Phase I Study of Pomalidomide in Relapsed or Refractory Waldenstrom Macroglobulinemia
Phase: PHASE1
Conditions: Recurrent Waldenstrom Macroglobulinemia, Refractory Waldenstrom Macroglobulinemia
Sponsor: M.D. Anderson Cancer Center

  Phase I study of Pomalidomide in relapsed or 
refractory Waldenström macroglobulinemia 
STUDY DRUG 
POMALIDOMIDE 
Celgene tracking 
Number: 
PO-WM-PI-0006 
DATE FINAL: 
Revised: 
8/25/2010 
02/14/2014 
CONFIDENTIAL 
The information contained in this document is regarded as confidential and, except to the extent 
necessary to obtain informed consent, may not be disclosed to another party unless law or regulations 
require such disclosure.  Persons to whom the information is disclosed must be informed that the 
information is confidential and may not be further disclosed by them. 

Confidential 
Page 2 of 54 
POMALIDOMIDE 
  Protocol :  
2 
PRINCIPAL INVESTIGATOR SIGNATURE PAGE 
Principal Investigator: 
Signature of Investigator 
Sheeba K. Thomas 
Date 
Printed Name of Investigator 
By my signature, I agree to personally supervise the conduct of this study 
and to ensure its conduct in compliance with the protocol, informed 
consent, IRB/EC procedures, instructions from Celgene representatives, 
the Declaration of Helsinki, ICH Good Clinical Practices guidelines, and 
the applicable parts of the United States Code of Federal Regulations or 
local regulations governing the conduct of clinical studies.

Confidential 
Page 3 of 54 
POMALIDOMIDE 
  Protocol :  
3 
STUDY PERSONNEL 
Supporter: 
Celgene Corporation 
86 Morris Ave, 
Summit,  NJ   07901 
1-800-742-3107
Study Location: 
University of Texas M.D. Anderson Cancer Center 
Principal Investigator: 
Sheeba K. Thomas 
UT M.D. Anderson Cancer Center 
Department of Lymphoma & Myeloma 
1515 Holcombe Boulevard, Unit 429 
Houston, TX 77030 
Office Phone: (713) 792-2860 
Email:  sthomas@mdanderson.org 
Study Coordinator: 
A. Georgina Melendez

 
Confidential 
Page 4 of 54  
POMALIDOMIDE                                                                                 Protocol :  
 
 
4 
Table of Contents 
Protocol Synopsis…………………………………………………………….. 1.0 
Schedule of Study Assessments………………………………………………..2.0 
Glossary of Abbreviations……………………………………………………..3.0 
Background and Rationale……………………………………………………..4.0 
Study Objectives and End Points………………………………………………5.0 
Investigational Plan…………………………………………………………….6.0 
Serious Adverse Events……………………………………………………….. 7.0 
Response Criteria……………………………………………………………… 8.0 
Protocol Amendments and Deviations………………………………………….9.0 
Data Management………………………………………………………………10.0 
Biostatistical Analysis………………………………………………………… 11.0 
Regulatory Considerations……………………………………………………..12.0 
References……………………………………………………………………...13.0 
Appendices………………………………………………………………………… 
A. Pomalidomide Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable 
Birth Control Methods  
B.  Pomalidomide Education and Counseling Guidance Document  
C.  Pomalidomide Information Sheet 
D. ECOG Performance Status 
E. NCI CTC Version 4.0 

 
Confidential 
Page 5 of 54  
POMALIDOMIDE                                                                                 Protocol :  
 
 
5 
1.0 Protocol Synopsis 
PROTOCOL TITLE:  Phase I study of Pomalidomide in relapsed or refractory 
Waldenström macroglobulinemia 
PROTOCOL NUMBER:  
PO-WM-PI-0006 
DATE PROTOCOL FINAL: 
 
STUDY DRUG: 
POMALIDOMIDE 
INDICATION: 
Relapsed or Refractory Waldenström 
Macroglobulinemia 
STUDY PHASE: 
I 
BACKGROUND AND RATIONALE:  Waldenström Macroglobulinemia is a low grade B-
cell lymphoproliferative disorder characterized by bone marrow infiltration with 
lymphoplasmacytic cells, together with demonstration of a monoclonal gammopathy, as 
defined by the Revised European-American Lymphoma and WHO classification 
systems.1 Patients with a disease-related hemoglobin level of less than 10 g/dL, a 
platelet count of less than 100 x 109/L, bulky adenopathy or organomegaly, symptomatic 
hyperviscosity, severe neuropathy, amyloidosis, cryoglobulinemia, cold agglutinin 
disease, or evidence of disease transformation should be considered for immediate 
therapy.2   When treatment is initiated, overall response rates to frontline therapy with 
combinations of nucleoside analogs, alkylating agents and the anti-CD20 antibody, 
rituximab, have been high.3  However, complete responses are infrequent, eventual 
relapse from disease is inevitable, and the disease remains incurable.  Accordingly, 
novel strategies are needed to improve treatment of this disease. 
 
Thalidomide is an immunomodulatory agent that induces the elaboration of 
immunostimulatory cytokines, including interleukin-2 and interferon- . Importantly, 
thalidomide induces the expansion of natural killer (NK) cells, and increases antibody-
dependent, cell-mediated cytotoxicity (ADCC). As monotherapy, thalidomide has modest 
activity in WM patients, producing response rates of 25%, while the combination of 
thalidomide plus steroids and/or clarithromycin produces response rates of 40%.4-6  Of 
further interest, a Phase II study that combined thalidomide with the anti-CD20 
monoclonal antibody, rituximab, showed an overall response rate of 64%.7 
Lenalidomide, a related immunomodulator (IMiD®), has also been studied with rituximab 
in Waldenström macroglobulinemia, but clinical investigation was halted before study 
completion due to the severity and frequency of anemia that was encountered (median 
hematocrit decrease of 4.8%).8  All patients enrolled on this study received 25mg of 
lenalidomide on days 1-21 of every 28 days, as per standard treatment of multiple 
myeloma.  However, in the absence of a phase I dose escalation study, the maximum 
tolerated dose of lenalidomide in patients with Waldenström macroglobulinemia remains 
unclear.   
Pomalidomide is a new IMiD® that has shown promising preliminary results in a Phase II 
study of patients with relapsed multiple myeloma.9  Accordingly, it merits investigation for 
the treatment of other plasma cell dyscrasias, including Waldenström 

 
Confidential 
Page 6 of 54  
POMALIDOMIDE                                                                                 Protocol :  
 
 
6 
macroglobulinemia.  In patients with relapsed myeloma, of whom 62% had received prior 
IMiD® therapy, pomalidomide combined with weekly dexamethasone produced an 
overall response rate of 63%.9 While 35% of patients developed grade 3 neutropenia in 
this phase II study, the rate of grade 3 thrombocytopenia and anemia was modest at 3% 
and 5% respectively. Given these low rates of grade 3 thrombocytopenia and anemia, 
the lack of grade ≥3 peripheral neuropathy, and the moderate rates of grade ≤2 
peripheral neuropathy (16%) in this study population, this agent hold the promise of both 
tolerability and efficacy in treating patients with Waldenström macroglobulinemia.   
STUDY OBJECTIVES: 
Primary:  To determine the maximum tolerated dose of pomalidomide in patients with 
relapsed or refractory Waldenstrom Macroglobulinemia 
Secondary:  To evaluate the safety and toxicity profile of pomalidomide in patients with 
relapsed or refractory Waldenstrom Macroglobulinemia 
               To evaluate the efficacy of pomalidomide in patients with relapsed or 
refractory Waldenstrom Macroglobulinemia 
STUDY DESIGN: This is a Phase 1, non-randomized, single institution study of 
pomalidomide in patients with symptomatic Waldenström macroglobulinemia (WM) 
whose disease has relapsed/and or is refractory to at least 1 prior line of therapy. 
 
There are four predefined dose levels (1, 2, 3, and 4) for pomalidomide. The study also 
includes two alternative dosing schedules (A and B). With schedule A, patients will be 
treated with the study drug for 28 days within each cycle.  With schedule B, patients will 
be treated for 21 days within each 28 day cycle. Schedule B will only be explored if the 
MTD is exceeded at dose level 1 (1 mg) within Schedule A. The first cohort of 3 patients 
will be treated at dose level 1 with schedule A (28-day dosing). If no dose limiting 
toxicities (DLTs) are observed then the next cohort of 3 patients will be treated at next 
higher dose level.  If one DLT is observed then 3 more patients will be treated at the 
same dose level.  At anytime if 2 or more DLTs are observed within 3 or 6 patients at 
dose level 1, then schedule A is considered too toxic and will be abandoned.  Patient 
enrollment will then be resumed using dose level 1 of dosing schedule B (21-day dosing) 
to determine the MTD. The purpose of schedule B is to prepare for the scenario that 
dosing schedule A is not tolerable.  
 
  
Dosing Schedule A 
Dosing Schedule B 
Dose level 1 
1 mg orally on days 1-28 
1 mg orally on days 1-21 
Dose level 2 
2 mg orally on days 1-28 
2 mg orally on days 1-21 
Dose level 3 
3 mg orally on days 1-28 
3 mg orally on days 1-21 
Dose level 4 
4 mg orally on days 1-28 
4 mg orally on days 1-21 
 
Dose escalation will continue in 1 mg increments until the MTD is reached. Once the 
MTD has been determined, an additional 6 patients will be treated at this dose level. 
 

 
Confidential 
Page 7 of 54  
POMALIDOMIDE                                                                                 Protocol :  
 
 
7 
Patients will continue receiving treatment until either disease progression or 
unacceptable toxicity develops.  
STUDY ENDPOINTS 
• 
Primary: 1) The primary endpoint is the maximum tolerated dose (MTD) of 
pomalidomide in patients with symptomatic Waldenström macroglobulinemia 
(WM) whose disease has relapsed/and or is refractory to at least 1 prior line of 
therapy. Tolerability of a given dose will be assessed after every 3 patients have 
been enrolled, until the maximum tolerated dose has been defined or, in the 
absence of dose limiting toxicities, the highest planned dose level is determined 
to have an acceptable toxicity profile. 
 
• 
Secondary:  1)The safety and toxicity profile of pomalidomide will be evaluated 
after all patients to be enrolled have completed 1 cycle of therapy; patients who 
received at least 1 dose of pomalidomide will be eligible for evaluation. 
                          2) The efficacy of pomalidomide will be measured as best response 
to therapy. For each patient, this will be determined at the completion of their 
course of therapy. The collective data will be summed at study completion.  
Patients will be considered evaluable if they have completed at least 1 cycle of 
therapy. 
STUDY DURATION:  3 years (expected) 
TOTAL SAMPLE SIZE:  maximum of 30 
DOSING REGIMEN(S):  
 
Schedule A: 
Dose level  1  : 1 mg orally on days 1-28 
Dose level  2  : 2 mg orally on days 1-28 
Dose level  3  : 3 mg orally on days 1-28 
Dose level  4  : 4 mg orally on days 1-28 
 
Schedule B: 
Dose level 1: 1 mg orally on days 1-21 
Dose level 2: 2 mg orally on days 1-21 
Dose level 3: 3 mg orally on days 1-21 
Dose level 4: 4 mg orally on days 1-21 
STUDY DRUG SUPPLIES: 
Celgene Corporation will supply 
pomalidomide as 0.5 mg, 1.0 mg and 2.0 
mg 
 
 
 

Celgene Corporation 
Confidential 
Page 8 of 54  
 
  
 
 
 
 
  Protocol  
 
 
8 
2.0   Schedule of Study Assessments *  
 
 
Procedure 
Screening 
≤ 28days from 
Baseline (First day 
study drug 
administration) 
Cycle 1 
Even 
Cycles  
 
Odd 
Cycles 
starting 
at cycle 
3 
 
Discontinuation 
From Study 
Drug 
“End of 
Treatment” 
End of 
Study safety 
assessment 
Follow-
Up 
Phase 
Day  
119 
 
Day  
819 
Day  
1519 
Day   
2219 
Day   
115 
Day 
115 
30 days (+/- 
1 week) 
post the last 
dose of 
study drug 
Every 6 
months 
Record prior medications, treatments 
X 
 
 
 
 
 
 
 
 
 
Record prior anti-cancer therapies 
X 
 
 
 
 
 
 
 
 
 
Physical examination, vital signs, weight * 
X 
X10 
 
 
 
X 
X 
 X11 
X 
 
ECOG performance status * 
X 
X10 
 
 
 
X 
X 
 X11 
X 
 
CT or MRI of the chest & abdomen / pelvis8,9 
X 
 
 
 
 
 
