one experienced in reproductive toxicity for further 


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evaluation and counseling.  The exposure of any pregnant female (e.g., caregiver or pharmacist) 
to POM is also an immediately reportable event. 
The investigator will follow the female subject until completion of the pregnancy, and must 
notify Celgene Drug Safety immediately about the outcome of the pregnancy (either normal or 
abnormal outcome) using the Follow-up Pregnancy Report Form, or approved equivalent form.
If the outcome of the pregnancy was abnormal (e.g., spontaneous or therapeutic abortion), the 
investigator should report the abnormal outcome as an AE.  If the abnormal outcome meets any 
of the serious criteria, it must be reported as an SAE to Celgene Drug Safety by facsimile, or 
other appropriate method, within 24 hours of the investigator’s knowledge of the event using the 
SAE Report Form, or approved equivalent form.
All neonatal deaths that occur within 28 days of birth should be reported, without regard to 
causality, as SAEs.  In addition, any infant death after 28 days that the investigator suspects is 
related to the in utero exposure to the IP should also be reported to Celgene Drug Safety by 
facsimile, or other appropriate method, within 24 hours of the investigator’s knowledge of the 
event using the SAE Report Form, or approved equivalent form.
11.4.2.
Male Subjects
If a female partner of a male subject taking investigational product becomes pregnant, the male 
subject taking IP should notify the investigator, and the pregnant female partner should be 
advised to call their healthcare provider immediately.   
11.5.
Reporting of Serious Adverse Events
Any AE that meets any criterion for an SAE requires the completion of an SAE Report Form in 
addition to being recorded on the AE screen of the eCRF.  All SAEs must be reported to Celgene 
Drug Safety within 24 hours of the investigator’s knowledge of the event by facsimile, or other 
appropriate method, using the SAE Report Form, or approved equivalent form.  This instruction 
pertains to initial SAE reports as well as any follow-up reports.
SPMs will be monitored as events of interest and must be reported as SAEs.  This includes any 
SPM, regardless of causal relationship to IP (POM with or without DEX), occurring at any time 
from the time of signing the ICD up to and including the long-term follow-up period.  Events of 
SPM are to be reported using the SAE report form or approved equivalent and must be 
considered an “Important Medical Event” even if no other serious criteria apply; these events 
must also be documented in the appropriate page(s) of the eCRF and subject’s source documents.  
Documentation on the diagnosis of the SPM must be provided at the time of reporting as a SAE 
(e.g., any confirmatory histology or cytology results, X-rays, CT scans, etc.).
The investigator is required to ensure that the data on these forms is accurate and consistent.  
This requirement applies to all SAEs (regardless of relationship to IP [POM with or without 
DEX]) that occur from the time the subject signs ICD to at least 28 days after treatment 
discontinuation and those made known to the investigator at anytime thereafter that are suspected 
of being related to IP (POM with or without DEX).  SAEs occurring prior to treatment will be 
captured.
SAEs, regardless of relationship to the IP, that occur from the time the subject signs ICD to at 
least 28 days after treatment discontinuation and those made known to the investigator at 


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anytime thereafter that are suspected of being related to IP (POM with or without DEX) must be 
reported to Celgene Drug Safety within 24 hours of the investigator’s knowledge of the event.   
The SAE report should provide a detailed description of the SAE and include summaries of 
hospital records and other relevant documents.  If a subject died and an autopsy has been 
performed, copies of the autopsy report and death certificate are to be sent to Celgene Drug 
Safety as soon as these become available.  Any follow-up data must be detailed in a subsequent 
SAE Report Form, or approved equivalent form, and sent to Celgene Drug Safety.  
Where required by local legislation, the investigator is responsible for informing the Institutional 
Review Board/ Ethics Committee (IRB/EC) of the SAE and providing them with all relevant 
initial and follow-up information about the event.  The investigator must keep copies of all SAE 
information on file including correspondence with Celgene and the IRB/EC.
11.5.1.
Safety Queries
Queries pertaining to SAEs will be communicated from Celgene Drug Safety to the site via
facsimile or electronic mail.  The response time is expected to be no more than five (5) business 
days.  Urgent queries (e.g., missing causality assessment) may be handled by phone.
11.6.
Expedited Reporting of Adverse Events
For the purpose of regulatory reporting, Celgene Drug Safety will determine the expectedness of 
events suspected of being related to POM based on the Investigator Brochure.
For countries within the European Economic Area (EEA), Celgene or its authorized 
representative will report in an expedited manner to Regulatory Authorities and Ethics 
Committees concerned, suspected unexpected serious adverse reactions (SUSARs) in accordance 
with Directive 2001/20/EC and the Detailed Guidance on collection, verification and 
presentation of adverse reaction reports arising from clinical trials on investigational products for 
human use (ENTR/CT3) and also in accordance with country-specific requirements. 
For the purpose of regulatory reporting in the EEA, Celgene Drug Safety will determine the 
expectedness of events suspected of being related to the other IP, DEX, based on the US 
Prescribing Information (PI). 
AEs such as PD, death related to PD (in the absence of serious IP-related events) and serious 
events due to the relapse of the studied indication will not be subject to expedited reporting by 
the sponsor to regulatory authorities.
Celgene or its authorized representative shall notify the investigator of the following 
information: 
Any AE suspected of being related to the use of IP in this study or in other studies that is both 
serious and unexpected (i.e., SUSAR);
Any finding from tests in laboratory animals that suggests a significant risk for human subjects 
including reports of mutagenicity, teratogenicity, or carcinogenicity.
Where required by local legislation, the investigator shall notify his/her IRB/EC promptly of 
these new serious and unexpected AE(s) or significant risks to subjects.


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The investigator must keep copies of all pertinent safety information on file including 
correspondence with Celgene and the IRB/EC (See Section 15.3 for record retention 
information).
Celgene Drug Safety Contact Information:
For Local Drug Safety Affiliate Office contact information, please refer to the Serious Adverse 
Event Report Form / Completion Guidelines or to the Pregnancy Report Form / Completion 
Guidelines.


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12.
DISCONTINUATIONS
The following events are considered sufficient reasons for discontinuing a subject from 
treatment:

AEs

PD

Withdrawal of consent from study treatment
The following events are considered sufficient reasons for discontinuing a subject from the 
study:

Withdrawal of consent from study 

Protocol violation

Death

Lost to follow-up

Completion of 5 years from last subject enrolled post-enrollment follow-up.
The reason for discontinuation from treatment and from study will be captured in the eCRFs and 
source document as applicable.


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13.
EMERGENCY PROCEDURES
13.1.
Emergency Contact
In emergency situations, the investigator should contact the responsible Clinical Research 
Physician/Medical Monitor or designee by telephone at the number(s) listed on the Emergency 
Contact Information page of the protocol (after title page).
In the unlikely event that the Clinical Research Physician/Medical Monitor or designee cannot be 
reached, please contact the global Emergency Call Center by telephone at the number listed on 
the Emergency Contact Information page of the protocol (after title page).This global Emergency 
Call Center is available 24 hours a day and 7 days a week.  The representatives are responsible 
for obtaining your call-back information and contacting the on call Celgene/Contract Research 
Organization Medical Monitor, who will then contact you promptly.
Note: The back-up 24 hour global emergency contact call center should only be used if you are 
not able to reach the Clinical Research Physician(s) or Medical Monitor or designee for 
emergency calls. 
13.2.
Emergency Identification of Investigational Products
This is an open-label study; therefore, IP will be identified on the package labeling.


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14.
REGULATORY CONSIDERATIONS
14.1.
Good Clinical Practice
The procedures set out in this study protocol pertaining to the conduct, evaluation, and 
documentation of this study are designed to ensure that Celgene, its authorized representative, 
and investigator abide by Good Clinical Practice (GCP), as described in International Conference 
on Harmonization (ICH) Guideline E6 and in accordance with the general ethical principles 
outlined in the Declaration of Helsinki.  The study will receive approval from an IRB/EC prior to 
commencement.  The investigator will conduct all aspects of this study in accordance with 
applicable national, state, and local laws of the pertinent regulatory authorities.
14.2.
Investigator Responsibilities
Investigator responsibilities are set out in the ICH Guideline for GCP and in the local 
regulations.  Celgene staff or an authorized representative will evaluate and approve all 
investigators who in turn will select their staff.
The Investigator should ensure that all persons assisting with the study are adequately informed 
about the protocol, amendments, study treatments, as well as study-related duties and functions.  
The investigator should maintain a list of Sub-investigators and other appropriately qualified 
persons to whom he or she has delegated significant study-related duties.
The Investigator is responsible for keeping a record of all subjects who sign an ICD and are 
screened for entry into the study.  Subjects who fail screening must have the reason(s) recorded 
in the subject’s source documents.
The Investigator, or a designated member of the Investigator’s staff, must be available during 
monitoring visits to review data, resolve queries and allow direct access to subject records (e.g., 
medical records, office charts, hospital charts and study-related charts) for source data 
verification. The investigator must ensure timely and accurate completion of eCRFs and queries.
14.3.
Subject Information and Informed Consent
The Investigator must obtain informed consent of a legal representative prior to any study related 
procedures.
Documentation that informed consent occurred prior to the study subject’s entry into the study 
and of the informed consent process should be recorded in the study subject’s source documents 
including the date.  The original ICD signed and dated by the study subject and by the person 
consenting the study subject prior to the study subject’s entry into the study, must be maintained 
in the investigator’s study files and a copy given to the study subject.  In addition, if a protocol is 
amended and it impacts on the content of the informed consent, the ICD must be revised.  Study 
subjects participating in the study when the amended protocol is implemented must be re-
consented with the revised version of the ICD.  The revised ICD signed and dated by the study 
subject and by the person consenting the study subject must be maintained in the investigator’s 
study files and a copy given to the study subject.  


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14.4.
Confidentiality
Celgene affirms the subject's right to protection against invasion of privacy and to be in 
compliance with ICH and other local regulations (whichever is most stringent).  Celgene requires 
the investigator to permit Celgene's representatives and, when necessary, representatives from 
regulatory authorities, to review and/or copy any medical records relevant to the study in 
accordance with local laws.
Should direct access to medical records require a waiver or authorization separate from the 
subject’s signed ICD, it is the responsibility of the investigator to obtain such permission in 
writing from the appropriate individual.
14.5.
Protocol Amendments
Any amendment to this protocol must be approved by the Celgene Clinical Research 
Physician/Medical Monitor.  Amendments will be submitted to the IRB/EC for written approval.  
Written approval must be obtained before implementation of the amended version occurs.  
Amendments that are administrative in nature do not require IRB/EC approval but will be 
submitted to the IRB/EC for information purposes.
14.6.
Institutional Review Board/Independent Ethics Committee Review 
and Approval
Before the start of the study, the study protocol, ICD, and any other appropriate documents will 
be submitted to the IRB/EC with a cover letter or a form listing the documents submitted, their 
dates of issue, and the site (or region or area of jurisdiction, as applicable) for which approval is 
sought.  If applicable, the documents will also be submitted to the authorities in accordance with 
local legal requirements.
IP can only be supplied to an investigator by Celgene or its authorized representative after 
documentation on all ethical and legal requirements for starting the study has been received by 
Celgene or its authorized representative.  This documentation must also include a list of the 
members of the IRB/EC and their occupation and qualifications.  Before the first subject is 
enrolled in the study, all ethical and legal requirements must be met.
The IRB/EC and, if applicable, the authorities, must be informed of all subsequent protocol 
amendments in accordance with local legal requirements.  Amendments must be evaluated to 
determine whether formal approval must be sought and whether the ICD should also be revised.
The investigator must keep a record of all communication with the IRB/EC and, if applicable, 
between a Coordinating investigator and the IRB/EC.  This statement also applies to any 
communication between the Investigator (or Coordinating investigator, if applicable) and 
regulatory authorities.
Any advertisements used to recruit subjects for the study must be reviewed by Celgene and the 
IRB/EC prior to use.  


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14.7.
Ongoing Information for Institutional Review Board / Ethics 
Committee
If required by legislation or the IRB/EC, the investigator must submit to the IRB/EC:

Information on serious or unexpected AEs as soon as possible; 

Periodic reports on the progress of the study;

Deviations from the protocol or anything that may involve added risk to subjects.
14.8.
Closure of the Study
Celgene reserves the right to terminate this study at any time for reasonable medical or 
administrative reasons.  Any premature discontinuation will be appropriately documented 
according to local requirements (e.g., IRB/EC, regulatory authorities, etc...).
In addition, the investigator or Celgene has the right to discontinue a single site at any time 
during the study for medical or administrative reasons such as:

Unsatisfactory enrollment;

GCP noncompliance;

Inaccurate or incomplete data collection;

Falsification of records;

Failure to adhere to the study protocol.


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15.
DATA HANDLING AND RECORDKEEPING 
15.1.
Data/Documents
The Investigator must ensure that the records and documents pertaining to the conduct of the 
study and the distribution of the investigational product are complete, accurate, filed and 
retained.  Examples of source documents include: hospital records; clinic and office charts; 
laboratory notes; memoranda; subject’s diaries or evaluation checklists; dispensing records; 
recorded data from automated instruments; copies or transcriptions certified after verification as 
being accurate copies; microfiche; x-ray film and reports; and records kept at the pharmacy, and 
the laboratories, as well as copies of eCRFs or CD-ROM.
15.2.
Data Management
Data will be collected via eCRF.  This data will be electronically verified through use of 
programmed edit checks specified by the clinical team.  Discrepancies in the data will be brought 
to the attention of the clinical team, and investigational site personnel, if necessary.  Resolutions 
to these issues will be reflected in the database.  An audit trail within the system will track all 
changes made to the data.
15.3.
Record Retention
Essential documents must be retained by the investigator for a minimum of 2 years after the last 
approval of a marketing application in an ICH region and until there are no pending or 
contemplated marketing applications in an ICH region, or at least 2 years have elapsed since the 
formal discontinuation of clinical development of the IP.  The Investigator must retain these 
documents for the time period described above or according to local laws or requirements, 
whichever is longer.  Essential documents include, but are not limited to, the following:

Signed ICD for all subjects;

Subject identification code list, screening log (if applicable), and enrollment log;

Record of all communications between the investigator and the IRB/EC;

Composition of the IRB/EC;

Record of all communications between the investigator, Celgene, and their authorized 
representative(s);

List of Sub-investigators and other appropriately qualified persons to whom the 
investigator has delegated significant study-related duties, together with their roles in 
the study, curriculum vitae, and their signatures;

Copies of CRFs (if paper) and of documentation of corrections for all subjects;

IP accountability records;

All other source documents (subject records, hospital records, laboratory records, 
etc.); 


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
All other documents as listed in Section 8 of the ICH consolidated guideline on GCP 
(Essential Documents for the Conduct of a Clinical Trial).
The Investigator must notify Celgene if he/she wishes to assign the essential documents to 
someone else, remove them to another location or is unable to retain them for a specified period.  
The Investigator must obtain approval in writing from Celgene prior to destruction of any 
records.  If the Investigator is unable to meet this obligation, the Investigator must ask Celgene 
for permission to make alternative arrangements.  Details of these arrangements should be 
documented. 
All study documents should be made available if required by relevant health authorities.  
Investigator/Institution should take measures to prevent accidental or premature destruction of 
these documents.


