Conditions: Graft vs Host Disease Graft-Versus-Host Disease
Keywords: Immune Modulatory Systemic Absorption Oral Agent
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 34
Healthy volunteers: no

Brief summary:
Background:

\- Pomalidomide is a drug that alters the body's immune response. It may help people who have chronic graft-versus-host disease (GvHD). GvHD may appear after a stem cell transplant, when immune cells in the transplant try to attack tissues in the person who received the transplant. GvHD is not easy to treat, and often does not respond to standard treatments. Researchers want to see if pomalidomide is a safe and effective treatment for GvHD.

Objectives:

\- To test the safety and effectiveness of pomalidomide for GvHD that has not responded to standard treatments.

Eligibility:

\- Individuals at least 18 years of age who have GvHD that has not responded to standard treatments.

Design:

* Participants will be screened with a physical exam and medical history. Blood and urine samples will also be collected. A lung function test and imaging studies will also be given.
* Participants will take pomalidomide capsules once a day for 4-week periods called cycles.
* Treatment will be monitored with frequent blood tests and imaging studies. Saliva samples and skin and mouth tissue biopsies will also be collected during treatment.
* Treatment will continue for six cycles (6 months), unless the GvHD gets worse or side effects are too severe. If the GvHD has improved at the end of the six cycles, participants may be able to continue to take pomalidomide for up to six more cycles.

Detailed description:
BACKGROUND:

* Chronic graft-versus-host disease (cGvHD) is the leading cause of non-relapse morbidity and mortality in persons after allogeneic hematopoietic cell transplants.
* About 50% of persons with cGvHD have disease refractory to systemic corticosteroids and there is no standard second-line therapy.
* Thalidomide, a drug with immune-modulating effects, was active in advanced cGvHD but was difficult to use at appropriate doses.
* Pomalidomide is related to thalidomide but with higher potency and more favorable toxicity profile. It is active in multiple myeloma and myeloproliferative neoplasm associated myelofibrosis. Preliminary data in humans with cGvHD are encouraging but data are limited.

OBJECTIVES:

\- Primary: Determine whether pomalidomide is effective in persons with moderate or severe cGvHD not controlled by corticosteroids.

ELIGIBILITY:

Inclusion Criteria

* Moderate or severe cGvHD per National Institutes of Health (NIH) criteria
* Age 18 to 75 years old
* Karnofsky performance score greater than or equal to 60%
* Has cGvHD that did not respond to high-dose corticosteroids (average 0.5 mg/kg/d prednisone for greater than or equal to 8 weeks) or second-line therapy
* Receiving stable or tapering doses of systemic therapy in the preceding 4 weeks
* Agree to adhere to methods of contraception and other fertility control measures as prescribed by the protocol

Exclusion Criteria

* Acute GvHD (classic and late per NIH criteria)
* Absolute neutrophils \<1.0x10(9)/L, platelets \<75x10(9)/L, estimated creatinine clearance \<50 mL/min/1.73m(2)
* NIH lung score 3
* Pregnant or lactating
* Uncontrolled infection

DESIGN:

Randomized phase 2 trial with the single stage selection design. Patients will receive either a constant low dose of pomalidomide (0.5 mg/day) for six months or a strategy of increasing dose of pomalidomide from 0.5 mg/d up through each individual patient's maximum tolerated dose, with escalations by 0.5 mg/d every 2 weeks to a maximum of 2.0 mg/d. As an early stopping rule for futility, if after 7 patients have enrolled on either arm, 0 have responded, then no further patients will be accrued to that arm as soon as this can be determined. To protect patient safety, an early stopping rule will be implemented. With two arms, each of which has a maximal accrual of 16 patients, up to 32 evaluable patients will be randomized. Response assessments will occur every 3 months with primary efficacy endpoint evaluated at 6 months. Patients with responding disease will continue therapy for another 6 months.

Arms:
arm 1: 0.5 mg/day with Dose Escalation by 0.5 mg/day increments every 2 weeks to a maximum of 2.0 mg/day arm 2: 0.5 mg/day without Dose Escalation

Interventions: intervention 1: Pomalidomide
Intervention descriptions: intervention 1: 0.5 mg/day with and/or without Dose Escalation and 0.5 mg/day- 2.0 mg/day by mouth (PO) QD(every day) of each 28 day cycle

Protocol document:
Prot_SAP_003.pdf: 
Abbreviated Title: Pomalidomide for cGvHD
Version Date: 4/29/2025
                                                                                                                               1
Abbreviated Title: Pomalidomide for cGvHD
NIH Protocol #: 12C0197
NCT #: NCT01688466
Version Date: 4/29/2025
Title: A Randomized Phase 2 Single-Center Study of Pomalidomide for Chronic GVHD 
NCI Principal Investigator: 
Najla El Jurdi, MD
                                                
Immune Deficiency Cellular Therapy Program (IDCTP)
Center for Cancer Research (CCR)
National Cancer Institute (NCI)
National Institutes of Health (NIH)
10 Center Drive, RM 8D44C
9000 Rockville Pike
Bethesda, MD 20892
                                                 
Phone: 240-858-3287  
Email : najla.eljurdi@nih.gov
Drug Name:
Pomalidomide
IND Number:
115336
Sponsor:
Center for Cancer Research
Manufacturer:
Celgene 
Protocol tracking number: PO-GvHD-NCI-0046


Abbreviated Title: Pomalidomide for cGvHD
Version Date: 4/29/2025
2
PRÉCIS
Background:
•
Chronic graft-versus-host disease (cGvHD) is the leading cause of non-relapse morbidity and 
mortality in persons after allogeneic hematopoietic cell transplants. 
•
About 50% of persons with cGvHD have disease refractory to systemic corticosteroids and 
there is no standard second-line therapy.     
•
Thalidomide, a drug with immune-modulating effects, was active in advanced cGvHD but was 
difficult to use at appropriate doses.  
•
Pomalidomide is related to thalidomide but with higher potency and more favorable toxicity 
profile. It is active in multiple myeloma and myeloproliferative neoplasm–associated 
myelofibrosis. Preliminary data in humans with cGvHD are encouraging but data are limited. 
Objective:
•
Primary: Determine whether pomalidomide is effective in persons with moderate or severe 
cGvHD not controlled by corticosteroids.
Eligibility:
•
Inclusion Criteria
o
Moderate or severe cGvHD per NIH criteria
o
Age 18 to 75 years old
o
Karnofsky performance score >60%
o
Has cGvHD that did not respond to high-dose corticosteroids (average 0.5 mg/kg/d 
prednisone for >8 weeks) or second-line therapy
o
Receiving stable or tapering doses of systemic therapy in the preceding 4 weeks
o
Agree to adhere to methods of contraception and other fertility control measures as 
prescribed by the protocol
•
Exclusion Criteria
o
Acute GvHD (classic and late per NIH criteria) 
o
Absolute neutrophils <1.0x109/L, platelets <75x109/L, estimated creatinine clearance <50 
mL/min/1.73m2
o
NIH lung score 3
o
Pregnant or lactating 
o
Uncontrolled infection
Design: 
Randomized phase 2 trial with the single stage selection design. Patients will receive either a 
constant low dose of pomalidomide (0.5 mg/day) for six months or a strategy of increasing dose 
of pomalidomide from 0.5 mg/d up through each individual patients’ maximum tolerated dose, 
with escalations by 0.5 mg/d every 2 weeks to a maximum of 2.0 mg/d. As an early stopping rule 
for futility, if after 7 patients have enrolled on either arm, 0 have responded, then no further 
patients will be accrued to that arm as soon as this can be determined. To protect patient safety, 
an early stopping rule will be implemented. With two arms, each of which has a maximal accrual 
of 16 patients, up to 32 evaluable patients will be randomized. Response assessments will occur 


Abbreviated Title: Pomalidomide for cGvHD
Version Date: 4/29/2025
3
every 3 months with primary efficacy endpoint evaluated at 6 months. Patients with responding 
disease will continue therapy for another 6 months.


Abbreviated Title: Pomalidomide for cGvHD
Version Date: 4/29/2025
4
TABLE OF CONTENTS
PRÉCIS............................................................................................................................................2
TABLE OF CONTENTS ................................................................................................................4
STATEMENT OF COMPLIANCE ................................................................................................7
1
INTRODUCTION ...................................................................................................................7
1.1
Study Objectives ...............................................................................................................7
1.2
Background and Rationale................................................................................................7
1.3
Pomalidomide .................................................................................................................12
1.3.3.1 Pharmacokinetics and Product Metabolism in Humans ................................................14
1.4
Study Design and Rationale............................................................................................21
2
ELIGIBILITY ASSESSMENT AND ENROLLMENT .......................................................22
2.1
Eligibility Criteria ...........................................................................................................22
2.2
Required Testing and Counseling for FCBP and Partners of FCBP...............................24
2.3
Screening Evaluation ......................................................................................................24
2.4
Registration Procedures ..................................................................................................25
2.5
Treatment Assignment and Randomization procedures .................................................25
2.6
Baseline Evaluation.........................................................................................................26
3
STUDY IMPLEMENTATION .............................................................................................26
3.1
Study Design...................................................................................................................26
3.2
Drug Administration .......................................................................................................28
3.3
Dose Modifications.........................................................................................................29
3.4
Questionnaires.................................................................................................................31
3.5
Study Calendar................................................................................................................32
3.6
Criteria for Removal from Protocol Therapy and Off Study Criteria.............................37
4
CONCOMITANT MEDICATIONS/MEASURES...............................................................37
4.1
Concomitant Corticosteroid Therapy and Tapering Guideline.......................................37
4.2
Other Treatments for cGvHD .........................................................................................38
4.3
Venous Thromboembolism Prophylaxis.........................................................................38
4.4
Other Allowed Concomitant Therapy.............................................................................38
4.5
Prohibited Concomitant Therapy....................................................................................39
5
BIOSPECIMEN COLLECTION...........................................................................................39
5.1
Correlative Studies for Research.....................................................................................39


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5.2
Sample Storage, Tracking and Disposition.....................................................................40
6
DATA COLLECTION AND EVALUATION .....................................................................41
6.1
Data Collection ...............................................................................................................41
6.2
Response Criteria ............................................................................................................43
6.3
Toxicity Criteria..............................................................................................................46
7
NIH REPORTING REQUIREMENTS/DATA AND SAFETY MONITORING PLAN.....46
7.1
Definitions.......................................................................................................................46
7.2
OHSRP Office of Compliance and Training / IRB Reporting........................................47
7.3
NCI Clinical Director Reporting.....................................................................................47
7.4
NIH Required Data and Safety Monitoring Plan............................................................47
8
SPONSOR PROTOCOL/SAFETY REPORTING................................................................48
8.1
Definitions.......................................................................................................................48
8.2
Assessment of Safety Events ..........................................................................................49
8.3
Reporting of Serious Adverse Events .............................................................................49
8.4
Safety Reporting Criteria to the Pharmaceutical Collaborators......................................50
8.5
Reporting Pregnancy.......................................................................................................50
8.6
Regulatory Reporting for Studies Conducted Under CCR-Sponsored IND...................50
8.7
Sponsor Protocol Deviation Reporting ...........................................................................51
9
CLINICAL MONITORING..................................................................................................51
10
STATISTICAL CONSIDERATIONS ...............................................................................51
11
COLLABORATIVE AGREEMENTS...............................................................................52
11.1
Cooperative Research and Development Agreement (CRADA)................................52
12
HUMAN SUBJECTS PROTECTIONS.............................................................................53
12.1
Rationale For Subject Selection ..................................................................................53
12.2
Participation of Children .............................................................................................53
12.3
Participation of NIH Subjects Unable to Give Consent..............................................53
12.4
Evaluation of Benefits and Risks/Discomforts ...........................................................53
12.5
Risks/Benefits Analysis...............................................................................................54
12.6
Consent Process and Documentation ..........................................................................54
13
REGULATORY AND OPERATIONAL CONSIDERATIONS.......................................55
13.1
Study Discontinuation and Closure.............................................................................55
13.2
Quality Assurance and Quality Control ......................................................................55


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13.3
Conflict of Interest Policy ...........................................................................................56
13.4
Confidentiality and Privacy.........................................................................................56
14
PHARMACEUTICAL INFORMATION ..........................................................................57
14.1
Pomalidomide..............................................................................................................57
15
REFERENCES ...................................................................................................................60
16
APPENDICES ....................................................................................................................66
16.1
APPENDIX A: Performance Status Criteria...............................................................66
16.2
APPENDIX B: Measurement of Pomalidomide Serum Levels..................................67
16.3
APPENDIX C: Diagnostic Criteria of Chronic GVHD ..............................................68
16.4
APPENDIX D: Clinical Differentiation of Acute and Chronic GVHD......................72
16.5
APPENDIX E: Organ Specific and Global Scoring of Chronic GVHD.....................73
16.6
APPENDIX F: Global Scoring of cGvHD..................................................................76
16.7
APPENDIX G: Chronic GVHD Assessment (Clinician) Form..................................77
16.8
APPENDIX H: Calculations for Partial Response in Chronic GVHD .......................81
16.9
APPENDIX I: Calculations for Progression in Chronic GVHD.................................82
16.10
APPENDIX J: Chronic GVHD Cutaneous Assessment Worksheet  (Adult) .............83
16.11
APPENDIX K: Lee Symptom Scale...........................................................................85
16.12
Appendix L: Pomalidomide Pregnancy Prevention Risk Management Plans ............87
16.13
Appendix M: Pomalidomide Risks of Fetal Exposure, Pregnancy Testing Guidelines 
and Acceptable Birth Control Methods .....................................................................................88
16.14
Appendix N: Pomalidomide Information Sheet..........................................................92
16.15
Appendix O: Medication Diary...................................................................................94
16.16
Appendix P: Data Collection Elements Required By Protocol...................................97
16.17
Appendix Q:Chronic GVHD Composite Assessment Scale – Evaluation Tools .......99
16.18
Appendix R: Chronic GVHD Composite Assessment Scale BARTHEL INDEX 
SCORE 132
16.19
Appendix S: Chronic GVHD Composite Assessment Scale Frenchay activities Index
134
16.20
Appendix T: QUALITY OF LIFE ASSESSMENTS (obtained at baseline then 
yearly) 138


Abbreviated Title: Pomalidomide for cGvHD
Version Date: 4/29/2025
7
STATEMENT OF COMPLIANCE
The trial will be carried out in accordance with International Council for Harmonisation Good 
Clinical Practice (ICH GCP) and the following: 
• United States (US) Code of Federal Regulations (CFR) applicable to clinical studies (45 
CFR Part 46, 21 CFR Part 50, 21 CFR Part 56, 21 CFR Part 312, and/or 21 CFR Part 812) 
National Institutes of Health (NIH)-funded investigators and clinical trial site staff who are 
responsible for the conduct, management, or oversight of NIH-funded clinical trials have 
completed Human Subjects Protection and ICH GCP Training.
The protocol, informed consent form(s), recruitment materials, and all participant materials will 
be submitted to the Institutional Review Board (IRB) for review and approval.  Approval of both 
the protocol and the consent form must be obtained before any participant is enrolled.  Any 
amendment to the protocol will require review and approval by the IRB before the changes are 
implemented to the study.  In addition, all changes to the consent form will be IRB-approved; an 
IRB determination will be made regarding whether a new consent needs to be obtained from 
participants who provided consent, using a previously approved consent form.
1
INTRODUCTION
1.1
STUDY OBJECTIVES
1.1.1
Primary Objective: 
1.1.2
Determine whether pomalidomide is effective in persons with moderate or severe chronic 
graft-versus-host disease (cGvHD) not controlled by corticosteroids.
1.1.3
Secondary Objectives:
1.1.3.1
Determine whether pomalidomide is safe in persons with moderate or severe cGvHD not 
controlled by corticosteroids.
1.1.3.2
Determine the immune-modulatory effects of pomalidomide in persons with moderate or 
severe cGvHD.
1.1.3.3
Determine limited pharmacokinetics after oral administration of pomalidomide. 
1.2
BACKGROUND AND RATIONALE 
1.2.1
Chronic Graft-Versus-Host Disease
cGvHD is an important late complication of allogeneic hematopoietic cell transplantation. It is a 
leading cause of mortality in persons more than 2 years post transplant.1,2 Symptoms of cGvHD 
usually appear within 2 years post transplant. Incidences range from 6%-80% depending on 
recipient age, donor type (related or unrelated, HLA matched or mismatched), graft type (blood, 
bone marrow or umbilical cord), graft manipulation or donor lymphocyte infusions.3 Chronic 
GvHD is strongly associated with prior acute GvHD (aGvHD).4,5 Traditionally the cutoff point 
between aGvHD and cGvHD was day 100 post transplant. In 2005 an NIH consensus project 
proposed two main GVHD categories, each with two subcategories: (1) “classic” aGvHD 
occurring within 100 days post transplant and (2) “persistent, recurrent or late” aGvHD. The broad 


Abbreviated Title: Pomalidomide for cGvHD
Version Date: 4/29/2025
8
category of cGvHD includes: (1) “classic” cGvHD (without features or characteristics of aGvHD) 
and (2) an “overlap syndrome” with concordant features of cGvHD and aGvHD.3 cGvHD is a 
multi-organ alloimmune and autoimmune disorder characterized by immune dysregulation, 
immunodeficiency, impaired organ function and decreased survival.  It requires prolonged ongoing 
immunosuppression and inter-disciplinary management. 
1.2.1.1
Pathophysiology
The pathophysiology of cGvHD is poorly understood. T- (both Th1 and Th2) and B-cells play a 
role in the pathogenesis of cGvHD, suggesting a general loss of tolerance, including abnormalities 
in the function of regulatory T-cells (Tregs). Natural Tregs (CD4+,CD25+,FoxP3+) maintain self-
tolerance.6 Studies in mice indicate Tregs can suppress GvHD and that a deficiency of Tregs 
worsens GHD.7 There are conflicting data in humans concerning role of Tregs in the development 
of cGvHD.8 A recent study suggested in vivo administration of low-dose IL-2 as a potential Treg-
mediated therapeutic approach for severe cGvHD.9 
Several studies suggested that aGvHD is associated with predominant Th1-type immune response 
and cGvHD with Th2-type immune response. Th1 cells produce interferon- γ (IFN-γ) that mediates 
cell immunity, and Th2 cells produce interleukin (IL)-4, IL-5 and IL-13, which mediate humoral 
immunity. Following T-cell dysregulation, there is consequently cytokine dysregulation. In 
persons with cGvHD, higher levels of tumor necrosis factor-α, IL- 6, transforming growth factor-
β, IL-1β and lower levels of INF-γ and IL-10 are reported.1,10-13 
Autoimmunity and autoreactive T-cells have an important role in cGvHD. Some studies have 
shown that host thymus is not required for induction of cGvHD and that quiescent autoreactive T- 
and B-cells in transplants from non-autoimmune donors may be activated and expanded to cause 
cGvHD.14 In contrast, involvement of thymus-dependent pathways in cGvHD development begins 
with injury to the thymus from a chemotherapy-conditioning regimen or aGvHD, leading to loss 
of B-cells with their ability to produce antibodies and to present antigen, which may enhance 
development of cGvHD. Autoantibodies like anti-nuclear, anti-mitochondrial, anti-parietal, anti–
smooth muscle and anti–parotid are present in persons with cGvHD.15,16 Also, persons with 
autoantibodies had more cGvHD-associated symptoms than persons without autoantibodies.15 
Autoantibodies against platelet-derived growth factor receptor (PDGFR) may play a role in 
cGvHD.17 These PDGFR-α autoantibodies stimulate thyrosine phosphorylation in a cascade of 
events contributing inflammation and fibrosis. 
The studies report elevated levels of BAFF (B-cell activating factor of the TNF family), which is 
produced by T-cells and granulocytes. BAFF supports differentiation and survival of normal B-
cells in persons with cGvHD and autoimmune diseases.7,18 Fuji et al. showed that in early-onset 
cGvHD, there are elevated sBAFF, sIL-2Rα, sCD13, and anti-dsDNA levels. In late-onset cGvHD, 
sBAFF, anti-dsDNA and ANA are higher, suggesting that the B-cell activation is predominant.19 
These observations create rationale for treatments with anti-CD20 antibodies in cGvHD.20All of 
these pathways are potential targets for cGvHD therapy. However, to date no laboratory parameter 
is considered a reliable biomarker for the diagnosis, measurement of severity, prognosis or 
therapeutic effect in cGvHD.  
1.2.1.2
Clinical Manifestations
The usually affected organs in cGvHD are the skin, eyes, mouth, gut, liver, lungs, joints and 
genitourinary tract. Examples of diagnostic skin manifestations are sclerotic features and 