X21 
X 
 
 
Chest x-ray 18 
X  
 
 
 
 
 
X 
X 
 
 
Bone survey 1 
 X  
 
 
 
 
 
X 
X 
 
 
CT or MRI of the brain2  
X  
 
 
 
 
 
X 
X 
 
 
Bone marrow aspirate and biopsy 
(unilateral)17 
X 
 
 
 
 
 
 
 
 
 
ECG 
X 
 
 
 
 
 
 
X 
 
 
Hematology 3  
X 
X10 
 
X 
 
X 
X 
 X11 
X 
 
Serum chemistry 4 
X 
X10 
 
X 
 
X 
X 
 X11 
X 
 
Pregnancy testing 5 
 X6  
X6 
X6 
X6 
X6 
X6 
X6 
X6 
 
 
Pomalidomide Counseling7 
 
X 
 
 
 
X 
X 
X 
 
 
Baseline lesion assessment 
X 
 
 
 
 
 
 
 
 
 
Dispense Cycle 1 study drug12, 15  
 
X 
 
 
 
 
 
 
 
 
Response assessment labs13, 14  
X 
X 
 
 
 
X  
X 
X 
 
 
Record adverse events 11 
X 
X 
 
X 
 
X 
X 
X11 
X 
 
Record concomitant therapies/procedures 
 
 
 
X 
 
X 
X 
X 
 
 
Dispense study drug for next cycle 12, 15 
 
 
 
 
 
X 
X 
 
 
 
Perform drug accountability 
 
 
 
 
 
X 
X 
X 
 
 
Obtain Follow-Up anti-cancer treatments16 
 
 
 
 
 
 
 
 
 
X 
Obtain Follow-Up survival information16 
 
 
 
 
 
 
 
 
 
X 
Hep B surface antigen 20 
X 
 
 
 
 
 
 
 
 
 
Hep C antibody 20 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Celgene Corporation 
Confidential 
Page 9 of 54  
 
  
 
 
 
 
  Protocol  
 
 
9 
* If Physical examination, vital signs, weight and ECOG performance status were done within 7 days of Day 1, they do not need to be repeated at Study 
Day 1. 
An unscheduled visit can occur at any time during the study.  Source must be maintained for these unscheduled visits. The date for the visit and any data 
generated must be recorded on the appropriate CRF.  Source documents for these unscheduled visits must also be maintained. 
 
 
1If subject had previously positive bone survey or if symptoms suggest metastases. 
2 This will only be performed if symptoms raise suspicion of CNS lesions. 
3 Complete blood count with differential, PT and PTT (within 5 days prior to Day 1 of each cycle); If PT and PTT are within normal limits at screening, and 
patient is not on anticoagulant therapy that affects these levels, they need only be repeated at discontinuation of study drug. 
4 Electrolytes, BUN, Creatinine, Calcium, Magnesium, Phosphorous, Albumin, Total Bilirubin (fractionated, if elevated), ALT, AST, Alkaline Phosphatase, 
Beta 2 microglobulin;  A Thyroid Stimulating Hormone (TSH) level is to be drawn at Screening, and as clinically indicated.  T3 and T4 levels may be 
assessed as clinically indicated. Cryocrit, Cold Agglutinin Titer and serum viscosity are to be drawn at screening; if abnormal on screening, they are to be 
repeated at treatment discontinuation (within 5 days prior to Day 1 of each cycle). 
5 Indicated for females of childbearing potential.  A female of childbearing potential (FCBP) is a sexually mature female who: 1) has not undergone a 
hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time 
in the preceding 24 consecutive months).  
6 Pregnancy tests (either urine or serum ß HCG) must occur 10 – 14 days prior, and again within 24 hours prior to initiation of pomalidomide.  FCBP with 
regular or no menstruation must have a pregnancy test weekly for the first 4 weeks and then every 28 days while on therapy (including breaks in therapy); 
at discontinuation of pomalidomide and at Day 28 post the last dose of pomalidomide.  Females with irregular menstruation must have a pregnancy test 
weekly for the first 4 weeks and then every 14 days while on therapy (including breaks in therapy), at discontinuation of pomalidomide and at Day 14 and 
Day 28 post the last dose of pomalidomide (see Appendix A: Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control 
Methods).  
7 All patients must be counseled about pregnancy precautions, risks of fetal exposure and other risks.  The counseling must be done on Day 1 of each 
cycle (or at a minimum of every 28 days) and at drug discontinuation. See Appendix  A:  Pomalidomide Risks of Fetal Exposure, Pregnancy Testing 
Guidelines and Acceptable Birth Control Methods and Appendix B:  Pomalidomide Education and Counseling Guidance Document  
8 If these CT/MRI assessments show no adenopathy or hepatosplenomegaly at screening, they will only be repeated at discontinuation of study drug. 
  These imaging studies should be performed within 7 days prior to Day 1 of each odd cycle. 
9 All PRs and CRs must be confirmed by repeat scans no less than 6 weeks after the criteria for response are first met. The first response assessment will 
take place at completion of cycle 2. 
10 If screening assessments were done within 7 days of Cycle 1, Day 1, they do not need to be repeated on Cycle 1, Day 1.  
11 An additional safety assessment will be done 30 days (+/- 1 week) following the last dose of study drug. 
12 Only enough pomalidomide for 1 cycle of therapy may be provided to the patient each cycle. 
13 Serum and urine protein electrophoresis; Quantitative serum IgG, IgA, and IgM; Free serum kappa and lambda light chains; 
   Serum and urine immunofixation studies will be performed at screening, and to evaluate for and confirm CR. Response assessment labs should be 
performed within 5 days prior to Day 1 of each cycle. 
 14 All PRs and CRs must be confirmed by repeat Response Assessment labs no less than 6 weeks after the criteria for response are first met.  
15 Day 1 may be delayed up to 7 days to accommodate holidays/weekends/inclement weather and other unforeseen events. 
16  Information may be obtained without having the subject visit the study center (i.e. phone call).  
17 To be repeated if a complete remission is suspected  

Celgene Corporation 
Confidential 
Page 10 of 54  
 
  
 
 
 
 
  Protocol  
 
 
10
18 Chest x-ray will only be performed as part of the screening evaluation and when CR/MRI of the chest is indicated as part of the patient’s restaging 
evaluation. 
19 Assessments to be performed at Cycle 1 Days 1, 8, 15 and 22 may be performed +/- 2 business days from the planned date to accommodate holidays, 
inclement weather and other unforeseen events. 
20  Hep B  -we will check Hep B surface antigen. If positive, we will check Hep B surface antibody and Hep B viral DNA. If Hep B surface antibody is 
negative and/or Hep B viral DNA shows circulating virus, patient will be excluded ; Hep C – we will check Hep C Antibody. If positive, we will check Hep C 
Viral PCR. If it shows circulating virus, patient will be excluded 
21 Starting with Cycle 3, CT scans will be performed every 4 months for the first 2 years, every 6 months for the next 2 years, and then once a year 
thereafter.   
 
 

 
          Page 11 of 54  
POMALIDOMIDE  
                         Protocol:  
 
 
11
3.0   Glossary of Abbreviations 
ADCC - antibody-dependent cytotoxic T-cell activity  
AE -      adverse event 
CAS -   Chemical Abstract Service 
CFR -   Code of Federal Regulations 
CR -     complete response 
CRF -   case report form 
DLT -   dose limiting toxicity 
DMC -  data monitoring committee 
DVT -   deep vein thrombosis 
EC -     ethics committee 
EMEA - European Medicines Agency 
FDA -   Food and Drug Administration 
FCBP - females of childbearing potential 
GCP -   Good Clinical Practice 
ICH -    International Conference on Harmonisation 
IMiD -   immunomodulatory agent 
IND -   Investigational New Drug 
IRB -    institutional review board 
MM -    multiple myeloma 
MPT -   melphalan-prednisone-thalidomide 
MTD -   maximum tolerated dose 
NCI CTCAE v.4.0– National Cancer Institute Common Toxicity Criteria Adverse Events 
version 4.0 
PD - progressive disease 
PR - partial response 
SAE - severe adverse event 
TD - thalidomide-dexamethasone 
TPP - Targeted Product Profile 
UTMDACC – University of Texas M.D. Anderson Cancer Center 

 
          Page 12 of 54  
POMALIDOMIDE  
                         Protocol:  
 
 
12
VGPR - very good partial response 
WM - Waldenström Macroglobulinemia 
WWDSS - Celgene Corporation World Wide Drug Safety Surveillance 
 
4 Background and Rationale 
4.1 Introduction 
Waldenström Macroglobulinemia(WM) is a low grade B-cell lymphoproliferative disorder 
characterized by bone marrow infiltration with lymphoplasmacytic cells, together with 
demonstration of a monoclonal gammopathy, as defined by the Revised European-
American Lymphoma and World Health Organization classification systems.1 Patients with 
a disease-related hemoglobin level of less than 10 g/dL, a platelet count of less than 100 x 
109/L, bulky adenopathy or organomegaly, symptomatic hyperviscosity, severe neuropathy, 
amyloidosis, cryoglobulinemia, cold agglutinin disease, or evidence of disease 
transformation should be considered for immediate therapy.2   When treatment is initiated, 
overall response rates to frontline therapy with combinations of nucleoside analogs, 
alkylating agents and the anti-CD20 antibody, rituximab, have been high.3  However, 
complete responses are infrequent, eventual relapse from disease is inevitable, and the 
disease remains incurable.  Accordingly, novel strategies are needed to improve treatment 
of this disease. 
 
The emergence of immunomodulatory agents such as thalidomide, lenalidomide and more 
recently pomalidomide, has altered the therapeutic paradigm for multiple myeloma (MM), a 
plasma cell dyscrasia related to WM.4-9 
 
Thalidomide was initially developed as a sedative, but in the 1950s was found to be an 
effective anti-emetic for women with morning sickness.  Because of its teratogenic effects 
(phocomelia), it was removed from the market in the early 1960s. However, in the 1980s, 
studies in erythema nodosum leprosy, Behcet’s syndrome, and graft versus host disease 
led to subsequent approval of the drug by the United States Food and Drug Administration 
(1998) for the treatment of erythema nodosum leprosy.10-15   
 
The in vitro anti-angiogenic properties of thalidomide led researchers at the University of 
Arkansas to evaluate thalidomide’s clinical efficacy in patients with multiple myeloma.  In a 
pilot study, one of five patients treated, achieved near complete remission.16 A subsequent 
phase II clinical trial in patients with relapsing or refractory disease, confirmed a partial 
response rate of 25%.17  Multiple studies have since confirmed single agent response rates 
between 24-36% in relapsed and/or refractory patients, and 34-36% in previously untreated 
patients with multiple myeloma. 18, 19 
 
Following the approval and establishment of thalidomide-containing regimens, such as 
melphalan-prednisone-thalidomide (MPT) and thalidomide-dexamethasone (TD), as 
standard first-line therapy for newly diagnosed MM, lenalidomide, a related IMiD, was 

 
          Page 13 of 54  
POMALIDOMIDE  
                         Protocol:  
 
 
13
approved in combination with high-dose pulsed dexamethasone for the treatment of 
patients with previously treated MM.  
 
Given thalidomide’s activity in MM, it has also been studied in Waldenström's 
Macroglobulinemia, a related plasma cell dyscrasia. As monotherapy, thalidomide has 
modest activity in patients with WM, producing response rates of 25%; the combination of 
thalidomide plus steroids and/or clarithromycin produces response rates of 40%.4-6  Treon 
et al. have also recently reported results of a Phase II study combining thalidomide with the 
anti-CD20 antibody, rituximab, which had an overall response rate of 64%.7 Lenalidomide 
has also been studied in WM, but clinical investigation was halted before study completion 
due to the severity and frequency of anemia and thrombocytopenia that were encountered.8 
 
Despite the success of these novel agents, MM and WM remain incurable and most 
patients will eventually relapse and progress after multiple lines of different therapeutic 
regimens.  
 