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16.
QUALITY CONTROL AND QUALITY ASSURANCE
All aspects of the study will be carefully monitored by Celgene or its authorized representative 
for compliance with applicable government regulations with respect to current GCP and standard 
operating procedures.
16.1.
Study Monitoring and Source Data Verification
Celgene ensures that appropriate monitoring procedures are performed before, during and after 
the study.  Before the study is initiated at a site visit or at an investigator meeting, all aspects of 
the study are reviewed with the Investigator and the staff.  Prior to enrolling subjects into the 
study, a Celgene representative will review the protocol, eCRFs, procedures for obtaining 
informed consent, record keeping, and reporting of AEs/SAEs with the Investigator.  Monitoring 
will include on-site visits with the Investigator and his/her staff as well as any appropriate
communications by mail, email, fax, or telephone.  At each monitoring visit, the facilities, IP
storage area, eCRFs, subject’s source documents, and all other study documentation will be 
inspected/reviewed by the Celgene representative for accuracy, adherence to the protocol and 
GCPs.
Accuracy will be checked by performing source data verification that is a direct comparison of 
the entries made onto the eCRFs against the appropriate source documentation.  Any resulting 
discrepancies will be reviewed with the Investigator and/or his/her staff.  Any necessary 
corrections will be made directly to the eCRFs or via queries by the Investigator and/or his/her 
staff.  Monitoring procedures require that informed consents, adherence to inclusion/exclusion 
criteria and documentation of SAEs and their proper recording be verified.  Additional 
monitoring activities may be outlined in a study-specific monitoring plan.
16.2.
Audits and Inspections
In addition to the routine monitoring procedures, a GCP Quality Assurance unit exists within 
Celgene.  Representatives of this unit will conduct audits of clinical research activities in 
accordance with Celgene Standard Operating Procedures (SOPs) to evaluate compliance with 
GCP guidelines and regulations.
The Investigator is required to permit direct access to the facilities where the study took place, 
source documents, CRFs and applicable supporting records of study subject participation for 
audits and inspections by IRB/ECs, regulatory authorities (e.g., FDA, EMA, Health Canada) and 
company authorized representatives.  The Investigator should make every effort to be available 
for the audits and/or inspections.  If the Investigator is contacted by any regulatory authority 
regarding an inspection, he/she should contact Celgene immediately.


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17.
PUBLICATIONS
The results of this study may be published in a medical publication, journal, or may be used for 
teaching purposes.  Additionally, this study and its results may be submitted for inclusion in all 
appropriate health authority study registries, as well as publication on health authority study 
registry websites, as required by local health authority regulations. 
Selection of first authorship will follow Celgene’s publication policy which typically is based on 
several considerations, including, but not limited to study participation, contribution to the 
protocol development, and analysis and input into the manuscript, related abstracts, and 
presentations in a study.  The primary publication is agreed to derive from the data set from the 
entire study.  Publications related to individual country subsets will follow the primary 
publication unless there is specific importance related to the observation and agreement with 
Celgene is gained.












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19.
APPENDICES
Appendix A:  Declaration of Helsinki
The Declaration of Helsinki can be found at: http://www.wma.net/e/policy/b3.htm.










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Appendix C:  Skeletal (Bone) Survey 
The following are the minimum plain radiological films required for the skeletal (bone) survey: 

Lateral skull 

AP and lateral cervical spine 

AP and lateral thoracic spine 

AP and lateral lumbar spine 

PA chest 

AP pelvis 

AP upper extremities, shoulder to elbow 

AP lower extremities, hip to knee 
Other radiological films may be necessary to view symptomatic areas or known pre-existing 
lesions in skeletal regions not included in the films above.
If clinically indicated CT scans are allowed but they should meet the same requirements as 
above.


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Appendix D: Pomalidomide Pregnancy Risk Minimization Plan for Celgene 
Clinical Trials
This appendix applies to all subjects receiving pomalidomide therapy.  The following Pregnancy 
Risk Minimization Plan documents are included in this Appendix: 
a.
Pomalidomide Risks of Fetal Exposure, Pregnancy Testing Guidelines and 
Acceptable Birth Control Methods (Appendix D-1); 
3. Pomalidomide Education and Counselling Guidance Document (Appendix D-2); 
4. Pomalidomide Information Sheet (Appendix D-3).
1. The Pomalidomide Risks of Fetal Exposure, Pregnancy Testing Guidelines and 
Acceptable Birth Control Methods document (Appendix D-1) provides the following 
information:

Potential risks to the fetus associated with pomalidomide exposure

Definition of Female of Childbearing Potential (FCBP)

Pregnancy testing requirements for subjects receiving pomalidomide who are females 
of childbearing potential

Acceptable birth control methods for both female of childbearing potential and male 
subjects receiving pomalidomide in the study

Requirements for counselling of all study subjects receiving pomalidomide about 
pregnancy precautions and the potential risks of fetal exposure to pomalidomide
2. The Pomalidomide Education and Counselling Guidance Document (Appendix D-2) 
must be completed and signed by either a trained counselor or the Investigator at the 
participating clinical center prior to each dispensing of pomalidomide study treatment.  A 
copy of this document must be maintained in the subject records.
3. The Pomalidomide Information Sheet (Appendix D-3) will be given to each subject 
receiving pomalidomide study therapy.  The subject must read this document prior to 
starting pomalidomide study treatment and each time they receive a new supply of study
drug.


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Appendix D-1:  Pomalidomide Risks of Fetal Exposure, Pregnancy Testing 
Guidelines and Acceptable Birth Control Methods 
Risks Associated with Pregnancy
Pomalidomide was found to be teratogenic in a developmental study in rabbits.  Pomalidomide is 
an analogue of thalidomide.  Thalidomide is a known human teratogen that causes severe life-
threatening human birth defects.  If pomalidomide is taken during pregnancy, it may cause birth 
defects or death to an unborn baby.
Criteria for Females of Childbearing Potential (FCBP)
This protocol defines a female of childbearing potential as a sexually mature woman who: 1) has 
not undergone a hysterectomy or bilateral oophorectomy or 2) has not been naturally 
postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) 
for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 
consecutive months).
Counseling
For a female of childbearing potential, pomalidomide is contraindicated unless all of the 
following are met (ie, all females of childbearing potential must be counseled concerning the 
following risks and requirements prior to the start of pomalidomide study therapy): 

She understands the potential teratogenic risk to the unborn child

She understands the need for effective contraception, without interruption, 28 days 
before starting study treatment, throughout the entire duration of study treatment, 
dose interruption and 28 days after the end of study treatment

She should be capable of complying with effective contraceptive measures

She is informed and understands the potential consequences of pregnancy and the 
need to notify her study doctor immediately if there is a risk of pregnancy

She understands the need to commence the study treatment as soon as study drug is 
dispensed following a negative pregnancy test

She understands the need and accepts to undergo pregnancy testing based on the 
frequency outlined in this protocol (Appendix D-1)

She acknowledges that she understands the hazards and necessary precautions 
associated with the use of pomalidomide
The investigator must ensure that females of childbearing potential:

Comply with the conditions for pregnancy risk minimization, including confirmation 
that she has an adequate level of understanding

Acknowledge the aforementioned requirements


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For a female NOT of childbearing potential, pomalidomide is contraindicated unless all of the
following are met (ie, all females NOT of childbearing potential must be counseled concerning 
the following risks and requirements prior to the start of pomalidomide study therapy): 

She acknowledges that she understands the hazards and necessary precautions 
associated with the use of pomalidomide
The effect of pomalidomide on spermatogenesis is not known and has not been studied.  
Therefore, male subjects taking pomalidomide must meet the following conditions (ie, all males 
must be counseled concerning the following risks and requirements prior to the start of 
pomalidomide study therapy):

Understand the potential teratogenic risk if engaged in sexual activity with a pregnant 
female or a female of childbearing potential

Understand the need for the use of a condom even if he has had a vasectomy, if 
engaged in sexual activity with a pregnant female or a female of childbearing 
potential.  
Contraception
Females of childbearing potential (FCBP) enrolled in this protocol must agree to use two reliable 
forms of contraception simultaneously or to practice complete abstinence from heterosexual 
contact during the following time periods related to this study: 1) for at least 28 days before 
starting study drug; 2) while participating in the study; 3) dose interruptions; and 4) for at least 
28 days after study treatment discontinuation. (NOTE: True abstinence: When this is in line with 
the preferred and usual lifestyle of the subject. [Periodic abstinence (e.g., calendar, ovulation, 
symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of 
contraception]).
The two methods of reliable contraception must include one highly effective method and one 
additional effective (barrier) method.  All FCBP must be referred to a qualified provider of 
contraceptive methods if needed.  The following are examples of highly effective and additional 
effective methods of contraception:  

Highly effective methods:

Intrauterine device (IUD)

Hormonal (birth control pills, injections, implants)

Tubal ligation

Partner’s vasectomy

Additional effective methods:

Male condom

Diaphragm

Cervical Cap
Because of the increased risk of venous thromboembolism in subjects with multiple myeloma 
taking pomalidomide and dexamethasone, combined oral contraceptive pills are not 


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recommended.  If a subject is currently using combined oral contraception the subject should 
switch to another one of the effective methods listed above.  The risk of venous 
thromboembolism continues for 4−6 weeks after discontinuing combined oral contraception.  
The efficacy of contraceptive steroids may be reduced during co-treatment with dexamethasone. 
Implants and levonorgestrel-releasing intrauterine systems are associated with an increased risk 
of infection at the time of insertion and irregular vaginal bleeding.  Prophylactic antibiotics 
should be considered particularly in subjects with neutropenia. 
Pregnancy Testing
Medically supervised pregnancy tests with a minimum sensitivity of 25 mIU/mL must be 
performed for females of childbearing potential, including females of childbearing potential who 
commit to complete abstinence, as outlined below.
Before Starting Study Drug
Female Subjects
All FCBP must have two negative pregnancy tests (sensitivity of at least 25 mIU/mL) prior to 
starting study drug.  The first pregnancy test must be performed within 10-14 days prior to the 
start of study drug and the second pregnancy test must be performed within 24 hours prior to the 
start of study drug.  The subject may not receive study drug until the study doctor has verified 
that the results of these pregnancy tests are negative.
Male Subjects
Must practice complete abstinence or  agree to use a condom during sexual contact with a 
pregnant female or a female of childbearing potential while participating in the study, during 
dose interruptions and for at least 28 days following study drug discontinuation, even if he has 
undergone a successful vasectomy.  
During study participation and for 28 days following study drug discontinuation 
Female Subjects

All FCBP with regular or no menstrual cycles must agree to have pregnancy tests 
weekly for the first 28 days of study participation and then every 28 days while on 
study, at study drug discontinuation, and at Day 28 following study drug 
discontinuation.  If menstrual cycles are irregular, the pregnancy testing must occur 
weekly for the first 28 days and then every 14 days while on study, at study drug 
discontinuation, and at Days 14 and 28 following study drug discontinuation.  

At each visit, the investigator must confirm with the FCBP that she is continuing to 
use two reliable methods of birth control.  

Counseling about pregnancy precautions and the potential risks of fetal exposure 
must be conducted at a minimum of every 28 days. 

If pregnancy or a positive pregnancy test does occur in a study subject, study drug 
must be immediately discontinued.


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
Pregnancy testing and counselling must be performed if a subject misses her period or 
if her pregnancy test or her menstrual bleeding is abnormal.  Study drug treatment 
must be discontinued during this evaluation.

Females must agree to abstain from breastfeeding during study participation and for 
at least 28 days after study drug discontinuation.
Male Subjects

Counseling about the requirement for complete abstinence or condom use during
sexual contact with a pregnant female or a female of childbearing potential and the 
potential risks of fetal exposure to pomalidomide must be conducted at a minimum of 
every 28 days.  

If pregnancy or a positive pregnancy test does occur in the partner of a male study 
subject during study participation, the investigator must be notified immediately.
Additional Precautions

Subjects 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.

Subjects should not donate blood during therapy and for at least 28 days following 
discontinuation of study drug.

Male subjects should not donate semen or sperm during therapy or for at least 28 days 
following discontinuation of study drug.

Only enough study drug for one cycle of therapy may be dispensed with each cycle of 
therapy. 


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Appendix D-2:  Pomalidomide Education and Counselling Guidance 
Document 
To be completed prior to each dispensing of study drug.
Protocol Number: ____________________________________________
Subject Name (Print): __________________ DOB: _____/_____/_____ (mm/dd/yyyy)
(Check the appropriate box to indicate risk category)
Female:

If female, check one:
FCBP (Female of childbearing potential): sexually mature female who: 1) has not 
undergone a hysterectomy (the surgical removal of the uterus) or bilateral 
oophorectomy (the surgical removal of both ovaries) or 2) has not been naturally 
postmenopausal (amenorrhea following cancer therapy does not rule out 
childbearing potential) for at least 24 consecutive months (ie, has had menses at 
any time during the preceding 24 consecutive months)
NOT FCBP
Male:

Do Not Dispense study drug if:

The subject is pregnant.

No pregnancy tests were conducted for a FCBP.

The subject states she did not use TWO reliable methods of birth control (unless 
practicing complete abstinence of heterosexual contact) at least 28 days prior to 
therapy, during therapy and during dose interruption.
FCBP:
I verified that the required pregnancy tests performed are negative.
I counseled FCBP regarding the following:

Potential risk of fetal exposure to pomalidomide:  If pomalidomide is taken during 
pregnancy, it may cause birth defects or death to any unborn baby.  Females are 
advised to avoid pregnancy while taking pomalidomide.  The teratogenic potential of 
pomalidomide in humans cannot be ruled out.  All FCBP must agree not to become 
pregnant while taking pomalidomide. 

Using TWO reliable methods of birth control at the same time or complete abstinence 
from heterosexual contact (at least 28 days prior to therapy, during therapy, during 
dose interruption and 28 days after discontinuation of study drug).