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9
poikiloderma, lichen-type and hyperkeratotic plaques in the mouth or bronchiolitis obliterans in 
lung biopsy.3 The clinical manifestations of the disease are reminiscent of the autoimmune diseases 
such as systemic sclerosis, systemic lupus erythematosus or Sjögren syndrome.3 According to the 
NIH consensus global scoring system, cGvHD is categorized as mild, moderate or severe. 
Systemic immune-suppressive therapy is usually indicated in persons with cGvHD involving 3 or 
more organs or with a severity score of 2 or higher in any organ. Systemic therapy is also to be 
considered  in persons with thrombocytopenia (platelets <100x109/L) or progressive onset during 
prednisone treatment.4 cGvHD eventually leads to impaired functional performance, deteriorating 
quality of life, increased risk of infections and death.21-25 
1.2.1.3
Treatment
Initial therapy for cGvHD is well established consisting of prednisone with or without a calcineurin 
inhibitor. However, only about 50% of persons have a durable response.6 There are no standard 
recommendations for second-line treatment of cGvHD and there is no FDA approved agent. 
Recommendations for therapy are based on a long list of poorly standardized phase 2 trials or 
retrospective case analyses.26  Diverse drugs (about 40 are described) are used, including sirolimus, 
tacrolimus, mycophenolate, methotrexate, extracorporeal photopheresis, monoclonal antibodies, 
pentostatin, imatinib and others. Choice between drugs is based on logistics, cost, failed prior 
treatments, toxicity profile and subject or clinician preferences.
For many years cGvHD has been difficult to address because of the lack of standardized criteria 
for diagnosis, staging and response to therapy. Recently, as an effort of the NIH-sponsored 
Consensus Development Project, a new series of guidelines have been published addressing 
diagnosis and staging, histopathology, biomarkers, assessment of response to therapy, ancillary 
therapy, supportive care and the design of clinical trials.22,27-31 Typically, cGvHD usually lasts 2 
to 5 years, and approximately 85% of survivors are able to discontinue systemic immune 
suppression. Five-year survival rates for persons who develop cGvHD range from 30% to 40% for 
high-risk persons and persons with cGvHD resistant to steroid therapy to 70% for standard-risk 
cGvHD persons. Treatment goals in management of cGvHD include both alleviation of symptoms 
and the control and reversion of the destructive immunological process. Therapy for cGvHD is 
largely unsatisfactory and persons should be treated on investigational clinical protocols whenever 
possible.23
1.2.2
Thalidomide in cGvHD
Thalidomide is effective in modulating cGvHD in rodents and has been tried for the prophylaxis 
and treatment of cGvHD in humans.32 Thalidomide was found to have immune modulating effects 
from reduced production of TNF-α, costimulation of T-cells to produce IL-2 and IFNγ, inhibition 
of other cytokines such as IL-1β, IL-6 and IL-12 and down-regulation of cell surface adhesion 
molecules involved in leukocyte migration.26,33 It also has anti-angiogenic properties.34 Since the 
report by Vogelsang et al. in 1992 presenting thalidomide as a safe and effective treatment for 
severe cGvHD, several other phase 2 studies in children and adults reproduced these findings in 
salvage treatment of cGvHD. Historically, thalidomide is the third most commonly tested drug in 
trials of cGvHD second-line therapy.35 Vogelsang et al. treated 44 persons with cGvHD who were 
high risk at diagnosis (21) or refractory (23) to conventional treatment with thalidomide for 3 
months after a complete response (CR) and for 6 months after a partial response (PR). High-risk 
cGvHD was defined as having 2 out of following 3 characteristics: evolving from aGvHD, 
lichenoid skin or mucous-membrane changes and hepatic dysfunction. Absolute survival was 64%, 


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10
78% among persons receiving salvage therapy and 48% among those with high-risk cGvHD. 
Complete CR was achieved in 14 persons (7 high risk, 7 salvage), PR in 12 (1 high risk, 11 salvage) 
and no response in 18 (13 high risk, 5 salvage). The main side effects were sedation, neuropathy 
and constipation.36 In the United States, thalidomide is FDA approved for erythema nodosum 
leprosum and in combination with dexamethasone for newly diagnosed multiple myeloma.37  
Six other phase 2 studies have suggested efficacy of thalidomide in high-risk or refractory cGvHD 
(Table 1). Most trials were small but 3 had more than 30 subjects. Complete and partial remissions 
(variously defined) were reported with overall response rates of 20% to 86%. Heney et al.38 
reported responses in 5 of 6 persons, best in cutaneous involvement; 2 persons developed 
peripheral neuropathy. In a study in children by Rovelli et al., 10 subjects responded (6 CR, 4 
PR).39 Forsyth reported a thalidomide-responsive case of pulmonary cGvHD (brochiolitis 
obliterans).40 Staumont-Salle reported a response in lichenoid vulvar lesions.41 In study by Browne 
et al.,42 38% of subjects with cGvHD responded (46% children, 25% adults). In a 1995 study by 
Parker et al., 20% of subjects had sustained responses, and 36% discontinued because of side 
effects, including sedation, constipation, neuritis, neutropenia and rash. In a phase 2 study by Cole 
et al., 5 children received doses 100 to 800 mg—1 CR and 4 PRs were reported. Side effects were 
minimal, and there was no neuropathy.43 Kulkarni et al. reported 13 CRs and 8 PRs in 59 subjects 
with cGvHD at thalidomide doses of 600 to 1200 mg/d. Two subjects had polyneuropathy, 2 had 
deep vein thrombosis (DVT) and 1 had thrombocytopenia. Mehta treated 6 children with cGvHD.44 
One child had a CR and one a PR. One child had a rash, eosinophilia and pancreatitis shortly after 
starting thalidomide, which resolved only after discontinuing thalidomide. 
Two randomized trials (with approximately 50 subjects each) using thalidomide as part of the 
front-line therapy in cGvHD are reported.45,46 In one open-label, add-on to steroids and 
cyclosporine study, comparable response rates were seen in the thalidomide and control cohorts.45 
The second study was a placebo-controlled trial using initial doses of 200 to 800 mg/d. 
Thalidomide had to be discontinued in 92% of persons in contrast to 65% in the placebo group due 
to intolerance, mostly neutropenia, sedation and neuropathy.46 A third randomized trial of 
thalidomide in cGvHD was performed by Chao et al. for cGvHD prevention.47 This study showed 
increased incidence of cGvHD and inferior survival in the thalidomide arm with such strategy.47 
Collectively, these data suggest efficacy of thalidomide as salvage therapy for cGvHD but not for 
prevention or as front-line therapy.26  
In summary, several phase 2 trials report response rates of 20% to 83% with thalidomide doses of 
100 to 1600mg/d.26,34 Thalidomide doses higher than 200 mg/d are poorly tolerated. Phase 3 trials 
show, however, no benefit of thalidomide for front-line therapy and detrimental effect in cGvHD 
prevention. These data suggest that although thalidomide may be active at high doses in rodents, 
these doses cannot be reliably and safely achieved in humans. Developing pomalidomide, which 
has similar immune-modulating effects as thalidomide but less toxicity, is of considerable interest 
in cGvHD.
Table 1. Studies of Thalidomide in cGvHD
Reference
Dose 
(mg/day)
No. 
of 
Persons
Toxicities
Response Rate
Phase 2 salvage therapy
Heney 
et 
al.38 
1991
100-200
6
2 PNS not stopped
2 CR, 3 PR


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Reference
Dose 
(mg/day)
No. 
of 
Persons
Toxicities
Response Rate
Vogelsang et al.36 
1992, 
steroid 
refractory or high-
risk cGvHD
800-1600
44
4 PNS, 91% sedation 
during first week, 24, 
at least single episode 
of constipation
14 CR, 12 PR
Cole et al.43 1994 
100-800
5
1 constipation
1 CR, 4PR
Parker 
et 
al.48 
1995
400-1200
80
3 PNS, 7 somnolence, 
3 constipation, 6 skin 
rash, 10 neutropenia
9 CR, 7 PR
Rovelli et al.39 
1998
100-800
14
0
6 CR, 4 PR
Browne et al.42 
2000
200-800
37
1 
constipation, 
2 
somnolence, 1 mild 
PNS, 2 severe whole-
body erythema, one 
recovered, one died 
(toxic 
epidermal 
necrolysis)
1 CR, 13 PR
Kulkarni 
S. 
49 
2003 (thalidomide 
in 
combination 
with 
CSP, 
prednisone 
and 
azathioprine)
600-1200 
59
2 PNS, 2 DVT, 1 
thrombocytopenia
13 CR, 8 PR
Phase 3 front-line therapy
Koc et al.46 2000
thalidomide 
versus 
placebo, 
given 
in 
combination with 
CSP 
(or 
tacrolimus) 
and 
prednisone
200-800 
52 
(26 
thalidomide, 
26 placebo)
14 
neutropenia 
(stopped), 
11 
neurologic symptoms 
(stopped), 
17 
sedation, 
 
10 
constipation
Treatment 
with 
the
study drug was 
discontinued 
before resolution 
of cGvHD in 23 
(92%) of persons
Arora et al.45 2001
CSP 
and 
prednisone versus 
CSP, prednisone,
and thalidomide
200-800 
(adults)
0.75-3 mg/kg 
(children)
54 
(27 
in 
each arm)
17 
sleepiness, 
1 
seizures, 
14 
constipation, 13 PNS, 
2 TTP/HUS
CR+PR 
similar 
response in both 
groups at 2, 6 
months 
and 
1 
year; no clinical 
benefit 
when 
included in initial 
therapy
Phase 3 prevention


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12
Reference
Dose 
(mg/day)
No. 
of 
Persons
Toxicities
Response Rate
Chao et al47 1996, 
randomized at day 
80 after transplant 
200 mg BID
59 
subjects 
randomized, 
54 evaluable 
(26 placebo, 
28 
thalidomide)
Increased 
incidence 
of 
cGvHD 
and 
inferior 
survival 
in 
thalidomide 
arm
Abbreviations: PNS, polyneuropathy symptoms; CR, complete response; PR, partial response; 
DVT, deep venous thrombosis; CSP, cyclosporine; TTP/HUS, thrombotic thrombocytopenic 
purpura/hemolytic uremic syndrome.
1.3
POMALIDOMIDE
Pomalidomide is a novel immune-modulatory drug, a thalidomide analogue with 4,000-fold 
greater inhibition of TNF-α production relative to thalidomide (Celgene Corp data on file50). The 
pharmacodynamic (PD) properties of pomalidomide are of potential therapeutic benefit in the 
treatment of various hematologic malignancies (such as multiple myeloma and myeloproliferative 
neoplasm [MPN]–associated myelofibrosis and other hematologic disorders (like β-thalassemia 
and sickle cell disease) as well as solid cancers (prostate, thyroid and lung cancer). In addition, 
several features of pomalidomide suggest it may be useful in treating cGvHD, including: (1) in 
vitro suppression of TNF-α (human monocytes);51 (2) increasing Th1 (mouse cancer vaccine, 
human CD4+ T-cells in vitro);52,53 (3) suppression of Th2 (mouse cancer vaccine);52 and (4) 
stimulation of IL-12 and sIL-2Rα (humans).54 However, other effects of  pomalidomide may have 
potential adverse effects in cGvHD, including: (1) increased CD45RO+ (memory) CD4 and CD8 
T-cells (humans);54 (2) decreased Tregs;55 (3) increased Th2 (polarized human CD4+ T-cells in 
vitro);53 and (4) increased B-cells (in vitro human CD19+ cells).56 Because the precise 
pathogenesis of cGvHD is unknown (and may be different in different persons), it is impossible to 
predict the effect of therapy with pomalidomide outside of the context of a clinical trial.
1.3.1
Preclinical Studies
In a series of in vitro studies, pomalidomide exhibited several immune-modulating properties such 
as potent inhibition of TNF-α activity, IL-1β, IL-6, IL-12, monocyte chemoattractant protein 
(MCP)-1 and macrophage inflammatory protein, and production and inhibition of cellular 
cyclooxygenase-2, as well as modulation of angiogenesis. Pomalidomide also augmented the 
activity of natural killer (NK) cells and enhanced antibody-dependent cell-mediated cytotoxicity 
of targeted tumor cells in combination with therapeutic antibodies to tumor-specific surface 
antigens. Pomalidomide enhances T-cell stimulation by augmenting T-cell proliferation, 
increasing production of IL-2, IFN-γ and RANTES, and decreasing IL-10 production. 
Furthermore, pomalidomide is a potent inhibitor of the proliferation of multiple myeloma cell lines 
in vitro and has been shown to be active in subjects with relapsed or refractory myeloma.54,57 Based 
on its numerous mechanisms of carcinoma growth inhibition, pomalidomide is being tested as part 
of induction chemotherapy regimens and as post-induction maintenance therapy for solid cancers.
More information emerged recently about the specific mode of pomalidomide action as cereblon 
(CRBN), the primary target for thalidomide teratogenicity58, is now identified also as an essential 


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target for pomalidomide anti-myeloma activity.59 The immediate result of this binding is interferon 
regulatory factor 4 (IRF4) down-regulation, which is also essential for Th-17 cell development.60,61  
1.3.2
Animal Models
Oral pomalidomide is rapidly absorbed in rats and monkeys and the bioavailability is dose 
dependent, at high doses 100mg/kg, the bioavailability was low (15%) however at 2mg/kg the 
bioavailability was 100%. Following intravenous (IV) administration to rats and monkeys, 
pomalidomide exhibited low clearance (240 to 286 mL/h/kg), a moderate volume of distribution 
(2.2 to 2.5 L/kg), and a moderately long terminal half-life (approximately 6 hours). Renal excretion 
of metabolites was the predominant route of clearance in animal models. The toxicity of 
pomalidomide after oral and IV dosing was studied in rats and mice. There were no deaths and no 
significant clinical observations in rodents given a single dose of pomalidomide at 2000 mg/kg 
orally or up to 50 mg/kg IV. No treatment-related macroscopic changes were observed. In rats 
administered a single dose of 10, 25 and 50 mg/kg pomalidomide by IV injection, the high dose 
produced piloerection, hunching, and tachypnea. Palpebral closure was observed at doses of 25 
and 50 mg/kg, and hyperpnea at 50 mg/kg. The severity and persistence of clinical observations 
increased with increased dose. Pomalidomide at oral doses of 100, 500 or 1500 mg/kg was well 
tolerated when given once daily to male and female rats for 90 consecutive days. Therefore, the 
no-observable-adverse-effect level (NOAEL) under the conditions of this study was 1500 mg/kg.
A 13-week study evaluated the toxicity and toxicokinetics of pomalidomide in male and female 
cynomolgus monkeys after oral doses of 0.05, 0.2, 2 or 10 mg/kg. Lesions in the bone marrow, 
spleen, and thymus were observed in animals dosed at 2 and 10 mg/kg. Based on the results from 
this study, the NOAEL was 0.2 mg/kg/day; the maximum plasma concentration (Cmax) and the 
area under the plasma concentration-time curve (AUC) values at this dosage were 
approximately150 ng/mL and 600 ngh/mL, respectively. Since the monkey was identified as the 
most sensitive species in the toxicology program, the NOAEL of 0.2 mg/kg/day was used to 
calculate the human equivalent dose of 0.06 mg/kg or 3.8 mg for a 60 kg person. External and 
cardiac malformations were observed in fetuses of pregnant rabbits that were administered 
pomalidomide orally at 10, 100 and 250 mg/kg/day. A relationship was noted between increasing 
pomalidomide dose and the number of fetuses affected, as well as the frequency of occurrence of 
each type of malformation. Based on these data, it was concluded that pomalidomide causes fetal 
malformations in rabbits. A nonclinical safety PD study demonstrated no major safety concerns 
with cardiac and respiratory functions in dogs, rats or monkeys. In rats and monkeys pomalidomide 
administrated orally was absorbed fairly rapidly (Tmax of 2 to 4 hours) and had low oral 
bioavailability (13%-15%). Renal excretion was the predominant route of clearance in animal 
models. 
In the mouse model of bleomycin-induced skin fibrosis, pomalidomide exerted potent anti-fibrotic 
effects and not only prevented progression of experimental fibrosis, but also induced regression of 
established fibrosis.  In this model, pomalidomide reduced dermal thickening and reduced the 
numbers of myofibroblasts in the skin, whether it was administered prophylactically or 
therapeutically. These results show that pomalidomide exerts potent anti-fibrotic effects and not 
only prevents the progression, but also induces a regression of established fibrosis in a nonclinical 
model of skin fibrosis (Celgene, unpublished). 
In multiple myeloma, pomalidomide induces growth arrest and/or apoptosis of multiple myeloma 
cells (via caspase-8 death receptor pathway), and it also reduces stromal cell expression of vascular 