4.2  POMALIDOMIDE  
Pomalidomide is an IMiD analogue of thalidomide that, among other anti-tumor properties, 
on an equimolar basis in vitro, displays equivalent anti-angiogenic activity, about 8-fold 
greater activity in stimulation of apoptosis, at least 10-fold greater activity in inhibition of 
cellular COX-2 production and over 4,000-fold greater activity in inhibition of cellular TNF-
alpha production relative to thalidomide.20,21    Pomalidomide has also been shown to 
stimulate antibody-dependent cytotoxic T-cell activity (ADCC).20   
At tolerated doses (MTD = 2 mg QD and 5 mg QOD), pomalidomide has been shown to be 
active in subjects with relapsed or refractory multiple myeloma (MM).20,22,23  In 45 subjects 
who received doses of  pomalidomide ranging, by cohort, up to 10 mg daily, the most 
commonly occurring dose-limiting toxicity (DLT) was reversible neutropenia.  As with other 
IMiDs administered to subjects receiving concomitant systemic steroids, deep vein 
thrombosis (DVT) was seen (in 1 subject each in this study and in its subsequent named 
patient supply rollover program).20,24 
Recently, efficacy and safety data from a phase II study, by Lacy et al., were published.9  
Sixty patients with relapsed or refractory multiple myeloma were enrolled.  Pomalidomide 
was given orally at a dose of 2 mg daily on days 1-28 of a 28-day cycle and 
dexamethasone was given orally at a dose of 40 mg daily on days 1, 8, 15, 22 of each 
cycle.  Patients also received aspirin 325 mg once daily for thromboprophylaxis.  The study 
endpoints were the response rate in patients taking pomalidomide plus dexamethasone 
including patients with lenalidomide resistant refractory multiple myeloma, and safety of 
pomalidomide plus dexamethasone. Thirty eight patients achieved objective response 
(63%) including CR in 3 patients (5%), VGPR in 17 patients (28%), and PR in 18 patients 
(30%).   The CR + VGPR rate was 33%.  Grade 3 or 4 hematologic toxicity occurred in 23 
patients (38%) and consisted of anemia in three patients (5%), thrombocytopenia in two 
patients (3%) and neutropenia in 21 (35%).  Among those that developed grade 3/4 
neutropenia, all first experienced the neutropenia in cycle 1-3; no new patients experienced 
grade 3/4 neutropenia in cycle 4 or later.  The most common non-hematological grade 3/4 

 
          Page 14 of 54  
POMALIDOMIDE  
                         Protocol:  
 
 
14
toxicities were fatigue (17%) and pneumonia (8%).  Other grade 3/4 non-hematological 
toxicities that occurred in less than 5% included diarrhea, constipation, hyperglycemia, and 
neuropathy.  One patient (1.6%) had a thromboembolic event of deep vein thrombosis.   
Complete and updated adverse events are available in the Investigational Drug Brochure 
and the IND Safety Letters. 
4.3 Rationale for Treatment in this Setting 
On the strength of the response rates and favorable toxicity profile seen in patients with 
relapsed and/or refractory MM, this study will evaluate the maximum tolerated dose of 
pomalidomide in patients with WM, whose disease has relapsed and/or is refractory to at 
least one line of prior therapy.  The safety and toxicity profile of pomalidomide and 
preliminary data on efficacy will also be collected will also be assessed. 
5 Study Objectives and Endpoints 
5.1 Objectives 
5.1.1 Primary objectives 
• 
To determine the maximum tolerated dose (MTD) of pomalidomide in patients with 
relapsed or refractory Waldenstrom Macroglobulinemia 
5.1.2 Secondary study objectives 
• 
To evaluate the safety and toxicity profile of pomalidomide in patients with relapsed 
or refractory Waldenstrom Macroglobulinemia 
• 
To evaluate the efficacy of pomalidomide in patients with relapsed or refractory 
Waldenstrom Macroglobulinemia 
5.2 Endpoints 
5.2.1 Primary Endpoint 
• 
The primary endpoint of this study is to determine the maximum tolerated dose of 
pomalidomide in patients with symptomatic Waldenström macroglobulinemia (WM) 
whose disease has relapsed/and or is refractory to at least 1 prior line of therapy. 
Tolerability of a given dose will be assessed after every 3 patients have been 
enrolled, until the maximum tolerated dose has been defined or, in the absence of 
dose limiting toxicities, the highest planned dose level is determined to have an 
acceptable toxicity profile. 

 
          Page 15 of 54  
POMALIDOMIDE  
                         Protocol:  
 
 
15
5.2.2 Secondary Endpoints 
• 
The safety and toxicity profile of pomalidomide will be evaluated after all patients to 
be enrolled have completed 1 cycle of therapy; patients who received at least 1 
dose of pomalidomide will be eligible for evaluation. 
 
• 
The efficacy of pomalidomide will be measured by best response to therapy during. 
It will be assessed as the best response during each patient’s course of therapy. 
The collective data will be summed at study completion.  Patients will be considered 
evaluable if they have completed at least 1 cycle of therapy. 
6  Investigational Plan 
6.1 Overall design 
This is a Phase 1 study of single agent pomalidomide in patients with symptomatic 
Waldenström macroglobulinemia (WM) whose disease has relapsed/and or is refractory to 
at least 1 prior line of therapy. 
 
To determine the maximum tolerated dose (MTD), patients will be enrolled in cohorts of 3, 
and the study will follow a standard 3+3 statistical dose-finding design as outlined in 
Section 11.0.  Once the maximum tolerated dose has been determined, and additional 6 
patients will be enrolled at that dose level to better assess the safety and toxicity profile of 
that dose and schedule.   
 
6.1.1 Investigational Drug  
6.1.1.1 Pomalidomide Description 
Pomalidomide, 4-amino-2-(2, 6-dioxo-3-piperidyl) isoindoline-1’-one)-1, 3-dione, belongs to 
the IMiD class of compounds.  The Chemical Abstract Service (CAS) registry number for 
Pomalidomide is 19171-19-8.  The chemical structure of the active pharmaceutical 
ingredient (API) is as follows:  
 
Pomalidomide has an asymmetric carbon atom and can therefore exist as the optically 
active forms S (-) and R (+).  Pomalidomide has been developed as a racemate.  

 
          Page 16 of 54  
POMALIDOMIDE  
                         Protocol:  
 
 
16
 
6.1.1.2 CLINICAL PHARMACOLOGY 
Mechanism of Action:  
Pomalidomide, a thalidomide analogue, is an immunomodulatory agent that, among other 
anti-tumor properties, on an equimolar basis in vitro, displays equivalent anti-angiogenic 
activity, about 8-fold greater activity in stimulation of apoptosis, at least 10-fold greater 
activity in inhibition of cellular COX-2 production and over 4,000-fold greater activity in 
inhibition of cellular TNF-alpha production relative to thalidomide [9,10].    Pomalidomide 
has also been shown to stimulate antibody-dependent cytotoxic T-cell activity (ADCC) [11].   
6.1.1.3 Dose and tolerability: 
Pomalidomide was safe at doses of up to 50 mg in a phase 1 single dose study in normal, 
healthy male volunteers and up to 5 mg QOD or 2 mg QD in a phase 1 multi-dose clinical 
study in subjects with relapsed or refractory multiple myeloma; DLTs seen in subjects 
receiving higher doses were predominantly hematopoetic (i.e., neutropenia), and lower 
grade, self-limited neutropenia was also seen in some of the 1 and 2 mg QD and 5 mg 
QOD recipients. In a multi-dose, phase 2 clinical study of subjects with prostate cancer, 2 
mg QD dosing was well tolerated and, unlike the multiple myeloma subjects who received 1 
and 2 mg QD doses, only an overall shift to lower neutrophil counts was noted. No clinically 
relevant neutropenic AEs were observed, and no grade 3 or 4 neutropenic events occurred. 
It is, therefore, likely that subjects with solid tumors that do not extensively involve the bone 
marrow will have a higher pomalidomide MTD than subjects with hematologic 
malignancies. 
6.1.1.4 Supplier(s) 
Celgene Corporation will supply pomalidomide. 
6.1.1.5 Dosage form 
Pomalidomide will be supplied as 0.5 mg, 1.0 mg, and 2.0 mg capsules for oral 
administration.   
6.1.1.6 Packaging 
Pomalidomide will be shipped to the pharmacy at the study site in individual bottles.   
Bottles will contain a sufficient number of capsules to last for one cycle of dosing. Study 
drug must be dispensed in the original packaging with the label clearly visible.   
6.1.1.7 Labeling 
Pomalidomide investigational supplies are dispensed to the patients in individual bottles of 
capsules.  Each bottle will identify the contents as study medication.  In addition, the label 
will bear Celgene’s name, quantity contained and the standard caution statement as 
follows:  Caution: New drug - Limited by Federal law to investigational use.  Pomalidomide 
should not be handled by FCBP unless wearing gloves.  All bottles will contain the following 
warning label:  “WARNING: POTENTIAL FOR HUMAN BIRTH DEFECTS.” 

 
          Page 17 of 54  
POMALIDOMIDE  
                         Protocol:  
 
 
17
 The study drug label must be clearly visible.  Additional labels must not cover the Celgene 
label. 
6.1.1.8 Receipt of study drug 
The Investigator or designee is responsible for taking an inventory of each shipment of 
study drug received, and comparing it with the accompanying study drug accountability 
form.  The Investigator will verify the accuracy of the information on the form, sign and date 
it, retain a copy in the study file, and return a copy to Celgene or its representative.   
6.1.1.9 Storage 
At the study site, all investigational study drugs will be stored in a locked, safe area to 
prevent unauthorized access. 
The study drug should be stored at room temperature away from direct sunlight and 
protected from excessive heat and cold. 
6.1.1.10 Unused study drug supplies 
Any unused study drug is to be disposed of as per UTMDACC institutional policy.  If any 
study drug is lost or damaged, its disposition should be documented in the source 
documents.  Patients will be instructed to return empty bottles or unused capsules.   
6.1.1.11 Drug dispensing requirements 
In investigational studies, pomalidomide will be dispensed through a qualified healthcare 
professional (including but not limited to, nurses, pharmacists and physicians).  These 
healthcare professionals will be trained by Celgene in requirements specific to counseling 
of subjects.  Once trained, these healthcare staff will counsel subjects prior to medication 
being dispensed to ensure that the subject has complied with all requirements including 
use of birth control and pregnancy testing (FCBP) and that the subject understands the 
risks associated with pomalidomide.  This step will be documented with a completed 
Education and Counseling Guidance Document (Appendix B), and no drug will be 
dispensed until this step occurs. Counseling includes verification with the patient that 
required pregnancy testing was performed and results were negative. 
A Pomalidomide Information Sheet (Appendix C) will be supplied to the patient each time 
that pomalidomide is dispensed. 
Pomalidomide (POMALYST®) will be provided to research subjects for the duration of their 
participation in this trial at no charge to them or their insurance providers.  Pomalidomide 
will be provided in accordance with the Celgene Corporation’s POMALYST REMS™  
program.  Per the standard   POMALYST REMS™ program requirements, all physicians 
who prescribe pomalidomide for research subjects enrolled into this trial, and all research 
subjects enrolled into this trial, must be registered in and must comply with all requirements 
of the POMALYST REMS™ program.   
 
Only enough pomalidomide capsules for 1 cycle of therapy may be provided to the 
patient each cycle.  

 
          Page 18 of 54  
POMALIDOMIDE  
                         Protocol:  
 
 
18
6.2 Screening and Eligibility 
The Investigator is responsible for keeping a record of all subjects who sign an Informed 
Consent Form for entry into the study.  All subjects will be screened for eligibility.  
Screening procedures are outlined in Section 2, Schedule of Study Assessments and 
unless otherwise specified, must take place within 28 days prior to initiation of therapy.  
Approximately 21 subjects with symptomatic Waldenström Macroglobulinemia will be 
screened for enrollment and must meet the eligibility criteria below. 
6.2.1 Inclusion Criteria 
Subjects must meet the following inclusion/exclusion criteria to be eligible for the study. 
Inclusion criteria  
1. Understand and voluntarily sign an informed consent form. 
2. Age ≥18 years at the time of signing the informed consent form. 
3. Able to adhere to the study visit schedule and other protocol requirements. 
4. Waldenström's Macroglobulinemia that has relapsed and/or is refractory to at least 
one prior line of therapy  
5. All previous cancer therapy, including radiation, hormonal therapy and surgery, 
must have been discontinued at least 4 weeks prior to treatment in this study.  
6. ECOG performance status of ≤ 2 at study entry (see Appendix D). 
7. Laboratory test results within these ranges: 
• 
Serum creatinine ≤ 2.0 mg/dL 
• 
Creatinine clearance >45 ml/min 
• 
Total bilirubin ≤ 3 x Upper Limit of Normal (ULN) or Direct Bilirubin  ≤ 2 x ULN 
• 
AST (SGOT) and ALT (SGPT) ≤ 2 x ULN 
• 
Platelet count ≥ 20 K/μL 
• 
Absolute neutrophil count  ≥ 500 K/μL 
8. Disease free of prior malignancies for ≥ 5 years with exception of currently treated 
basal cell, squamous cell carcinoma of the skin, or carcinoma “in situ” of the cervix 
or breast.  
9. Females of childbearing potential (FCBP)† must have a negative serum or urine 
pregnancy test with a sensitivity of at least  25 mIU/mL within 10 – 14 days prior to 
                                               
 
† 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., has had menses at any time in the preceding 24 consecutive months). 
 