That even if she has amenorrhea she must comply with advice on contraception.  


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
Use of one highly effective method and one additional method of birth control AT 
THE SAME TIME.  The following are examples of highly effective and additional 
effective methods of contraception:  

Highly effective methods:

Intrauterine device (IUD)

Hormonal (birth control pills, injections, implants)

Tubal ligation

Partner’s vasectomy

Additional effective methods:

Male condom

Diaphragm

Cervical Cap

Pregnancy tests before and during treatment, even if the subject agrees not to have 
reproductive heterosexual contact.  Two pregnancy tests will be performed prior to 
receiving study drug, one within 10-14 days and the second within 24 hours of the 
start of study drug.

Frequency of pregnancy tests to be done:

Every week during the first 28 days of this study and a pregnancy test every 28 
days during the subject’s participation in this study if menstrual cycles are regular 
or every 14 days if cycles are irregular.

If the subject missed a period or has unusual menstrual bleeding.  

When the subject is discontinued from the study and at Day 28 after study drug 
discontinuation if menstrual cycles are regular.  If menstrual cycles are irregular, 
pregnancy tests will be done at discontinuation from the study and at Days 14 and 
28 after study drug discontinuation.

Stop taking study drug immediately in the event of becoming pregnant and to call 
their study doctor as soon as possible. 

NEVER share study drug with anyone else.

Do not donate blood while taking study drug and for 28 days after stopping study 
drug.

Do not breastfeed a baby while participating in this study and for at least 28 days after 
study drug discontinuation.

Do not break, chew, or open study drug capsules.

Return unused study drug to the study doctor.
4. Provide Pomalidomide Information Sheet to the subject.


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FEMALE NOT OF CHILDBEARING POTENTIAL (NATURAL MENOPAUSE FOR AT 
LEAST 24 CONSECUTIVE MONTHS, A HYSTERECTOMY, OR BILATERAL 
OOPHORECTOMY):

I counseled the female NOT of childbearing potential regarding the following:

Potential risk of fetal exposure to pomalidomide (Refer to item #2 in FCBP)

NEVER share study drug with anyone else.

Do not donate blood while taking study drug and for 28 days after stopping study 
drug.

Do not break, chew, or open study drug capsules

Return unused study drug capsules to the study doctor.
5. Provide Pomalidomide Information Sheet to the subject.
MALE:

I counseled the male subject regarding the following:

Potential study drug fetal exposure to pomalidomide (Refer to item #2 in FCBP).

To engage in complete abstinence or use a condom when engaging in sexual 
contact (including those who have had a vasectomy) with a pregnant female or a 
female of childbearing potential,  while taking study drug, during dose 
interruptions and for 28 days after stopping study drug.

Males should notify their study doctor when their female partner becomes 
pregnant and female partners of males taking study drug should be advised to call 
their healthcare provider immediately if they get pregnant

NEVER share study drug with anyone else.

Do not donate blood while taking study drug and for 28 days after stopping study 
drug.

Do not donate semen or sperm while taking study drug and for 28 days after 
stopping study drug.

Do not break, chew, or open study drug capsules.

Return unused study drug capsules to the study doctor.
6. Provide Pomalidomide Information Sheet to the subject.
Investigator/Counselor Name (Print): ____________________
(circle applicable)
Investigator/Counselor Signature: _______________________ 
Date: _____/_____/_____
(circle applicable)
**Maintain a copy of the Education and Counselling Guidance Document in the subject 
records.**


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Appendix D-3:  Pomalidomide Information Sheet 
FOR SUBJECTS ENROLLED IN CLINICAL RESEARCH STUDIES
Please read this Pomalidomide Information Sheet before you start taking study drug and each 
time you get a new supply.  This Pomalidomide Information Sheet does not take the place of an 
informed consent to participate in clinical research or talking to your study doctor or healthcare 
provider about your medical condition or your treatment.  
What is the most important information I should know about pomalidomide?
1. Pomalidomide may cause birth defects (deformed babies) or death of an unborn baby.  
Pomalidomide is similar to the medicine thalidomide.  It is known that thalidomide 
causes life-threatening birth defects.  Pomalidomide has not been tested in pregnant 
women but may also cause birth defects.  Pomalidomide was found to cause birth defects 
when tested in pregnant rabbits.  If you are a female who is able to become pregnant:

Do not take study drug if you are pregnant or plan to become pregnant

You must either not have any sexual relations with a man or use two reliable, separate 
forms of effective birth control at the same time: 

for 28 days before starting study drug

while taking study drug 

during dose interruptions of study drug 

for 28 days after stopping study drug 

You must have pregnancy testing done at the following times:

within 10 – 14 days and again 24 hours prior to the first dose of study drug 

weekly for the first 28 days

every 28 days after the first month or every 14 days if you have irregular 
menstrual periods

if you miss your period or have unusual menstrual bleeding

28 days after the last dose of study drug (14 and 28 days after the last dose if 
menstrual periods are irregular)

Stop taking study drug if you become pregnant during treatment

If you suspect you are pregnant at any time during the study, you must stop study 
drug immediately and immediately inform your study doctor.  The study doctor 
will report all cases of pregnancy to Celgene Corporation. 

Do not breastfeed while taking study drug

The study doctor will be able to advise you where to get additional advice on 
contraception.


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If you are a female not of childbearing potential:
In order to ensure that an unborn baby is not exposed to pomalidomide, your study doctor 
will confirm that you are not able to become pregnant.
If you are a male:
The effect of pomalidomide on sperm development is not known and has not been 
studied.  The risk to the fetus in females of child bearing potential whose male partner is 
receiving pomalidomide is unknown at this time.  
1. Male subjects (including those who have had a vasectomy) must either not have any sexual 
relations with a pregnant female or a female who can become pregnant, or must use a 
condom during sexual contact with a pregnant female or a female that can become pregnant:

While you are taking study drug 

During dose interruptions of study drug 

For 28 days after you stop taking study drug  
b. Male subjects should not donate sperm or semen while taking study drug and for 
28 days after stopping study drug. 
c.
If you suspect that your partner is pregnant any time during the study, you must 
immediately inform your study doctor.  The study doctor will report all cases of 
pregnancy to Celgene Corporation.  Your partner should call their healthcare 
provider immediately if they get pregnant.
7. Restrictions in sharing study drug and donating blood:
1. Do not share study drug with other people.  It must be kept out of the reach of children 
and should never be given to any other person.
2. Do not donate blood while you take study drug and for 28 days after stopping study drug. 
3. Do not break, chew, or open study drug capsules.
4. You will be supplied with no more than one cycle of study drug 
5. Return unused study drug capsules to your study doctor.
Additional information is provided in the informed consent form and you can ask your study 
doctor for more information.


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Appendix E: National Cancer Institute-Common Terminology Criteria for 
Adverse Events 
The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), 
Version 4.0 (May 2009) can be viewed on-line at the following NCI web site:
http://ctep.cancer.gov/reporting/ctc.html.












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Appendix G:  Staging Systems for Multiple Myeloma
Table 9:
Staging Systems for Multiple Myeloma
Stage
Durie-Salmon Criteriaa
ISS Criteriab
I
All of the following:
Hemoglobin value > 10 g/dL
Serum calcium value normal or <  12 mg/dL
Bone x-ray, normal bone structure (scale 0), or solitary bone 
plasmacytoma only
Low M-component production rates
IgG value < 5 g/dL; 
IgA value < 3 g/dL
Urine light chain M-component on
electrophoresis < 4 g/24h
Serum beta-2 microglobulin < 3.5 mg/L
Serum albumin ≥ 3.5 g/dL
II
Neither Stage I nor Stage II
Neither Stage I nor Stage III
III
One or more of the following:
Hemoglobin value < 8.5 g/dL
Serum calcium value normal or > 12 mg/dL
Advanced lytic bone lesions  (scale 3)
High M-component production rates
IgG value > 7 g/dL; 
IgA value > 5 g/dL
Urine light chain M-component on
electrophoresis > 12 g/24h
Serum beta-2 microglobulin ≥ 5.5 mg/L
Subclassification Criteria
A  Normal renal function (serum creatinine value < 2.0 mg/dL)
B  Abnormal renal function (serum creatinine value ≥ 2.0 mg/dL)
Not applicable


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Appendix H: ECOG Performance Status Scale
Table 10:
Eastern Cooperative Oncology Group Performance Status Grade
Description
Grade
Fully active, able to carry on all pre-disease activities without restriction.
0
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.
1
Ambulatory and capable of all self-care but unable to carry out any work activities.  Up and 
about more than 50% of waking hours.
2
Capable of only limited self care, confined to bed or chair more than 50% of waking hours.
3
Completely disabled.  Cannot carry on any self-care.  Totally confined to bed or chair.
4
Dead
5
 


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Appendix I: International Myeloma Working Group Response Criteria
Table 11:
International Myeloma Working Group Response Criteria
Response Category
Response Criteriaa
SCR
CR as defined below plus
Normal FLC ratio and
Absence of clonal cells in bone marrow
b by immunohistochemistry or immunofluorescence
c
CR
Negative immunofixation on the serum and urine and disappearance of any soft tissue 
plasmacytomas and ≤ 5% plasma cells in bone marrowb
VGPR
Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 
90% or greater reduction in serum M-protein plus urine M-protein level < 100 mg per 24 
hours
PR
≥ 50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by ≥ 90% 
or to < 200 mg per 24 hours
If the serum and urine M-protein are unmeasurabled a ≥ 50% decrease in the difference 
between involved and uninvolved FLC levels is required in place of the M-protein criteria
If serum and urine M-protein are unmeasurable, and the serum free light assay is also 
unmeasurable, ≥ 50% reduction in plasma cells is required in place of M-protein provided 
baseline bone marrow plasma cell percentage was ≥ 30%
In addition to the above, if present at baseline a ≥ 50% reduction in the size of soft tissue 
plasmacytomas is also required
SDe
Not meeting criteria for CR, VGPR, PR, or progressive disease
Relapse Categoryf
Relapse Criteria
Progressive disease
Requires only one of the following:
Increase of ≥ 25% from nadir in:
Serum M-component and/or (the absolute increase must be ≥ 0.5 g/dl)
g
Urine M-component and/or (the absolute increase must be ≥ 200 mg/24 hours)
In subjects without measurable serum and urine M-protein levels the difference between 
involved and uninvolved FLC levels, the absolute increase must be > 100 mg/l.
Bone marrow plasma cell percentage, the absolute % must be ≥ 10%
h
Definite development of new bone lesions or soft tissue plasmacytomas increase in the size 
of existing bone lesions or soft tissue plasmacytomas.
Development of hypercalcemia (corrected serum calcium > 11.5 mg/dl or 2.65 mmol/l) that 
can be attributed solely to the plasma cell proliferative disorder.


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Table 11:
International Myeloma Working Group Response Criteria (Continued)
Relapse Categoryf
Relapse Criteria
Clinical relapse
Clinical relapse requires one or more of:
(Not used for TTP or 
PFS)
Development of new soft tissue plasmacytoma or bone lesions
Definite increase in the size of existing plasmacytomas or bone lesions.  A definite increase 
is defined as a 50% (and at least 1 cm) increase as measured serially by the sum of the 
products of the cross-diameters of the measurable lesion
Hypercalcemia (> 11.5 mg/dl [2.65 mmol/l])
Decrease in hemoglobin of ≥ 2 g/dl (1.25 mmol/l)
Rise in serum creatinine by 2 mg/dl or more (177 μmol/l or more)
Relapse from CR i
Any one or more of the following:
Reappearance of serum or urine M-protein by immunofixation or electrophoresis
Development of ≥ 5% plasma cells in the bone marrow
h
Appearance of any other sign or progression
a All response categories require two consecutive assessments made at any time before the institution of any new therapy; all 
categories also require no known evidence of progressive or new bone lesions if radiographic studies were performed.  
Radiographic studies are not required to satisfy these response criteria.
b Confirmation with repeat biopsy not necessary.
c Presence/absence of clonal cells is based upon the κ/λ ratio by immunohistochemistry and/or immunofluorescence requires a 
minimum of 100 plasma cells for analysis.  An abnormal ration reflecting presence of an abnormal clone is κ/λ of > 4:1 or < 
1:2.
d Applicable only to subjects who have ‘measurable’ disease defined by at least one of the following three measurements: Serum 
M-protein ≥ 1 g/dl, Urine M-protein ≥ 200 mg/24hour, Serum FLC assay involved FLC level ≥ 10 mg/dl provided serum FLC 
ration is abnormal.
e Not recommended for use as an indicator of response; stability of disease is best described by providing the time too 
progression estimates).
f All relapse categories require two consecutive assessments made at any time before classification as relapse or disease 
progression and/or the institution of any new therapy.
g For progressive disease, serum M-component increases of ≥ 1 g/dl are sufficient to define relapse if starting M-component is ≥ 
5 g/dl.
h Relapse from CR has the 5% cutoff versus 10% for other categories or relapse.
i To only be used if the end point studied is disease free survival.  For purposes of calculating time to progression and 
progression-free survival, CR subjects should also be evaluated using criteria listed above for progressive disease.


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Appendix J:  Pharmacokinetic Sample Handling Instructions
All required labels will be prepared by the Central Lab.  Labels must contain the following 
information:

Protocol No.: CC-4047-MM-010

Subject ID number

Visit: e.g., Cycle 1, Day 15

Nominal Collection Time (if applicable): e.g, pre-dose

Sample Type: Plasma (primary) or Plasma (back-up)
All blood and plasma collection tubes and storage vials should be labeled and chilled on wet ice 
prior to sample collection and processing.
Blood Sample Collection

Fill an ice bucket with a sufficient amount of ice to pre-chill all collection tubes 
before blood draw.

Collect approximately 3 mL of whole blood into a pre-chilled K3 EDTA tube. 

Accurately record the time of blood collection.

Gently invert the tube 3 to 5 times and immerse it in the ice bath immediately to 
prevent possible compound degradation at room temperature.
Blood Sample Processing to Obtain Plasma

Within 30 minutes of collection, the blood sample must be centrifuged at 1,500 g 
(about 3,000 rpm) for 10 min at 4°C to obtain plasma with refrigerated centrifuge   

Transfer approximately 1 mL of plasma into each of the two pre-labeled, pre-chilled, 
citric acid-containing polypropylene storage tubes (one primary and one back-up, to 
be provided by Celgene).  Keep storage tubes on ice before they are ready to be 
transferred into a freezer.

Within 60 minutes of blood collection, transfer plasma samples in storage vials into a 
–20°C freezer, where they will remain stored until shipping.