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14
endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), which decreases 
angiogenesis. 62 One characteristic of immune-modulatory drugs is their potency to act as a co-
stimulus of T-cell receptor ligation, leading to increased production of IL-2 and INF-γ, indicative 
of a Th1 phenotype.63 Pomalidomide promotes T-cell differentiation via the augmentation of T-
bet, which leads to upregulation of INF-γ.63 It also increases antibody-dependent cell cytotoxicity.  
1.3.3
Experience in Humans
Pomalidomide is active in multiple myeloma and MPN-associated myelofibrosis. It has been also 
used to treat cGvHD. Given at doses up to 3 mg/day is usually well tolerated and main toxicities 
are neutropenia and thrombocytopenia, there have been no drug-related deaths in clinical trials 
with pomalidomide (summarized in Table 2). 
1.3.3.1 Pharmacokinetics and Product Metabolism in Humans
A phase-1, single-center, single-blind, placebo-controlled, ascending single oral dose study (CC-
4047 1398/132) was conducted to evaluate the safety, tolerability, pharmacokinetics, and 
pharmacodynamics of pomalidomide in 30 healthy male subjects, aged 19 to 55 years.  
Pomalidomide was administered orally in capsule form at 5 dose levels comprised of 1, 5, 10, 25, 
and 50 mg, and corresponding to 0.01, 0.07, 0.13, 0.30, and 0.59 mg/kg, respectively, when 
adjusted for group mean body weight.  At each dose level, 4 subjects received pomalidomide and 
2 subjects received placebo in a fasted state.  A total of 20 subjects each received a single oral 
dose of pomalidomide in doses ranging from 1 mg to 50 mg, and 10 received placebo. Following 
each dose level of pomalidomide, the absorption of pomalidomide was moderately rapid.  The 
maximum plasma concentration (Cmax) occurred at a median tmax of 2.5 to 6 hours postdose.  The 
systemic exposure of pomalidomide as determined from the area under the plasma concentration-
time curve [AUC(0-tz) and AUC(0-∞)] increased in an approximately dose-proportional manner, 
whereas Cmax increased in a subproportional manner.  After reaching Cmax, plasma concentrations 
of pomalidomide declined in an apparent biphasic manner.  The geometric mean terminal 
elimination half-life (t1/2) ranged from 8.2 to 10.8 hours, with no apparent dose-related trend.  
Less than 3% of the administered dose was excreted in urine as unchanged pomalidomide across 
all dose levels.
A phase-1b, single-center, ascending dose, open-label study (CDC-407-00-001) was conducted 
to identify the MTD and evaluate the safety and efficacy of pomalidomide in male and female 
subjects with relapsed or refractory Multiple Myeloma (MM). Pomalidomide was administered 
orally in capsule form at doses of 1, 2, 5, and 10 mg in either once daily dosing (Cohort 1) or 
alternate day dosing (Cohort 2) for 4 weeks.  The study design did not allow for a precise 
calculation of subject numbers, as the number of subjects per dose group was dependent on the 
frequency of DLT.  Subjects were enrolled in groups of 3 per dose group beginning with the 1-
mg dose group.  If no DLT were experienced (in one dose group) at a given dose level, the 
subsequent group of 3 subjects were to receive the next highest dose.  If 1 of the 3 subjects in a 
dose group experienced a DLT, that cohort would then be expanded to 6 subjects.  If 2 or more 
subjects in a cohort of up to 6 subjects experienced a DLT, no additional escalation of dose 
would occur.  Escalations would occur until an MTD was established or the maximum dose of 
10 mg/day was reached.  A DLT was defined as a Grade 3 or higher non-hematologic toxicity or 
a Grade 4 or higher hematologic toxicity using the NCI CTC.  A total of 45 subjects were 
enrolled in the study; 24 subjects in Cohort 1 and 21 subjects in Cohort 2.  Blood samples for the 


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15
analysis of pomalidomide were collected from 28 subjects and included in the pharmacokinetic 
analysis.  Dose levels of pomalidomide evaluated in the pharmacokinetic assessment were 1, 2, 
5, and 10 mg once daily and 5 mg on alternate days.  Blood and urine samples for analysis of 
plasma and urinary pomalidomide concentrations were collected for up to 24 hours after dosing 
on Day 1 and Week 4 (Day 29).  Plasma concentrations (Geometric means and coefficient of 
variation percent [CV%]) of pomalidomide in subjects with MM on Day 1 and Week 4 are 
summarized in Figure 1 and Figure 2.
Figure 1:
Plasma Concentrations of Pomalidomide on Day 1
OD = once daily; QOD = every other day.
Plasma concentration (ng/mL)
   0.0
  20.0
  40.0
  60.0
  80.0
 100.0
Time post-dose (h)
0
2
4
6
8
10
12
14
16
18
20
22
24























































 1 mg CC-4047 od   
 2 mg CC-4047 od   
 5 mg CC-4047 od   
 10 mg CC-4047 od    5 mg CC-4047 qod   







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16
Figure 2:
Plasma Concentrations of Pomalidomide on Week 4
OD = once daily; QOD = every other day.
Following administration of pomalidomide at dose levels of 1, 2, 5, and 10 mg once daily and 5 
mg every other day to subjects with MM, absorption of pomalidomide was steady with median 
tmax ranging from 1.5 to 4.0 hours postdose on Day 1 and Week 4.  The mean t1/2 of 
pomalidomide was similar across dose levels and dosing days being approximately 7 to 8 hours.
At the 1 and 2 mg daily dose levels, there was slightly greater accumulation of pomalidomide in 
plasma upon multiple dosing than predicted.  However, at the 5 mg daily and 5 mg alternate day 
dose levels, there was little or no accumulation of pomalidomide upon multiple dosing.
There was a less than dose proportional increase in AUC(0-) and Cmax for pomalidomide  over 
the 1 to 10 mg dose range on Day 1, with a more pronounced sub-proportional increase in both 
parameters on Week 4 over the 1 to 5 mg dose range. 
The fraction of the dose excreted in the urine as unchanged drug was low for all dosing 
regimens, with a maximum of 4.5% being eliminated up to 24 hours after dosing on Day 1 and 
Week 4 for individual subjects.
1.3.3.2 Clinical studies with Pomalidomide
In a phase 1 single-center, single-blind, placebo-controlled, ascending single-dose study, 
pharmacokinetics (PK), PD and safety of pomalidomide were studied in 30 healthy male subjects. 
The results demonstrated that pomalidomide administered at a dose of 1 to 50 mg has an acceptable 
safety profile. Adverse events (AEs) reported in the study were mild or moderate in nature and no 
clinically significant changes in any laboratory or other parameters, except a dose-related decrease 
in the CD4+ cell count, were observed. 
A phase 1b study was conducted to identify the maximum tolerated dose (MTD) and evaluate 
safety and efficacy of pomalidomide in persons with relapsed or refractory multiple myeloma. A 
Plasma concentration (ng/mL)
   0.0
  20.0
  40.0
  60.0
  80.0
 100.0
Time post-dose (h)
0
2
4
6
8
10
12
14
16
18
20
22
24






































 1 mg CC-4047 od   
 2 mg CC-4047 od   
 5 mg CC-4047 od   
 10 mg CC-4047 od    5 mg CC-4047 qod   







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17
total of 24 persons were treated with the dose-escalating regimen (1, 2, 5 and 10 mg). The MTD 
was 2 mg. Pomalidomide was well tolerated with no serious nonhematological AEs and excellent 
disease responses. Fifty-eight percent of persons developed grade 3/4 neutropenia and 16% of 
persons developed DVT. 64 In this study, the cytokines were measured and it was noticed that the 
serum IL-12 and sIL-2 levels increased during the first 4 weeks of treatment. IL-12 is derived from 
monocytes and macrophages and has a key role in amplifying a Th1-type response.65 No 
significant changes and no correlation was found between IL-6, TNF-α, IL-10, VEGF and bFGF 
levels and paraprotein response.  
A standard dose escalation phase 1 study was conducted to determine the MTD of pomalidomide 
at 1 mg, 2 mg, 5 mg, and 10 mg on alternate days in persons with relapsed myeloma. Patients were 
evaluated prior to study enrolment and weekly for the first month and monthly thereafter. The 
overall response rate (>50% reduction in paraprotein) to pomalidomide monotherapy was 50%. 
Hematological monitoring over 4 weeks showed significant decline in hemoglobin, white blood 
cells, and neutrophils. Platelets decreased but without statistical significance. Significant decrease 
was noticed in the B-cell percentage (P=0.002) and absolute B-cell number. The CD3+ percentage 
and CD8+ percentage increased (P=0.003, P=0.007). The CD4+ percentage and absolute as well 
as NK cell percentage were increased but without statistical significance. There was a significant 
negative association between B-cell percentage or absolute B-cell count at 4 weeks and maximal 
percentage change in paraprotein (P=0.05, P=0.03). 
Tefferi et al. published a phase 2 randomized, multicenter, double-blind study of pomalidomide in 
MPN-associated myelofibrosis. Four arms were studied pomalidomide (2 mg) plus placebo, 
pomalidomide (2 mg) plus prednisone, pomalidomide (0.5 mg) plus placebo and pomalidomide 
(0.5 mg) plus prednisone. Pomalidomide was well tolerated. Anemia response rate was up to 40%. 
There was relatively low incidence of grade ≥3 neutropenia and thrombocytopenia. How 
pomalidomide works in MPN-associated myelofibrosis is unclear, but it is known that TNF-α 
directly inhibits erythropoiesis in vitro.66 In this study it was also described that overall bone 
marrow cellularity, degree of fibrosis, or cytogenetic findings did not change (bone marrow 
examination was done in 4 responders who completed 1 year treatment with pomalidomide with 
or without prednisone. 
A multicenter, randomized, phase 2 study of pomalidomide in combination with low-dose 
dexamethasone was conducted in patients with relapsed/refractory myeloma who received prior 
therapy (lenalidomide or bortezomib). Pomalidomide 2 mg po daily was given on days 1 through 
28 of a 28-day cycle. Dexamethasone 40 mg daily was given on days 1, 8, 15 and 22 of each cycle. 
Thirty-eight patients achieved objective response (63%), including CR in 5%, very good PR in 
28% and PR in 30%. Responses were seen in 40% of lenalidomide-refractory persons, 37% 
thalidomide-refractory and 60% of bortezomib-refractory persons. Toxicity was primary 
myelosuppression. Grade 3 or 4 hematologic toxicity consisted of anemia (5%), thrombocytopenia 
(3%) and neutropenia (32%). 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. One patient experienced thromboembolic event. The most common non-
hematologic grade 3 or 4 toxicities consisted of fatigue (17%) and pneumonia (8%); less than 5% 
of patients experienced neuropathy, diarrhea, constipation or hyperglycemia. One patient (1.6%) 
had a thromboembolic event of DVT.
In a phase 1/2 study in MPN-associated myelofibrosis with 19 patients, 3 mg was determined to 
be the MTD, but no efficacy was observed at that dose. Two of three patients in the 3.5 mg cohort 


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18
had dose-limiting myelosuppression. Overall, 7 subjects had an anemia response and 2 a spleen 
response.
In another trial of pomalidomide in MPN-associated myelofibrosis, low-dose pomalidomide (0.5 
mg/day) was given to 58 persons. Anemia response was documented only in persons with 
JAK2V617F (24 vs 0%; P=0.03). Nine of the 10 anemia responders became red blood cell–
transfusion independent. Fourteen of 24 persons with platelets ≤100x10e9 /L had a greater than 
50% increase in platelets. Grade 3 or 4 thrombocytopenia/neutropenia occurred rarely. This study 
established low-dose pomalidomide as effective and safe in MPN-associated myelofibrosis with 
anemia. 
1.3.3.1
Pomalidomide in cGvHD
Pusic et al. reported results of a phase 2 study of pomalidomide in patients with cGvHD not 
controlled by corticosteroids.67 Eight subjects received 3 mg/day with dose reductions to 2 mg, 1 
mg and 0.5 mg. Seven subjects required dose reduction because of muscle cramps, tremor and 
fatigue. Five subjects discontinued therapy for worsening of cGvHD of the skin and mouth (N=1), 
pain (N=1) and no response (N=3). No bone marrow suppression, somnolence, constipation or 
DVT were observed. Three persons reached the primary evaluation endpoint at 6 months at the 2 
mg dose (N=2) or 1 mg dose (N=1). The 3 patients had global PRs per NIH criteria (skin erythema, 
GI) and <PR ongoing improvements in the skin, mouth and eyes. This study established feasibility 
of giving pomalidomide to humans with cGvHD and the absence of serious side effects at doses 
less than 2 mg/day.      


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                                                                                                                               19
Table 2. Clinical Studies of Pomalidomide
Reference
Setting
Study 
Design
Study 
Duration
Dose
N
MTD
Toxicities
Response Rate
Phase 1
Celgene, 
not 
published
Healthy 
volunteers
Single-blind, 
placebo-
controlled, 
ascending 
single dose
1, 5, 10, 25, 
50 mg
30, 10 
received 
placebo
N/A
Mild or moderate 
AEs; no clinically 
significant changes 
in any laboratory 
parameter tested
N/A
Streetly et 
al.,200864
Relapsed 
MM
Standard 
dose 
escalation
4 weeks
1, 2, 5, 10 
mg
20
5 mg
10 mg, grade 4 
neutropenia in 3/3 
pts, DVT 0%
10% CR and >50% 
reduction in 
paraprotein in 50%
Schey et 
al., 200465
Relapsed or 
refractory 
MM
Dose 
escalating 
regimen 
4 weeks
1, 2, 5, 10 
mg
24
2 mg
Grade 3/4 
neutropenia in 
58% pts and DVT 
in 16%
17% CR, >25% 
reduction in 
paraprotein in 67% , 
>50% reduction  in 
paraprotein in 54%
Phase 2 
Tefferi et 
al. 200937
Anemia 
associated 
with 
myelofibrosis
Randomized, 
double-
blind, 
multicenter
Up to 12 
28-day 
treatment 
cycles
4 arms (2 
mg+ 
placebo, 
2 mg + 
prednisone, 
0.5 mg + 
prednisone, 
and 
prednisone 
+ placebo
84
2 mg 
Relatively low 
incidence of grade 
≥3 neutropenia and 
thrombo-cytopenia
Response in anemia 
20 pts (40%)
23%, 2 mg/d + 
placebo; 16%,
2 mg/d + 
prednisone; 36%,
0.5 mg/d + 
prednisone; 19%, 
prednisone + 
placebo


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20
Mesa et 
al., 2009 68
Myelofibrosis
Phase 1/2, 
multicenter 
dose 
escalation
28 days
2.5, 3.0 and 
3.5 mg/day; 
no efficacy 
at 3 mg, 
dose 
reduction to 
0.5 mg
19
3 mg
DLT myelosuppre-
ssion in 2/3 pts in 
3.5 mg cohort
7 pts anemia 
response, 2 spleen 
response
Lacy et al., 
2009 69
Relapsed 
MM
Multicenter
2 mg/d 
on days 
1-28 of a 
28-day 
cycle, 
dexame-
thasone 
40 mg  
on days 
1, 8, 15, 
22
2mg/day
60
Primarily 
myelosuppression. 
Grade 3 or 4 
hemato-logic 
toxicity consisted 
of anemia (5%), 
thrombo-cytopenia 
(3%) and 
neutropenia (32%)
Objective response 
in 63%, including 
CR in 5%, very 
good PR in 28% 
and PR in 30%
Begna et 
al., 201170
Myelofibrosis 
(JAK2V617F 
positive)
Single-
center
28-day 
cycles: 
84% pts 
had ≥3 
cycles
0.5 mg/day, 
after 6 
cycles 
2 mg/day
58
2 mg
No AE reason for 
stopping therapy. 1 
pt neuropathy, 1 pt 
grade3/4 thrombo-
cytopenia 
10 (17%) anemia 
response, 20% 
anemia RR in pts 
who received ≥3 
cycles
Pusic et 
al., 201067
cGvHD
Multicenter, 
response 
evaluated 
every 3 
months
3 mg/day 
with dose 
reductions 
to 2, 1 and 
0.5 mg/day
8
3 mg
Muscle cramps, 
tremor and fatigue
2 CRs, 1 PR
(3 pts reached  
6 months)


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                                                                                                                               21
1.4
STUDY DESIGN AND RATIONALE
Better therapies for cGvHD are needed. In about 50% of persons with cGvHD, the disease does 
not respond to corticosteroids, and there is no standard second-line therapy or FDA-approved drug 
for cGvHD. Thalidomide is an immune-modulating drug effective in a rodent model of cGvHD 
and in humans for salvage therapy after failure of steroids, but at doses expected to be effective it 
is associated with troublesome side effects including somnolence, neuropathy and constipation, 
which precluded wider use in this population. Pomalidomide is a new immune-modulating drug 
that is more potent than thalidomide and has been shown in early trials in cancer and cGvHD to 
be without the toxicities that limited the use of thalidomide. Several biological features of 
pomalidomide suggest that this drug may be useful in treating cGvHD. Since the precise 
pathogenesis of cGvHD is unknown, the most compelling evidence for testing pomalidomide in a 
clinical trial is the encouraging efficacy data with thalidomide. Preliminary studies of 
pomalidomide in persons with cGvHD suggest absence of typical thalidomide-related side effects 
or significant myelosuppression and a preliminary suggestion of efficacy if doses of less than 3 
mg/day could be given for at least 6 months (the typical primary response evaluation time point in 
cGvHD trials). 
The use of the NIH Consensus Diagnosis, Staging Criteria now provides an updated, standardized 
assessment of persons with cGvHD for inclusion in clinical trials.71,72 Although NIH Consensus 
Response Criteria are not yet validated in large clinical trials there are preliminary data on validity 
and reproducibility that provide guidance for further use and testing.73
At the intramural NCI there is a well-established clinical research infrastructure, the “NIH Chronic 
GVHD Study Group,” that is uniquely qualified to conduct drug development studies and cGvHD 
assessments in a multi-disciplinary specialty setting. This environment is also uniquely conducive 
for further studies of cGvHD biology and in vivo pomalidomide effects by using the ETIB 
immunology pre-clinical core and the established cGvHD murine models expertise. The proposed 
study is not only expected to address a specific clinical therapeutic question related to 
pomalidomide in cGvHD but also allows establishment of experience with this important group of 
agents in general in patients after allogeneic hematopoietic stem cell transplantation.      
The proposed study is a randomized phase 2 trial with the single stage selection design Patients 
will receive either a constant low dose of pomalidomide (0.5 mg/day) for six months or a 
strategy of increasing dose of pomalidomide from 0.5 mg/d up through each individual patients’ 
maximum tolerated dose, with escalations by 0.5 mg/d every 2 weeks to a maximum of 2.0 mg/d. 
To protect patient safety, an early stopping rule will be implemented as outlined in section 8. 
With two arms, each of which has a maximal accrual of 16 patients, up to 32 evaluable patients 
will be randomized. Response assessments will occur every 3 months with primary efficacy 
endpoint evaluated at 6 months. Patients with responding disease will continue therapy for 
another 6 months.


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2
ELIGIBILITY ASSESSMENT AND ENROLLMENT 
2.1
ELIGIBILITY CRITERIA
2.1.1
Inclusion Criteria
2.1.1.1
Moderate or severe cGvHD diagnosed and staged per NIH criteria (Filipovich et al 
2005)22, Appendix C , Appendix D, Appendix E and Appendix F.. 
2.1.1.2
>18-75 years of age, because no dosing or adverse event data are currently available on 
the use of pomalidomide in persons <18 years of age
2.1.1.3
Has cGvHD that did not respond to high-dose corticosteroids (average 0.5 mg/kg/d 
prednisone for >8 weeks) or second-line systemic therapy 
2.1.1.4
If taking systemic therapy for cGvHD at the time of enrollment, must be on a stable or 
tapering schedule in the preceding 4 weeks (extracorporeal photopheresis has to be 
stopped at least by 4 weeks before enrollment)  
2.1.1.5
Karnofsky performance score >60% (Appendix A)
2.1.1.6
Life expectancy >3 months
2.1.1.7
Stable primary malignancy for previous 3 months
2.1.1.8
Agree to adhere to methods of contraception and other fertility control measures as 
prescribed by the protocol
•
Agents of this class are known to be teratogenic, women of child-bearing potential and 
men must agree to use effective forms of contraception (hormonal or barrier method of 
birth control; abstinence) prior to study entry and for the duration of study participation. 
Should a woman become pregnant or suspect she is pregnant while she or her partner 
is participating in this study, she should inform her treating physician immediately.
•
Female Subjects
o Females of childbearing potential (FCBP)0F† must have a negative serum or urine 
pregnancy test with a sensitivity of at least 25 mIU/mL within 10 – 14 days prior 
to and again within 24 hours of 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 use a latex condom during sexual contact with a FCBP even if they have 
had a vasectomy. All patients must be counseled every 28 days about pregnancy 
precautions and risks of fetal exposure through the POMALYST REMS™ 
program. See Appendix M: Risks of Fetal Exposure, Pregnancy Testing 
Guidelines and Acceptable Birth Control Methods. 
•
Male Subjects 
o
Must agree to use a latex condom during sexual contact with females of 
childbearing potential while participating in the study and for at least 28 days 
† 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).