 

 
          Page 19 of 54  
POMALIDOMIDE  
                         Protocol:  
 
 
19
starting pomalidomide and must either commit to continued abstinence from 
heterosexual intercourse or begin TWO acceptable methods of birth control, one 
highly effective method and one additional effective method AT THE SAME TIME, 
at least 28 days before she starts taking  pomalidomide.  FCBP must also agree to 
ongoing pregnancy testing.  Men must agree to practice complete abstinence or 
agree use a latex condom during sexual contact with a FCBP while participating in 
the study, during dose interruptions and for at least 90 days following study drug 
discontinuation, even if they have had a successful vasectomy.  All patients must be 
counseled at a minimum of every 28 days about pregnancy precautions and risks of 
fetal exposure.  See Appendix A Risks of Fetal Exposure, Pregnancy Testing 
Guidelines and Acceptable Birth Control Methods, AND also Appendix B: Education 
and Counseling Guidance Document 
10. Able to take aspirin (325mg) daily as prophylactic anticoagulation (patients 
intolerant to ASA may use therapeutic dose warfarin or low molecular weight 
heparin). 
11. All study participants must be registered into the mandatory POMALYST REMS™ 
program, and be willing and able to comply with the requirements of the 
POMALYST REMS™ program. 
6.2.2 Exclusion criteria   
1. Any serious medical condition, laboratory abnormality, or psychiatric illness that 
would prevent the subject from signing the informed consent form. 
2. Pregnant or breast feeding females. (Lactating females must agree not to breast 
feed while taking pomalidomide or for 28 days after stopping pomalidomide). 
3. Any medical or psychiatric condition, including the presence of laboratory 
abnormalities, which places the subject at unacceptable risk if he/she were to 
participate in the study, or confounds the ability to interpret data from the study. 
4. Use of any other experimental drug or therapy within 28 days of the first dose of 
study drug. 
5. Known hypersensitivity to thalidomide or lenalidomide. 
6. The development of erythema nodosum if characterized by a desquamating rash 
while taking thalidomide or similar drugs. 
7. Any prior use of pomalidomide. 
8. Concurrent use of other anti-cancer agents or treatments. 
9. Known positive for HIV or acute hepatitis A or acute or chronic active hepatitis B or 
C. 
10. Grade >2 peripheral neuropathy 

 
          Page 20 of 54  
POMALIDOMIDE  
                         Protocol:  
 
 
20
11. Neutrophil count <1000K/μL and/or platelet count <100K/μL unless infiltration by 
Waldenström’s Macroglobulinemia equals or exceed 60% of bone marrow 
cellularity. 
6.3 Visit schedule and assessments 
Screening Assessments and all on-study scheduled visits and assessments are outlined in 
Section 2, Table of Study Assessments.  
At treatment discontinuation, subjects will undergo off study evaluations as per the 
Schedule of Assessments, Section 2.   In addition, a safety assessment will be done 
approximately 30 days after the last dose of study drug.  Subsequently, subjects will be 
contacted by the site study coordinator at a minimum of every 6 months, until death or 12 
months from the last dose of study drug administration, whichever occurs first.  At these 
follow-ups, the study coordinator will collect information about cancer therapies 
administered after participation in this study (including dates of treatment), and for survival 
unless the patient withdraws consent. The information on subsequent treatment and 
survival status may be obtained without having the subject visit the study center (i.e. phone 
call).   If the information is obtained by phone call then written documentation of the 
communication must be available for review in the source documents.  
6.4 Drug Administration 
6.4.1 Treatment assignments 
This is a Phase I non-randomized study. Eligible patients will be allocated to treatment in 
the order in which they sign the informed consent and that all documentation needed to 
confirm eligibility has been completed.  A maximum of 30 subjects will be enrolled and 
treated with single agent pomalidomide.  Starting at dose level 1 in Schedule A, the study 
will enroll patients in cohorts of 3, following a standard 3 +3 statistical design. (see Section 
11.0).  
 
Definition of Dose Limiting Toxicity (DLT):   
Toxicity will be evaluated according to the NCI CTCAE version 4.0, (see Appendix E) 
1) Non-hematologic dose limiting toxicity (DLT) is defined as any grade ≥3 non-
hematological toxicity occurring during the first 28 days (first cycle) of treatment, with the 
specific exception of: 
• 
Isolated Grade 3 elevation of liver function tests (LFTs) without associated clinical 
symptoms, lasting for ≤ 7 days in duration. 
• 
Isolated Grade 3 elevation of amylase without associated clinical symptoms 
• 
Grade 3 hypocalcemia, hypokalemia, hypomagnesemia, hyponatremia, or 
hypophosphatemia which responds to medical intervention. 
 
2) Hematological dose limiting toxicity is defined as Grade ≥ 3 neutropenia with fever ≥ 
38.5, Grade 4 neutropenia lasting for ≥ 7 days in duration, or any Grade 4 anemia or 
thrombocytopenia occurring during the first 28 days (first cycle) of treatment. 

 
          Page 21 of 54  
POMALIDOMIDE  
                         Protocol:  
 
 
21
 
Definition of Maximum Tolerated Dose (MTD):  MTD is defined as the highest dose level 
in which 6 patients have been treated with less than 2 instances of DLT.   
 
6.4.2 Dosing regimen 
There are four predefined dose levels (1, 2, 3, and 4) for pomalidomide, and two alternative 
dosing schedules (A and B). With schedule A, patients will be treated with the study drug 
for 28 days within each cycle.  With schedule B, patients will be treated for 21 days within 
each 28 day cycle. Schedule B will only be explored if the MTD is exceeded at dose level 1 
within Schedule A. The first cohort of 3 patients will be treated at dose level 1 with schedule 
A (28-day dosing). If no dose limiting toxicities (DLTs) are observed then the next cohort of 
3 patients will be treated at next higher dose level.  If one DLT is observed then 3 more 
patients will be treated at the same dose level.  At anytime if 2 or more DLTs are observed 
within 3 or 6 patients at dose level 1, then schedule A is considered too toxic and will be 
abandoned.  Patient enrollment will then be resumed using dose level 1 of dosing schedule 
B (21-day dosing) to determine the MTD. The purpose of schedule B is to prepare for the 
scenario that dosing schedule A is not tolerable.  
 
 
Table 1 
 
  
Dosing Schedule A 
Dosing Schedule B 
Dose level 1 
1 mg orally on days 1-28 
1 mg orally on days 1-21 
Dose level 2 
2 mg orally on days 1-28 
2 mg orally on days 1-21 
Dose level 3 
3 mg orally on days 1-28 
3 mg orally on days 1-21 
Dose level 4 
4 mg orally on days 1-28 
4 mg orally on days 1-21 
 
Dose escalation will continue in 1 mg increments until the MTD is reached. Once the MTD 
has been determined, an additional 6 patients will be treated at this dose level. 
 
An additional 6 patients will be treated at the MTD. 
 
Dosing will be each night at approximately the same time.  Pomalidomide should be taken 
with a glass of water on an empty stomach.  Only enough pomalidomide for one cycle 
of therapy will be supplied to the patient each cycle. 
 
Patients will continue receiving treatment with pomalidomide until disease progression or 
unacceptable toxicity develops. 
 

 
          Page 22 of 54  
POMALIDOMIDE  
                         Protocol:  
 
 
22
Patients are to receive oral aspirin (325mg) as prophylactic anti-thrombotic treatment 
unless it is contraindicated, or the patient has a platelet count of less than 50,000. If the 
patient is intolerant of aspirin and has a platelet count of 50,000 or greater, the investigator 
is to prescribe therapeutic dose warfarin or low molecular weight heparin. 
 
Pomalidomide capsules should be swallowed whole, and should not be broken, chewed or 
opened. Pomalidomide should be taken without food, at least 2 hours before or 2 hours 
after a meal. 
 
If a dose of pomalidomide is missed, it should be taken as soon as possible on the same 
day.  If it is missed for the entire day, it should not be made up, rather it should be taken at 
the next scheduled time point. 
Patients who take more than the prescribed dose of pomalidomide should be instructed to 
seek emergency medical care if needed and contact study staff immediately.   
6.4.3 Special Handling Instructions 
Females of childbearing potential should not handle or administer pomalidomide unless 
they are wearing gloves. 
6.4.4 Record of administration 
Accurate records of all study drug administration (including dispensing and dosing) will be 
made in the source documents.  Accurate records of all prophylactic anti-thrombotic 
treatment compliance will also be made in the source documents. 
6.4.5   Dose Modification or Interruption 
Pomalidomide Dose Reductions 
Dose reduction(s) will be allowed for any subject who develops a DLT during Cycle 1 or 
beyond Cycle 1 who develops a toxicity that, in the opinion of the Investigator, requires a 
dose-reduction. 
For treatment interruptions during a cycle, the (28- or 21-day) schedule of each cycle will 
continue to be followed.  Missed doses of pomalidomide are not made up.   
For treatment interruptions that delay the scheduled start of a new cycle, when toxicity has 
resolved as required to allow the start of a new cycle (Section 6.5), the restart day of 
therapy becomes Day 1 of the next cycle. 
 
The following table provides the dose reduction sequence for pomalidomide: 
Table 2: 
Schedule of Pomalidomide Dose Reduction 

 
          Page 23 of 54  
POMALIDOMIDE  
                         Protocol:  
 
 
23
 
If the DLT/Toxicity 
occurred or recurred at 
--- (mg/dose/d 1-28 or d 1-
21 depending on 
Schedule): 
Reduce dose to 
--- (mg/dose/d 1-28 or d 1-
21 depending on 
Schedule): 
Pomalidomide 
4 
3 
 
3 
2 
 
2 
1 
 
1 
0.5 
 
Dosing interruptions and reductions are not permitted during Cycle 1 unless the subject 
experiences a DLT.  Dose interruptions and reductions are permitted beyond Cycle 2.  
Examples of possible reasons for and extent of dose modification management are outlined 
in Table 3.  The events listed are not all-inclusive and are based on observations pooled 
from studies with all compounds in the IMiD® class of drugs.  Therefore, these events may 
occur but are not necessarily expected.  The investigator may choose to modify 
pomalidomide dosing further downward or discontinue pomalidomide treatment for any 
adverse event. 
Study drug may be held (up to 21 days) and subsequent dose reductions made as outlined 
in Table 3.  If study drug needs to be held > 21 days, the patient is to be taken off study.  
Once a dose has been reduced, it cannot be re-escalated. 
At the discretion of the Investigator, the use of G-CSF will be permitted to manage 
neutropenic fever or a Grade 4 neutropenia. 
 
Table 3: 
Pomalidomide Dosage Modifications for cycles ≥ 2  
Common Terminology 
Criteria (CTCAE) Version 
4.0 
Adverse Event 
Dose Change for 
Pomalidomide 
Allergy/Immunology 
Allergic reaction/ 
hypersensitivity (including 
drug fever)  
Grade 2 
Hold study drug until 
resolved to < Grade 1; 
Decrease dose by 1 dose 
level 
Allergy/Immunology 
Allergic reaction/ 
hypersensitivity (including 
drug fever)  
Grade 3 or 4 
Discontinue Study Drug 

 
          Page 24 of 54  
POMALIDOMIDE  
                         Protocol:  
 
 
24
Common Terminology 
Criteria (CTCAE) Version 
4.0 
Adverse Event 
Dose Change for 
Pomalidomide 
Blood/Bone Marrow 
Neutropenia (ANC)  
Grade 3 with fever or 4 
Day 2-14 of cycle: Hold 
study drug. Follow CBC 
weekly; If neutropenia has 
resolved to ≤ grade 2 
restart at next lower dose 
level until the end of the 
cycle. 
Day ≥ 15 of cycle: 
Hold study drug for 
remainder of cycle.  Begin 
next cycle at next lower 
dose level 
Blood/Bone Marrow 
Thrombocytopenia  
Grade 3 or 4 
Day 2-14 of cycle: 
Hold study drug. Follow 
CBC weekly;  
If thrombocytopenia 
resolves to ≤ grade 2 
restart at next lower dose 
level and continue the cycle 
until Day 28 or Day 21 if 
previously reduced. 
Hold anticoagulation for 
platelet count < 50,000 
Day ≥ 15 of cycle: 
Hold study drug. Begin next 
cycle at next lower dose. 
Hold anticoagulation for 
platelet count < 50,000 
Blood/Bone Marrow 
Anemia  
Grade 3 or 4 
Hold study drug and treat 
anemia as needed until 
Hgb ≤ grade 2; Decrease 
dose by 1 dose level 
Cardiac Arrhythmia 
Grade 2 
Hold study drug until 
resolved to < Grade 1; 
Decrease dose by 1 dose 
level 
Cardiac Arrhythmia 
Grade 3 or 4 
Discontinue study drug 
Vascular 
Thrombosis/embolism  
Grade 2, 3 or 4 
Hold study drug and 
anticoagulate.  Resume 
therapy at investigator’s 
discretion.  