Immediately record the time of sample entry into the freezer.
NOTE: All secondary (backup) samples will be maintained at the Central Lab until they are 
requested by the Celgene representative to be shipped to the bioanalytical laboratory (or another 
facility) or be destroyed at the investigator site.
PK Sample Shipment

All PK sample label information on the storage tubes have to be checked against the 
requisition form and then the samples must be shipped frozen and on dry ice to the 
central lab.


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Sample Collection Documents to Accompany Shipment(s)
A copy of the completed specimen inventory log(s) must accompany the shipment, and must list 
the following information at minimum:

Sponsor name: Celgene Corp

Celgene Study Number: CC-4047-MM-010

Subject ID Numbers

Visit: e.g., Cycle 1, Day 15

Nominal collection times

Sample types (eg, primary plasma or back-up plasma)


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Appendix K:  List of Abbreviations 
Table 12:
List of Abbreviations    
Abbreviation
Definition
ADCC
Antibody-dependent cell-mediated cytotoxicity
AE
Adverse event
ALC
Absolute lymphocyte count
ALT
Alanine aminotransferase
ANC
Absolute neutrophil count
ASCT
Autologous stem cell transplant
AST
Aspartate aminotransferase
BMSC
Bone marrow stromal cell
CR
Complete response
CrCl
Creatinine clearance
CRF
Case report form
CT
Computerized tomography
DEX
Dexamethasone
DLT
Dose limiting toxicity
DMC
Data monitoring committee
DoR
Duration of response
DVT
Deep vein thrombosis
EAP
Expanded access program
ECG
Electrocardiogram
ECOG
Eastern Cooperative Oncology Group
eCRF
Electronic case report form
EEA
European Economic Area
EMP
Extramedullary plasmacytoma
ER
Exposure-response
ESMO
European Society for Medical Oncology
EU
European Union
FCBP
Females of childbearing potential
FISH
Fluorescence in situ hybridization


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Table 12:
List of Abbreviations (Continued)
Abbreviation
Definition
FLC
Free light-chain
GCP
Good clinical practice
GCSF
Granulocyte colony-stimulating factor
GFR
Glomerular filtration rate
GGT
Gamma glutamyl transpeptidase
HCG
Human chorionic gonadotropin
HD-DEX
High-dose dexamethasone
HIV
Human immunodeficiency virus
ICD
Informed consent document
ICH
International Conference on Harmonization
IFE
Immunofixation
Ig
Immunoglobulin
IL
Interleukin
IMWG
International Myeloma Working Group
IP
Investigational product
IRB/EC
Institutional review board/ Ethics Committee
ITT
Intention-to-treat
IVRS/IWRS
Interactive voice/web response system
LD-DEX
Low-dose dexamethasone
LLN
Lower limit of normal 
LPS
Lipopolysaccharide
MDRD
Modification of Diet in Renal Disease
MedDRA
Medical Dictionary for Regulatory Activities
MM
Multiple myeloma
MR
Minor response
MRI
Magnetic resonance imaging
MTD
Maximum tolerated dose
NCCN
National Comprehensive Cancer Network
NCI-CTCAE
National Cancer Institute Common Terminology Criteria for Adverse 
Events
ORR
Overall response rate


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Table 12:
List of Abbreviations (Continued)
Abbreviation
Definition
OS
Overall survival
PD
Progressive disease
PD
Pharmacodynamics 
PE
Pulmonary embolism
PFS
Progression-free survival
PK
Pharmacokinetics
POM
Pomalidomide
PP
Per protocol
QTc
QT corrected
PR
Partial response
RBC
Red blood cell
RR
Response rate
SAE
Serious adverse event
SCR
Stringent complete response
SD
Stable disease
SGOT
Serum glutamic oxaloacetic transaminase
SGPT
Serum glutamic pyruvic transaminase
SNP
Single-nucleotide polymorphism 
SOP
Standard Operating Procedures
SPEP
Serum protein electrophoresis
SPM
Second primary malignancy
SUSAR
Suspected unexpected serious adverse reaction
TEAE
Treatment-emergent adverse event
TNF
Tumor necrosis factor
TNM
Tumor, node, metastasis
TTP
Time to disease progression
ULN
Upper limit of normal
UPEP
Urine protein plectrophoresis
US
United States
VGPR
Very Good Partial Response
vs.
Versus 
VTE
Venous thrombotic event


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Abbreviation
Definition
WBC
White blood cells

SAP_001.pdf: 
Official Title of Study: 
A MULTICENTER, SINGLE-ARM, OPEN-LABEL STUDY WITH POMALIDOMIDE IN COMBINATION 
WITH LOW DOSE DEXAMETHASONE IN SUBJECTS WITH REFRACTORY OR RELAPSED AND 
REFRACTORY MULTIPLE MYELOMA 
NCT Number: NCT01712789 
Document Date (Date in which document was last revised): March 6, 2015 


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STATISTICAL ANALYSIS PLAN
A MULTICENTER, SINGLE-ARM, OPEN-LABEL
STUDY WITH POMALIDOMIDE IN COMBINATION 
WITH LOW DOSE DEXAMETHASONE IN SUBJECTS
WITH REFRACTORY OR RELAPSED AND
REFRACTORY MULTIPLE MYELOMA
STRATUS
STUDY DRUG:
Pomalidomide (CC-4047)
PROTOCOL NUMBER:
CC-4047-MM-010
ORIGIONAL DATE:
19 September 2013
AMENDMENT 1 DATE:
06 March 2015
Prepared by:
Celgene Corporation
CONFIDENTIAL
The information contained in this document is regarded as confidential 
and, except to the extent necessary to obtain informed consent, may not 
be disclosed to another party unless such disclosure is required by law or 
regulations.  Persons to whom the information is disclosed must be 
informed that the information is confidential and may not be further 
disclosed by them.


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INDEX
ABBREVIATIONS ..........................................................................................................................7
1.
INTRODUCTION ........................................................................................................9
1.1.
Summary of Change..................................................................................................9
2.
OBJECTIVES.............................................................................................................11
3.
INVESTIGATIONAL PLAN .........................................................................................12
3.1.
Overall Study Design and Plan ................................................................................12
3.2.
Study Populations...................................................................................................13
3.3.
Study Endpoints......................................................................................................13
3.4.
Stratification , Randomization and Blinding ............................................................14
3.5.
Sample Size.............................................................................................................14
4.
GENERAL STATISTICAL CONSIDERATIONS ...............................................................15
4.1.
Reporting Conventions ...........................................................................................15
4.1.1.
Dates Handling .......................................................................................................15
4.1.2.
Calculation Using dates...........................................................................................16
4.1.3.
Calculation of Cycles...............................................................................................17
4.1.4.
P value reporting ....................................................................................................17
4.1.5.
Duplicate Subject Identification Number ................................................................18
5.
ANALYSIS POPULATIONS.........................................................................................19
5.1.
Safety Population ...................................................................................................19
5.2.
Intention-to-Treat Population.................................................................................19
5.3.
Efficacy Evaluable Population .................................................................................19
6.
SUBJECT DISPOSITION.............................................................................................20
7.
DEMOGRAPHICS, BASELINE CLINICAL CHARACTERISTICS, AND MEDICAL AND 
TREATMENT HISTORIES ..........................................................................................22
7.1.
Demographic and Baseline Clinical Characteristics..................................................22
7.2.
Medical History ......................................................................................................22
7.3.
Prior Medications ...................................................................................................23
7.4.
Other Medical History related to Refractory or Relapsed and Refractory 
Multiple Myeloma ..................................................................................................23
7.5.
Cytogenetic Analysis...............................................................................................23
8.
STUDY TREATMENTS AND EXTENT OF EXPOSURE ...................................................24


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8.1.
Treatment Duration................................................................................................24
8.2.
Cumulative Dose.....................................................................................................24
8.3.
Dose Exposure........................................................................................................24
8.4.
Average Daily Dose.................................................................................................24
8.5.
Dose Intensity.........................................................................................................24
8.6.
Relative Dose Intensity ...........................................................................................24
8.7.
Dose Modifications.................................................................................................25
10.
STATISTICAL ANALYSIS OF EFFICACY ENDPOINTS ....................................................27
10.1.1.
Overall Response Rate............................................................................................27
10.1.2.
Time to Response ...................................................................................................27
10.1.3.
Time to Event Analyses...........................................................................................27
11.
STATISTICAL ANALYSIS OF SAFETY ENDPOINTS .......................................................32
11.1.1.
Adverse Events.......................................................................................................32
Adverse Events of Special Interest.............................................................................................32
11.1.2.
Second Primary Malignancies .................................................................................34
11.1.3.
Deaths....................................................................................................................34
11.1.4.
Clinical Laboratory Evaluations ...............................................................................34
11.1.5.
Vital Signs ...............................................................................................................34
11.1.6.
Electrocardiogram ..................................................................................................35
11.1.7.
ECOG Performance Status ......................................................................................35
12.
PHARMACOKINETIC ANALYSIS ................................................................................36
12.1.
Software for Analysis..............................................................................................36
12.2.
Analysis population ................................................................................................36
12.3.
Pharmacokinetic Analysis .......................................................................................36
12.3.1.
Data handling .........................................................................................................36
12.3.2.
Statistical Analysis ..................................................................................................36
 
13.
EXPOSURE-RESPONSE ANALYSIS.............................................................................37


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APPENDICES..............................................................................................................................40
Appendix A: Date Imputation Guideline ....................................................................................40
Appendix B: Tables Graphs and Listings.....................................................................................43


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LIST OF TABLES
Table 1: Event and Censoring Rules for Progression Free Survival .............................................28


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SIGNATURE PAGE


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ABBREVIATIONS
Abbreviation 
Explanation
AE
Adverse Event
AMA
American Medical Association
ATC
Anatomical Therapeutic Chemical
AUC
Area under the curve
BP
Blood Pressure
CIs
Confidence Intervals
CR
Complete Response
CRF
Case Report Form
CSR
Clinical study report
CTCAE
Common Terminology Criteria for Adverse Events
DDI
Delivered Dose Intensity
DoR
Duration of response
ECG
Electrocardiogram
ECOG
Eastern Cooperative Oncology Group
EE
Efficacy Evaluable
FCBP
Female of child bearing potential
FISH
Fluorescence in situ Hybridization
IMWG
International Myeloma Working Group
ICD
Informed consent document
IP(s)
Investigational Product(s)
ITT
Intention-to-treat
IVRS
Interactive voice response system
IWRS
Interactive web response system
LD-DEX
Low-Dose Dexamethasone
MedDRA
Medical Dictionary for Regulatory Activities
MM
Multiple Myeloma
mmHg
millimeter of mercury
NCI 
National Cancer Institute 


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Abbreviation 
Explanation
ORR
Overall Response Rate
OS
Overall Survival
PD
Progressive Disease / Pharmacodynamics
PDI
Planned Dose Intensity
PFS
Progression Free Survival
PK
Pharmacokinetics
POM
Pomalidomide
PP
Per-protocol
PR
Partial Response
RDI
Relative Dose Intensity
SAP
Statistical Analysis Plan
SAS
Statistical Analysis Systems
sCR
Stringent Complete Response
SD
Stable Disease
SPM
Second Primary Malignancy
TEAE
Treatment-Emergent Adverse Event
TTP
Time to Progression
TTR
Time to Response
VGPR
Very Good Partial Response
WHO
World Health Organization


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1.
INTRODUCTION
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1.1.
Summary of Change
Major revisions from the 19 September 2013 version to the current version are:

The efficacy evaluable population has been substituted for the per-protocol 
population for the analysis of the following endpoints: overall response rate (ORR), 
time to response (TTR), duration of response (DoR), time to progression (TTP), 
progression free survival (PFS) and overall survival (OS).

Removal of all sub-group analyses.
The following aspects of data handling methods are modified with more details added:

Additional censoring and event rules for PFS and DoR.

Correction of the calculation for cycle length.

Clarification of the definition of ‘baseline’.
The following points are additions to this SAP version:


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
Clarification that the PK and PD related table, figures and listings will be provided in 
a separate delivery document.

Clarification that the cytogenetic sub-group analysis will be provided in a separate 
report. 

Identification of drug classification groups of prior anti-multiple myeloma (MM) 
drugs.

Additional imputation rules for incomplete dates with regards to diagnosis date, 
prior and subsequent anti-myeloma therapy dates.


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2.
OBJECTIVES
The primary objective of the study is to evaluate the safety of the combination of POM and LD-
DEX in a large cohort of subjects with refractory MM or relapsed and refractory MM.
The secondary objectives of the study are to:

Analyze the population pharmacokinetics of POM and assess POM exposure 
response relationships in subjects with refractory MM or relapsed and refractory 
MM administered POM and LD-DEX.

Evaluate efficacy of the combination of POM and LD-DEX in subjects with refractory 
MM or relapsed and refractory MM.

Evaluate the relationship between cytogenetic profiles and the combination of POM 
and LD-DEX in terms of response and outcome.
 
 
 
 
 


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3.
INVESTIGATIONAL PLAN
3.1.
Overall Study Design and Plan
This study is a multicenter, single-arm, open label study of POM in combination with LD-DEX in 
subjects with refractory or relapsed and refractory MM.  Approximately 720 subjects who 
satisfy study inclusion and exclusion criteria will be enrolled into the study (for detailed subject 
eligibility see sections 7.2 and 7.3 of Protocol CC-4047-MM-010). There are three periods to this 
study: The screening period (defined as days -28 to 0 prior to start of the investigational 
product [IP]), the Treatment period starting at the moment of first administration of the IP 
defined as Cycle 1 Day 1 until start of follow-up, and the Follow-up period which starts at the 
time of the permanent IP discontinuation and which continues until all subjects have been 
followed for up to 5 years after the last issued interactive voice/web response system
(IVRS/IWRS) enrollment date if still alive and not lost-to-follow-up, or longer if clinically 
relevant.
Subjects will undergo screening within 28 days prior to Cycle 1 Day 1 and be treated in 28-day 
cycles.  Subjects will remain on treatment with the IP until a specific event, including, but not 
limited to, progressive disease (PD), intolerance due to toxicity, death, withdrawal of consent,
non-compliance with the IP, and becoming lost-to-follow-up.
An outline of study time points and corresponding assessments due at those times are 
presented in Table 1: Table of Events (see section 5 of Protocol CC-4047-MM-010). Safety
assessments will be performed during the Screening period and on Day1 (± 1 day) of each cycle 
as well as the time of IP discontinuation. Additional safety assessments (hematology, serum 
chemistry and estimation of renal function) shall be performed on day 15 (± 2 days) of cycles 1 
to 6 while vital signs shall also be collected at a follow-up visit to take place within 28 days post 
discontinuation of the IP. 
Pregnancy testing for females of child bearing potential (FCBP) and pregnancy counseling shall 
be assessed during the Screening period, Day 1 (± 1 day) of each cycle and at the time of the IP
discontinuation. An additional pregnancy test for FCBP shall be conducted within 28 days post 
IP discontinuation.
Efficacy measurements shall be collected during the Screening period, at Day 1 (± 1 day) of each 
cycle and within 28 days post IP discontinuation, with the exception of response assessments 
which will not be collected during the Screening period. Survival status and recording of 
subsequent anti-myeloma regimens will be recorded within 28 days post IP discontinuation and 
during the Follow-up period every 3 months (84 ± 14 days). 
Note that the visit (or assessment) occurring just prior to initiation of the IP is defined as 
“baseline” (i.e., Day 1 of Cycle 1). However, data from the Screening period will be substituted 
for a given measure if data at Day 1 Cycle 1 is not available.
Dose modifications and interruptions of the IP are permitted throughout the study.