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23
following discontinuation of study drug even if he has undergone a successful 
vasectomy 
o
Will be warned that sharing study drug is prohibited and will be counseled about 
pregnancy precautions and potential risks of fetal exposure
o
Must agree to abstain from donating blood, semen, or sperm during study 
participation and for at least 28 days after discontinuation of study drug. 
o
Must agree that if a pregnancy or a positive pregnancy test does occur in a study 
subject or the partner of a male study subject during study participation, study 
drug must be immediately discontinued.
•
Patients must agree to not share study drug with anyone during participation in the 
study.
2.1.1.9
Ability of subject to understand and the willingness to sign a written informed consent 
document.
2.1.1.10 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.
2.1.2
Exclusion Criteria
2.1.2.1
Acute GvHD, classic (<day 100) or late-onset (>day 100) Appendix D
2.1.2.2
Systemic immune suppression or systemic therapy for cGvHD started within preceding 
4 weeks including extracorporeal photopheresis
2.1.2.3
Hypersensitivity to thalidomide, lenalidomide or pomalidomide
2.1.2.4
Any serious medical condition which places the subject at an unacceptable risk if he or 
she were to participate in the study or confounds the ability to interpret data from the 
study, including, but not limited to, symptomatic congestive heart failure, unstable angina 
pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit 
compliance with study requirements.
2.1.2.5
Neutrophil <1.0x109/L, platelets <75x109/L, estimated creatinine clearance <50 
mL/min/1.73m2 
(Cockroft-Gault 
formula) 
total 
bilirubin 
>3 
mg/dL, 
transaminase >3xUNL 
2.1.2.6
Uncontrolled infection
2.1.2.7
Active HIV-1, HBV and/or HCV infection
2.1.2.8
Uncontrolled arrhythmias or symptomatic heart disease or LVEF <45%
2.1.2.9
Other cancer except that for which the transplant was done <2 years before study entry, 
except non-melanoma skin cancer or carcinoma in situ of the uterine cervix or breast
2.1.2.10 Taking other investigational drugs
2.1.2.11 NIH lung score 3 (Appendix E)
2.1.2.12 Pregnant women are excluded from this study because pomalidomide has potential for 
teratogenic effects.  Because there is an unknown but potential risk for adverse events in 
nursing infants secondary to treatment of the mother with pomalidomide, breastfeeding 
must be discontinued while the mother is taking study drug and for at least 28 days after 
discontinuation of study drug.  These potential risks may also apply to other agents used 
in this study.


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24
2.1.3
Recruitment
Subjects will be recruited from NIH Clinical Center hematopoietic stem cell transplant clinics but 
could be referred from the outside institutions. Study participants will be primarily recruited from 
the 04-C-0281 cGvHD natural history study protocol, which currently has more than 260 persons 
registered and enrolls approximately 3 persons per month, most of them with moderate or severe 
cGvHD. Referrals will be also accepted from the other NIH protocols or from the extramural 
community. Every effort will be made to screen potential candidates through the existing 04-C-
0281 natural history protocol, which is a non-therapeutic study as part of pre-enrollment 
evaluations. The patient population enrolled on this study is expected to be representative of the 
population of persons receiving allogeneic hematopoietic stem cell transplantation at the NIH and 
nationwide. 
2.2
REQUIRED TESTING AND COUNSELING FOR FCBP AND PARTNERS OF FCBP
2.2.1
During study participation and for 28 days following discontinuation of study drug:
•
Pregnancy tests 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).
•
Pregnancy tests must occur 10 – 14 days 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 M: Pomalidomide Risks of Fetal Exposure, 
Pregnancy Testing Guidelines and Acceptable Birth Control Methods).   
•
All patients must be counseled about pregnancy precautions, risks of fetal exposure and 
other risks. The counseling must be done every 28 days and at drug discontinuation 
through the POMALYST REMS™ program. See Appendix M: Pomalidomide Risks 
of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control 
Methods.
2.3
SCREENING EVALUATION
Screening procedures may be performed on a CCR screening protocol, most commonly on 04-C-
0281 “Natural History of Chronic GVHD.” All studies must be completed within 8 weeks prior to 
enrollment:
•
History and physical exam, Karnofsky performance score
•
Documentation of cGvHD diagnosis, NIH organ and global severity stage 
•
CBC, platelets, differential, PT/PTT, serum chemistries (including sodium, potassium, 
chloride, CO2, calcium, magnesium, phosphorus, blood urea nitrogen [BUN], creatinine, 
glucose, albumin, total protein, alkaline phosphatase, total bilirubin, AST [SGOT], ALT 


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25
[SGPT], lactate dehydrogenase [LDH], and uric acid), urinalysis, urine pregnancy testing, 
TSH
•
Infectious serology markers (HIV-1, HBV, HCV) 
•
Determination of estimated creatinine clearance
•
Pulmonary function testing, CT of the chest (BOS sequence), cardiac ECHO, ECG
•
Social work screening consult   
For baseline evaluations, please see Section 2.6. 
2.4
REGISTRATION PROCEDURES
Authorized staff must register an eligible candidate with NCI Central Registration Office (CRO) 
within 24 hours of signing consent.  A registration Eligibility Checklist from the web site 
(http://home.ccr.cancer.gov/intra/eligibility/welcome.htm) must be completed and sent via 
encrypted email to:  NCI Central Registration Office (HOIS) <ncicentralregistration-
l@mail.nih.gov.  After confirmation of eligibility at Central Registration Office, CRO staff will 
call pharmacy to advise them of the acceptance of the patient on the protocol prior to the release 
of any investigational agents.  Verification of Registration will be forwarded electronically via e-
mail to the research team. A recorder is available during non-working hours. 
2.5
TREATMENT ASSIGNMENT AND RANDOMIZATION PROCEDURES
Cohorts
Number
Name
Description
1
cGvHD Patients
Patients with moderate or severe cGvHD as per NIH criteria that 
has not responded to high-dose corticosteroids or second-line 
therapy.
Arms
Number
Name
Description
1
Experimental 1
0.5 mg/day without Dose Escalation
2
Experimental 2
0.5 mg/day with Dose Escalation by 0.5 mg/day increments every 2 
weeks to a maximum of 2.0 mg/day
Randomization and Arm Assignment
Randomization will be done at the time of enrollment by the Central Registration Office, which 
will perform the randomization using randomization assignments determined by the study 
statistician. Subjects will be randomized to one of two treatment arms: low dose (0.5 mg/d) and 
high dose (0.5, escalating every two weeks to 1.0. 1.5 or 2.0 mg/d) pomalidomide. If one of the 
arms closes due to futility, toxicity or completion, enrollment  will continue to the remaining arm.


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26
2.6
BASELINE EVALUATION
Following studies will be performed at the baseline before/after the enrollment and within four 
weeks prior to starting taking the study drug unless otherwise indicated below:
•
History and physical exam, Karnofsky performance score
•
CBC, platelets, differential, PT/PTT, serum chemistries (including sodium, potassium, 
chloride, CO2, calcium, magnesium, phosphorus, blood urea nitrogen [BUN], creatinine, 
glucose, albumin, total protein, alkaline phosphatase, total bilirubin, AST [SGOT], ALT 
[SGPT], lactate dehydrogenase [LDH], and uric acid), CRP, total complement and C3 and 
C4, urine pregnancy testing (once within 10-14 days prior to the start of study drug and 
again within 24 hours prior to the start of study drug), immunoglobulin levels, TBNK, 
blood CMV PCR, drug levels if pertinent (e.g., cyclosporine, tacrolimus, sirolimus) 
•
MRI of the involved extremity if clinically indicated (acceptable if done within 8 weeks)    
•
Documentation of cGvHD per NIH criteria (diagnostic, distinct, other and common 
manifestations), NIH organ and global stage, baseline assessments (form A and form B) 
per NIH response criteria, date of cGvHD diagnosis, prior and current treatments, 
prednisone or other steroids oral dose, and other patient, donor and transplant 
characteristics per Appendix Q. 
•
Specialty evaluations of cGvHD: dermatology, ophthalmology, dental, rehabilitation and 
occupational therapy, gynecology if applicable (can be done up to two weeks after starting 
study drug, except for dermatology and dental evaluations which must be done prior to 
starting study drug)
•
Diagnostic and research biopsies of the skin and mouth (all persons), and other organs 
(only if clinically indicated) 
•
ECG
•
Research laboratory (blood, saliva, urine)
•
Study drug dispensation
•
Subject diary review  
•
Documentation of concurrent medications
3
STUDY IMPLEMENTATION
3.1
STUDY DESIGN
The study is a randomized phase 2 trial with the single stage selection design. It is known from 
prior trials that the maximum tolerated dose of pomalidomide is about 3 mg/d in persons with bone 
marrow disorders receiving prior therapies for cancer, in cGvHD doses <3mg/d have been well 
tolerated. This study will explore clinical toxicity of gradual escalation of pomalidomide doses <3 
mg/d in subjects with cGvHD. Patients will receive either a constant low dose of pomalidomide 
(0.5 mg/day) for six months or a strategy of increasing dose of pomalidomide from 0.5 mg/d up 
through each individual patients’ maximum tolerated dose, with escalations by 0.5 mg/d every 2 
weeks to a maximum of 2.0 mg/d. In each of the two arms, the trial will use a single stage design. 


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27
As an early stopping rule for futility as outlined in section 8, if after 7 patients have enrolled on 
either arm, 0 have responded, then no further patients will be accrued to that arm as soon as this 
can be determined. To protect patient safety, an early stopping rule will be implemented. With two 
arms, each of which has a maximal accrual of 16 patients, up to 32 evaluable patients will be 
randomized. Safety assessments and pregnancy testing for FCBP will be performed at scheduled 
intervals as described in the Study Calendar. 
Response will be assessed every 3 months while taking pomalidomide following the criteria in 
Section 6.2. The primary efficacy endpoint will be evaluated at 6 months. Efficacy outcome is 
defined as clinical response (CR or PR) in subjects who enter the study with stable cGvHD or 
stable disease for ≥3 mo for subjects with progressive cGvHD at study-entry. (Stability will be 
assessed by the clinician and by the clinical exam at the screening evaluation based on the clinician 
estimate of the disease trajectory during the 3 months pre-randomization). Subjects who meet the 
response criteria at 6 months will continue therapy for another 6 months. If in the subject’s best 
interest, efforts will be made to provide access to study drug on compassionate basis beyond the 
12-month study endpoint. 
Patients who discontinue therapy for any reason will be followed for up to 24 months after starting 
pomalidomide as described in Section 6.1.3. 
Concurrent topical and ancillary treatments for cGvHD are allowed per standards of care and will 
be recorded (see Section 4).27 Other systemic immune suppression must stay stable or be tapered 
(systemic immunosuppression taper should be attempted no earlier than after 4-6 weeks on study), 
throughout the treatment with pomalidomide (with up to 2 steroid pulses allowed for disease 
stabilization per Section 4.1). 
Study Schema
Screening 
(Days 
-28 to -1)
Randomization
16 evaluable 
pts/arm 
Response evaluations every 3 months during 
treatment (primary endpoint at 6  months)
0.5 mg/d
2.0 mg/d
Dose escalation in 
0.5 mg/d increments 
every 2 weeks
0.5 mg/d
No dose escalation
No further dose escalation
3.1.1
Dose-Limiting Toxicity
DLT will be defined as any grade ≥3 adverse event which is thought to be probably or 
definitively related to the investigational drug administration (notable exceptions where grades 2 
or lower can be considered as DLTs are indicated in Table 4 below in Section 3.3). In addition, 
any persons who are unable to tolerate the dose to which they are assigned will be counted as a 
DLT at the maximum dose explored for that patient. The time frame for evaluation in which 
toxicity will count towards a DLT will be up to 28 days after therapy received at a given dose 


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level. In addition, a grade ≥ 3 AE will not be considered as DLT if the adverse event is attributed 
to a GVHD flare and responds to steroid pulse therapy as outlined in section 4.1. Whether treated 
on either arm, if there are 2 patients in the first 6 who experience a DLT from a given dose level, 
then no further patients will be treated at that dose level on the trial, regardless of arm. 
Furthermore, when more than 6 patients have received a given dose level, if at any time 33% or 
more patients experience a DLT when treated at that dose level, then no further patients will be 
treated at that dose level. Data from all subjects who receive >1 dose of pomalidomide will be 
include in the safety analysis.
3.1.2
Dose Escalation
All subjects, independently of the randomization arm, will start pomalidomide at 0.5 mg/d.  Those 
randomized to the high-dose arm will escalate to the target dose level by increasing the 
pomalidomide dose in 0.5 mg increments (Table 3) every 2 weeks to the next level. If the 
escalation is not tolerated, the patient will be treated on the next lower dose level. MTD designation 
will be given to the highest dose in which no more than 1 DLT occurred per cohort. 
Table 3. Pomalidomide Dose Escalation Steps (high-dose arm)
Dose Level
Dose
Starting Dose (level 1)
0.5 mg daily on Days 1-14
Dose Level 2
1.0 mg daily on Days 15-28
Dose Level 3
1.5 mg daily on Days 29-42
Dose Level 4
2.0 mg daily on Days 43-56
3.2
DRUG ADMINISTRATION
Pomalidomide will be given as 0.5 mg, 1.0 mg, or 2.0 mg capsules to be taken orally once a day 
on days 1–28 of a 28-day cycle. Each daily dose of pomalidomide should be taken at approximately 
the same time of day. Patients will be asked to complete a medication diary (Appendix P).
Pomalidomide capsules should be swallowed whole, and should not be broken, chewed or opened.   
If a dose of pomalidomide is missed, it should be taken as soon as possible on the same day. If it 
is missed for the entire day, it should not be made up.
Patients who take more than the prescribed dose of pomalidomide should be instructed to seek 
emergency medical care if needed and contact study staff immediately.  
Patients are instructed to fast (water or clear fluids only) for at least 2 hours prior to taking a dose 
to at least 1 hour post dosing.  Pomalidomide should not be swallowed concurrently with other 
allowed medications while on-study.
3.2.1
Drug Dispensing
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 


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29
this trial, must be registered in and must comply with all requirements of the POMALYST 
REMS™ program.  
Drug will be shipped on a per patient basis by the contract pharmacy to the NIH pharmacy for 
IND studies.  Only enough pomalidomide for one cycle of therapy will be supplied to the patient 
each cycle.  This is in accordance with the POMALYST REMS™ program.
Only enough pomalidomide capsules for 1 cycle of therapy may be provided to the patient 
each cycle. 
Patients will be asked to maintain a dairy and bring to the next appointment all remaining capsules. 
3.3
DOSE MODIFICATIONS
Patients requiring dose reduction will be reassigned to one of the lower dose cohorts being 
evaluated: 0.5, 1.0 or 1.5 mg. Patients may be dose reduced to the lowest possible dose, i.e. 0.5 
mg. For any dose reductions or if study drug needs to be held greater than 35 days, the Principal 
Investigator (PI) or Lead Associate Investigator (LAI) must be contacted. Once a dose has been 
reduced, it cannot be re-escalated. At the discretion of the PI, the use of granulocyte colony-
stimulating factor (G-CSF) will be permitted to manage neutropenic fever or a Grade 4 
neutropenia. Given the potentially long treatments delays, patients must have received 75% of 
the doses prescribed to be considered evaluable for the primary study endpoint. 
Table 4. Dose Modifications
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
Blood/Bone Marrow
Neutropenia (ANC) - Grade 3 with 
fever or Grade 4
Hold study drug until < Grade 2; 
Decrease dose by 1 dose level
Blood/Bone Marrow
Thrombocytopenia - Grade 3 or 4
Hold study drug until <Grade 2; 
Decrease dose by 1 dose level
Blood/Bone Marrow
Anemia - Grade 3 or 4
Hold study drug and treat anemia 
as needed until Hgb within 0.5 
g/dL of lower limit of normal; 
Decrease dose by 1 dose level


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30
Common 
Terminology 
Criteria (CTCAE) 
Version 4.0
Adverse Event
Dose Change for Pomalidomide
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
Prolonged QTs 
Interval
Grade 3 (>0.50 second)
Hold study drug; decrease dose by 
1 dose level and restart when 
resolved to < Grade 2
Prolonged QTs 
Interval
Grade 
4 
(>0.50 
second, 
life 
threatening symptoms)
Discontinue study drug  
Vascular
Thrombosis/embolism - Grade 2, 3 
or 4
Discontinue study drug 
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 
Rash / desquamation - Grade 2
Discontinue study drug 
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


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Common 
Terminology 
Criteria (CTCAE) 
Version 4.0
Adverse Event
Dose Change for Pomalidomide
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
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; Decrease dose by 1 
dose level
Neurology
Neuropathy cranial/motor/ sensory - 
Grade 4
Discontinue study drug
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
3.4
QUESTIONNAIRES
Patient self-report questionnaires administered in this study are part of the standard NIH chronic 
consensus recommended criteria for the evaluation of cGvHD in clinical trials.29 These 
standardized assessments are designed to evaluate patient quality of life (SF-36, FACT-BMT), 
functional performance (HAP) and symptoms (Lee symptom scale, symptom intensity scale). The 
purpose of these evaluations is to assess the potential benefit of the administered therapy as 
compared to the baseline. These forms have been extensively used, published and validated. These 
forms are also standard part of many NCI CCR cGvHD protocols (Appendix G). In a recent study 
median time for persons to complete these forms was 15 minutes (range 8-22 minutes).73  


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                                                                                                                               32
3.5
STUDY CALENDAR
BL
3 
mos
6 
mos
9 
mos
Assessments
Screening 
BL/  
C1 
D1
C1 
D15 
(+/-2 
days)
C2 
D1 
(+/-2 
days)
C2 
D15 
(+/-2 
days)
C3 
D1 
(+/-2 
days)
C3 
D15 
(+/-2 
days)
C4 
D1 
(+/-3 
days)
C5,6 
D1 
(+/-2 
days)
C7 
D1 
(+/-3 
days)
C8,9 
D1 
(+/-2 
days)
C10 
D1 
(+/-3 
days)
C11,
12 
D1 
(+/-2 
days)
C12
D28 
(+/-3 
days)
Informed Consent
X
Randomization
X
Pomalidomide po qd2
X
X
X
X
X
X
X
X
X2
X2
X2
X2
X2
History and Physical 
Exam 
X
X
X
X
X
X
X
X
X
X
X
X
X
Confirmation of 
cGvHD3
X
Body Photography 
X
X
cGVHD 3 Month 
Trajectory (stable vs. 
progressive) 
X
Pulmonary Function 
Testing
X
X
X
X
X
Diagnostic Imaging4
X
X
X
X
Pregnancy Test5
X
X
X
X
X
X
X
X
X
X
X
POMALYST REMS™ 
program 6
X
X
X
X
X
X
X
X
X
X
X 
cGvHD Therapies 
Recording
X
Throughout the study


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BL
3 
mos
6 
mos
9 
mos
Assessments
Screening 
BL/  
C1 
D1
C1 
D15 
(+/-2 
days)
C2 
D1 
(+/-2 
days)
C2 
D15 
(+/-2 
days)
C3 
D1 
(+/-2 
days)
C3 
D15 
(+/-2 
days)
C4 
D1 
(+/-3 
days)
C5,6 
D1 
(+/-2 
days)
C7 
D1 
(+/-3 
days)
C8,9 
D1 
(+/-2 
days)
C10 
D1 
(+/-3 
days)
C11,
12 
D1 
(+/-2 
days)
C12
D28 
(+/-3 
days)
Vital Signs
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Height
X
Weight
X
X
X
X
X
X
X
X
X
X
X
X
X
X
ECHO
X
ECG7
X
X
X
X
X
X
Gynecological Exam
X14
X
Karnofsky Performance 
Status
X
X
X
X
CBC w/ differential, 
platelets8
X
X
X
X
X
X
X
X
X
X
X
X 
X 
Serum Chemistry8
X
X
X
X
X
X
X
X
X
X
X
X 
X 
CRP, total complement, 
C3, C4
X
X
X
X
X
X
X
Urinalysis
X
X
X
X
TSH, free T4
X
X
X
X
cGvHD Assessment and 
Response Calculation9
X
X
X
X
AE Monitoring
Throughout the study
Concurrent Drugs
X
Throughout the study


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BL
3 
mos
6 
mos
9 
mos
Assessments
Screening 
BL/  
C1 
D1
C1 
D15 
(+/-2 
days)
C2 
D1 
(+/-2 
days)
C2 
D15 
(+/-2 
days)
C3 
D1 
(+/-2 
days)
C3 
D15 
(+/-2 
days)
C4 
D1 
(+/-3 
days)
C5,6 
D1 
(+/-2 
days)
C7 
D1 
(+/-3 
days)
C8,9 
D1 
(+/-2 
days)
C10 
D1 
(+/-3 
days)
C11,
12 
D1 
(+/-2 
days)
C12
D28 
(+/-3 
days)
Skin and Oral Biopsies, 
saliva collection10
X
X
TBNK
X
X
X
X
X
X
X
X
X
X
X
X
X
Blood and urine for 
Immunologic Studies11
X
X
X
X
X
Blood for PK Studies12
X
X
X
X
X
X
X
X
X
Study drug 
dispensation/ 
return/accountability
X
X
X
X
X
X
X
X
X
X
X
X
Rehabilitation medicine
X14
X
Occupational therapy 
Consults
X14
X
X
X
Dermatology
X
X
Ophthalmology
X14
X
Schirmer’s without 
anesthesia 
X
X
X
X
NIH Advanced 
Directives form15
X
1 Clinic visits can occur ± 3 days. All procedures at protocol-driven time points are performed at the NIH Clinical Center, but if 
circumstances make this impossible, these data points will be collected in collaboration with referring physicians.   