 
          Page 25 of 54  
POMALIDOMIDE  
                         Protocol:  
 
 
25
Common Terminology 
Criteria (CTCAE) Version 
4.0 
Adverse Event 
Dose Change for 
Pomalidomide 
Dermatology/ Skin 
Rash non-desquamation  
Grade 3 
Hold study drug until 
resolved to < Grade 1.  
Decrease dose by 1 dose 
level 
Dermatology/ Skin 
Rash non-desquamation 
Grade 4 
Discontinue study drug 
Dermatology/ Skin 
Rash / desquamation  
Grade 3, 4 
Discontinue study drug 
Grade 2 
The dose may be modified 
or discontinued at the 
investigators discretion. 
Dermatology/ Skin 
Rash Erythema multiforme 
Discontinue study drug 
Endocrine 
Elevated or Reduced 
Thyroid Function Test 
results without symptoms of 
hyper- or hypo-thyroidism 
Confirm test results and if 
significant, refer for therapy; 
Do not alter study drug 
regimen 
Endocrine 
Elevated or Reduced 
Thyroid Function Test 
results with symptoms of 
hyper- or hypo-thyroidism 
Hold study drug; Evaluate 
etiology and refer for 
appropriate therapy; 
Restart at the prior dose 
once symptoms have 
resolved and thyroid 
function has been stabilized 
with medical and/or surgical 
intervention 
Neurology 
Neuropathy cranial/motor/ 
sensory  
Grade 2 (unless baseline 
was grade 2) 
Hold study drug; Restart at 
same or 1 dose level lower 
once event has resolved to 
< Grade 1 
Neurology 
Neuropathy cranial/motor/ 
sensory  
Grade 3 or recurrence of 
Grade 2 
Hold study drug until 
resolved to < Grade 1 or 
baseline if baseline was 
grade 2; Decrease dose by 
1 dose level 
Neurology 
Neuropathy cranial/motor/ 
sensory  
Grade 4 
Discontinue study drug 

 
          Page 26 of 54  
POMALIDOMIDE  
                         Protocol:  
 
 
26
Common Terminology 
Criteria (CTCAE) Version 
4.0 
Adverse Event 
Dose Change for 
Pomalidomide 
Other pomalidomide related 
toxicity 
Grade 3 or Grade 4 
Hold pomalidomide 
therapy; Decrease dose by 
1 dose level and restart 
when resolved to < Grade 2 
 
 
6.5 Instructions for initiation of a New Cycle  
A new course of treatment may begin on the scheduled Day 1 of a new cycle if: 
• 
The ANC is ≥1.0K/μL, or ≥ the baseline ANC, if the baseline ANC was <1.0K/μL. 
• 
The platelet count is ≥100K/μL, or ≥ the baseline platelet count, if the baseline 
platelet count was less than 100K/μL.  
• 
Any drug-related rash, neuropathy or cardiac event that may have occurred has 
resolved to ≤ grade 1 severity or baseline. 
• 
Any other drug-related adverse events that may have occurred have resolved to ≤ 
grade 2 severity.  
 
If these conditions are not met on Day 1 of a new cycle, the subject will be evaluated 
weekly and a new cycle of treatment will not be initiated until the toxicity has resolved as 
described above.  A maximum delay of 21 days is allowed for any given cycle. If these 
conditions remain unmet on Day 21, the patient is to be taken off of the protocol.  
 
If anti-thrombotic prophylaxis (aspirin, else warfarin or low molecular weight heparin) was 
held during a given cycle for a platelet count <50 K/μL, it should be resumed as soon as the 
platelet count recovers to ≥ 50 K/μL. 
 
6.5.1 Treatment compliance 
At all times, when dispensing study drug, research center personnel will review the 
instructions, printed on the packaging, with subjects. Subjects will be asked to maintain a 
diary to record the drug administration. Subjects will be asked to bring any unused study 
drug and empty study drug containers to the research center at their next visit.  Research 
personnel will count and record the number of used and unused study drug capsules at 
each visit and reconcile with the patient diary.   

 
          Page 27 of 54  
POMALIDOMIDE  
                         Protocol:  
 
 
27
6.6 Concomitant therapy   
6.6.1 Recommended concomitant therapy   
Subjects should receive full supportive care, including transfusions of blood and blood 
products, antibiotics, and anti-emetics when appropriate.  
6.6.1.1 Anticoagulation Consideration   
Pomalidomide increases the risk of thrombotic events in patients who are at high risk or 
with a history a thrombosis, in particular when combined with other drugs known to cause 
thrombosis.  
Patients are to receive oral aspirin (325mg) as prophylactic anti-thrombotic treatment 
unless it is contraindicated, or the patient has a platelet count of less than 50,000. If the 
patient is intolerant of low-dose aspirin and has a platelet count of at least 50,000, the 
investigator should prescribe therapeutic dose warfarin or low molecular weight heparin. If 
warfarin is used, close monitoring of the international normalized ratio (INR) is required.  
6.6.2 Prohibited concomitant therapy 
Concomitant use of sargramostim (GM-CSF), other anti-cancer therapies, including 
radiation, thalidomide, or other investigational agents is not permitted while subjects are 
receiving study drug during the treatment phase of the study. 
6.7 Discontinuation of Study Treatment  
Treatment will continue until occurrence of any of the following events.   
• 
Disease progression  
• 
Adverse event(s) that, in the judgment of the Investigator, may cause severe or 
permanent harm or which rule out continuation of the treatment regimen. 
• 
Major violation of the study protocol. 
• 
Withdrawal of consent 
• 
Lost to follow up 
• 
Death 
• 
Pregnancy 
 
6.8 
Follow-Up   
Subjects who discontinue treatment for any reason will be contacted by the site study 
coordinator at a minimum of every 6 months, until death or 12 months from the last dose of 
study drug administration, whichever occurs first.  At these follow-ups, the study 
coordinator will collect information about cancer therapies administered after participation in 

 
          Page 28 of 54  
POMALIDOMIDE  
                         Protocol:  
 
 
28
this study (including dates of treatment), and for survival unless the patient withdraws 
consent.  The information on subsequent treatment and survival status  may be obtained 
without having the subject visit the study center (i.e. phone call).   If the information is 
obtained by phone call then written documentation of the communication must be available 
for review in the source documents. 
At treatment discontinuation, subjects will undergo a safety assessment approximately 30 
days (+/- 1 week) post the last dose of study drug.  In addition, off study evaluations per the 
Schedule of Assessments, Section 2 will be done. 
7 Adverse events 
7.1 Serious Adverse Event (SAE) Definition  
An adverse event or suspected adverse reaction is considered “serious” if, in the view of 
either the investigator or the sponsor, it results in any of the following outcomes: 
 
•    Death 
•    A life-threatening adverse drug experience – any adverse experience that places the 
patient, in the view of the initial reporter, at immediate risk of death from the adverse 
experience as it occurred. It does not include an adverse experience that, had it 
occurred in a more severe form, might have caused death. 
•    Inpatient hospitalization or prolongation of existing hospitalization 
•    A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions. 
•    A congenital anomaly/birth defect. 
 
Important medical events that may not result in death, be life threatening, or require 
hospitalization may be considered a serious adverse drug experience when, based upon 
appropriate medical judgment, they may jeopardize the patient or subject and may require 
medical or surgical intervention to prevent one of the outcomes listed in this definition. 
Examples of such medical events include allergic bronchospasm requiring intensive 
treatment in an emergency room or at home, blood dyscrasias or convulsions that do not 
result in inpatient hospitalization, or the development of drug dependency or drug abuse 
(21 CFR 312.32). 
 
•    Important medical events as defined above, may also be considered serious 
adverse events. Any important medical event can and should be reported as an 
SAE if deemed appropriate by the Principal Investigator or the IND Sponsor, IND 
Office. 
 
•    All events occurring during the conduct of a protocol and meeting the definition of a SAE 
must be reported to the IRB in accordance with the timeframes and procedures outlined 
in “The University of Texas M. D. Anderson Cancer Center Institutional Review Board 
Policy for Investigators on Reporting Unanticipated Adverse Events for Drugs and 
Devices”.  Unless stated otherwise in the protocol, all SAEs, expected or unexpected, 
must be reported to the IND Office, regardless of attribution (within 5 working days of 
knowledge of the event). 
 

 
          Page 29 of 54  
POMALIDOMIDE  
                         Protocol:  
 
 
29
•    All life-threatening or fatal events, that are unexpected, and related to the study drug, 
must have a written report submitted within 24 hours (next working day) of knowledge 
of the event to the Safety Project Manager in the IND Office. 
 
•    Unless otherwise noted, the electronic SAE application (eSAE) will be utilized for 
safety reporting to the IND Office and MDACC IRB.  
 
•    Serious adverse events will be captured from the time of the first protocol-
specific intervention, until 30 days after the last study treatment/intervention, 
unless the participant withdraws consent. Serious adverse events must be 
followed until clinical recovery is complete and laboratory tests have returned to 
baseline, progression of the event has stabilized, or there has been acceptable 
resolution of the event. 
 
•    Additionally, any serious adverse events that occur after the 30 day time period 
that are related to the study treatment must be reported to the IND Office. This 
may include the development of a secondary malignancy. 
 
 
Reporting to FDA: 
 
•    Serious adverse events will be forwarded to FDA by the IND Sponsor (Safety Project 
Manager IND Office) according to 21 CFR 312.32. 
 
It is the responsibility of the PI and the research team to ensure that serious adverse 
events are reported according to the Code of Federal Regulations, Good Clinical 
Practices, the protocol guidelines, the sponsor’s guidelines, and Institutional Review 
Board policy. 
 
 
 
7.2 Adverse Drug Reaction Reporting 
Toxicity will be scored using CTCAE Version 4.0 for toxicity and adverse event reporting 
(see Appendix E).  A copy of the CTCAE Version 4.0 can be downloaded from the CTEP 
homepage (HTTP://CTEP.INFO.NIH.GOV).  All appropriate treatment areas should have 
access to a copy of the CTCAE Version 4.0.  All adverse clinical experiences, whether 
observed by the investigator or reported by the patient, must be recorded, with details 
about the duration and intensity of each episode, the action taken with respect to the test 
drug, and the patient’s outcome.  The investigator must evaluate each adverse experience 
for its relationship to the test drug and for its seriousness. 
 
Abnormal laboratory results will be documented on adverse event worksheets. The 
investigator must appraise all abnormal laboratory results for their clinical significance.  If 
any abnormal laboratory result is considered clinically significant, the investigator must 
provide details about the action taken with respect to the test drug and about the patient’s 
outcome.  Completed worksheets will be signed by the principal investigator and 
subsequently scanned into the electronic medical record upon completion of a patient’s 
study participation. 

 
          Page 30 of 54  
POMALIDOMIDE  
                         Protocol:  
 
 
30
7.3 Pregnancies 
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 pomalidomide, or 
within 4 weeks of the subject’s last dose of pomalidomide, are considered immediately 
reportable events. Pomalidomide is to be discontinued immediately. The pregnancy, 
suspected pregnancy, or positive pregnancy test must be reported to Celgene Drug Safety 
immediately by facsimile, or other appropriate method, using the Pregnancy Initial Report 
Form, or approved equivalent form. 
The female subject should be referred to an obstetrician-gynecologist, preferably one 
experienced in reproductive toxicity for further evaluation and counseling. 
 
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 Pregnancy Follow-up 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 
immediately 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 after28 days that the Investigator suspects 
is related to the in utero exposure to pomalidomide should also be reported to Celgene 
Drug Safety immediately 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 . 
 
 
Male Subjects 
If a female partner of a male subject taking investigational product becomes pregnant, the 
male subject taking IP should notify the Investigator immediately, and the pregnant female 
partner should be advised to call their healthcare provider immediately. 
 
 
7.4 Celgene Drug Safety Contact Information: 
 
Celgene Corporation      
Global Drug Safety and Risk Management    
Connell Corporate Park      
300 Connell Dr.  Suite 6000     
Berkeley Heights, NJ  07922        
Fax: 
 
(908) 673-9115 
e-mail:  
drugsafety@celgene.com 
 

 
          Page 31 of 54  
POMALIDOMIDE  
                         Protocol:  
 
 
31
7.5 Investigator Reporting Responsibilities 
The conduct of the study will comply with all FDA safety reporting requirements.   
 