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Subjects will remain on study until a specific event, including, but not limited to, becoming lost-
to-follow-up, death and withdrawal of consent.
The first full analysis of the primary and secondary endpoint will be conducted once all enrolled 
subjects have completed up to 2 cycles of the IP if having not stopped therapy earlier.
A final, updated, analysis will be conducted at the time of study close, the point when all 
subjects will have discontinued from the study, i.e. 5 years from the last issued IVRS enrollment 
date if having not discontinued from the study before this point.
3.2.
Study Populations
The study population includes refractory MM subjects or relapsed and refractory MM subjects. 
All subjects must have documented progressive disease (PD) on or within 60 days of their last 
treatment, after receiving at least 2 lines of treatment, and must have received a minimum of 2 
consecutive cycles of prior treatment regimens that included bortezomib and lenalidomide, 
either in combination or in separate regimens. These include:

Subjects classified as refractory must have progressed during or within 60 days of 
treatment with bortezomib and/or lenalidomide.

Subjects classified as relapsed, who previously responded to bortezomib and/or 
lenalidomide with at least partial response (PR) must have progressed within 6 
months of ending treatment with bortezomib and/or lenalidomide.

Subjects who have not achieved at least minimal response (MR) who have 
developed intolerance or toxicity after a minimum of 2 cycles of bortezomib.

Subjects who are eligible for or who are planning to receive bone marrow transplant 
are not eligible for this study.
3.3.
Study Endpoints
The primary endpoint is:

The incidence of adverse events (AE) (type, frequency, seriousness, severity, 
relationship to POM and /or DEX, and outcomes), including second primary malignancy 
(SPM).
The secondary endpoints are:

POM exposure

POM population PK and exposure response

Overall response rate (ORR)


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
Time to response (TTR)

Duration of response (DoR)

Progression free survival (PFS)

Time to progression (TTP)

Overall survival (OS)

Analysis of cytogenetic profiles
3.4.
Stratification , Randomization and Blinding
Subjects will not be randomized or blinded due to the study being a single-arm study.
3.5.
Sample Size
Approximately 720 subjects across twenty-one European countries will be enrolled into this 
study. This sample size has been determined to enable the characterisation of currently 
infrequent AEs. As such, a sample size of 720 subjects will allow detection of any infrequent AE, 
defined as an AE with a frequency of 0.4% (3/720), assuming a study power of 95%. Under this 
calculation, an infrequent event with a frequency of 0.4% will be confirmed if at least 1 of 720
evaluable subjects experiences such an event.


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4.
GENERAL STATISTICAL CONSIDERATIONS
In general and unless otherwise noted, continuous variables will be summarised using the 
following summary statistics; N, Mean, Standard Deviation, Median, Minimum and Maximum.  
Categorical variables will be summarized using frequency tabulations (i.e., counts and 
percentages).  In the case of missing categorical data, an “unknown” category will be created
for reporting purposes, but subjects or records included in this category will not be included in 
the denominator when calculating percentages.
4.1.
Reporting Conventions
Summary tables, listings, and any supportive SAS output will include a “footer” of explanatory 
notes that will indicate, at a minimum, the following: 

Program source (e.g., SAS program name and the path that generates the output)

Data extraction date (e.g., the database lock date, run date)
The purpose of the data extraction date is to link the output to a final database, either active or 
archived, that is write-protected for replication and future reference.  An output date will also 
appear on each output page and will indicate the date the output was generated by the analysis 
program. Individual source listings will display all the relative values supporting corresponding 
tables and figures.
4.1.1.
Dates Handling
Dates will be stored as numeric variables in the SAS analysis files and reported in DDMMMYYYY 
format (i.e., the Date9. datetime format in SAS).  Dates in the clinical database are classified 
into the categories of procedure dates, log dates, milestone dates, outcome dates, and special 
dates.

Procedure Dates are the dates on which given protocol-specified procedure are 
performed.  They include the dates of laboratory testing, physical examinations, 
tumor scans, etc.  They should be present whenever data for a protocol-specified 
procedure is present and should only be missing when a procedure is marked as 
NOT DONE in the database.  Procedure dates will not be imputed.

Log Dates are dates recorded in the case report form (CRF) data logs.  Specifically, 
they are the start and end dates for AEs and concomitant medications/procedures.  
They should not be missing unless an event or medication is marked as ongoing in 
the database.  Otherwise, incomplete log dates will be imputed according to the 
rules in Appendix A of this SAP: Date Imputation Guideline (e.g., for duration or cycle 
assignment etc.). However, in listings, log dates will be shown as recorded without 
imputation.


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
Milestone Dates are dates of protocol milestones such as enrollment date, study 
drug start date, study termination, etc.  They should not be missing if the milestone 
occurs for a subject.  They will not be imputed.

Outcome Dates are dates corresponding to study endpoints such as survival, disease 
progression, etc.  In most cases they are derived either from a milestone (e.g., the 
survival date is derived from the death date), or a procedure date (e.g., the 
progression date is derived from the date of the tumor scan that was used to 
determine progression).  They may be subject to endpoint-specific censoring rules if 
the outcome event, for instance, did not occur; otherwise they are not subject to 
imputation.

Special Dates cannot be classified in any of the above categories and they include, 
for example, the date of birth.  They may be subject to variable-specific censoring 
and imputation rules (see Section 4.1.2. below).
Dates recorded in comment fields will not be imputed or reported in any specific format. 
4.1.2.
Calculation Using dates
Calculations using dates (e.g., subject’s age or relative day after the first dose of the IP) will 
adhere to the following conventions: 

Study days after the start day of study drug will be calculated as the difference 
between the date of interest and the first date of dosing of the IP plus 1 day. The 
generalised calculation algorithm for a relevant day is:
STUDY DAY = [(TARGET DATE – DSTART) + 1], where DSTART = the start day of study 
drug.
Study days before the start day of study drug will be calculated as the difference 
between the date of interest and the first date of the IP.
Note that Study Day 1 is the first day of treatment of study drug. Negative and zero
study days are reflective of observations obtained during the baseline/screening 
period.  Note: Partial date for the first study drug is not imputed in general. All effort 
should be tried to avoid incomplete study drug start date. 

For all efficacy analyses, time-to-event days for efficacy endpoints will be calculated 
as the difference between the date of event and the enrollment date plus 1 day.

Age (expressed in days) is calculated as:
AGE = [CONSENT – DATE OF BIRTH + 1], where CONSENT = the date the informed 
consent document (ICD) was signed.
In practice, age will be transformed into years by dividing the difference by 365.25 
days, then truncating the divided difference to the nearest year.
o
Prefer using calculated age from clinical database. When not available, may 
use calculated age from the CRF or the IVRS


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o
Partial birth date: impute a missing day as the 15th day of the month; impute 
a missing month as July; set age as missing if year is missing

Intervals that are presented in weeks will be transformed from days (as calculated 
above) to weeks by using (without truncation) the following conversion formula:
WEEKS = DAYS /7

Intervals that are presented in months will be transformed from days (as calculated 
above) to months by using (without truncation) the following conversion formula:
MONTHS = DAYS /30.4167
4.1.3.
Calculation of Cycles
The start date of each treatment cycle will be calculated based on study drug exposure records 
for each subject. The start date of the first cycle will be the date when the subject receives any 
study drug.
Once the start dates, e.g., S1, S2, S3… are calculated, the end date of each cycle is calculated as 
the day before the start date of the following cycle, i.e., Ei = Si+1 - 1. For the last cycle, the end
date (if missing or less than 28 days after start of cycle) will be calculated as the start date plus
the prescribed cycle length (28) - 1, or the death date, or the discontinuation date, whichever is 
earlier. 
The cycle number for each date of interest, e.g., AE or lab, will be calculated based on the cycle 
window set by their start and end dates. If a date is on or after Si and before Si+1, the 
corresponding cycle number will be cycle i.
Once the cycles are derived, they can be used to attribute adverse events to a specific cycle 
based upon the following rules: the start date of the adverse event should be included in a 
given cycle or if the start date does not fit in any defined cycle, the adverse event will be 
attributed to the previous cycle if the AE has started within 28 days after the end of the cycle.
4.1.4.
P value reporting
Although formal hypothesis testing is not planned for the analysis, should any testing be 
undertaken (e.g., a paired t-test for change in vital signs measurements), p values will be 
reported per the American Medical Association (AMA) Style Guide.  Specifically, in tables, 
column headers for p values will be referred to as “P value."  Actual p values will contain no 
leading zeros.  All p values will be reported as exact numbers to 2 decimal places, regardless of 
significance, unless they are lower than 0.01, in which case they should be presented to 3 
decimal places. Furthermore, in the event a p value is between 0.045 and < 0.050, three 
decimal places will be reported. For p values lower than 0.001 will be expressed as “< .001.”


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4.1.5.
Duplicate Subject Identification Number
Subjects entered twice with two different subject identification numbers will have the inactive 
identification number allocated to a dummy site to avoid duplicate information appearing in 
tables and listings. 


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5.
ANALYSIS POPULATIONS
5.1.
Safety Population
The safety population includes all enrolled subjects who received at least one dose of the IP and 
shall be used for analysis of all safety endpoints (e.g. the incidence of AEs and SPMs).
5.2.
Intention-to-Treat Population
The intention-to-treat (ITT) population is defined as all enrolled subjects (subjects receiving an
IVRS enrollment date) regardless of whether they received any IP or not. The ITT population
shall be used for the analysis of all efficacy endpoints (i.e. ORR, TTR, DoR, PFS, TTP and OS).
5.3.
Efficacy Evaluable Population
The efficacy evaluable (EE) population is defined as all ITT subjects who take at least one dose 
of IP, who have baseline disease measurement and at least one post-baseline disease 
measurement or PFS event. The EE population should be used for analyses of the following 
endpoints: ORR, TTR, DoR, TTP, PFS and OS.
For the purpose of the clinical study report (CSR) deliverables, the EE population substitutes the 
Per-protocol population outlined in the study protocol.


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6.
SUBJECT DISPOSITION
A summary of subject disposition (analysis population allocation, subjects entered, subjects 
discontinued, along with primary reason for both IP and study discontinuation) will be
presented for each of the analysis populations (ITT Population and Safety Population) and will 
be summarized using frequency and corresponding percentage.
Reasons for discontinuing the IP will be collected on the CRF and will be summarised for all 
subjects with the following categories possible:

Death

Adverse event

Pregnancy

Progressive disease

Lack of efficacy

Recovery

Withdrew consent

Non-compliance with the study drug

Lost to follow-up

Study terminated by sponsor

Transition to commercially available treatment

Protocol violation (specify)

Other (specified)
Among those who discontinue the IP, the number of subjects who then discontinue from the 
study versus those that enter follow-up will be summarised.
Reasons for discontinuing the study will be collected on the CRF and will be summarized for all 
subjects with the following categories possible:

Screen failure

Death

Adverse event

Pregnancy

Progressive disease


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
Lack of efficacy

Recovery

Withdrew consent

Non-compliance with the study drug

Lost to follow-up

Study terminated by sponsor

Transition to commercially available treatment

Protocol violation (specify)

Other (specified)
A summary tabulation will be provided for subjects enrolled by study center. Duration of study 
participation, defined as the time from IVRS enrollment date to IP discontinuation date (or the 
date of last visit for subjects still receiving the IP at the time of study close), will be summarized.
A separate listing will be provided for subjects who have signed consent but are not enrolled 
because of not meeting all inclusion/exclusion criteria (i.e., screen failure subjects). The reasons 
for screen failure will be tabulated.
Protocol deviations and violations will be presented in a data listing and summarized by 
categories in summary tables per deviation/violation type using frequency and corresponding 
percentage of occurrence.


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7.
DEMOGRAPHICS, BASELINE CLINICAL CHARACTERISTICS, AND MEDICAL 
AND TREATMENT HISTORIES
Summaries for the demographics and baseline characteristics will be produced for the safety
and ITT populations individually. Summaries of medical history and prior therapies and 
medications will be produced for subjects in the ITT population. Individual subject listings will 
be provided to support summary tables.
7.1.
Demographic and Baseline Clinical Characteristics
Subjects’ age, height, weight and other baseline continuous characteristics (e.g., vital signs, 
laboratory data) will be summarized with summary statistics (n, mean, standard deviation, 
median, minimum and maximum), while gender, ethnicity, race, and other baseline categorical 
characteristics [e.g., age category (<65 vs. ≥ 65), electrocardiogram (ECG) interpretation, 
Eastern Cooperative Oncology Group (ECOG) performance status] will be reported using 
frequency tabulations showing frequency and corresponding percentages. Baseline is defined 
as the last measurement before the first dose of the IP (or the last measurement before 
enrollment in case the first dose date is missing). When there are retested values, the retest 
values will be used for the analysis.
Stage of MM and duration in years of MM will be summarized descriptively. Serum and urine 
heavy chain type, light chain type, and type of light chain disease from immunofixation will be 
tabulated descriptively. Presence of bone lesions, presence of plasmacytoma, development of 
hypercalcemia, increasing Myeloma paraprotein will be tabulated descriptively.
7.2.
Medical History
Medical and surgical history will be coded using the Medical Dictionary for Drug Regulatory 
Activities (MedDRA) Version 15.0 or higher. System organ class and preferred term will be 
summarized by frequency and percentage. Prior Anti-myeloma Therapies, Radiotherapy, and 
Surgeries.
Prior anti-myeloma drugs will be summarized using frequency tabulations by preferred term 
[World Health Organization (WHO) dictionary term version in use at the time of analysis]. A 
summary of last prior anti-MM drugs (i.e., drugs included in the last anti-MM regimen prior to 
study entry) will also be produced.
Exposure (Y/N) to selected prior anti-MM therapies and regimens and refractory (Y/N) to 
selected prior anti-MM drugs and regimens will also be summarized using frequency 
tabulations.