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2 Pomalidomide at assigned doses for 6 months; another 6-month course of treatment will be allowed for patients with response 
(see Section 3.1.1). Only patients who continue therapy beyond 6 months will be required to have clinical monitoring tests 
during cycles 7 through 12.
3 Use NIH diagnostic criteria for cGvHD  (Appendix C). In addition, use Appendix D for clinical differentiation of acute versus 
cGvHD.
4 MRI if indicated and chest CT at baseline and if indicated, at response assessments.
5 Pregnancy tests for females of childbearing potential must follow pregnancy testing requirements as outlined in the POMALYST 
REMS™ program. A female of childbearing potential (FCBP) is a sexually mature female who: 1) has not undergone a 
hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has 
had menses at any time in the preceding 24 consecutive months).
Pregnancy tests must occur 10–14 days 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 
M).   
6 All patients must be counseled about pregnancy precautions, risks of fetal exposure and other risks through the POMALYST 
REMS™ program.  The counseling must be done on at a minimum of every 28 days and at drug discontinuation. See Appendix 
M.
7 ECG at indicated intervals baseline, at C2D1, C3D1, C4D1, C7D1 and as clinically indicated. Prolongation of QTc > 0.5 s or 
QTc interval increases from baseline > 0.06 s is considered as a safety concern.
8 CBC with differential and platelets, serum chemistries (including sodium, potassium, chloride, CO2, calcium, magnesium, 
phosphorus, blood urea nitrogen [BUN], creatinine, glucose, albumin, total protein, alkaline phosphatase, total bilirubin, AST 
[SGOT], ALT [SGPT], lactate dehydrogenase [LDH], and uric acid) at least every other week the first 3 months, then monthly 
until 9 months,then on day 28 of cycle 12. Platelets should be repeated when clinically indicated (e.g., suspected 
thromboembolic events).
9 Includes primary and secondary measurement of response, performance scale, global rating, and Lee Symptom Scale (Appendix 
G through Appendix K).
10Skin and oral biopsies and saliva collection will be performed before treatment and after 6 months of pomalidomide, with intent 
to sample as close to the same area as possible (Section 5.1.1)


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11Blood for Immunologic studies will be collected (Section 5.1.2). A larger 100ml blood (12 R&G CPT) plus a 3ml theophylline 
citrate blood (for TGFb) will be collected only at baseline, at 3 months (beginning of cycle 4) and the 6 months evaluation (at the 
end of cycle 6)
12For determining serum pomalidomide levels, a 3-mL blood sample will be collected 2 hours (± 15 minutes) after initial oral 
administration and repeated every 2 weeks (20-24 hours after the last oral dose and 2 hours after the dose) until the 3-month 
evaluation, point then monthly until the 6-month evaluation (Section 5.1.3). Pre- dosing PK can be done 18-30 hours post last 
dose of pomalidomide.
13Patients who discontinue study drug for any reason will be followed for survival and cGvHD course and therapy for up to 2 
years from the start of study drug (see Section 6.1.3).
14Can be done up to two weeks after starting study drug
15As indicated in section 10.3, all subjects will be offered the opportunity to complete an NIH advanced directives form.  This 
should be done preferably at baseline but can be done at any time during the study as long as the capacity to do so is retained.  
The completion of the form is strongly recommended, but is not required.
Patients may undergo additional subspecialty evaluations by Gynecology, Dermatology, Opthalmology, Dentistry, Physical Medicine 
and Rehabilitation and Occupational Medicine at any additional time points as indicated clinically or during the off study visit per 
investigator discretion.


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3.6
CRITERIA FOR REMOVAL FROM PROTOCOL THERAPY AND OFF STUDY CRITERIA
Prior to removal from study, effort must be made to have all subjects complete a safety visit 
approximately 30 days following the last dose of study therapy.
3.6.1
Criteria for removal from protocol therapy
•
Completion of 6- or 12-month course of protocol therapy (depending on the level of 
response)
•
Progressive cGvHD or malignancy requiring new line of systemic therapy
•
Participant requests to be withdrawn from active therapy
•
Unacceptable toxicity as defined in Section 3.3
•
Dose interruption longer than 35 days
•
Positive pregnancy test
•
Investigator discretion
The PI is to be notified of all discontinuations from study drug. The reason for dose 
modification/discontinuation should be recorded in the CRF and in the patient’s medical records.
3.6.2
Off-Study Criteria
•
Completed 2-year follow-up period
•
Subject withdrawal from follow-up period
•
Patient lost for follow-up
•
Death
•
PI decision to end this study 
3.6.3
Off Protocol Therapy and OffStudy Procedure
Authorized staff must notify Central Registration Office (CRO) when a subject is taken off- 
protocol therapy and when a subject is taken off study. A Participant Status Update Form from 
the web site (http://home.ccr.cancer.gov/intra/eligibility/welcome.htm) main page must be 
completed and sent via encrypted email to:  NCI Central Registration Office (HOIS) 
ncicentralregistration-l@mail.nih.gov .
4
CONCOMITANT MEDICATIONS/MEASURES
All medications (prescription and non-prescription), treatments and therapies taken throughout the 
study must be recorded on the appropriate page of the CRF. Patients will be advised to contact the 
study team before starting any new medications.
4.1
CONCOMITANT CORTICOSTEROID THERAPY AND TAPERING GUIDELINE
During the study, persons may remain on corticosteroids with intent to taper it. A steroid taper 
will be allowed to begin earliest at 4-6 weeks after starting on protocol, with a 10% (of starting 


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38
dose) decrease per week. The study allows maximum two total pulses of steroids with 
subsequent rapid taper, one at the beginning of pomalidomide therapy in case of GvHD flares 
associated with the study drug initiation and/or another one later for any flares or worsening of 
cGvHD symptoms during steroid or other immunosuppression taper. Typical corticosteroid pulse 
is defined as up to 2 mg/kg/day prednisone or equivalent tapered to the pre-pulse baseline within 
3 weeks. Steroid pulses require the PI’s approval. If the patient has a GVHD flare and no other 
reasons to hold the drug for an AE the patient would continue pomalidomide administration 
concomitantly with steroid pulse. Administration steroid pulses will be carefully recorded in the 
protocol case report forms. 
4.2
OTHER TREATMENTS FOR CGVHD
Patients who are taking concomitant systemic agents for control of cGvHD, such as calcineurin 
inhibitors (e.g., tacrolimus or cyclosporine) or other immunosuppressants (e.g., mycophenolate 
or sirolimus) must be on a stable dose in the preceding 4 weeks with an intent to stop if possible 
after corticosteroids are at stable or supplementation doses (maximum 7.5 mg prednisone/day) or 
discontinued. Patient should not receive any investigational drugs or initiate any systemic 
therapy for cGvHD once started on pomalidomide. Patient should not be undergoing 
extracorporeal photopheresis (ECP) concomitantly with study drug, and if they had ECP in the 
past, a minimum of 4 weeks should have passed since its discontinuation.
4.3
VENOUS THROMBOEMBOLISM PROPHYLAXIS
Pomalidomide may increase the risk of thrombotic events in persons who are at high risk or with 
a history of thrombosis, in particular when combined with other drugs known to cause thrombosis. 
When pomalidomide is combined with other agents such as steroids (e.g., dexamethasone, 
prednisone), anthracyclines (doxorubicin) and erythropoietin, the risk of thrombosis may be 
increased. All persons if receiving study treatment in addition to any of these other agents must 
also agree to take venous thromboembolism (e.g., at minimum aspirin 325 mg/day) or some other 
form of prophylaxis as deemed appropriate by the PI, such as low molecular weight or 
unfractionated heparin.74 Patients should continue to receive anti-thrombotic therapy for the 
duration of pomalidomide therapy and 5 days after pomalidomide is discontinued.
Because of the increased risk of venous thromboembolism in patients 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.
4.4
OTHER ALLOWED CONCOMITANT THERAPY
Ancillary therapy and supportive care considered necessary for the patient’s wellbeing may be 
administered at the discretion of the PI and will follow the NIH Blood and Marrow Transplant 
Consortium 
guidelines 
for 
supportive 
care: 
http://intranet.cc.nih.gov/bmt/clinicalcare/guidelines.shtml. Any ancillary or supportive care 
which may have some effect on efficacy analysis will be carefully recorded in the CRF. Patients 
are allowed to take topical steroids at a maximum of 1% hydrocortisone concentration potency 
equivalence.


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4.5
PROHIBITED CONCOMITANT THERAPY
Radiation therapy, cancer chemotherapy, biologic or immunotherapy is prohibited during 
participation in this study. Concomitant use of other investigational agents is not permitted while 
persons are receiving study drug. 
5
BIOSPECIMEN COLLECTION
5.1
CORRELATIVE STUDIES FOR RESEARCH
Note:  All samples will be sent for storage until analysis as detailed in Section 5.2 under 
appropriate storage conditions. 
5.1.1
Skin Biopsy and Oral Biopsy 
Skin and oral research biopsies will be performed before treatment and after 6 months of 
pomalidomide treatment (with intent to sample as close to the same area as possible) for 
assessment of sclerotic or lichen-planus like disease by H&E and pathologist evaluation. 
Immunohistochemistry methods will be applied to look for myofibroblast markers and pSMAD in 
the sclerotic skin, for T-cell infiltrates, and IFN-induced factors in the oral mucosa and 
erythematous skin. The advantage of histology is the greater amount of information on cell 
populations and functional changes in situ of the disease. These biopsies will be obtained by one 
of the study investigators and processed, stored and analyzed. A biopsy sample will be also sent 
to the NCI pathology laboratory. Patients will have an option to decline such research biopsy and 
this will not be considered as protocol deviation. Biopsy samples collected on the 04-C-0281 
cGvHD natural history study can be also used for these studies if obtained in the timeframe as part 
of the screening evaluations for this study.        
5.1.2
Immunologic Analyses Using Plasma and PBMCs
1. Blood: Blood will be collected, and PBMC and plasma will be cryopreserved for later batch 
analyses of markers relevant to cGvHD activity. Plasma will be collected with 
theophylline-citrate anticoagulant (to prevent platelet breakdown) for assessment of TGFb 
and PDGF, which may be relevant to fibrosis.  Heparinized plasma will be assayed for 
markers of cGvHD activity (including but not limited to BAFF, and IFN-induced 
chemokines). PBMC will be cryopreserved for subsequent flow cytometry of cell 
populations and sorting of monocytes for transcriptional analysis of genes upregulated in 
active cGvHD. The primary collection of blood for these analyses of pomalidomide effect 
on cGvHD will be at baseline and at 3 and 6 month evaluation time point. At these three 
timepoints one theophylline citrate plasma tube (for TGFb) and 12 red and green topped 
heparin CPT tubes (total of 100 cc) will be collected; a final collection will be done on 
patients continuing treatment until 12 months.
2. Plasma will be assayed for BAFF, IFN-induced chemokines and MCP-1. Separate 
collection of theophylline-citrate blood (different anticoagulant to prevent platelet 
breakdown) will be performed for assessment of TGFb and PDGF. 
3. Monocyte transcriptome: Monocytes will be sorted from PBMC for Nanostring evaluation 
of the monocyte transcriptome. This would be done on cryopreserved cells at the end of 
the study. Monocytes circulate throughout the body, are responsive to a variety of cytokines 


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in tissues affected by cGvHD and maybe therefore serve as a reporter for changes in 
cGvHD-affected tissues.
4. Lymphocyte populations. Changes in circulating populations of lymphocytes will be 
assessed by flow cytometry on whole blood to determine changes in CD3, CD4, CD8, B 
and NK populations. At baseline, at the start of each cycle up to the 3 month time point 
and at 6 and 12 months, one 3ml lavender (EDTA) tube will be drawn and 
lymphophenotyping will be performed using Clinical center’s CLIA certified 
Immunophenotyping panel and reported in the CRIS. Further research assessments of the 
percentages of regulatory T cells, of naïve, memory and effector T cells and of B cell 
transitional, naïve and memory populations will be done in the ETIB Preclinical Core (Fran 
Hakim) on the baseline and at 3 month evaluation time points until 12 months post 
enrollment. Active cGvHD has been associated with decreases in Treg populations, 
reduced thymopoiesis (fewer naïve T cells) and increases in CD21- transitional B cell 
populations. Urine will be collected at 3 month intervals for assessment of biomarkers in 
urine as compared with blood.
The assays indicated are designed to assess the alterations in skin, oral mucosa and in circulating 
lymphocytes and plasma that may result from pomalidomide. If there is a decline in TGFb 
production or response, then this may be evident in TGFb levels in the plasma and in degree of 
fibrosis (by pathologist evaluation) and extent of pSMAD2/3 in sclerotic skin. If there is an 
increase in Th1 cells or a shift in Treg populations, this may be reflected in circulating T cell 
populations, plasma cytokines and tissue infiltrates. 
5.1.3
Measurement of Pomalidomide Serum Levels  
The objective of measuring pomalidomide serum levels is for the documentation of systemic 
absorption. A 6-mL blood sample will be collected 2 hours (+/- 20 minutes, exact time elapsed 
post-dosing will be recorded on PK sheets) after initial oral administration and repeated peak and 
trough every 2 weeks (20-28 hours after the last oral dose and 2 hours post-dose) until the 3-month 
evaluation, then monthly until the 6-month evaluation. Pre- dosing PK can be done 18-30 hours 
post last dose of pomalidomide. Actual dosing dates and times will be recorded. Detailed 
instruction for sample collection, processing, storage, and handling can be found in Appendix B. 
These sample collections will occur at the protocol scheduled evaluation visits at the NIH Clinical 
Center. 
The determination of pomalidomide concentrations in plasma samples, as well as the 
pharmacokinetic data analysis, will be performed by the Clinical Pharmacology Program. Samples 
will be analyzed using a validated LC-MS/MS method. 
5.2
SAMPLE STORAGE, TRACKING AND DISPOSITION
Samples will be ordered in CRIS and tracked through a Clinical Trial Data Management system. 
Should a CRIS screen not be available, the CRIS downtime procedures will be followed. 
Samples will not be sent outside NIH without appropriate approvals and/or agreements, if 
required. 


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41
5.2.1
Sample Procedures
Blood and tissue samples, collected for the purpose of research under IRB-approved protocols of 
the Experimental Transplantation and Immunology Branch (ETIB)/Immune Deficiency Cellular 
Therapy Program (IDCTP) will be stored and may be archived by the Biospecimen Processing 
Core (BPC), with the exception of blood samples for pomalidomide analysis, which will be 
stored separately by the Clinical Pharmacology Program (CPP) until analysis. These will be 
barcoded, with data entered and stored in the Labmatrix utilized by the BPC. This is a secure 
program, with access to Labmatrix limited to defined Figg lab personnel, who are issued 
individual user accounts. Installation of Labmatrix is limited to computers specified by Dr. Figg. 
These computers all have a password restricted login screen. 
Labmatrix creates a unique barcode ID for every sample and sample box, which cannot be traced 
back to patients without Labmatrix access. The data recorded for each sample includes the 
patient ID, name, trial name/protocol number, time drawn, cycle time point, dose, material type, 
as well as box and freezer location. Patient demographics associated with the clinical center 
patient number are provided in the system. For each sample, there are notes associated with the 
processing method (delay in sample processing, storage conditions on the ward, etc.).
Barcoded samples are stored in locked freezers at -20 or -80°C (sera and plasma) or under liquid 
nitrogen (cells), or as otherwise applicable according to stability requirements. These freezers are 
located onsite in the BPC and offsite at NCI Frederick Central Repository Services in Frederick, 
MD. Visitors to the laboratory are required to be accompanied by laboratory staff at all times. 
Access to stored clinical samples is restricted. Samples will be stored until requested by a 
researcher named on the protocol. All requests are monitored and tracked in Labmatrix. All 
researchers are required to sign a form stating that the samples are only to be used for research 
purposes associated with this trial (as per the IRB approved protocol) and that any unused 
samples must be returned to the BPC. It is the responsibility of the NCI Principal Investigator to 
ensure that the samples requested are being used in a manner consistent with IRB approval.
5.2.1.1
Protocol Completion/Sample Destruction 
Following completion of this study, samples will remain in storage as detailed above. Access to 
these samples will only be granted following IRB approval of an additional protocol, granting 
the rights to use the material. 
If, at any time, a patient withdraws from the study and does not wish for their existing samples to 
be utilized, the individual must provide a written request. Following receipt of this request, the 
samples will be destroyed or returned to the participant, if so requested. The PI will record any 
loss or unanticipated destruction of samples as a deviation. Reporting will be per the 
requirements of section 7.27.2.
6
DATA COLLECTION AND EVALUATION 
6.1
DATA COLLECTION
The PI will be responsible for overseeing entry of data into a 21 CFR Part 11-compliant data 
capture system provided by the NCI CCR and ensuring data accuracy, consistency and 
timeliness. The principal investigator, associate investigators/research nurses and/or a contracted 


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42
data manager will assist with the data management efforts. Primary and final analyzed data will 
have identifiers so that research data can be attributed to an individual human subject participant.
All adverse events, including clinically significant abnormal findings on laboratory evaluations, 
regardless of severity, will be followed until return to baseline or stabilization of event. Patients 
will be followed for adverse events for a minimum of 30 days after the last administration of 
investigational agent/intervention and have an attribution of at least possibly related to the 
agent/intervention should be recorded and reported as per sections 7.2, 7.3 and 7.4 or until 
removal from study treatment, whichever comes first.
An abnormal laboratory value will be considered an AE if the laboratory abnormality is 
characterized by any of the following:
•
Results in discontinuation from the study
•
Is associated with clinical signs or symptoms 
•
Requires treatment or any other therapeutic intervention
•
Is associated with death or another serious adverse event, including hospitalization. 
•
Is judged by the Investigator to be of significant clinical impact
•
If any abnormal laboratory result is considered clinically significant, the investigator will 
provide details about the action taken with respect to the test drug and about the patient’s 
outcome.
End of study procedures: Data will be stored according to HHS, FDA regulations, and NIH 
Intramural Records Retention Schedule as applicable. 
Loss or destruction of data: Should we become aware that a major breech in our plan to protect 
subject confidentiality and trial data has occurred, the IRB will be notified. 
6.1.1
Eligibility Checklist
The eligibility checklist is to be completed at study entry and forwarded to protocol research nurse 
who will forward the checklist to the Central Registration Office. 
6.1.2
Protocol Deviations and Non-Compliance
Any protocol non-compliance or deviations should be directly reported to the PI and to the NIH 
IRB per Section 7.2.  
6.1.3
Follow-up
All persons will be followed for SAEs for 30 days after last dose of pomalidomide. Patients who 
discontinue therapy for any reason will be invited for a follow up visit at 3 months after last dose, 
then followed up by a phone call to the patient and/or the primary physician’s office at 12 and 24 
months after starting the first dose of pomalidomide. The phone call will focus on a) survival status 
and cause of death if pertinent, b) ongoing systemic treatment for cGvHD and date of 
discontinuation, c) primary malignancy progression, d) any second primary malignancy, e) return 
to work part-time or full-time. Primary and contributing causes of death are to be recorded in the 
CRF and the patient’s medical record.