IND Annual Reports 
If the FDA has granted an IND number, it is a requirement of 21 CFR 312.33, that an 
annual report is provided to the FDA within 60-days of the IND anniversary date.  21 CRF 
312.33 provides the data elements that are to be submitted in the report.  The Annual 
Report should be filed with the UTMDACC IND Office, who will then forward it to the FDA.  
An additional copy should be placed in the study's Regulatory Binder, and a copy provided 
to Celgene Corporation as a supporter of this study as follows: 
 
 
Celgene Corporation 
 
Attn: Medical Development 
 
300 Connell Dr. Suite 6000 
 
Berkeley Heights, NJ 07922 
 
Tel: (908) 673-9000 
 
All adverse experience reports must include the patient number, age, sex, weight, severity 
of reaction (mild, moderate, severe), relationship to study drug (probably related, unknown 
relationship, definitely not related), date and time of administration of test medications and 
all concomitant medications, and medical treatment provided.   The investigator is 
responsible for evaluating all adverse events to determine whether criteria for “serious” and 
as defined above are present.  The investigator is responsible for reporting adverse events 
to Celgene as described below. 
7.5.1 Expedited reporting by investigator to Celgene 
Serious adverse events (SAE) are defined above.  The investigator should inform Celgene 
in writing using a Celgene SAE form or MEDWATCH 3500A form of any SAE within 24 
hours of being aware of the event.   This form must be completed and supplied to the 
UTMDACC IRB, UTMDACC IND Office, and Celgene within 24 hours/1 business day. The 
initial report must be as complete as possible, including an assessment of the causal 
relationship between the event and the investigational product(s) if available.  Information 
not available at the time of the initial report (e.g., an end date for the adverse event or 
laboratory values received after the report) must be documented on a follow-up M.D. 
Anderson Cancer Center SAE form..  A final report to document resolution of the SAE is 
required.  The M.D. Anderson Protocol number (2009-0972) and the Celgene protocol 
number (PO-WM-PI-0006) should be included on SAE reports to Celgene.  A copy of the 
fax transmission confirmation of the SAE report to Celgene should be attached to the SAE 
and retained with the patient records. 
7.5.2 Report of Adverse Events to the Institutional Review Board 
The principal investigator is required to notify his/her Institutional Review Board of a serious 
adverse event according to institutional policy.   
7.5.3 Investigator Reporting to the FDA 
Adverse drug reactions that are Serious, Unlisted/unexpected, and at least possibly 
associated to the drug, and that have not previously been reported in the Investigators 

 
          Page 32 of 54  
POMALIDOMIDE  
                         Protocol:  
 
 
32
brochure, or reference safety information document should be reported promptly to the 
Food and Drug Administration (FDA) in writing by each investigator/physician engaged in 
clinical research.  A clear description of the suspected reaction should be provided along 
with an assessment as to whether the event is drug or disease related.   
 
Serious adverse events will be forwarded to the FDA by the IND Sponsor (Safety Project 
Manager IND Office) according to 21 CFR 312.32. 
7.6 Adverse event updates/IND safety reports 
Celgene shall notify the Investigator via an IND Safety Report of the following information: 
 
• 
Any AE associated with the use of study drug in this study or in other studies that is 
both serious and unexpected. 
• 
Any finding from tests in laboratory animals that suggests a significant risk for 
human subjects including reports of mutagenicity, teratogenicity, or carcinogenicity. 
 
The Investigator shall notify his/her IRB/EC promptly of these new serious and unexpected 
AE(s) or significant risks to subjects. 
 
The Investigator must keep copies of all AE information, including correspondence with 
Celgene and the IRB/EC, on file (see Section 12.4 for records retention information). 
8 Response Criteria25 
Baseline disease assessments must occur within ≤ 28 days of study drug administration. 
 Response assessments will be performed after each cycle of pomalidomide has been 
administered.  Response will be assessed by either the principal investigator on a sub-
investigator, and then documented in the UTMDACC protocol data management system 
(PDMS).  Because of the IgM flare phenomenon26, progressive disease cannot be 
confirmed until the response assessment performed after the second cycle of 
pomalidomide, has been reviewed. All partial and complete responses must be confirmed 
with a second efficacy assessment, performed at least 6 weeks later. 
 
Definitions of response: 
1. Complete response (CR): categorized by the disappearance of serum and urine 
monoclonal protein determined by immunofixation, absence of malignant cells in the 
bone marrow determined by histologic evaluation, resolution of 
adenopathy/organomegaly (confirmed by computed tomography [CT] scan) and no 
signs or symptoms attributable to WM. Reconfirmation of the CR status is required 
≥6 weeks later with a second immunofixation. 
2. Partial response (PR): categorized by ≥50% reduction of serum monoclonal IgM 
concentration determined by protein electrophoresis, ≥50% decrease in 

 
          Page 33 of 54  
POMALIDOMIDE  
                         Protocol:  
 
 
33
adenopathy/organomegaly on physical examination or on CT scan and no new 
symptoms or signs of active disease. 
3. Minor response (MR): categorized by a ≥25% but <50% reduction of serum 
monoclonal IgM concentration determined by protein electrophoresis and no new 
symptoms or signs of active disease. 
4. Stable disease (SD): categorized by a <25% reduction and <25% increase of 
serum monoclonal IgM concentration determined by protein electrophoresis, without 
progression of adenopathy/organomegaly, cytopenias or clinically significant  
symptoms caused by disease and/or signs of WM. 
5. Progressive disease (PD): categorized by a ≥25% increase of serum monoclonal 
IgM concentration determined by protein electrophoresis confirmed by a second 
measurement or progression of clinically significant findings caused by disease (e.g. 
anemia, thrombocytopenia, leukopenia or bulky adenopathy/organomegaly) or 
symptoms (e.g. unexplained recurrent fever ≥38.4ºC, drenching night sweats, ≥10% 
weight loss, hyperviscosity, neuropathy or symptomatic cryoglobulinemia) 
attributable to WM. 
Definition of Relapse/Progression after response: 
1. Relapse from CR: categorized by the appearance of the monoclonal protein in 
serum or urine, confirmed by a second determination, recurrence of bone marrow 
involvement by lymphoplasmacytic cells, recurrence/development of 
lymphadenopathies/splenomegaly or symptoms/signs attributable to WM. 
 
2. Progression from PR: categorized by ≥25% increase of serum monoclonal IgM 
concentration from the lowest attained response value determined by protein 
electrophoresis, confirmed by a second measurement or progression of clinically 
significant signs (anemia, thrombocytopenia, leukopenia, or bulky 
adenopathy/organomegaly) or symptoms (e.g. unexplained recurrent fever ≥38.4ºC, 
drenching night sweats, ≥10% weight loss, hyperviscosity, neuropathy, or 
symptomatic cryoglobulinemia) attributable to WM.  An absolute increase of 5g/L 
(confirmed on a second determination) is required in order to define disease 
progression when the only criterion for progressive disease is the increase of M 
protein size.  In a patient with a localized large mass and/or a high level of lactic 
dehydrogenase, at relapse or progression, a biopsy should be considered to assess 
the possibility that transformation to diffuse large B cell lymphoma has occurred. 

 
          Page 34 of 54  
POMALIDOMIDE  
                         Protocol:  
 
 
34
9 Protocol Amendments/Deviations 
9.1 Protocol amendments 
Any amendment to this protocol must be agreed to by the Principal Investigator and 
reviewed and approved by Celgene.  Amendments should only be submitted to IRB/Ethics 
Committee (EC) after consideration of Celgene review.  Written verification of IRB/EC 
approval will be obtained before any amendment is implemented.   
10 Data Management 
10.1 Analyses and Reporting 
Data will be analyzed and reported after the maximum tolerated dose has been defined, 
and data regarding the safety and toxicity profile of the drug is available. All subsequent 
data collected will be analyzed and reported in a follow-up clinical report.  
10.2 Data Monitoring Committee 
The Data Monitoring Committee (DMC) will be composed of medical and statistical 
independent reviewers and will meet to review the efficacy and safety data and determine a 
risk/benefit analysis in this subject population.  The purpose of the DMC is to advise on 
serious safety considerations, lack of efficacy and any other considerations within the 
charge to the Committee.  The DMC may request additional meetings or safety reports as 
deemed necessary upon discussion with Celgene and its representatives.  The DMC may 
stop the study following review of results from each interim analysis.  Appropriate efficacy 
and safety data summaries will be provided to the DMC for the final analysis. 
10.3 Study monitoring and auditing 
10.3.1 Investigator responsibilities 
Investigator responsibilities are set out in the ICH guideline for Good Clinical Practice 
(GCP) and in the US Code of Federal Regulations. 
Investigators must enter study data onto UTMDACC’s protocol data management system 
(PDMS).  The Investigator will permit study-related monitoring visits and audits by the 
UTMDACC IND Office, Celgene or its representatives, IRB/EC review, and regulatory 
inspection(s) (e.g., FDA, EMEA, TPP), providing direct access to the facilities where the 
study took place, to source documents, to CRFs, and to all other study documents. 
The Investigator, or a designated member of the Investigator’s staff, must be available at 
some time during monitoring visits to review data and resolve any queries and to allow 
direct access to the subject’s records (e.g., medical records, office charts, hospital charts, 
and study related charts) for source data verification.  The data collection must be 

 
          Page 35 of 54  
POMALIDOMIDE  
                         Protocol:  
 
 
35
completed prior to each visit and be made available to the UTMDACC IND Office and the 
Celgene representative so that the accuracy and completeness may be checked. 
11   Biostatistical Analysis 
11.1 Overview 
This is a Phase I study of single agent pomalidomide in patients with symptomatic 
Waldenström macroglobulinemia whose disease has relapsed and/or is refractory to at 
least one prior line of therapy. 
 
The objectives of this phase I study are to assess the safety profile of pomalidomide in 
patients with relapsed Waldenström macroglobulinemia and to determine the maximum 
tolerated dose (MTD) of pomalidomide in this patient population. 
 
 
There are four predefined dose levels (1, 2, 3, and 4) for pomalidomide. The study also 
includes two alternative dosing schedules (A and B). With schedule A, patients will be 
treated with the study drug for 28 days within each cycle.  If the MTD is exceeded at dose 
level 1 of Schedule A, Schedule B will be explored. With schedule B, patients will be 
treated for 21 days within each cycle. 
 
Non-hematologic dose limiting toxicity (DLT) is defined as any grade ≥3 non-hematological 
toxicity occurring during the first cycle (28 days on dosing schedule A and 21 days on 
dosing schedule B) of treatment, with the specific exception of: 
• 
Isolated Grade 3 elevation of liver function tests (LFTs) without associated clinical 
symptoms, lasting for ≤ 7 days in duration. 
• 
Isolated Grade 3 elevation of amylase without associated clinical symptoms 
• 
Grade 3 hypocalcemia, hypokalemia, hypomagnesemia, hyponatremia, or 
hypophosphatemia which responds to medical intervention. 
 
Hematological dose limiting toxicity is defined as Grade ≥4 neutropenia lasting for ≥ 7 days 
in duration, any Grade 4 anemia or thrombocytopenia, or any Grade 5 hematologic toxicity 
occurring during the first cycle (28 days on dosing schedule A and 21 days on dosing 
schedule B) of treatment. 
 
The standard “3+3” design is applied with 4 pre-defined dose levels. The first cohort of 3 
patients will be treated at dose level 1 with schedule A (28-day dosing). If no DLT is 
observed then the next cohort of 3 patients will be treated at next higher dose level.  If one 
DLT is observed then 3 more patients will be treated at the same dose level.  At anytime if 
2 or more DLTs are observed within 3 or 6 patients at dose level 1, then schedule A is 
considered too toxic and will be abandoned.  The trial will then be restarted at dose level 1 
using dosing schedule B (21-day dosing) to determine the MTD. If dose level 1 with 
schedule A is well tolerated (less than 2 DLT), then the MTD will be determined with dosing 
schedule A, and dosing schedule B will not be used.  The purpose of schedule B is to 
prepare for the scenario that dosing schedule A is not tolerable.  
 