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Prior anti-MM drugs will also be classified to one of the following drug classes and tabulated: 
Immunomodulatory compounds, Proteasome inhibitors, Corticsteroids, Alkylators, 
Anthracyclines, Nitrosourreas, Alkaloids, Platinum, and other novel agents.
Evidence of disease progression on the last lenalidomide-containing regimen, evidence of 
disease progression the last Bortezomib-containing regimen and evidence of the most recent 
disease progression (i.e., progression on the last treatment if it did not include lenalidomide 
and/or Bortezomib).
7.3.
Prior Medications
Prior medications are defined as medications that were started before the start of the study
treatment (regardless whether or not ended before the start of the study treatment). Prior
medications that continue into study treatment period will also be reported as concomitant
therapy.
All prior medications will be summarized in frequency tabulations. The Anatomical Therapeutic
Chemical (ATC) coding scheme of the WHO dictionary term (according to the version in use at 
the time of analysis) will be used to group medications into relevant categories for these 
tabulations.
7.4.
Other Medical History related to Refractory or Relapsed and 
Refractory Multiple Myeloma
Prior venous thromboembolic events, prior cancer history and corresponding treatments will be 
summarized with summary statistics or frequency distributions, as appropriate.
7.5.
Cytogenetic Analysis
Subjects will be considered as having a ‘modified high risk’ cytogenetic profile if having either a 
17 p Deletion or t(t;14) translation abnormality based on adequate cytogenetic sample(s).
Subjects will be considered as having a ‘standard risk’ cytogenetic profile if having neither a 17 
p Deletion nor a t(t;14) translation abnormality based on adequate cytogenetic sample(s).
The cytogenetic sub-group analysis will be provided in a separate report.


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8.
STUDY TREATMENTS AND EXTENT OF EXPOSURE
Treatment duration, cumulative dose, dose exposure, average daily dose, relative dose 
intensity, and dose modification will be assessed separately for POM and LD-DEX as well as 
combined.  Summary statistics will be reported for treatment duration, cumulative dose, dose 
exposure, average daily dose, dose intensity, relative dose intensity, and dose 
modification/interruption. 
8.1.
Treatment Duration
The treatment duration (weeks) is defined as:
[(last cycle end date) – (date of the first study drug administration) + 1] / 7
where ‘last cycle end date’ is defined in section 4.1.3: Calculation of Cycles, in this document.
Summary statistics will be provided for treatment duration for overall treatment (i.e., either 
pomalidomide or dexamethasome, whichever is earliest for the ‘date of the first study drug 
administration’ and whichever is later for the ‘last cycle end date’), as well as for pomalidomide 
and dexamethasone separately.
Additional summaries will be created for all treated subjects, displaying number of subjects 
treated by the number of cycles administered. 
8.2.
Cumulative Dose
Cumulative dose is defined as the sum of all doses taken across the treatment period (in 
milligrams) and will be calculated for pomalidomide and dexamethasone separately.
8.3.
Dose Exposure
Dose exposure in days is defined as the total number of actual days on drug during the 
treatment period and will be calculated for pomalidomide and dexamethasone separately.
8.4.
Average Daily Dose
Average daily dose will be calculated as the cumulative dose divided by dose exposure and will 
be calculated for pomalidomide and dexamethasone separately.
8.5.
Dose Intensity
The delivered dose intensity (DDI) is defined as the cumulative dose delivered divided by the 
treatment duration and will be calculated for pomalidomide and dexamethasone separately.
8.6.
Relative Dose Intensity
The relative dose intensity (RDI) is calculated as the DDI divided by the planned dose intensity
(PDI) whereby the DDI is calculated as the total dose delivered divided by the total time to 
complete the delivery:


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
For POM, the PDI is (4*21)/28 = 3 mg per day.

For LD-DEX, the PDI is (40*4)/28 = 160/28 mg per day for subjects 75 years old and 
(20*4)/28 = 80/28 mg per day for subjects > 75 years old.
The RDI will be calculated for pomalidomide and dexamethasone separately
8.7.
Dose Modifications
Dose reductions and interruptions will be summarized for subjects who had at least one dose 
reduction or interruption. In addition, summary statistics (frequency of patients and median 
number of days) will be produced for time to first dose reduction/interruption as well as the 
number of reduction/interruptions per subject.




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10.
STATISTICAL ANALYSIS OF EFFICACY ENDPOINTS
All efficacy analyses will be performed using the ITT population and the EE population. The ITT 
population shall form the primary analysis while the EE population shall form the sensitivity 
analysis of the endpoints.
10.1.1.
Overall Response Rate
Under the IMWG uniform response criteria, a response is defined as being either a stringent 
complete response (sCR), complete response (CR), very good partial response (VGPR) or a 
partial response (PR). Investigator’s assessment of response will be used for the response 
analysis. The overall response rate (ORR) is defined as the percentage of subjects with a 
confirmed disease response (sCR, CR, VGPR, or PR) according to the International Myeloma 
Working Group International Myeloma Working Group International Myeloma Working 
Group(IMWG) uniform response criteria, over the number of subjects included in the analysis. 
For the response to be confirmed, a consecutive disease assessment must achieve the same 
response or better. Confirmed responses that are documented after the initiation of another
anti-myeloma treatment will not be counted as responses. Subjects without a disease
assessment will be considered a non-responder for the purpose of the ORR. The ORR shall be 
presented along with the corresponding Clopper-Pearson 95% confidence interval (CI).
The proportion of subjects in each response category [i.e. sCR, CR, VGPR, PR, stable disease 
(SD), PD, relapse, relapse from CR, and Not Evaluable] as well as the proportion of subjects 
without any disease assessment will be calculated.
10.1.2.
Time to Response
TTR is calculated as the time from study enrollment, defined as the IVRS enrollment date, until 
a documented disease response (either SCR, CR, VGPR or PR). Subjects not observed with a 
response will not be included in the analysis. The analysis will consist of presenting the number 
of subjects available for analysis of TTR, the mean and median time as well as the minimum and  
maximum time to reach a response. 
10.1.3.
Time to Event Analyses
Four time to event endpoints (DoR, TTP, PFS, and OS) will be analysed for this study. Response 
values (as determined by the site investigator based on the IMWG uniform response criteria)
categorised as PD, relapse and relapse after CR indicate that the subject had a disease 
progression, while other response values (i.e. sCR, CR, VGPR, PR and SD) indicate that the 
subject did not have a disease progression.
For each time to event endpoint, the Kaplan-Meier method will be used to estimate the survival 
distribution function.  The median, 25 and 75 percentile of the survival distribution along with 


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the two-sided 95% CI for the median will be estimated.  In addition, the event rates at 6, 12 and 
24 month time-points will be computed, along with the standard errors. The plots of survival 
curves using Kaplan-Meier estimates will be presented as appropriate. 
10.1.3.1.
Duration of Response
Duration of response is defined as the time from the first documented disease response to the 
IP (either SCR, CR, VGPR or PR) until the first recorded disease progression on the IMWG 
assessment of response CRF or LTFU CRF, whichever occurs first, or death if no disease 
progression recorded (refer to PFS for complete event details) for responders.
Censoring of subjects not experiencing an event are similar to PFS outlined in Table 1 with the 
following exceptions:
-
If a subject is still on therapy and therefore has no LTFU CRFs, then censor at time of last 
response assessment, otherwise, 
-
If the subject did not have a disease progression during therapy but has entered into long 
term follow-up and still no disease progression is indicated, then censor at the time of the last 
completed LTFU CRF.
10.1.3.2.
Progression-Free Survival
Progression Free Survival is calculated as the time from study enrollment, defined as the IVRS 
enrollment date, until either PD or death (any cause). Subjects without an event (either a
documented PD or death) at the time of study end will be censored at the time of their last 
documented disease assessment or at the IVRS enrollment date if no disease assessment was 
conducted. A subject with a documented PD directly following a missing assessment, if not 
having previously had a documented PD, will be censored at the time of the assessment directly 
preceding the missing assessment.
Missing assessments are defined as 2 or more consecutive missing assessments, considered as 
> 66 days (during the treatment period) or > 192 days (during the long-term follow-up phase) 
between the last adequate assessment and the date of the event, or, >94 days if there is no 
assessment after enrollment and the subject having an event.
Table 1 below includes the event and censoring rules for PFS.
Table 1: Event and Censoring Rules for Progression Free Survival
Scenario
Date Subject has Event or is Censored
Comment
Progression documented at 
scheduled assessment
EMA and FDA Guidelines: Event date = 
first disease assessment date where a PD 
is documented
A subject with a 
documented PD directly 
following a missing 
assessment, if having not 


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Scenario
Date Subject has Event or is Censored
Comment
had a PD observed 
previously, shall be 
censored at the time of 
the last documented 
assessment or the IVRS 
enrollment date if there is 
no prior response 
assessment.
Progression documented 
between scheduled 
assessment
EMA Guidelines: Event = date of 
documented progression.
FDA Guidelines: Event data = last 
scheduled adequate assessment prior to 
the unscheduled assessment; if no 
adequate assessment at scheduled visits 
existed prior to the unscheduled 
assessment, then event date = date of 
unscheduled assessment.
Subject did not
progress nor die
EMA and FDA Guidelines: Censored date: 
date of last adequate assessment without 
PD; if no adequate assessment existed 
then censored at date of enrollment.
Subject died without initial 
documented progression
EMA and FDA Guidelines: Event date = 
date of death.
Per FDA Guidelines if the 
death date is after AMT 
then the patient is 
censored at the last 
assessment date.
For events during the 
treatment period:
Death or progression from 
the follow-up within 2 cycles 
(2 x 28 +10-day window = 66 
days) after the latest of: 
treatment period 
discontinuation date, last 
cycle end date of study drug, 
and last adequate 
assessment date during 
treatment period
For events during the long-
term follow-up phase:
Death or progression within 6 
months (6 x 30.25 + 10-day 
window = 192 days) after the 
last assessment
EMA and FDA Guidelines: Event date = 
date of death or documented progression if 
occurring before death.


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Scenario
Date Subject has Event or is Censored
Comment
For treatment period:
Death or progression from 
the follow-up more than 2 
assessment cycles (2 x 28 
+10-day window = 66 days) 
after the latest of: treatment 
period discontinuation date, 
last cycle end date of study 
drug, and last adequate 
assessment date during 
treatment period
For long-term follow-up 
phase:
Death or progression from 
the follow-up more than 2 
assessment cycles, i.e. 6 
months (6 x 30.25 + 10-day 
window = 192 days) after the 
last assessment
EMA and FDA Guidelines: Censor date = 
date of last adequate assessment with 
evidence of no progression; if no adequate 
assessment existed then censor at date of 
enrollment.
New anti-myeloma/non-
protocol treatment started 
prior to progression/death
EMA Guidelines: Event date = date of 
documented progression/death.
FDA Guidelines: Censor date = date of last 
adequate assessment with evidence of no 
progression; if no adequate assessment 
exits then censor at the date of enrollment.
Death or progression during 
the treatment period after an 
extended lost-to-follow-up 
time (two or more missed 
scheduled assessments)
EMA Guidelines: Event date = date of 
documented progression or death.
FDA Guidelines: Censor date = date of last 
adequate assessment with evidence of no 
progression; if no adequate assessment 
exits then censor at the date of enrollment.
Abbreviations: CR = complete response; DoR = Duration of response; OS = overall survival; PD = Disease 
progression; PFS = Progression free survival; PR = Partial response; sCR = stringent complete response; TTP = Time 
to progression; VGPR = very good partial response.
10.1.3.3.
Time to Progression
Time to progression is calculated as the time from study enrollment, defined as the IVRS 
enrollment date,  until the first recorded disease progression on the IMWG assessment of 
response CRF or LTFU CRF, whichever occurs first, or death due to PD (refer to PFS for complete 
event details).


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Censoring of subjects not experiencing an event are similar to PFS outlined in Table 1 with the 
following exceptions:
-
If a subject is still on therapy and therefore has no LTFU CRFs, then censor at time of last 
response assessment, otherwise,
-
If the subject did not have a disease progression during therapy but has entered into long 
term follow-up and still no disease progression is indicated, then censor at the time of the last 
completed LTFU CRF.
10.1.3.4.
Overall Survival
Overall survival is calculated as the time from study enrollment, defined as the IVRS enrollment
date, until death due to any cause. Subjects who do not have death data at the time of study 
end/analysis will be censored at the time they were last known to be alive. 