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6.2
RESPONSE CRITERIA
6.2.1
Definitions
Evaluable for efficacy: Patients who complete 6 months of therapy will be evaluable for the 
secondary endpoint of efficacy assessment. Patients who progress earlier will be also included in 
the analysis of efficacy.   
6.2.2
Efficacy Analysis
The primary evaluation point is overall response at 6 months using the NIH cGvHD response 
criteria measures.29 The overall response score will be assessed as CR, PR, SD or PD as per NIH 
guidelines. The organ-specific and other subcomponents of the overall response score will be 
analyzed individually and absolute values recorded.
Up to 2 corticosteroid pulses will be allowed, one for initial flares and one for late flares as 
described in Section 4.1.  
Response will be assessed every 3 months from the start of pomalidomide. To ensure 
comparability, baseline and on-study methods for response assessment will be performed using 
identical grading, scale or techniques. The Chronic GVHD Assessment (Clinician) Form will be 
completed at each 3-month evaluation visit [Appendix G]. Included in that form are both organ-
specific primary measurements and clinician-assessed secondary measurements. The response of 
each affected organ will be evaluated and an overall response (CR, PR, stable disease) will be 
determined. 
6.2.2.1
Response Criteria
Efficacy will be assessed using NIH consensus criteria measuring for therapeutic response in 
clinical trials for cGvHD29:
•
CR is defined as complete resolution in all of signs and symptoms at all affected organs 
or tissues. 
•
PR is defined as improvement in  1 organ or tissue with no progression in any other 
affected organ or tissue. The calculations for PR and progressive disease (PD) are 
provided in Appendix H and Appendix I. 
•
Response < PR is defined as change towards improvement from the pre-treatment 
baseline but not meeting the criteria for CR or PR. 
•
Stable Disease is defined as no change in cGvHD, SD will be considered as response 
in patients with documented cGvHD progression over preceding 3 months. 
•
Flare is defined as exacerbation of cGvHD manifestations during withdrawal of 
immunosuppressive therapy which do not exceed those at the beginning of the trial and 
improves after reinstatement of previous treatment.
•
Progressive disease is defined as failure of therapy to control cGvHD. The calculations 
for progressive disease (PD) are provided in Appendix I. Assessment by Organ-
Specific Criteria. Patients who progress prior to 6 months evaluation will be also 
evaluable for the primary efficacy endpoint. 
•
Mixed response (improvement in some organs but worsening in others) will be 
categorized as progressive disease. 


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As outlined in Section 3.5, type of involved organ, location and its measurements will be 
recorded at scheduled evaluations and reported on the appropriate CRF, equal to “Chronic 
GVHD Assessment (Clinician) Form,” (Appendix G). All other measurements not being 
included in primary assessment but clinically related to cGvHD (e.g., change of pigmentation) 
will be reported in the source documents. 
Skin and skin appendages:  Skin assessments include 4 anatomic level of skin involvement: 
(1) erythematous rash (epidermal), 
(2) movable sclerosis (dermal), 
(3) non-moveable sclerosis, hidebound skin, or involvement of subcutaneous tissue and 
fascia (subcutaneous) and 
(4) ulceration (full thickness loss of epidermal tissue). 
The first 3 measurements should be taken separately and recorded in metric notation using a body 
surface area (BSA). A cutaneous assessment worksheet for recording the BSA is provided 
(Appendix J). The size of ulcer should be measured the longest diameter (LD) of the largest ulcer. 
Eyes:  The primary measurement of lacrimal gland function in cGvHD is using the Schirmer’s 
test. The test should be performed without anesthesia for both eyes (OU) unless physically 
inapplicable. The measurement of each eye and the average of measurements will be recorded in 
the CRF.
Mouth:  Mouth assessments include: 
(1) mucosal erythema by 0-3 grading based on the color intensity, (2) lichen-type 
hyperkeratosis by 0-3 grading based on the percentage of oral surface area,(3 ulceration by 
0-6 based on percentage of oral surface area, and (4) mucoceles by 0-3 grading based on 
its total number of presence. 
Hematopoietic:  The measurements of hematopoietic response include:
(1) platelet count, 
(2) eosinophil count and percentage. 
White blood cell (WBC) count will be recorded on the Assessment Form but will not be 
used for response assessment. 
Gastrointestinal tract:  Gastrointestinal (GI) symptoms are graded through interview by the 
investigator according to 0-3 severity scales. 
Liver: Involvement of liver is graded according to the levels of bilirubin and liver enzymes (AST 
and ALT). 
Lung:  The forced expiratory volume in the first second (FEV1) and single breath diffusion lung 
capacity for carbon monoxide (DLCO) is included as components for the lung function score 
(LFS). LFS is computed by the extent of FEV1 and DLCO compromise (>80% = 1, 70 – 79% = 
2, 60 – 69% = 3, 50 – 59% = 4, 40 – 49% = 5, <40% = 6). Scores for FEV1 and DLCO are added 
and the sum reduced to an overall category according to following table (Table 5). Absolute values 
of both FEV1 and DLCO should be recorded in the CRF.
Table 5. Categories of the Lung Function Score


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Category
Lung Function
Lung Function Score
I
Normal
2
II
Mild decrease
3 – 5
III
Moderate decrease
6 – 9
IV
Severe decrease
10 – 12
Global chronic GVHD Rating:  The overall clinical impression of patient’s cGvHD will be 
recorded on a 4-point (0-3) scale on the Chronic GVHD Assessment (Clinician) Form.  
Chronic GVHD Improvement Scale:  The overall changes of patient’s cGvHD symptoms during 
previous 3 months will be recorded on a 7-point (-3 to +3) scale on the Chronic GVHD Assessment 
(Clinician) Form.
Chronic GVHD Symptom Severity Scale:  The overall severity of patient’s cGvHD symptoms 
will be recorded on an 11-point (0-10) numeric scale on the Chronic GVHD Assessment 
(Clinician) Form.
Karnofsky Performance Scale:  The Karnofsky Performance Scale will be only recorded on the 
Chronic GVHD Assessment (Clinician) Form but not used as a measure of response. 
Lee symptom scale was developed as a 30-item symptom scale with 7 subscales to capture the 
cGvHD-specific symptom burden (Appendix K). This symptom scale showed to correlate with 
persons’ self-assessed mild, moderate, and severe cGvHD manifestations in cross-sectional 
validation analysis. “Lee total score” will be calculated per Lee et al.75 Longitudinal assessments 
showed that changes in overall health status correlated best with changes in quality of life as 
measured by the SF-36 and FACT-BMT. We will not use “Lee symptom scale” as a measure of 
pomalidomide efficacy but as supplemental information on the quality of life. 
NIH organ 0-3 scoring (Appendix E) will be also collected at the evaluation endpoints.22 
Although not initially developed for response assessments, the evidence is emerging in some 
domains (skin, eyes) about potential use of this scale as a simple and valid assessment of cGvHD 
change over time.    
6.2.2.2
Summary of Response Measures
i. Primary response measures
1. Skin (BSA), erythema, moveable, non-moveable
2. Eyes (Schirmer)
3. Mouth (modified OMRS)
4. Liver (bilirubin, AST, ALT)
5. GI tract (GI response scale)


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6. Lung (FEV, DLCO, LFS)     
7. Clinician assessment scale (3-point, 7-point change, 11-point 
global)
8. ROM visual Carpenter scale (1-7 and 1-4)
9. NIH organ scoring  
ii.     Secondary assessments 
1. Platelet count, CRP, C3, C4, albumen
2. 2 and 6 minute walk time
3. Grip strength  
4. Lee symptom scale
5. HAP, SF-36, Karnofsky
6. MRI (if positive baseline)
7. Disabilities of the Arm Hand and Shoulder (DASH)
6.2.2.3
Other endpoints to be recorded at the evaluation time points: Need for secondary systemic 
therapy for GvHD, malignancy progression, discontinuation of immune suppression, 
steroid doses, other immunosuppressive drug doses, intensity of immunosuppression, 
NIH global severity (Appendix P), survival, progression-free/malignancy-free survival, 
disability-free survival.   
6.3
TOXICITY CRITERIA
The following adverse event management guidelines are intended to ensure the safety of each 
patient while on the study.  The descriptions and grading scales found in the revised NCI 
Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE 
reporting.  All appropriate treatment areas should have access to a copy of the CTCAE version 
4.0.  A copy of the CTCAE version 4.0 can be downloaded from the CTEP web site: 
(http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_40). 
7
NIH REPORTING REQUIREMENTS/DATA AND SAFETY MONITORING PLAN
7.1
DEFINITIONS
Please refer to definitions provided in Policy 801: Reporting Research Events found at: 
https://irbo.nih.gov/confluence/pages/viewpage.action?pageId=36241835#Policies&Guidance-
800Series-ComplianceandResearchEventReportingRequirements..


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7.2
OHSRP OFFICE OF COMPLIANCE AND TRAINING / IRB REPORTING
7.2.1
Expedited Reporting 
Please refer to the reporting requirements in Policy 801: Reporting Research Events and Policy 
802 Non-Compliance Human Subjects Research found at: 
https://irbo.nih.gov/confluence/pages/viewpage.action?pageId=36241835#Policies&Guidance-
800Series-ComplianceandResearchEventReportingRequirements.. Note: Only IND Safety 
Reports that meet the definition of an unanticipated problem will need to be reported per these 
policies.
7.2.2
IRB Requirements for PI Reporting at Continuing Review
Please refer to the reporting requirements in Policy 801: Reporting Research Events found at: 
https://irbo.nih.gov/confluence/pages/viewpage.action?pageId=36241835#Policies&Guidance-
800Series-ComplianceandResearchEventReportingRequirements.. 
7.3
NCI CLINICAL DIRECTOR REPORTING 
Problems expeditiously reviewed by the OHSRP in the NIH eIRB system will also be reported to 
the NCI Clinical Director/designee; therefore, a separate submission for these reports is not 
necessary.
In addition to those reports, all deaths that occur within 30 days after receiving a research 
intervention should be reported via email unless they are due to progressive disease. 
To report these deaths, please send an email describing the circumstances of the death to 
NCICCRQA@mail.nih.gov within one business day of learning of the death.
7.4
NIH REQUIRED DATA AND SAFETY MONITORING PLAN
Serious adverse events potentially attributable to the study medication or procedures will be 
reported to IRB. If trends are noted and/or risks warrant it, accrual will be interrupted and/or the 
protocol and/or consent document will be amended accordingly.
7.4.1
Principal Investigator/Research Team 
The clinical research team will meet on a regular weekly basis when participants are being 
actively treated on the trial to discuss each participant. Decisions about dose level enrollment and 
dose escalation if applicable will be made based on the toxicity data from prior participants. 
All data will be collected in a timely manner and reviewed by the principal investigator or a lead 
associate investigator. Events meeting requirements for expedited reporting as described in 
section 7.2.1 will be submitted within the appropriate timelines.  
The principal investigator will review adverse event and response data on each participant to 
ensure safety and data accuracy. The principal investigator will personally conduct or supervise 
the investigation and provide appropriate delegation of responsibilities to other members of the 
research staff. 


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8
SPONSOR PROTOCOL/SAFETY REPORTING
8.1
DEFINITIONS
8.1.1
Adverse Event 
Any untoward medical occurrence in a patient or clinical investigation subject administered a 
pharmaceutical product and which does not necessarily have a causal relationship with this 
treatment. An adverse event (AE) can therefore be any unfavorable and unintended sign 
(including an abnormal laboratory finding), symptom, or disease temporally associated with the 
use of a medicinal (investigational) product, whether or not related to the medicinal 
(investigational) product (ICH E6 (R2))
8.1.2
Serious Adverse Event (SAE)
An adverse event or suspected adverse reaction is considered serious if in the view of the 
investigator or the sponsor, it results in any of the following:
•
Death,
•
A life-threatening adverse event (see section 8.1.3)
•
Inpatient hospitalization or prolongation of existing hospitalization 
o
A hospitalization/admission that is pre-planned (i.e., elective or scheduled surgery 
arranged prior to the start of the study), a planned hospitalization for pre-existing 
condition, or a procedure required by the protocol, without a serious deterioration in 
health, is not considered a serious adverse event.
o
A hospitalization/admission that is solely driven by non-medical reasons (e.g., 
hospitalization for patient or subject convenience) is not considered a serious adverse 
event. 
o
Emergency room visits or stays in observation units that do not result in admission to 
the hospital would not be considered a serious adverse event. The reason for seeking 
medical care should be evaluated for meeting one of the other serious criteria.
•
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.
8.1.3
Life-threatening 
An adverse event or suspected adverse reaction is considered "life-threatening" if, in the view of 
either the investigator or sponsor, its occurrence places the patient or subject at immediate risk of 
death. It does not include an adverse event or suspected adverse reaction that, had it occurred in a 
more severe form, might have caused death. (21CFR312.32)


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8.1.4
Severity
The severity of each Adverse Event will be assessed utilizing the CTCAE version 4.0.
8.1.5
Relationship to Study Product
All AEs will have their relationship to study product assessed using the terms:  related or not 
related.  
•
Related – There is a reasonable possibility that the study product caused the adverse 
event. Reasonable possibility means that there is evidence to suggest a causal relationship 
between the study product and the adverse event.
•
Not Related – There is not a reasonable possibility that the administration of the study 
product caused the event.
8.2
ASSESSMENT OF SAFETY EVENTS
AE information collected will include event description, date of onset, assessment of severity 
and relationship to study product and alternate etiology (if not related to study product), date of 
resolution of the event, seriousness and outcome. The assessment of severity and relationship to 
the study product will be done only by those with the training and authority to make a diagnosis 
and listed on the Form FDA 1572 as the site principal investigator or sub-investigator.  AEs 
occurring during the collection and reporting period will be documented appropriately regardless 
of relationship.  AEs will be followed through resolution.
SAEs will be:
•
Assessed for severity and relationship to study product and alternate etiology (if not 
related to study product) by a licensed study physician listed on the Form FDA 1572 as 
the site principal investigator or sub-investigator.
•
Recorded on the appropriate SAE report form, the medical record and captured in the 
clinical database.
•
Followed through resolution by a licensed study physician listed on the Form FDA 1572 
as the site principal investigator or sub-investigator.
For timeframe of recording adverse events, please refer to section Error! Reference source not 
found.. All serious adverse events recorded from the time of first investigational product 
administration must be reported to the sponsor. 
8.3
REPORTING OF SERIOUS ADVERSE EVENTS
Any AE that meets protocol-defined serious criteria or meets the definition of Adverse Event of 
Special Interest that require expedited reporting must be submitted immediately (within 24 hours 
of awareness) to OSRO Safety using the CCR SAE report form.  
All SAE reporting must include the elements described in section 8.2.
SAE reports will be submitted to the Center for Cancer Research (CCR) at: 
OSROSafety@mail.nih.gov and to the CCR PI and study coordinator.  CCR SAE report form 