 
          Page 36 of 54  
POMALIDOMIDE  
                         Protocol:  
 
 
36
  
Dosing Schedule A 
Dosing Schedule B 
Dose level 1 
1 mg orally on days 1-28 
1 mg orally on days 1-21 
Dose level 2 
2 mg orally on days 1-28 
2 mg orally on days 1-21 
Dose level 3 
3 mg orally on days 1-28 
3 mg orally on days 1-21 
Dose level 4 
4 mg orally on days 1-28 
4 mg orally on days 1-21 
 
 
The “3+3” algorithm is as follows: (1) If 0 out of 3 patients experiences DLT at the end of 
first cycle, the next cohort of 3 patients will be treated at the next higher dose level.  (2) If 1 
out of 3 patients develop a DLT, an additional 3 patients will be treated at the same dose 
level.  If no more DLTs develop at this dose, i.e. 1 out of a total of 6 patients develops a 
DLT, the dose escalation will continue for the next cohort of 3 patients.  (3) At any given 
dose, if more than 1 out 3 patients or 1 out of 6 patients experience DLT, the dose level 
exceeds the MTD and 3 more patients will be treated at the next lower dose if there are 
less than 6 patients already treated at that dose. Following the above scheme, MTD is 
defined as the highest dose level in which 6 patients have been treated with less than 2 
instances of DLT.   
Analysis Plan 
Toxicity data will be summarized using frequency tables.  The types and severity of toxicity 
will be evaluated.  
11.2 Datasets to be analyzed 
Data from all subjects who receive any study drug will be included in the determination of 
the maximum tolerated dose, unless they withdrew from the study before completing 1 
cycle of therapy for reasons other than tolerability/toxicity.  
Data from all subjects who receive any study drug will be included in the safety analyses. 
Subjects who enter the study but do not take any of the study drug(s), and have had this 
confirmed, will not be evaluated for safety. 
Data from all subjects who received at least 1 cycles of therapy will be used in the analysis 
of drug efficacy. 
11.3 Safety evaluation 
Data from all subjects who receive any study drug will be included in the safety analyses. 
Subjects who enter the study but do not take any of the study drug(s) and have had this 
confirmed, will not be evaluated for safety. 

 
          Page 37 of 54  
POMALIDOMIDE  
                         Protocol:  
 
 
37
The severity of the toxicities will be graded according to the NCI CTCAE v4.0 whenever 
possible.  
11.4 Interim analyses  
11.4.1 Interim analysis strategy 
Accrual will continue until maximum number of patients reaches or the trial is terminated 
according to the monitoring rules. No interim analyses are planned. 
 11.4.2 Efficacy 
No interim analysis of efficacy will be performed. 
11.5 Safety 
Safety monitoring rules are detailed in Section 10.3. 
 
11.6 Sample size and power considerations 
Given 4 predefined dose levels and potential modification to dosing schedule B after 
treating 6 patients at dose level 1 with schedule A, it is anticipated that up to 30 eligible 
patients are required for the dose-finding portion of this phase I trial.   
12 
Regulatory Considerations 
12.1 Institutional Review Board/Ethics Committee approval 
The protocol for this study has been designed in accordance with the general ethical 
principles outlined in the Declaration of Helsinki.  The review of this protocol by the IRB/EC 
and the performance of all aspects of the study, including the methods used for obtaining 
informed consent, must also be in accordance with principles enunciated in the declaration, 
as well as ICH Guidelines, Title 21 of the Code of Federal Regulations (CFR), Part 50 
Protection of Human Subjects and Part 56 Institutional Review Boards. 
The Investigator will be responsible for preparing documents for submission to the relevant 
IRB/EC and obtaining written approval for this study.  The approval will be obtained prior to 
the initiation of the study. 
The approval for both the protocol and informed consent must specify the date of approval, 
protocol number and version, or amendment number. 
Any amendments to the protocol after receipt of IRB/EC approval must be submitted by the 
Investigator to the IRB/EC for approval.  The Investigator is also responsible for notifying 
the IRB/EC of any serious deviations from the protocol, or anything else that may involve 
added risk to subjects. 

 
          Page 38 of 54  
POMALIDOMIDE  
                         Protocol:  
 
 
38
Any advertisements used to recruit subjects for the study must be reviewed and approved 
by the IRB/EC prior to use. 
12.2 Informed consent 
The Investigator must obtain informed consent of a subject or his/her designee prior to any 
study related procedures as per GCPs as set forth in the CFR and ICH guidelines. 
Documentation that informed consent occurred prior to the subject’s entry into the study 
and the informed consent process should be recorded in the subject’s source documents.  
The original consent form signed and dated by the subject and by the person consenting 
the subject prior to the subject’s entry into the study, must be maintained in the 
Investigator’s study files. 
12.3 Subject confidentiality 
Celgene affirms the subject’s right to protection against invasion of privacy.  In compliance 
with United States federal regulations, Celgene requires the Investigator to permit 
Celgene’s representatives and, when necessary, representatives of the FDA or other 
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 statement of informed consent, it is the responsibility of the Investigator to obtain 
such permission in writing from the appropriate individual. 
12.4 Study records requirements 
The Investigator must ensure that the records and documents pertaining to the conduct of 
the study and the distribution of the study drug, that is copies of CRFs and source 
documents (original documents, data, and records [e.g., hospital records; clinical and office 
charts; laboratory notes; memoranda; subject’s diaries or evaluation checklists; SAE 
reports, pharmacy dispensing records; recorded data from automated instruments; copies 
or transcriptions certified after verification as being accurate copies; microfiches; 
photographic negatives, microfilm, or magnetic media; x-rays; subject files; and records 
kept at the pharmacy, at the laboratories, and at medico-technical departments involved in 
the clinical study; documents regarding subject treatment and study drug accountability; 
original signed informed consents, etc.]) be retained by the Investigator for as long as 
needed to comply with national and international regulations (generally 2 years after 
discontinuing clinical development or after the last marketing approval).  The Investigator 
agrees to adhere to the document/records retention procedures by signing the protocol. 

 
          Page 39 of 54  
POMALIDOMIDE  
                         Protocol:  
 
 
39
12.5 Premature discontinuation of study 
12.5.1 Single center 
The responsible local clinical Investigator as well as Celgene has the right to discontinue 
this study at any time for reasonable medical or administrative reasons in any single center.  
Possible reasons for termination of the study could be but are not limited to: 
• 
Unsatisfactory enrollment with respect to quantity or quality. 
• 
Inaccurate or incomplete data collection. 
• 
Falsification of records. 
• 
Failure to adhere to the study protocol. 
12.5.2    Study as a whole 
Celgene reserves the right to terminate this clinical study at any time for reasonable 
medical or administrative reasons. 
Any possible premature discontinuation would be documented adequately with reasons 
being stated, and information would have to be issued according to local requirements 
(e.g., IRB/EC, regulatory authorities, etc.). 

 
          Page 40 of 54  
POMALIDOMIDE  
                         Protocol:  
 
 
40
13 
References 
1. Owen RG, Treon SP, Al-Katib A, et al: Clinicopathological definition of 
Waldenstrom's macroglobulinemia: Consensus panel recommendations from the 
Second International Workshop on Waldenstrom's Macroglobulinemia. Semin Oncol 
30:110-115, 2003 
 
2. Kyle RA, Treon SP, Alexanian R, et al: Prognostic markers and criteria to initiate 
therapy in Waldenstrom's macroglobulinemia: Consensus panel recommendations 
from the Second International Workshop on Waldenstrom's Macroglobulinemia. 
Semin Oncol 30:116-120, 2003 
 
3.   Dimopoulos MA, Gertz MA, Kastritis E., Update on Treatment Recommendations 
from the Fourth International Workshop on Waldenstrom’s Macroglobulinemia. J 
Clin Oncol 2009; 27(1): 120-6. 
 
4.   Dimopoulos MA, Zomas A, Viniou NA, et al. Treatment of Waldenström's 
      Macroglobulinemia with thalidomide. J Clin Oncol. 2001;19:3596–3601. 
 
5.   Coleman M, Leonard J, Lyons L, et al. BLT-D (Biaxin, low dose thalidomide, and 
      dexamethasone) for the treatment of myeloma and Waldenstrom's 
      Macroglobulinemia. Leuk Lymphoma. 2002;43:1777–1782. 
 
6.   Dimopoulos MA, Tsatalas C, Zomas A, et al. Treatment of Waldenstrom's 
      Macroglobulinemia with single agent thalidomide or with combination of 
      clarithromycin, thalidomide and dexamethasone. Semin Oncol. 2003;30:265–269. 
 
7.   Treon SP, Soumerai JD, Branagan AR et al., Thalidomide and Rituximab in 
      Waldenstrom Macroglobulinemia. Blood 2008; 112(12) :4452-7. 
 
8.   Treon SP, Soumerai JD, Branagan AR et al., Lenalidomide and Rituximab in 
            Waldenstrom Macroglobulinemia. Clin Cancer Res 2009; 15(1):355-60. 
 
 9.   Lacy, MQ, et al. Pomalidomide (CC4047) Plus Low-Dose Dexamethasone As 
       Therapy for Relapsed Multiple Myeloma. Journal of Clinical Oncology. 2009 Aug 
       31: Epub ahead of print. 
 
10.  FDA. Thalidomide approved for erythema nodosum leprosum J Am Med Assoc 
      1998;280:872. 
 
11. Hamza MH. Treatment of Behcet's disease with thalidomide. Clin Rheumatol 
     1986;5:365-71. 
 
12.  Lenz W, Pfeiffer RA, Kosenow W et al., Thalidomide and congenital abnormalities. 
       Lancet 1962; 279(7219):45-6. 
 
13. Pearson JM, Vedagiri, M. Treatment of moderately severe erythema nodosum 
      leprosum with thalidomide--a double-blind controlled trial. Lepr Rev 1969;40(2): 
     111-6. 

 
          Page 41 of 54  
POMALIDOMIDE  
                         Protocol:  
 
 
41
 
14. Saylan T, Saltik, I. Thalidomide in the treatment of Behcet's syndrome Arch 
      Dermatol 1982;118:536. 
 
15. Vogelsang GB, Farmer, E.R., Hess, A.D. et al., Thalidomide for the treatment of 
      chronic graft-versus-host disease. N Engl J Med 1992;326(16):1055-8. 
 
16. Singhal S, Mehta, J., Eddlemon, P. et al., Marked anti-tumor effect from anti- 
      angiogenesis therapy with thalidomide in high risk refractory multiple myeloma. 
      Blood 1998;92(318a). 
 
17. Singhal S, Mehta, J., Desikan, R. et al., Antitumor activity of thalidomide in 
      refractory multiple myeloma. N Engl J Med 1999;341(21):1565-71. 
 
18. Dimopoulos MA, Anagnostopoulos A, Weber D. Treatment of Plasma Cell 
      Dyscrasias with Thalidomide and Its Derivatives. J Clin Oncol 2003;21(23):4444-54. 
 
19. Glasmacher A, Hahn, C., Hoffmann, F. et al.,  A systematic review of phase-II trials 
of thalidomide monotherapy in patients with relapsed or refractory multiple 
myeloma. Br J Haematol 2006;132(5):584-93. 
 
20. Data on file: Celgene Corp.; Summit, NJ. 
 
21. Payvandi, F., Wu, L., Haley, M, et al.  “Immunomodulatory drugs inhibit expression 
of cyclooxygenase-2 from TNF-alpha, IL-1 beta, and LPS-stimulated human PBMC 
in a partially IL-10-dependent manner”; Cell Immunol. 230(2): 81-88, Aug. 2004. 
 
22. Schey, SA, Fields, P, Bartlett, JB, et al.  “Phase I study of an immunomodulatory 
thalidomide analog, CC-4047, in relapsed or refractory multiple myeloma”; J. Clin. 
Oncol. 22(16): 3269-3276, 15 Aug 2004. 
 
23. Suppiah, R, Srkalovic, JG, and Hussein, MA. “Immunomodulatory analogues of 
thalidomide in the treatment of multiple myeloma”; Clin. Lymphoma Myeloma 6(4): 
301-305, Jan. 2006. 
 
24. McCarthy, DA, Macey, MG, Streetly, M, et al. “The neutropenia induced by the 
thalidomide analogue CC-4047 in patients with multiple myeloma is associated with 
an increased percentage of neutrophils bearing CD64”; Int. Immunopharmacol. 6(7): 
1194-1203, Jul. 2006 (Epub 29 Mar. 2006).  
 
25. Kimby E, Treon SP, Anagnostopoulos A, et al., Update on Recommendations for 
Assessing Response from the Third International Workshop on Waldenstrom’s 
Macroglobulinemia. Clin Lymphoma Myeloma. 2006 Mar;6(5):380-3. 
 