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11.
STATISTICAL ANALYSIS OF SAFETY ENDPOINTS
All safety analyses will be performed on the safety population.
11.1.1.
Adverse Events
Adverse Events will be coded according to the Medical Dictionary for Regulatory Activities 
(MedDRA) version 15 or higher. The severity of AEs will be graded according to the NCIs CTCAE 
version 4.0. Summaries will be by system organ class and preferred term.
Treatment-emergent AEs (TEAEs) are defined as any AE occurring or worsening on or after the 
first treatment of the IP and within 28 days after the last dose. If a subject experiences the 
same preferred term multiple times then the event will be counted only once and by the 
greatest severity.
All TEAEs, TEAEs leading to IP discontinuation, TEAEs leading to dose reduction/interruption, 
TEAEs related to the IP, serious TEAEs, serious TEAEs related to study medication, and serious 
TEAEs leading to study medication discontinuation will be summarized by system organ class 
and preferred term. Summary of TEAEs with NCI-CTCAE grade 3 or 4 and with NCI-CTCAE grade 
5 will also be provided. Summary of TEAEs by dosing cycle will also be provided. Where 
necessary, adverse events will be categorized by using specified MedDRA hierarchy terms (i.e., 
SOC, HLGT, HLT, and PT), and/or by Standardized MedDRA Queries (SMQs);  the number and 
percentage of subjects with adverse events alone and/or with concurrent events, medical 
history, medications, laboratory values, etc., may be tabulated, and where possible, may be 
organized or displayed by specific parameters (e.g., time to occurrence, other demographics, 
exposure/duration/cycle, therapy period(s), etc.) .  Where necessary, and as the data allow, 
incidence rates will be calculated, summarized and displayed.
If a subject experiences the same preferred term multiple times then the subject will be 
counted only once by the greatest severity of that term when presented in tabulations.
An AE listing will be presented separately for individual subjects.
Adverse Events of Special Interest
Analysis of AEs of special interest will be presented with tabulations for: TEAEs of interest,
NCI-CTCAE grade 3 or 4 TEAEs of interest, TEAEs of interest related to study medication,
serious TEAEs of interest and TEAEs of interest leading to study medication discontinuation. The 
following AE of interest categories and preferred terms include but are not limited to:

neutropenia

febrile neutropenia

infection

thrombocytopenia

hemorrhage and bleeding

neuropathy

DVT (deep vein thrombosis)

PE (pulmonary embolism)


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
SPM (second primary malignancies)

muscular weakness

glucose intolerance

mood alteration

cataract

cardiovascular events/dysrhythmia

fluid retention/edema

hematopoietic cytopenias
In addition the following tables will be presented to further investigate the corresponding 
AEs of interest:

treatment emergent neutropenia and febrile neutropenia by GCSF usage on study

treatment emergent arterial thrombotic events with and without prophylaxis 
medications (where prophylaxis medication is defined as low-dose aspirin, low 
molecular weight heparin, or other equivalent antithrombotic or anticoagulant
within one week of prior to onset of event)

treatment emergent venous thrombotic events with and without prophylaxis 
medications (where prophylaxis medication is defined as low-dose aspirin, low 
molecular weight heparin, or other equivalent antithrombotic or anticoagulant
within one week of prior to onset of event)

treatment emergent DVT with and without concurrent PE (where concurrent PE is
defined as PE onset within +/- two weeks of onset of DVT, and before resolution of
DVT)

treatment emergent neuropathy by baseline neuropathy status

time to onset of neuropathy from enrollment

time to improvement/resolution of neuropathy from enrollment

time to worsening/new incidence of neuropathy from enrollment

neuropathy still ongoing at treatment discontinuation

treatment emergent grade 3 or higher infections and infestations and concurrent 
neutropenia (where concurrent grade 3 or 4 neutropenia is defined as grade 3 or 4 
neutropenia onset within +/- two weeks of onset of infection and infestation, and 
before resolution of infection and infestation)

treatment emergent grade 3 or higher neutropenia and concurrent infections and 
infestations (where concurrent grade 3 or 4 infections and infestations is defined as 
grade 3 or 4 infections and infestations onset within +/- two weeks of onset of 
neutropenia, and before resolution of neutropenia)

treatment emergent (grade 3 or higher) thrombocytopenia with concurrent
haemorrhage and bleeding (where concurrent bleeding is defined as bleeding onset 
within +/- two weeks of onset of thrombocytopenia, and before resolution of 
thrombocytopenia)


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
treatment emergent (grade 3 or higher) haemorrhage and bleeding with concurrent
thrombocytopenia (where concurrent grade 4 thrombocytopenia is defined as 
grade 4 thrombocytopenia onset within +/- two weeks of onset of bleeding, and 
before resolution of bleeding)

summary and incidence of second primary malignancy (SPM)
11.1.2.
Second Primary Malignancies
Second primary malignancies include any regardless of the causal relationship to the IP (POM 
with or without DEX).
11.1.3.
Deaths
Deaths during treatment period (i.e. after the first treatment of the IP and within 28 days after 
the last actual dose of study drug received) will be tabulated for the safety population. Deaths 
during the first 60 days of treatment and after 28 days after the last actual dose of study drug 
received will also be tabulated.  
11.1.4.
Clinical Laboratory Evaluations
Clinical laboratory values will be graded according to NCI CTC version 4.0 for applicable tests. 
Baseline grade and worst severity grade (both high and low, as appropriate) observed during 
the treatment period for selected laboratory results will be summarized. Furthermore, the shift
from baseline to the worst grade observed during the treatment period for selected laboratory 
results will also be presented.  Normal ranges will be used to determine the categories if High, 
Low and Normal for lab tests with no assigned severity grade.  Listings of clinical laboratory 
data with abnormal flags will be provided by subject and test.
11.1.5.
Vital Signs
For vital signs, a shift during treatment from baseline to worse for below-, within-, and above-
normal range categories will be displayed in cross–tabulations. Normal ranges are defined as 
follows:

Systolic blood pressure (BP) Normal (90 – 119 mmHg, inclusive)

Diastolic BP Normal (60 – 79 mmHg, inclusive)

Body Temperature Normal (36.1 – 37.8 degrees centigrade, inclusive)
Descriptive statistics (N, Mean, Standard Deviation, Median, Minimum and Maximum) of 
observed and change from baseline values will be presented.  


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11.1.6.
Electrocardiogram
The overall ECG interpretation will be summarized by presenting the number and percentage of
subjects with “Normal” “Abnormal, not clinically significant and “Abnormal, clinically
significant”. Shift from baseline to worst during study, as well as shift from baseline by cycle in 
the overall ECG interpretation will be displayed in cross–tabulations tabulations.
Other ECG measurements such as QTc will be tabulated with summary statistics (N, Mean,
Standard Deviation, Median, Minimum and Maximum) of observed and change from baseline
values presented.
11.1.7.
ECOG Performance Status
Shift from baseline to worst during study, shift from baseline to best during study, as well as
shift from baseline by cycle in ECOG performance status will be displayed in cross-tabulations.


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12.
PHARMACOKINETIC ANALYSIS
All PK and PD related table, figures and listings will be provided in a separate delivery 
document.
12.1.
Software for Analysis
The software to be used in the pharmacokinetic data analysis and data presentation includes:

SAS Version 9.1.3 or higher (SAS Institute, Inc., Cary, NC)

SigmaPlot Version 10.0 or higher (Systat Software, Inc., Point Richmond, CA)
12.2.
Analysis population
As a data cut-off date of May 4th 2015, all subjects who receive POM and have PK data will be 
included. If any subjects are found to be noncompliant with respect to dosing, or encounter 
other circumstances that could affect the evaluation of PK, a decision will be made on a case-
by-case basis as to their inclusion in the PK analysis.  Data excluded from PK analysis and/or 
statistical analysis will be included in the data listings, but not in the summaries.
12.3.
Pharmacokinetic Analysis
12.3.1.
Data handling
Pre-dose concentrations that are below the limit of quantification (BLQ) or missing will be 
assigned a number value of zero.
12.3.2.
Statistical Analysis
POM plasma concentrations will be listed and summarized by cycle using descriptive statistics 
(N, mean, SD, coefficient of variation [CV%], geometric mean, geometric CV%, median, Min, and 
Max).  Box-Whisker plot of POM plasma concentrations will be generated.
 


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13.
EXPOSURE-RESPONSE ANALYSIS
All analyses related to PK/PD data will be reported separately from the clinical study report.
 
 
The key exposure data are serum drug concentration, Cmax, Cmin and AUC derived from the 
population PK analysis. The key efficacy and safety endpoints include AEs, ORR, time to 
response, DoR, PFS, TTP, and OS. Other efficacy and safety endpoints may also be explored, as 
appropriate.
 
 
 
 






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APPENDICES 
Appendix A: Date Imputation Guideline
Impute Missing AE / Prior or Concomitant Medications Start Dates:
If the stop date is non-missing and the imputed start date is after the stop date, the stop date 
will be imputed by the stop date.
Missing day and month with non-missing year

If the year is the same as the year of first day on the IP, then the day and month of the 
start date of the IP will be assigned to the missing fields

If the year is prior to the year of first day on the IP, then December 31 will be assigned 
to the missing fields.

If the year is after the year of first day on the IP, then January 1 will be assigned to the 
missing fields.
Missing day only 

If the month and year are the same as the year and month of first day on the IP, then 
the start date of the IP will be assigned to the missing day.

If the month and year are before the year and month of first day on the IP, then the last 
day of the month will be assigned to the missing day.

If the month and year are after the year and month of first day on the IP, then the first 
day of the month will be assigned to the missing day.

If the stop date is non-missing and the imputed start date is after the stop date, the 
start date will be imputed by the stop date. 
Missing year 

Not imputed. Included as TEAE.
Impute Missing AE / Prior or Concomitant Medications  Incomplete Stop Date:
If the imputed stop date is before the start date then the imputed stop date will be equal to the 
start date.
Missing day and month with non-missing year

If the year of the incomplete stop date is the same as the year of the last dose date of 
the IP, then the day and month of the last dose date will be assigned to the missing 
fields. 


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
If the year of the incomplete stop date is prior to the year of the last dose date of the IP, 
then December 31 will be assigned to the missing fields. 

If the year of the incomplete stop date is after the year of the last dose date of the IP, 
then January 1 will be assigned to the missing fields.
Missing day only 

If the month and year of the incomplete stop date are the same as the month and year 
of the last dose date of the IP, then the day of the last dose date will be assigned to the 
missing day. 

If the month and year of the incomplete stop date are before the month and year of the 
last dose date of the IP, then the last day of the month will be assigned to the missing 
day. 

If the month and year of the incomplete stop date are after the month and year of the 
last dose date of the IP, then the first day of the month will be assigned to the missing 
day.
Missing year 

Not imputed. Included as TEAE.
Impute Missing Disease Diagnosis Dates:
For partial diagnosis dates, January will be assigned to the missing month; and the first day of 
the month will be assigned to the missing day.
Impute Incomplete Prior Evidence of Disease Progression Dates:
For partial prior disease progression dates, the first day of the month shall be imputed.
Impute Missing Dates in Prior Anti-myeloma Regimen:
For each prior anti-myeloma regimens, the regimen start/stop date, disease progression date, 
best response date, and date of first response for RR or better, will be collected. If the day of 
any date is missing, then the first day of the non-missing month will be assigned to the missing 
day; if month or year of the missing date is missing, then the date will not be imputed and 
treated as missing.
Impute Missing Dates in Subsequent Anti-myeloma Therapy:
Subjects will be allowed to take other anti-myeloma therapy after discontinuation from the 
study. The anti-myeloma therapy start/stop date will be collected. If the day of any date is 


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missing, then the last day of the non-missing month will be assigned to the missing day; if day 
and month are both missing, the December 31 of the non-missing year will be assigned to the 
missing day.


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Appendix B: Tables Graphs and Listings 
Tables Section 14.
Table Number
Table Title
14.1.1
Analysis Populations
14.1.2.1
Subject Disposition – Treatment Phase: All Populations
14.1.2.2
Subject Disposition – Long-term Follow-up Phase: All Populations
14.1.3
Summary of Reasons for Screen Failure: Screen Failure Subjects
14.1.4
Subjects Enrolled by Study Site: Intention to Treat Population
14.1.5
Summary of Protocol Violations: Intention to Treat Population
14.1.6
Summary Demographic and Baseline Characteristics: All Populations
14.1.7
Baseline Disease Characteristics: All Populations
14.1.8
Medical History: All Populations
14.1.9
Prior Cancer History: All Populations
14.1.10
Prior Medications: All Populations
14.1.11
Prior Therapies: All Populations
14.1.12
Summary of Prior Anti-myeloma Therapies by Drug Class: All Populations
14.1.13
Summary of Last Prior Anti-myeloma Therapies by Drug Class: All Populations
14.1.14
Refractory Status to Selected Prior Anti-myeloma Therapies: All Populations
14.1.15
Summary of Prior Anti-myeloma Treatment Lines and Regimens: All Populations
14.1.16
Evidence of Progression Status to Last Anti-myeloma Therapies: All Populations
14.1.17
Prior Cancer Surgeries for this Disease: All Populations
14.1.19
Prophylactic Medications During the Treatment Period: Safety Population


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14.1.21
Summary of Prior Venous Thromboembolic Events: All Populations
14.1.22
Summary of Cytogenetic Data: All Populations
14.2.1.1
Summary of Overall Response and Response Rates: All Populations
14.2.1.2
Overall Survival Follow-up: All Populations
14.2.2
Summary of Time to Response (TTR): All Populations
14.2.3
Summary of Duration of Response (DoR): All Populations
14.2.4
Summary of Time to Progression (TTP): All Population
14.2.5.1
Summary of Progression Free-Survival (PFS): According to EMA Guidelines: All Populations
14.2.5.2
Summary of Progression Free-Survival (PFS): According to FDA Guidelines: All Populations
14.2.6
Summary of Overall Survival (OS): All Populations
14.2.7
Summary of Subsequent Anti-myeloma Therapy: Intention to Treat Population
14.2.8
Summary of CC-4047 Plasma Concentrations (ng/mL) by Cycle: Pharmacokinetic Population
14.3.1.1
Summary of Treatment Duration: Safety Population
14.3.1.2.1
Summary of Dose Information: Safety Population
14.3.1.2.2
Summary of Dose Information by Cycle: Safety Population
14.3.1.3.1
Summary of Dose Reductions: Safety Population
14.3.1.3.2
Summary of Dose Reductions by Cycle: Safety Population
14.3.1.4.1
Summary of Dose Interruptions: Safety Population
14.3.1.4.2
Summary of Dose Interruptions by Cycle: Safety Population
14.3.2.1
Summary of Treatment Emergent Adverse Events: Safety Population
14.3.2.2.1
Treatment Emergent Adverse Events: Safety Population
14.3.2.2.2
Treatment Emergent Adverse Events with CTCAE Grade 2 or Higher Infections: Safety Population
14.3.2.3
Treatment Emergent Adverse Events with CTCAE Grades 3 or 4: Safety Population
14.3.2.4.1
Treatment Emergent Adverse Events Related to Any Study Drug: Safety Population
14.3.2.4.2
Treatment Emergent Adverse Events Related to Pomalidomide: Safety Population
14.3.2.4.3
Treatment Emergent Adverse Events Related to Low-Dose Dexamethasone: Safety Population
14.3.2.5.1
Treatment Emergent CTCAE Grade 3 or 4 Adverse Events Related to Any Study Drug: Safety 
Population