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and instructions can be found at: https://nih.sharepoint.com/:u:/r/sites/NCI-CCR-OCD-
Communications/SitePages/Forms-and-Instructions.aspx?csf=1&web=1&e=uWBXtI
Following the assessment of the SAE by OSRO, other supporting documentation of the event 
may be requested by the OSRO Safety and should be provided as soon as possible.
8.4
SAFETY REPORTING CRITERIA TO THE PHARMACEUTICAL COLLABORATORS
Reporting will be per the collaborative agreement. 
8.5
REPORTING PREGNANCY 
All required pregnancy reports/follow-up to OSRO will be submitted to: 
OSROSafety@mail.nih.gov and to the CCR PI and study coordinator.  Forms and instructions 
can be found here: https://nih.sharepoint.com/:u:/r/sites/NCI-CCR-OCD-
Communications/SitePages/Forms-and-Instructions.aspx?csf=1&web=1&e=uWBXtI
8.5.1
Maternal exposure
If a participant becomes pregnant during the course of the study, the study treatment should be 
discontinued immediately, and the pregnancy reported to the Sponsor no later than 24 hours of 
when the Investigator becomes aware of it. The Investigator should notify the Sponsor no later 
than 24 hours of when the outcome of the Pregnancy becomes known.
Pregnancy itself is not regarded as an SAE. However, congenital abnormalities or birth defects 
and spontaneous miscarriages that meet serious criteria (section 8.1.2) should be reported as 
SAEs. 
The outcome of all pregnancies  occurring from the first dose of study therapy until 28 days after 
the last dose of study therapy should be followed up and documented.
8.5.2
Paternal exposure
Male participants should refrain from fathering a child or donating sperm during the study and 
for 28 days after the last dose of Pomalidomide.
Pregnancy of the participant’s partner is not considered to be an AE. However, the outcome of 
all pregnancies occurring from the date of the first dose until 28 days after the last dose should, if 
possible, be followed up and documented. Pregnant partners may be offered the opportunity to 
participate in an institutional pregnancy registry protocol (e.g., the NIH IRP pregnancy registry 
study) to provide data about the outcome of the pregnancy for safety reporting purposes.
8.6
REGULATORY REPORTING FOR STUDIES CONDUCTED UNDER CCR-SPONSORED IND
Following notification from the investigator, CCR, the IND sponsor, will report any suspected 
adverse reaction that is both serious and unexpected.  CCR will report an AE as a suspected 
adverse reaction only if there is evidence to suggest a causal relationship between the study 
product and the adverse event.  CCR will notify FDA and all participating investigators (i.e., all 
investigators to whom the sponsor is providing drug under its INDs or under any investigator’s 
IND) in an IND safety report of potential serious risks from clinical trials or any other source, as 
soon as possible, in accordance to 21 CFR Part 312.32. 
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8.7
SPONSOR PROTOCOL DEVIATION REPORTING
A Protocol Deviation is defined as any non-compliance with the clinical trial Protocol, Manual 
of Operational Procedures (MOP) and other Sponsor approved study related documents, GCP, or 
protocol-specific procedural requirements on the part of the participant, the Investigator, or the 
study site staff inclusive of site personnel performing procedures or providing services in support 
of the clinical trial.
It is the responsibility of the study Staff to document any protocol deviation identified by the 
Staff or the site Monitor in the CCR Protocol Deviation Tracking System (PDTS) online 
application. The entries into the PDTS online application should be timely, complete, and 
maintained per CCR PDTS user requirements. 
In addition, any deviation to the protocol should be documented in the participant’s source 
records and reported to the reviewing IRB per their guidelines. OSRO required protocol 
deviation reporting is consistent with E6(R2) GCP: Integrated Addendum to ICH E6(R1): 4.5 
Compliance with Protocol; 5.18.3 (a), and 5.20 Noncompliance; and ICH E3 16.2.2 Protocol 
deviations.
9
CLINICAL MONITORING 
As a sponsor for clinical trials, FDA regulations require the CCR to maintain a monitoring 
program. The CCR’s program allows for confirmation of: study data, specifically data that could 
affect the interpretation of primary and secondary study endpoints; adherence to the protocol, 
regulations, ICH E6, and SOPs; and human subjects protection. This is done through 
independent verification of study data with source documentation focusing on:
•
Informed consent process
•
Eligibility confirmation
•
Drug administration and accountability
•
Adverse events monitoring
•
Response assessment.
The monitoring program also extends to multi-site research when the CCR is the coordinating 
center.
This trial will be monitored by personnel employed by a CCR contractor. Monitors are qualified 
by training and experience to monitor the progress of clinical trials. Personnel monitoring this 
study will not be affiliated in any way with the trial conduct.  
10 STATISTICAL CONSIDERATIONS  
It is known from prior trials that the pomalidomide MTD is about 3 mg/d in persons with bone 
marrow disorders receiving therapies for cancer. Due to high frequency of pomalidomide dose 
de-escalation observed in preliminary cGvHD experiences when given at 3 mg/d, this study will 
explore clinical toxicity of gradual escalation doses below 3.0 mg.
The primary objective of this study is to determine if patients with cGVHD will experience an 
acceptable level of clinical response when treated with either a constant low dose of 
pomalidomide (0.5 mg/day) for six months or a strategy of increasing dose of pomalidomide 
from 0.5 mg/d up through each individual patients’ maximum tolerated dose, with escalations by 


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0.5 mg/d every 2 weeks to a maximum of 2.0 mg/d. The study will thus randomize patients 
between fixed low dose and escalating dose to tolerance, and will be considered a randomized 
phase II trial with a selection design component.
In each of the two arms, the trial will be conducted using a single stage design. With 16 patients 
on each arm, an exact binomial test would have 90% power to detect a difference between a 5% 
response rate and a 30% response rate using a 0.10 one-sided significance level and an exact 
binomial test. In addition, after the trial has ended, the 80% and 95% confidence limits will be 
determined for each arm about the observed response proportion in order to aid in interpretation 
of the results. If there are 3 or more responses in 16 patients, this would be sufficient to rule out a 
5% response rate and demonstrate consistency with 30% or better response rates.
At the conclusion of the study, if both arms are able to accrue to the full 16 patients, the arm with 
the greater number of responses will be selected for further investigation subsequently. That is, if 
the fixed, low-dose arm, or the increasing dose level arm, has the greater number of responses, 
then that arm would be studied further. In the event of a tie, the lower dose arm would likely be 
preferred. As an example, if the true probabilities of response on the two arms were 0.10 and 
0.30, then the probability of correctly selecting the superior arm would be 93%, and if the true 
probabilities on the two arms were 0.15 and 0.30, the probability of correct selection would be 
84%.
As an early stopping rule for futility, if after 7 patients have enrolled on either arm, 0 have 
responded, then no further patients will be accrued to that arm as soon as this can be determined. 
In practice, this means that patients may continue to be accrued beyond 7 in an arm, but no more 
patients would be registered and treated on that arm once the first 7 were evaluated and no PRs 
or CRs were identified in those first 7.
To protect patient safety, an early stopping rule will be implemented as follows. For patients 
treated on either arm, if 2 patients in the first 6, or 33% of the patients at any time experience a 
DLT at a given dose level, no further patients will be treated at that given level on the trial. 
Furthermore, when more than 6 patients have received a given dose level, if at any time 33% or 
more patients experience a DLT when treated at that dose level, then no further patients will be 
treated at that dose level.  Thus, as an example, should there be 2 patients with a DLT in the first 
6 who are able to receive 2.0 mg/day on the dose escalating arm, then subsequent patients treated 
on that arm will not be escalated beyond 1.5 mg/day.
With two arms, each of which has a maximal accrual of 16 patients, up to 32 evaluable patients 
will be randomized. In order to allow for a very small number of patients who are not able to be 
evaluated at all for response, the accrual ceiling will be set at 35.
11 COLLABORATIVE AGREEMENTS
11.1 COOPERATIVE RESEARCH AND DEVELOPMENT AGREEMENT (CRADA)
Pomalidomide is provided by Celgene Corporation under CRADA # 02328 Celgene/NCI 
Clinical Research Leader: "Preclinical and Clinical Development of Celgene Corporation’s 
Proprietary Immunomodulatory Agent, CC4047 (Pomalidomide), as a Therapy for Graft-Versus-
Host Disease (GVHD)," executed July 13, 2010. 


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12 HUMAN SUBJECTS PROTECTIONS 
12.1 RATIONALE FOR SUBJECT SELECTION
No subjects will be excluded from participation based on sex, race or ethnicity. The study will be 
open to all subjects who satisfy the inclusion criteria and provide an informed consent to the 
protocol. 
12.2 PARTICIPATION OF CHILDREN
As there is no experience with pomalidomide in children, this study will be limited to subjects age 
18 years or older.
12.3 PARTICIPATION OF NIH SUBJECTS UNABLE TO GIVE CONSENT
Adults unable to give consent are excluded from enrolling in the protocol.  However re-consent 
may be necessary and there is a possibility, though unlikely, that subjects could become 
decisionally impaired. For this reason and because there is a prospect of direct benefit from 
research participation (section 10.5), all subjects ≥ age 18 will be offered the opportunity to fill 
in their wishes for research and care, and assign a substitute decision maker on the “NIH 
Advance Directive for Health Care and Medical Research Participation” form so that another 
person can make decisions about their medical care in the event that they become incapacitated 
or cognitively impaired during the course of the study. Note: The PI or AI will contact the NIH 
Ability to Consent Assessment Team (ACAT) for evaluation as needed for the following: an 
independent assessment of whether an individual has the capacity to provide consent; assistance 
in identifying and assessing an appropriate surrogate when indicated; and/or an assessment of the 
capacity to appoint a surrogate. For those subjects that become incapacitated and do not have 
pre-determined substitute decision maker, the procedures described in MEC Policy 87-4 and 
NIH HRPP 403 for appointing a surrogate decision maker for adult subjects who are (a) 
decisionally impaired, and (b) who do not have a legal guardian or durable power of attorney, 
will be followed.
12.4 EVALUATION OF BENEFITS AND RISKS/DISCOMFORTS
12.4.1 Related to Pomalidomide
Potential risks of pomalidomide include the range of toxicities described in Section 11.1.9 and the 
consent form. There may also be unexpected side effects. All subjects will be carefully monitored 
for side effects. 
12.4.2 Related to Blood Collection
Minor complications including bleeding, pain, and hematoma formation at the site of blood draws, 
or infections may rarely occur.
12.4.3 Related to Tissue Biopsy
Skin and oral punch biopsy is a minor surgical procedure that may be associated with temporary 
bleeding, hematoma at the site, local infection and postoperative discomfort. These risks are small 
(generally <5%) and transient.


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12.4.4 Related to Pregnancy
Pomalidomide is in a class of agents that is known to be teratogenic. Women of child-bearing 
potential and men must agree to adhere to methods of contraception and other fertility control 
measures as prescribed by the protocol. This will include counseling about pregnancy precautions 
and the potential risks of fetal exposure conducted at a minimum of every 28 days. Women of 
child-bearing potential must also undergo regular pregnancy testing. 
12.5 RISKS/BENEFITS ANALYSIS
Risks of participating in this trial include side effects from pomalidomide and risks of medical 
procedures (blood draws, oral and skin biopsy). Patients may receive benefit from the clinical 
monitoring or potentially experience improvement in cGvHD symptoms or quality of life. 
Therefore, this research represents more than minimal risk to subjects with prospect of direct 
benefit to individual subjects. 
12.6 CONSENT PROCESS AND DOCUMENTATION
The investigational nature and research objectives of this trial, the procedure and its attendant risks 
and discomforts will be carefully explained to the subject. The potential subject will be educated 
regarding the nature of the condition, proposed intervention, and outcome measures. Study 
subjects will be informed that participation is entirely voluntary and that withdrawal from the study 
can be made at any time without penalty of benefits to which they may be entitled. Informed 
consent will be obtained by Dr. Steven Pavletic or his designee. At any time during participation 
in the protocol if new information becomes available relating to risks, adverse events, or toxicities, 
this information will be provided orally or in writing to all enrolled or prospective participants. 
Documentation will be provided to the IRB and if necessary the informed consent amended to 
reflect relevant information.
12.6.1 Telephone re-consent procedure
Reconsent on this study may be obtained via telephone according to the following procedure: the 
informed consent document will be sent to the subject.  An explanation of the study will be 
provided over the telephone after the subject has had the opportunity to read the consent form.  
The subject will sign and date the informed consent. A witness to the subject’s signature will 
sign and date the consent.  The original informed consent document will be sent back to the 
consenting investigator who will sign and date the consent form with the date the consent was 
obtained via telephone.  A fully executed copy will be returned via mail for the subject’s records.  
The informed consent process will be documented on a progress note by the consenting 
investigator.
12.6.2 Short form consent process for non-English speaking patients
If there is an unexpected enrollment of a research participant for whom there is no translated extant 
IRB approved consent document, the principal investigator and/or those authorized to obtain 
informed consent will use the Short Form Oral Consent Process as described in MAS Policy M77-
2, OSHRP SOP 12, and 45 CFR 46.117 (b) (2).  The summary that will be used is the English 
version of the extant IRB approved consent document.  Signed copies of both the English version 
of the consent and the translated short form will be given to the subject or their legally authorized 
representative and the signed original will be filed in the medical record.


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Unless the PI is fluent in the prospective subject’s language, an interpreter will be present to 
facilitate the conversation. Preferably someone who is independent of the subject (i.e., not a family 
member) will assist in presenting information and obtaining consent. Whenever possible, 
interpreters will be provided copies of the relevant consent documents well before the consent 
conversation with the subject (24 to 48 hours if possible). 
We request prospective IRB approval of the use of the short form process and will notify the IRB 
at the time of continuing review of the frequency of the use of the Short Form.
13 REGULATORY AND OPERATIONAL CONSIDERATIONS 
13.1 STUDY DISCONTINUATION AND CLOSURE
This study may be temporarily suspended or prematurely terminated if there is sufficient 
reasonable cause.  Written notification, documenting the reason for study suspension or 
termination, will be provided by the suspending or terminating party to study participants, 
investigators, funding agency, the Investigational New Drug (IND) and regulatory authorities. If 
the study is prematurely terminated or suspended, the Principal Investigator (PI) will promptly 
inform study participants, the Institutional Review Board (IRB), and sponsor and will provide 
the reason(s) for the termination or suspension.  Study participants will be contacted, as 
applicable, and be informed of changes to study visit schedule.
 Circumstances that may warrant termination or suspension include, but are not limited to:
•
Determination of unexpected, significant, or unacceptable risk to participants
•
Demonstration of efficacy that would warrant stopping   
•
Insufficient compliance to protocol requirements
•
Data that are not sufficiently complete and/or evaluable
•
Determination that the primary endpoint has been met
•
Determination of futility
Study may resume once concerns about safety, protocol compliance, and data quality are 
addressed, and satisfy the sponsor, IRB and as applicable, Food and Drug Administration (FDA).
13.2 QUALITY ASSURANCE AND QUALITY CONTROL
Each clinical site will perform internal quality management of study conduct, data and biological 
specimen collection, documentation and completion.  An individualized quality management 
plan will be developed to describe a site’s quality management.
Quality control (QC) procedures will be implemented beginning with the data entry system and 
data QC checks that will be run on the database will be generated. Any missing data or data 
anomalies will be communicated to the site(s) for clarification/resolution.
Following written Standard Operating Procedures (SOPs), the monitors will verify that the 
clinical trial is conducted and data are generated and biological specimens are collected, 
documented (recorded), and reported in compliance with the protocol, International Council for 
Harmonisation Good Clinical Practice (ICH GCP), and applicable regulatory requirements (e.g., 
Good Laboratory Practices (GLP), Good Manufacturing Practices (GMP)). 


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The investigational site will provide direct access to all trial related sites, source data/documents, 
and reports for the purpose of monitoring and auditing by the sponsor, and inspection by local 
and regulatory authorities.
13.3 CONFLICT OF INTEREST POLICY
The independence of this study from any actual or perceived influence, such as by the 
pharmaceutical industry, is critical.  Therefore, any actual conflict of interest of persons who 
have a role in the design, conduct, analysis, publication, or any aspect of this trial will be 
disclosed and managed. Furthermore, persons who have a perceived conflict of interest will be 
required to have such conflicts managed in a way that is appropriate to their participation in the 
design and conduct of this trial.  The study leadership in conjunction with the National Cancer 
Institute has established policies and procedures for all study group members to disclose all 
conflicts of interest and will establish a mechanism for the management of all reported dualities 
of interest.
13.4 CONFIDENTIALITY AND PRIVACY
Participant confidentiality and privacy is strictly held in trust by the participating investigators, 
their staff, and the sponsor(s). This confidentiality is extended to cover testing of biological 
samples and genetic tests in addition to the clinical information relating to participants. 
Therefore, the study protocol, documentation, data, and all other information generated will be 
held in strict confidence. No information concerning the study or the data will be released to any 
unauthorized third party without prior written approval of the sponsor. 
All research activities will be conducted in as private a setting as possible.
The study monitor, other authorized representatives of the sponsor, representatives of the 
Institutional Review Board (IRB), and/or regulatory agencies may inspect all documents and 
records required to be maintained by the investigator, including but not limited to, medical 
records (office, clinic, or hospital) and pharmacy records for the participants in this study. The 
clinical study site will permit access to such records.
The study participant’s contact information will be securely stored at the/each clinical site for 
internal use during the study. At the end of the study, all records will continue to be kept in a 
secure location for as long a period as dictated by the reviewing IRB, Institutional policies, or 
sponsor requirements.
Study participant research data, which is for purposes of statistical analysis and scientific 
reporting, will be  stored at the NCI CCR. This will not include the participant’s contact or 
identifying information. Rather, individual participants and their research data will be identified 
by a unique study identification number. The study data entry and study management systems 
used by the clinical site(s) and by NCI CCR research staff will be secured and password 
protected. At the end of the study, all study databases will be archived at the NCI CCR.
To further protect the privacy of study participants, a Certificate of Confidentiality has been 
issued by the National Institutes of Health (NIH).  This certificate protects identifiable research 
information from forced disclosure. It allows the investigator and others who have access to 
research records to refuse to disclose identifying information on research participation in any 
civil, criminal, administrative, legislative, or other proceeding, whether at the federal, state, or 
local level. By protecting researchers and institutions from being compelled to disclose 


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information that would identify research participants, Certificates of Confidentiality help achieve 
the research objectives and promote participation in studies by helping assure confidentiality and 
privacy to participants.
14 PHARMACEUTICAL INFORMATION  
14.1 POMALIDOMIDE
14.1.1 Description
Pomalidomide, 4-amino-2-(2,6-dioxo-3-piperidyl)isoindoline-1’-one)-1,3-dione, is a novel 
immunomodulatory drug. The Chemical Abstract Service (CAS) registry number for 
pomalidomide is 19171-19-8. Pomalidomide is also known as CC-4047. The chemical structure 
of the active pharmaceutical ingredient is as follows: 
Pomalidomide has an asymmetric carbon atom and can therefore exist as the optically active forms 
S (-) and R (+). Pomalidomide is being developed as a racemate. 
Pomalidomide shares a number of the beneficial pharmacologic properties of thalidomide and 
lenalidomide, but it is a more potent anti-proliferative immunomodulating agent than either drug. 
14.1.2 Source
Celgene Corporation will supply pomalidomide 0.5 mg, 1.0 mg, and 2.0 mg capsules. 
Pomalidomide will be packaged in bottles containing capsules for 28 days of every 28-day cycle. 
Only a 28-day supply of pomalidomide may be provided to the patient for each 28-day cycle. Site 
will utilize commercial supply of anti-thrombotic agents for prophylactic purposes.
Celgene will supply drug free of charge. The initial drug shipment will be sent to NIH pharmacy.  
NIH pharmacy will order all subsequent drug orders.
14.1.3 Formulation and Preparation
Pomalidomide will be administered as 2.0 mg, 1.0 mg and/or 0.5 mg capsules to be taken orally. 
Each daily dose of pomalidomide should be taken at approximately the same time of day. No 
modification of capsules is necessary.   
14.1.4 Study Drug Packaging and Labeling
Pomalidomide investigational supplies are dispensed to the persons in individual bottles of 
capsules. Each bottle will identify the contents as study medication. The label for study drug 
supplied by Celgene will bear the Celgene Corporation name and address, the protocol number, 


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the quantity of study drug 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.”
14.1.5 Study Drug Receipt and Storage
The PI is responsible for taking an inventory of each shipment of study drug received, and 
comparing it with the accompanying study drug accountability form.  The PI or their designee 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.
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.
14.1.6 Administration Procedures
Females of childbearing potential should not handle or administer pomalidomide unless they are 
wearing gloves. 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.  
Accurate recording of all study drug administration (including dispensing and dosing) will be made 
in the source documents.
14.1.7 Study Drug Accountability
The PI or designee(s) is responsible for accounting for all study drug that is issued to and returned 
by the patient during the course of the study.
14.1.8 Study Drug Handling and Disposal
Celgene will instruct the Investigator(s) on the return or destruction of unused study drug.  If any 
study drug is lost or damaged, its disposition should be documented in the patient’s CRF and 
source documents. Study drug supplies will be retained at the clinical site pending instructions for 
disposition by Celgene.  Patients will be instructed to return empty bottles or unused capsules.
14.1.9 Expected Toxicities
Likely (more than 20%): Constipation, fatigue, myalgia, and rash.
Less Likely (less than 20%):  Anemia, thrombocytopenia, neutropenia, productive cough, dyspnea 
(with or without exertion), lung pain, nose bleeds, sore throat, discolored sputum, bloody sputum, 


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irritation of the upper respiratory tract, other  respiratory infections, fever, headache, bacterial or 
viral infections, bone pain, muscle cramps, joint swelling, parasthesias, nausea, diarrhea, bloating, 
dry mouth and irritation of the mouth, dry skin, redness of the skin, and itching, unusual weakness 
or dizziness, hypotension, flushing, and chest pain.
Rare (Less than 3%): pneumonia, vomiting, blood clots in persons receiving combination therapy 
with other cancer drug, erythropoeitin, and/or steroids.
Experience with pomalidomide in humans and animals is detailed in the background section. 
Neutropenia was the most frequently reported grade 3/4 AE in subjects with relapsed/refractory 
multiple myeloma. The majority of these occurred without associated infection and was the dose-
limiting toxicity observed during the dose finding portion of the study. Neutropenia was also the 
most frequently reported AE and SAE in subjects with multiple myeloma followed by 
thrombocytopenia and anemia. Subjects receiving pomalidomide have developed venous 
thromboembolic events (DVTs and pulmonary emboli) reported as SAEs. Anticoagulant 
prophylaxis is recommended as a precaution per protocol.
Pomalidomide was found to be teratogenic in a developmental study in rabbits. Precautions against 
fetal exposure are detailed throughout the protocol.
14.1.10Incompatibilities
Based on in vitro metabolism data, pomalidomide is not likely to precipitate drug-drug interactions 
especially due to inhibition or induction when co-administered with cytochrome P-450, substrates.
A food effect study with pomalidomide has not been conducted.