 
          Page 42 of 54  
POMALIDOMIDE  
                         Protocol:  
 
 
42
26. Ghobrial IM, Fonseca R, Greipp PR, et al., Initial immunoglobulin M 'flare' after 
rituximab therapy in patients diagnosed with Waldenstrom macroglobulinemia: an 
Eastern Cooperative Oncology Group Study. Cancer. 2004 Dec 1;101(11):2593-8.  
 
 
 
 
 
 

 
          Page 43 of 54  
POMALIDOMIDE  
                         Protocol:  
 
 
43
Appendices 
Appendix A:  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 (i.e., has had menses at any time in the 
preceding 24 consecutive months). 
Counselling 
For a female of childbearing potential, pomalidomide is contraindicated unless all of the 
following are met (i.e., all females of childbearing potential must be counselled 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 
pomalidomide 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 (Section 2). 
• 
She acknowledges that she understands the hazards and necessary precautions 
associated with the use of pomalidomide 
 
 
 

 
          Page 44 of 54  
POMALIDOMIDE  
                         Protocol:  
 
 
44
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 
 
For a female NOT of childbearing potential, pomalidomide is contraindicated unless all of 
the following are met (i.e., all females NOT of childbearing potential must be counselled 
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 patients taking pomalidomide must meet the following conditions (i.e., all 
males must be counselled 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 woman 
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 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 intercourse 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.  
The two methods of reliable contraception must include one highly effective method and 
one additional effective (barrier) method. 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:   
o Highly effective methods: 
 
Intrauterine device (IUD) 
 
Hormonal (birth control pills, injections, implants) 
 
Tubal ligation 
 
Partner’s vasectomy 
o Additional effective methods: 
 
Male condom 
 
Diaphragm 
 
Cervical Cap 

 
          Page 45 of 54  
POMALIDOMIDE  
                         Protocol:  
 
 
45
Because of the increased risk of venous thromboembolism in patients with multiple 
myeloma taking pomalidomide and dexamethasone, combined oral contraceptive pills are 
not recommended. If a patient is currently using combined oral contraception the patient 
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 patients 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 Patients: 
FCBP must have two negative pregnancy tests (sensitivity of at least 25 mIU/mL) prior to 
starting pomalidomide.  The first pregnancy test must be performed within 10-14 days prior 
to the start of pomalidomide and the second pregnancy test must be performed within 24 
hours prior to the start of pomalidomide.  The patient may not receive study drug until the 
Investigator has verified that the results of these pregnancy tests are negative. 
Male Patients: 
Must practice complete abstinence or  agree to use a condom during sexual contact with 
females of childbearing potential while participating in the study, during dose interruptions 
and for at least 90 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 Patients: 
• 
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 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 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 at each visit.   
• 
Counselling about pregnancy precautions and the potential risks of fetal exposure 
must be conducted at a minimum of every 28 days.  

 
          Page 46 of 54  
POMALIDOMIDE  
                         Protocol:  
 
 
46
• 
If pregnancy or a positive pregnancy test does occur in a study patient, 
pomalidomide must be immediately discontinued. 
• 
Pregnancy testing and counselling must be performed if a patient 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 Patients: 
• 
Counselling about the requirement for condom use during sexual contact with 
females of childbearing potential and the potential risks of fetal exposure must be 
conducted at a minimum of every 28 days.   
• 
If pregnancy or a positive pregnancy test does occur in the partner of a male study 
patient during study participation, the investigator must be notified immediately. 
Additional precautions 
• 
Patients should be instructed never to give this medicinal product to another person 
and to return any unused capsules to the Investigator at the end of treatment. 
• 
Patients should not donate blood during therapy and for at least 28 days following 
discontinuation of pomalidomide. 
• 
Male patients should not donate semen or sperm during therapy or for at least 90 
days following discontinuation of pomalidomide. 
• 
Only enough pomalidomide for one cycle of therapy may be dispensed with each 
cycle of therapy.  
 

 
          Page 47 of 54  
POMALIDOMIDE  
                         Protocol:  
 
 
47
Appendix B:  Pomalidomide Education and Counselling Guidance Document 
 
Protocol Number: ____________________________________________ 
Patient Name (Print): __________________ DOB: _____/_____/_____ (mm/dd/yyyy) 
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 (i.e., has had 
menses at any time during the preceding 24 consecutive months) 
⁯ 
NOT FCBP 
Male:    ⁯ 
To be completed prior to each dispensing of pomalidomide. 
 
Do Not Dispense pomalidomide if: 
• 
The patient is pregnant. 
• 
No pregnancy tests were conducted for a FCBP. 
• 
The patient states she did not use TWO reliable methods of birth control 
(unless practicing complete abstinence of heterosexual intercourse) [at least 
28 days prior, while taking pomalidomide, during dose interruption, and 28 
days after discontinuation of pomalidomide]. 
 
FCBP: 
 
1.    I verified that the required pregnancy tests performed are negative. 
 
2.    I counselled FCBP regarding the following: 
• 
Potential fetal harm:  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.  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 intercourse [at least 28 days prior, while taking 
pomalidomide, during dose interruption and 28 days after discontinuation of 
pomalidomide]. 
• 
Continuation of TWO reliable methods of birth control or complete abstinence if 
therapy is interrupted. 
• 
That even if she has amenorrhea she must comply with advice on contraception   

 
          Page 48 of 54  
POMALIDOMIDE  
                         Protocol:  
 
 
48
• 
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:   
o Highly effective methods: 
 
Intrauterine device (IUD) 
 
Hormonal (birth control pills, injections, implants) 
 
Tubal ligation 
 
Partner’s vasectomy 
o Additional effective methods: 
 
Male condom 
 
Diaphragm 
 
Cervical Cap 
• 
Pregnancy tests before and during treatment, even if the patient agrees not to have 
reproductive heterosexual intercourse.  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 pomalidomide. 
• Frequency of pregnancy tests to be done: 
o Every week during the first 28 days of this study and a pregnancy test every 
28 days during the patient’s participation in this study if menstrual cycles are 
regular or every 14 days if cycles are irregular.   
o If the patient missed a period or has unusual menstrual bleeding.   
o When the patient 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 pomalidomide immediately in the event of becoming pregnant and to 
call their study doctor as soon as possible.  
• 
NEVER share pomalidomide with anyone else. 
• 
Do not donate blood while taking pomalidomide and for 28 days after stopping 
pomalidomide. 
• 
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 pomalidomide capsules. 
• 
Return unused pomalidomide to the investigator. 
 
3.     Provide Pomalidomide Information Sheet to the patient. 
 
FEMALE NOT OF CHILDBEARING POTENTIAL (NATURAL MENOPAUSE FOR AT 
LEAST 24 CONSECUTIVE MONTHS, A HYSTERECTOMY, OR BILATERAL 
OOPHORECTOMY): 
 

 
          Page 49 of 54  
POMALIDOMIDE  
                         Protocol:  
 
 
49
1. I counselled the female NOT of childbearing potential regarding the following: 
• 
Potential fetal harm (Refer to item #2 in FCBP) 
• 
NEVER share pomalidomide with anyone else. 
• 
Do not donate blood while taking pomalidomide and for 28 days after stopping 
pomalidomide. 
• 
Do not break, chew, or open pomalidomide capsules 
• 
Return used pomalidomide capsules to the Investigator. 
2. Provide Pomalidomide Information Sheet to the patient. 
 
MALE: 
 
1.    I counselled the Male patient regarding the following: 
• 
Potential fetal harm (Refer to item #2 in FCBP). 
• 
To engage in complete abstinence or use a condom when engaging in sexual 
intercourse (including those who have had a vasectomy) with a female of 
childbearing potential,  while taking pomalidomide, during dose interruptions and for 
90 days after stopping pomalidomide. 
• 
Males should notify their study doctor when their female partner becomes pregnant 
and female partners of males taking pomalidomide should be advised to call their 
healthcare provider immediately if they get pregnant 
• 
NEVER share pomalidomide with anyone else. 
• 
Do not donate blood while taking pomalidomide and for 28 days after stopping 
pomalidomide. 
• 
Do not donate semen or sperm while taking pomalidomide and for 90 days after 
stopping pomalidomide. 
• 
Do not break, chew, or open pomalidomide capsules. 
• 
Return unused pomalidomide capsules to the investigator. 
 
2.    Provide Pomalidomide Information Sheet to the patient. 
 
Investigator/Counselor Name (Print): ____________________ 
 
 (circle applicable) 
 
Investigator/Counselor Signature: _______________________  
Date: 
_____/_____/_____ 
 
       (circle applicable) 
 
**Maintain a copy of the Education and Counselling Guidance Document in the patient records. ** 

 
          Page 50 of 54  
POMALIDOMIDE  
                         Protocol:  
 
 
50
Appendix C:  Pomalidomide Information Sheet 
FOR PATIENTS ENROLLED IN CLINICAL RESEARCH STUDIES  
Please read this Pomalidomide Information Sheet before you start taking 
pomalidomide and each time you get a new supply, since there may be new 
information. 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 pomalidomide if you are pregnant or plan to 
become pregnant 
• 
for 28 days before starting pomalidomide 
• 
while taking pomalidomide  
• 
during dose interruptions of pomalidomide  
• 
for 28 days after stopping pomalidomide  
• Stop taking pomalidomide if you become pregnant during 
pomalidomide treatment 
• Do not breastfeed while taking pomalidomide 
• You must have pregnancy testing done at the following times: 
• 
within 10 – 14 days and again 24 hours prior to the first 
dose of pomalidomide  
• 
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 pomalidomide (14 and 28 
days after the last dose if menstrual periods are irregular) 

 
          Page 51 of 54  
POMALIDOMIDE  
                         Protocol:  
 
 
51
• 
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 pomalidomide 
• 
while taking pomalidomide 
• 
during dose interruptions of pomalidomide  
• 
and for 28 days after stopping pomalidomide 
• 
The study doctor will be able to advise you where to get additional 
advice on contraception. 
• If you suspect you are pregnant at any time during the study, you 
must stop pomalidomide immediately and immediately inform your 
study doctor. The study doctor will report all cases of pregnancy to 
Celgene Corporation.  
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.   
• Male patients must either not have any sexual relations with a 
female who can become pregnant or a pregnant female or must 
use a condom during sexual intercourse with a pregnant female or a 
female that can become pregnant (including those who have had a 
vasectomy): 
- While you are taking pomalidomide  
- During dose interruptions of pomalidomide  
- For 90 days after you stop taking pomalidomide   
• Male patients should not donate sperm or semen while taking 
pomalidomide and for 90 days after stopping pomalidomide.  
• If you suspect that your partner is pregnant any time during the 
study, you must immediately inform your study doctor. The 
study doctor will report all cases of pregnancy to Celgene 
Corporation. 
 
2. Pomalidomide restrictions in sharing pomalidomide and donating 
blood: 

 
          Page 52 of 54  
POMALIDOMIDE  
                         Protocol:  
 
 
52
• Do not share pomalidomide with other people. It must be kept 
out of the reach of children and should never be given to any 
other person. 
• Do not give blood while you take pomalidomide and for 28 days 
after stopping pomalidomide.  
• Do not break, chew, or open pomalidomide capsules. 
• You will be supplied with no more than one cycle of pomalidomide  
• Return unused pomalidomide capsules to your study doctor. 
Additional information is provided in the informed consent form and you 
can ask your study doctor for more information. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
          Page 53 of 54  
POMALIDOMIDE  
                         Protocol:  
 
 
53
 
Appendix D – ECOG Performance Status Scale 
 
SCORE 
DESCRIPTION 
0 
Fully active, able to carry on all pre-disease performance 
without restriction. 
1 
Restricted in physically strenuous activity but ambulatory and 
able to carry out work of a light or sedentary nature, e.g., light 
house work, office work. 
2 
Ambulatory and capable of all self-care but unable to carry out 
any work activities.  Up and about more than 50% of waking 
hours. 
3 
Capable of only limited self-care, confined to bed or chair more 
than 50% of waking hours. 
4 
Completely disabled.  Cannot carry on any self-care.  Totally 
confined to bed or chair. 
5 
Dead. 
 

 
          Page 54 of 54  
POMALIDOMIDE  
                         Protocol:  
 
 
54
Appendix E : National Cancer Institute Common Toxicity Criteria 
Version 4.0 
 
TOXICITY WILL BE SCORED USING NCI CTC VERSION 4.0 FOR TOXICITY 
AND ADVERSE EVENT REPORTING.  A COPY OF THE NCI CTC VERSION 4.0 
CAN BE DOWNLOADED FROM THE CTEP HOMEPAGE: 
(HTTP://CTEP.INFO.NIH.GOV).  ALL APPROPRIATE TREATMENT AREAS HAVE 
ACCESS TO A COPY OF THE CTC VERSION