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14.3.2.5.2
Treatment Emergent CTCAE Grade 3 or 4 Adverse Events Related to Pomalidomide: Safety 
Population
14.3.2.5.3
Treatment Emergent CTCAE Grade 3 or 4 Adverse Events Related to Low-Dose Dexamethasone: 
Safety Population
14.3.2.6.1
Cause of Death During Treatment Period: Safety Population
14.3.2.6.2
Cause of Death During First 60 Days of Treatment: Safety Population
14.3.2.6.3
Cause of Death After 28 Days of End of Treatment: Safety Population
14.3.2.6.4
Cause of Death: Safety Population
14.3.2.6.5
Cause of Death During Screening Period: Non-enrolled Subjects
14.3.2.7
Treatment Emergent Grade 5 Adverse Events: Safety Population
14.3.2.8
Treatment Emergent Serious Adverse Events: Safety Population
14.3.2.9.1
Treatment Emergent Serious Adverse Events Related to Any Study Drug: Safety Population
14.3.2.9.2
Treatment Emergent Serious Adverse Events Related to Pomalidomide: Safety Population
14.3.2.9.3
Treatment Emergent Serious Adverse Events Related to Low-Dose Dexamethasone: Safety
Population
14.3.2.9.4
Treatment Emergent Serious Adverse Events Leading to Discontinuation of Any Study Drug: 
Safety Population
14.3.2.9.5
Treatment Emergent Serious Adverse Events Leading to Discontinuation of Pomalidomide: 
Safety Population
14.3.2.9.6
Treatment Emergent Serious Adverse Events Leading to Discontinuation of Low-Dose 
Dexamethasone: Safety Population
14.3.2.10.1
Treatment Emergent Adverse Events Leading to Discontinuation of Any Study Drug: Safety 
Population
14.3.2.10.2
Treatment Emergent Adverse Events Leading to Discontinuation of Pomalidomide: Safety 
Population
14.3.2.10.3
Treatment Emergent Adverse Events Leading to Discontinuation of Low-Dose Dexamethasone: 
Safety Population
14.3.2.11.1
Treatment Emergent Adverse Events Leading to Reduction of Any Study Drug: Safety Population


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14.3.2.11.2
Treatment Emergent Adverse Events Leading to Reduction of Pomalidomide: Safety Population
14.3.2.11.3
Treatment Emergent Adverse Events Leading to Reduction of Low-Dose Dexamethasone: Safety 
Population
14.3.2.12.1
Treatment Emergent Adverse Events Leading to Interruption of Any Study Drug: Safety 
Population
14.3.2.12.2
Treatment Emergent Adverse Events Leading to Interruption of Pomalidomide: Safety 
Population
14.3.2.12.3
Treatment Emergent Adverse Events Leading to Interruption of Low-Dose Dexamethasone: 
Safety Population
14.3.2.13.1
Treatment Emergent Adverse Events by CTCAE Grade 1/2 and 3/4: Safety Population
14.3.2.13.2
Treatment Emergent Adverse Events by CTCAE Grade: Safety Population
14.3.2.14.1
Treatment Emergent Grade 3 or 4 Adverse Events Related to Any Study Drug by CTCAE Grade: 
Safety Population
14.3.2.14.2
Treatment Emergent Grade 3 or 4 Adverse Events Related to Pomalidomide by CTCAE Grade: 
Safety Population
14.3.2.14.3
Treatment Emergent Grade 3 or 4 Adverse Events Related to Low-Dose Dexamethasone by 
CTCAE Grade: Safety Population
14.3.2.15.1
Treatment Emergent Adverse Events by Cycle: Safety Population
14.3.2.15.2
Treatment Emergent Grade 3 or 4 Adverse Events by Cycle: Safety Population
14.3.2.16.1
Summary of Treatment Emergent Adverse Events of Interest: Safety Population
14.3.2.16.2
Treatment Emergent Adverse Events of Interest: Safety Population
14.3.2.16.3
Treatment Emergent CTCAE Grade 3 or 4 Adverse Events of Interest: Safety Population
14.3.2.16.4.1
Treatment Emergent Adverse Events of Interest Related to Any Study Drug: Safety Population
14.3.2.16.4.2
Treatment Emergent Adverse Events of Interest Related to Pomalidomide: Safety Population
14.3.2.16.4.3
Treatment Emergent Adverse Events of Interest Related to Low-Dose Dexamethasone: Safety 
Population
14.3.2.16.5.1
Treatment Emergent CTCAE Grade 3 or 4 Adverse Events of Interest Related to Any Study Drug: 
Safety Population


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14.3.2.16.5.2
Treatment Emergent CTCAE Grade 3 or 4 Adverse Events of Interest Related to Pomalidomide: 
Safety Population
14.3.2.16.5.3
Treatment Emergent CTCAE Grade 3 or 4 Adverse Events of Interest Related to Low-Dose 
Dexamethasone: Safety Population
14.3.2.16.6
Treatment Emergent Serious Adverse Events of Interest: Safety Population
14.3.2.16.7.1
Treatment Emergent Serious Adverse Events of Interest Related to Any Study Drug: Safety 
Population
14.3.2.16.7.2
Treatment Emergent Serious Adverse Events of Interest Related to Pomalidomide: Safety 
Population
14.3.2.16.7.3
Treatment Emergent Serious Adverse Events of Interest Related to Low-Dose Dexamethasone: 
Safety Population
14.3.2.16.7.4
Treatment Emergent Serious Adverse Events of Interest Leading to Discontinuation of Any Study 
Drug: Safety Population
14.3.2.16.7.5
Treatment Emergent Serious Adverse Events of Interest Leading to Discontinuation of 
Pomalidomide: Safety Population
14.3.2.16.7.6
Treatment Emergent Serious Adverse Events of Interest Leading to Discontinuation of Low-Dose 
Dexamethasone: Safety Population
14.3.2.16.8.1
Treatment Emergent Adverse Events of Interest Leading to Discontinuation of Any Study Drug: 
Safety Population
14.3.2.16.8.2
Treatment Emergent Adverse Events of Interest Leading to Discontinuation of Pomalidomide: 
Safety Population
14.3.2.16.8.3
Treatment Emergent Adverse Events of Interest Leading to Discontinuation of Low-Dose 
Dexamethasone: Safety Population
14.3.2.16.9
Treatment Emergent Adverse Events of Interest by CTCAE Grade 1/2 and 3/4: Safety Population
14.3.2.16.10
Treatment Emergent Adverse Events of Interest by CTCAE Grade: Safety Population
14.3.2.16.11
Treatment Emergent Neutropenia by GCSF Usage on Study: Safety Population
14.3.2.16.12.1
Treatment Emergent Arterial Thrombotic Events With and Without Prophylaxis Medications: 
Safety Population


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14.3.2.16.12.2
Treatment Emergent Venous Thrombotic Events With and Without Prophylaxis Medications: 
Safety Population
14.3.2.16.12.3
Treatment Emergent DVT With and Without Concurrent Pulmonary Embolism [a]: Safety 
Population
14.3.2.16.13.1
Treatment Emergent Neuropathy by Baseline Neuropathy Status: Safety Population
14.3.2.16.13.2
Time to Onset of Neuropathy: Safety Population
14.3.2.16.13.3
Time to Improvement/Resolution of Neuropathy from Baseline: Safety Population (Subjects with 
Improvement/Resolution of Baseline Neuropathy)
14.3.2.16.13.4
Time to Worsening/New Incidents of Neuropathy from Baseline: Safety Population (Subjects 
with Worsening Baseline of Neuropathy or New Incidents of Neuropathy)
14.3.2.16.13.5
Neuropathy Still Ongoing at Treatment Discontinuation: Safety Population (Subjects Who had 
Treatment Emergent Neuropathy with Neuropathy Ongoing at Baseline)
14.3.2.16.14.1
Treatment Emergent Grade 3 or Higher Neutropenia and Concurrent Infections and Infestations 
Within Two Weeks: Safety Population
14.3.2.16.14.2
Treatment Emergent Grade 3 or Higher Infections and Infestations and Concurrent Neutropenia 
Within Two Weeks: Safety Population
14.3.2.16.14.3
Treatment Emergent Grade 3 or Higher Thrombocytopenia and Concurrent Hemorrhage and 
Bleeding Within Two Weeks: Safety Population
14.3.2.16.14.4
Treatment Emergent Grade 3 or Higher Hemorrhage and Bleeding and Concurrent 
Thrombocytopenia Within Two Weeks: Safety Population
14.3.2.16.14.5
Treatment Emergent Thrombocytopenia and Concurrent Hemorrhage and Bleeding Within Two 
Weeks: Safety Population
14.3.2.16.14.6
Treatment Emergent Haemorrhage and Bleeding and Concurrent Thrombocytopenia within Two 
Weeks: Safety Population
14.3.2.16.15.1
Summary of Second Primary Malignancies (SPM): Safety Population
14.3.2.16.15.2
Summary of Second Primary Malignancies: Time to Onset, Dosing Summary and Incidence Rate
per 100 Person-years: Safety Population
14.3.2.16.15.3
Summary of Second Primary Malignancies (SPM): Safety Population Subjects Who Died
14.3.2.16.15.4
Summary of Second Primary Malignancies (SPM): Safety Population Subjects Who are Alive


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14.3.2.16.15.5
Summary of Hospitalisations by Primary Cause: Safety Population
14.3.2.16.16
Summary of Non-Treatment Emergent Adverse Events: Intention to Treat Population
14.3.2.17
Treatment Emergent Adverse Events of Special Interest: Deep Vein Thrombosis/Pulmonary 
Embolism or Polyneuropathy: Safety Population
14.3.2.18
Treatment Emergent Adverse Events of Special Interest Meeting CTCAE Grade 3 or 4 Criteria: 
Deep Vein Thrombosis/Pulmonary Embolism or Polyneuropathy: Safety Population
14.3.4.1.1
Shift of CTCAE Grades from Baseline to Worst During Study in Laboratory Values (Chemistry): 
Safety Population
14.3.4.1.2
Shift of CTCAE Grades from Baseline to Worst During Study in Laboratory Values (Hematology): 
Safety Population
14.3.4.2.1
Shift from Baseline to Worst During Study in ECOG Performance Status: Safety Population
14.3.4.2.2
Shift from Baseline to Best During Study in ECOG Performance Status: Safety Population


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Figures Section 14.
Figure 
Number
Figure Title 
14.2.1
Kaplan-Meier Curve for Duration of Response: Intention to Treat Population
14.2.2
Kaplan-Meier Curve for Time to Progression: Intention to Treat Population
14.2.3.1
Kaplan-Meier Curve for Progression Free Survival Based on EMA Guidelines: Intention to Treat 
Population
14.2.3.2
Kaplan-Meier Curve for Progression Free Survival Based on FDA Guidelines: Intention to Treat 
Population
14.2.4
Kaplan-Meier Curve for Overall Survival: Intention to Treat Population
14.2.5
Waterfall Plot of Maximum Change in M-Protein from Baseline: Intention to Treat Population
14.2.6
Box-Whisker Plot of the Plasma Concentrations by Cycle
14.3.1
Time to Onset of Hematologic and Solid Tumor Second Primary Malignancies: Safety Population


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Listings Section 16.
Listing 
Number
Title of Listing
16.2.1
Discontinued Subjects
16.2.2
Protocol Violations
16.2.3
Participation in Previous Celgene Studies
16.2.4.1
Demographic and Baseline Characteristics
16.2.4.2
Medical History
16.2.4.3
Disease Diagnosis
16.2.4.4
Prior Anti-myeloma Therapy
16.2.4.5
Prior Radiation Therapy for Myeloma
16.2.4.6
Prior Cancer Surgery for Myeloma
16.2.4.7.1
Prior Stem Cell Transplant for Myeloma
16.2.4.7.2
Prior Therapies for Stem Cell Transplant Conditioning
16.2.4.8
Prior Bisphosphonate Therapy for Bone Lesions
16.2.4.9.1
Evidence of Most Recent Disease Progression
16.2.4.9.2
Evidence of Disease Progression with Last Lenalidomide-containing Regimen
16.2.4.9.3
Evidence of Disease Progression with Last Bortezomib-containing Regimen
16.2.4.10
Prior Medications
16.2.4.13
Cytogenetic Assessment
16.2.4.14
Skeletal Survey
16.2.4.15
Bone Marrow Assessment
16.2.4.16
Venous Thromboembolic Event 
16.2.4.17
Pregnancy Status and Test Results
16.2.4.18
Subject Eligibility
16.2.4.19
Prior Cancer History


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16.2.4.20
Prior Cancer History II  – Diagnostic Exams for Cancer Within 6 months Prior to Screening
16.2.4.21
Prior Procedures for Cancer Not Under Study
16.2.4.22
Prior Radiation Treatment for Cancers not Under Study
16.2.4.23
Prior Regimen Treatment for Cancers not Under Study
16.2.5
Study Drug Record: Pomalidomide and Low-Dose Dexamethasone
16.2.6.1
Investigator Assessment of Response (IMWG Criteria)
16.2.6.2
Variables for Determination of Myeloma Response
16.2.6.3
Clinical Plasmacytomas Assessment
16.2.6.4
Radiological Plasmacytomas Assessment
16.2.6.5.1
Subsequent Anti-myeloma Therapy
16.2.6.5.2
Subsequent Stem Cell Transplant for Myeloma
16.2.6.5.3
Subsequent Therapies for Stem Cell Transplant Conditioning
16.2.6.6
Follow-up Therapies
16.2.6.7
Long-term Progression Follow-up
16.2.6.8
Survival Follow-up
16.2.6.10
Individual CC-4047 Plasma Concentrations (ng/mL): Pharmacokinetic Population
16.2.7.1.1
Treatment Emergent Adverse Events
16.2.7.1.2
Pre-treatment and Post-treatment Adverse Events
16.2.7.1.3
Treatment Emergent Adverse Events Leading to Pomalidomide Discontinuation
16.2.7.1.4
Treatment Emergent Adverse Events Leading to Low-Dose Dexamethasone Discontinuation
16.2.7.1.5
Treatment Emergent CTCAE Grade 3 or 4 Adverse Events
16.2.7.1.6
Grade 5 Treatment Emergent Adverse Events
16.2.7.1.7
Treatment Emergent CTCAE Grade 2 or Higher Infections and Concomitant Antibiotic Medication
16.2.7.2
Serious Adverse Events
16.2.7.3.1
Deaths During Treatment Period
16.2.7.3.2
Deaths During First 60 Days of Treatment
16.2.7.3.3
Deaths After 28 Days of End of Treatment
16.2.7.3.4
Deaths for Enrolled Subjects
16.2.7.3.5
Deaths During Screening Period: Non-enrolled Subjects


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16.2.7.4
Adverse Events of Clinical Interest
16.2.8.1.1
Local Laboratory - Chemistry
16.2.8.1.2
Local Laboratory - Hematology
16.2.8.1.3
Local Laboratory – Urinalysis
16.2.8.1.4
Local Laboratory - Renal Function Assessment
16.2.8.1.5
Local Laboratory – Immunoglobulins
16.2.8.2
Local Serum Free Light Chain Assessment
16.2.8.3
Vital Signs
16.2.8.4
ECG
16.2.8.5
ECOG Performance Status
16.2.8.6
Healthcare Resource Utilisation
16.2.8.7
Second Primary Malignancies
16.2.8.8
Second Primary Malignancies Procedures
16.2.8.9
Second Primary Malignancy Regimen Therapy
16.2.8.10
Second Primary Malignancy Radiation Therapy