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Kuzmina Z, Eder S, Bohm A, et al. Significantly worse survival of patients with NIH-defined 
chronic graft-versus-host disease and thrombocytopenia or progressive onset type: 
results of a prospective study. Leukemia. 2011.
73.
Mitchell SA, Jacobsohn D, Thormann Powers KE, et al. A multicenter pilot evaluation of 
the National Institutes of Health chronic graft-versus-host disease (cGVHD) therapeutic 
response measures: feasibility, interrater reliability, and minimum detectable change. Biol 
Blood Marrow Transplant. 2011;17(11):1619-1629.
74.
Lyman GH, Khorana AA, Falanga A, et al. American Society of Clinical Oncology 
guideline: recommendations for venous thromboembolism prophylaxis and treatment in 
patients with cancer. J Clin Oncol. 2007;25(34):5490-5505.
75.
Lee S, Cook EF, Soiffer R, Antin JH. Development and validation of a scale to measure 
symptoms of chronic graft-versus-host disease. Biol Blood Marrow Transplant. 
2002;8(8):444-452.


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


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16.2 APPENDIX B: MEASUREMENT OF POMALIDOMIDE SERUM LEVELS
Blood and Plasma Sample Labeling
Labels must contain the following information:
•
Protocol No.: 
•
Subject ID number: 
•
Nominal Time Point: 
All blood and plasma collection tubes and storage vials should be labeled and chilled on wet ice 
prior to sample collection and processing.  
Blood Sample Collection
•
Research nurses will give the Figg lab 24 hours advance notice on PK blood draws. 
•
Fill an ice bucket with a sufficient amount of ice to pre-chill all collection tubes before 
blood draw.
•
Collect approximately 6 mL of whole blood into a pre-chilled 6-mL K3EDTA tube to 
which 1% hydrochloric acid has been added (supplied by Figg Laboratory).  Blood can 
be collected via direct vein puncture or indwelling catheter.
•
Accurately record the time of blood collection.
•
Gently invert the tube 3-5 times and immerse it into ice immediately to prevent possible 
compound degradation at room temperature.  
•
The date, cycle day, and exact time of each blood draw should be recorded on the 
sample tube and the PK sheet containing the study number and unique patient identifier.
•
Please page 102-11964 (Gareth Peters or alternate tech) for immediate pick-up. 
(Contact the Clinical Pharmacology Program (CPP) processing group in 10/5A09 at 
301-594-6131 or 301-402-3622 with any questions). 
Blood Sample Processing to Obtain Plasma
•
Within 30 minutes of collection, the blood sample must be centrifuged at 1,500 g (about 
3,000 rpm dependent upon the type of centrifuge) for 10 min at 4°C to obtain plasma.  
•
Using Eppendorf pipettes (or equivalent) to transfer approximately 0.7 mL of plasma 
into each of the two pre-labeled, pre-chilled, citric acid-containing polypropylene 
storage vials (one primary and one back-up, provide by Celgene).  Keep storage vials 
on ice before they are ready to be transferred into a freezer.
•
Within 60 minutes of blood collection, transfer plasma samples in storage vials into a 
–80oC freezer, where they will remain stored until analysis.
•
Immediately record the time of sample entry into the freezer.
•
Patient data will be entered into a secure and encrypted LabSamples database 
maintained by the Clinical Pharmacology Program, Office of the Clinical Director


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16.3 APPENDIX C: DIAGNOSTIC CRITERIA OF CHRONIC GVHD 
Organ or Site
Diagnostic 
Features1
Distinctive 
Features2
Others3
Common Features4
Skin
Poilkiloderma
Lichen planus-
like features
Sclerotic 
features
Morphea-like 
features
Lichen 
sclerosus-like 
features
Depigmentatio
n
Sweat impairment
Ichthyosis
Keratosis pilaris
Hypopigmentation
Hyperpigmentatio
n
Erythema
Maculopapular rash
Pruritus
Nails
Dystrophy
Longitudinal 
ridging, 
splitting, or 
brittle features
Onycholysis
Pterygium 
unguis
Nail loss 5,6
Scalp 
and 
body hair
New onset of 
scarring or 
nonscarring 
scalp alopecia7
Scaling, 
papulosquamo
us lesion
Thinning 
scalp 
hair, 
typically 
patchy, coarse, or 
dull 8
Premature 
grey 
hair


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Organ or Site
Diagnostic 
Features1
Distinctive 
Features2
Others3
Common Features4
Mouth
Lichen-type 
features
Hyperkeratotic 
plaques
Restriction of 
mouth opening 
from sclerosis
Xerostomia
Mucocele
Mucosal 
atrophy
Pseudomembra
nes 6
Ulcers6 
Gingivitis
Mucositis
Erythema
Pain
Eyes
New onset dry, 
gritty, or 
painful eyes 9
Cicatricial 
conjunctivitis
Keratoconjunct
ivitis sicca 9
Confluent areas 
of punctuate 
keratopathy
Photophobia
Periorbital 
hyperpigmentation
Blepharitis 10
Genitalia
Lichen planus-
like features
Vaginal 
scarring 
or 
stenosis
Erosions 6
Fissures 6
Ulcers 6
Lung
Bronchiolitis 
obliterans 
diagnosed with 
lung biopsy
Bronchiolitis 
obliterans 
diagnosed with 
PFTs 12 and 
radiology 9
BOOP 13
Muscle, 
Fascia, joints
Fasciitis
Joint stiffness or 
contractures 
secondary 
to 
sclerosis
Myositis or 
polymyositis
Edema
Muscle cramps
Arthralgia or 
arthritis


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Organ or Site
Diagnostic 
Features1
Distinctive 
Features2
Others3
Common Features4
Hematopoiet
ic 
and 
immune
Thrombocytopenia
Eosinophilia
Lymphopenia
Hypo- or 
hypergammaglobilin
emia
Autoantibodies 
(AIHA and ITP) 14
Other
Pericardial or pleural 
effusions
Ascites
Peripheral 
neuropathy
Nephrotic syndrome
Myasthenia gravis
Cardiac conduction 
abnormality or 
cardiomyopathy
1.Sufficient to establish the diagnosis of cGvHD
2.Seen in cGvHD, but insufficient alone to establish a diagnosis of cGvHD
3.Can be acknowledged as part of the cGvHD symptomatology if the diagnosis is confirmed
4.Seen with both acute and cGvHD
5.Usually symmetric, affects most nails
6.In all cases, infection, drug effects, malignancy, or other causes must be excluded.
7.After recovery from chemoradiation therapy
8.Not explained by endocrine or other causes
9.Diagnosis of cGvHD requires biopsy or radiology confirmation (or Schirmer test for eyes) 
10.Erythema of the eyelids with edema
11.Infants and children
12.Pulmonary function tests
13.Bronchiolitis obliterans-organizing pneumonia


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14.AIHA: autoimmune hemolytic anemia; ITP: idiopathic thrombocytopenic purpura


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16.4 APPENDIX D: CLINICAL DIFFERENTIATION OF ACUTE AND CHRONIC GVHD
Category
Time 
of 
Symptoms After 
HCT or DLI
Presence of 
Acute 
GVHD 
Features
Presence 
of 
Chronic GVHD 
Features2
Acute GVHD
   Classic acute GVHD
≤ 100 days
Yes
No
   Persistent, recurrent, or late-onset acute 
GVHD
> 100 days
Yes
No
Chronic GVHD
   Classic cGvHD
No time limit
No
Yes
   Overlap syndrome
No time limit
Yes
Yes
1. Abbreviations: HCT: hematopoietic cell transplantation; DLI: donor lymphocyte infusion 
2. See Appendix C for features


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16.5 APPENDIX E: ORGAN SPECIFIC AND GLOBAL SCORING OF CHRONIC GVHD
SCORE 0
SCORE 1
SCORE 2
SCORE 3
PERFORMANCE SCORE: 
KPS   ECOG   LPS
  Asymptomatic and 
fully active (ECOG 0; 
KPS or LPS 100%)
  Symptomatic, fully 
ambulatory, restricted 
only in physically 
strenuous activity 
(ECOG 1, KPS or 
LPS 80-90%)
  Symptomatic, 
ambulatory, capable 
of self-care, >50% of 
waking hours out of 
bed (ECOG 2, KPS 
or LPS 60-70%) 
  Symptomatic, 
limited self-care, 
>50% of waking hours 
in bed (ECOG 3-4, 
KPS or LPS <60%)
SKIN
Clinical features:
  Maculopapular rash
  Lichen planus-like 
features
  Papulosquamous 
lesions or ichthyosis
 Hyperpigmentation
  Hypopigmentation
  Keratosis pilaris
  Erythema
  Erythroderma 
  Poikiloderma
  Sclerotic features 
  Pruritus
  Hair involvement
  Nail involvement
% BSA 
involved
  No Symptoms 
  <18% BSA with 
disease signs but NO 
sclerotic features
  19-50% BSA OR 
involvement with 
superficial sclerotic 
features “not 
hidebound” (able to 
pinch)
  >50% BSA OR 
deep sclerotic features 
“hidebound” (unable to 
pinch) OR impaired 
mobility, ulceration or 
severe pruritus 
MOUTH
  No symptoms 
  Mild symptoms 
with disease signs but 
not limiting oral 
intake significantly
  Moderate 
symptoms with 
disease signs with 
partial limitation of 
oral intake
  Severe symptoms 
with disease signs on 
examination with 
major limitation of oral 
intake
LIP Print Name:______________________________  LIP Signature:_____________________________
Date of Evaluation:__________
Timepoint: Baseline__________Off Study___________ 


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SCORE 0
SCORE 1
SCORE 2
SCORE 3
GI TRACT
  No symptoms
  Symptoms such as 
dysphagia, anorexia, 
nausea, vomiting, 
abdominal pain or 
diarrhea without 
significant weight loss 
(<5%)
  Symptoms 
associated with mild 
to moderate weight 
loss (5-15%)
 Symptoms 
associated with 
significant weight loss 
>15%, requires 
nutritional supplement 
for most calorie needs 
OR esophageal 
dilation
LIVER
  Normal LFT
 Elevated Bilirubin, 
AP*, AST or ALT <2 
x ULN
  Bilirubin >3 mg/dl 
or Bilirubin, 
enzymes 2-5 x ULN 
  Bilirubin or 
enzymes > 5 x ULN
LUNGS*
FEV1
DLCO
  No symptoms
  FEV1 > 80% 
OR LFS=2
  Mild symptoms 
(shortness of breath 
after climbing one 
flight of steps)
  FEV1 60-79% OR 
LFS 3-5
  Moderate 
symptoms (shortness 
of breath after 
walking on flat 
ground)
  FEV1 40-59% 
OR LFS 6-9
  Severe symptoms 
(shortness of breath  at 
rest; requiring 02)
  FEV1 <39% OR 
LFS 10-12
EYES
Mean tear test (mm):
  >10
  6-10
  <5
  Not done
  No symptoms 
  Mild dry eye 
symptoms not 
affecting ADL 
(requiring eyedrops < 
3 x per day) OR 
asymptomatic signs of  
keratoconjunctivitis 
sicca
  Moderate dry eye 
symptoms partially 
affecting ADL 
(requiring drops > 3 
x per day or punctal 
plugs), WITHOUT 
vision impairment
  Severe dry eye 
symptoms significantly 
affecting ADL (special 
eyeware to relieve 
pain) OR unable to 
work because of ocular 
symptoms OR loss of 
vision caused by 
keratoconjunctivitis 
sicca
LIP Print Name:______________________________  LIP Signature:_____________________________
Date of Evaluation:__________
Timepoint: Baseline__________Off Study___________ 


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SCORE 0
SCORE 1
SCORE 2
SCORE 3
JOINTS AND FASCIA
  No symptoms
  Mild tightness of 
arms or legs, normal 
or mild decreased 
range of motion 
(ROM) AND not 
affecting ADL
  Tightness of arms 
or legs OR joint 
contractures, 
erythema due to 
fasciitis, moderate 
decrease ROM AND 
mild to moderate 
limitation of ADL
  Contractures WITH 
significant decrease of 
ROM AND significant 
limitation of ADL 
(unable to tie shoes, 
button shirts, dress self 
etc.) 
GENITAL TRACT
 No symptoms 
 Symptomatic with 
mild signs on exam 
AND no effect on 
coitus and minimal 
discomfort with 
gynecologic exam
 Symptomatic with 
moderate signs on 
exam AND with 
mild dyspareunia or 
discomfort with 
gynecologic exam
 Symptomatic WITH 
advanced signs 
(stricture, labial 
agglutination or severe 
ulceration) AND 
severe pain with coitus 
or inability to insert 
vaginal speculum
* AP may be elevated in growing children, and not reflective of liver dysfunction
Other indicators, clinical manifestations or complications related to cGVHD (check all that apply and assign a score to its 
severity (0-3) based on its functional impact (none – 0,mild -1, moderate -2, severe – 3)
 ﭐEsophageal stricture or web___ ﭐPericardial Effusion___ ﭐPleural Effusion(s)___
 ﭐAscites (serositis)___ ﭐNephrotic syndrome___ ﭐPeripheral Neuropathy___
 ﭐMyasthenia Gravis___ ﭐCardiomyopathy___ ﭐEosinophilia > 500μl___
 ﭐPolymyositis___                ﭐCardiac conduction defects___ ﭐCoronary artery involvement___
 ﭐPlatelets <100,000/μl ___ ﭐProgressive onset
 ﭐOTHERS: ________
LIP Print Name:______________________________  LIP Signature:_____________________________
Date of Evaluation:__________
Timepoint: Baseline__________Off Study___________ 
When discrepancy exists between pulmonary symptom or PFT scores the higher value should be used for final scoring. Scoring 
using the Lung Function Score (LFS) is preferred, but if DLCO is not available, grading using FEV1 should be used. The percent 
predicted FEV1 and DLCO (adjusted for hematocrit but not alveolar volume) should be converted to a numeric score as follows: 
>80% = 1; 70-79% = 2; 60-69% = 3; 50-59% = 4; 40-49% = 5; <40% = 6. The LFS = FEV1 score + DLCO score, with a possible 
range of 2-12. 


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16.6 APPENDIX F: GLOBAL SCORING OF CGVHD
Stage
Definition
Mild
Only 1 or 2 organs or site (except the lung)
No clinically significant functional impairment (maximum of score 1 in 
all affected organs or sites)
Moderate
At least 1 organ or site with clinically significant but no major disability 
(maximum score of 2 in any affected organ or site), 
                   or
3 or more organs or sites with no clinically significant functional 
impairment (maximum score of 1 in all affected organs or sites)
Severe
Major disability caused by cGvHD (score of 3 in any organ or site)
Lung function score ≥ 2


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16.7 APPENDIX G: CHRONIC GVHD ASSESSMENT (CLINICIAN) FORM
Current Patient Weight: ___________________     Today’s Date: ________________________        MR#/Name: ____
Component
Findings
Scoring (see skin score worksheet) 
Erythematous rash of any sort 
                        % BSA (max 100%) 
Moveable sclerosis  
                        % BSA (max 100%) 
Non-moveable sclerosis (hidebound/non-pinchable) or 
subcutaneous sclerosis/fasciitis 
                        % BSA (max 100%) 
Skin 
 
Ulcer(s): select the largest ulcerative lesion, and 
measure its longest dimension in cm and mark location 
of ulcer 
 
Location:   ___________________ 
 
Longest dimension: __________cm 
Eyes 
Bilateral Schirmer’s Tear Test 
(without anesthesia)  
in persons 9 years or older 
Right Eye:                                        mm of 
wetting 
Left Eye:                                                      mm of 
wetting 
Mouth 
 
Mucosal 
change 
No 
evidence 
of CGVHD
Mild
Moderate
Severe
Erythema None 
0 
Mild erythema or
moderate erythema
(<25%) 
1 
Moderate (≥25%) 
or 
Severe 
erythema (<25%) 
2 
Severe erythema
(≥25%)  
3 


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Lichenoid None 
0 
Hyperkeratotic 
changes(<25%) 
1 
Hyperkeratotic 
changes(25-50%) 
2 
Hyperkeratotic 
changes (>50%) 
3 
Ulcers 
None 
0 
None 
0 
Ulcers involving 
(≤20%) 
3 
Severe 
ulcerations 
(>20%) 
6 
Mucoceles*
None 
0 
1-5 mucoceles 
1  
6-10 
scattered 
mucoceles 
2  Over 
10
mucoceles 
3 
 
*Mucoceles scored for 
lower labial and soft 
palate only
 
Total score for
all 
mucosal
changes
 
Blood Counts 
Platelet 
Count  
(K/uL)                       
  
                                   
ULN (K/uL) 
Total WBC (K/uL) ULN (K/uL) 
Eosinophils (% )
Liver Function 
Tests 
Total 
serum 
bilirubin (mg/dL)
 
                           
ULN (mg/dL) ALT (U/L) 
ULN (U/L) 
Alkaline 
Phosphatase (U/L) 
ULN (U/L) 
Gastrointestinal-Upper GI  
• Early satiety OR 
• Anorexia     OR 
0= no symptoms 
1=mild, occasional symptoms, with little reduction in oral intake during the past week 
2=moderate, intermittent symptoms, with some reduction in oral intake during the past week 


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• Nausea & Vomiting 
3=more severe or persistent symptoms throughout the day, with marked reduction in oral intake, on 
almost every day of the past week 
Gastrointestinal-
Esophageal 
• Dysphagia     OR 
• Odynophagia 
0= no esophageal symptoms 
1=Occasional dysphagia or odynophagia with solid food or pills during the past week 
2=Intermittent dysphagia or odynophagia with solid foods or pills, but not for liquids or soft foods, 
during the past week 
3=Dysphagia or odynophagia for almost all oral intake, on almost every day of the past week 
Gastrointestinal-Lower GI 
• Diarrhea 
0= no loose or liquid stools during the past week 
1= occasional loose or liquid stools, on some days during the past week 
2=intermittent loose or liquid stools throughout the day, on almost every day of the past week, without 
requiring intervention to prevent or correct volume depletion 
3=voluminous diarrhea on almost every day of the past week, requiring intervention to prevent or 
correct volume depletion 
Lungs 
• Bronchiolitis Obliterans 
Pulmonary Function Tests with 
Diffusing Capacity  (attach report for 
person> 5 yrs old) 
FEV-1 
                                   
(% Predicted)
Single 
Breath 
DLCO 
(adjusted for hemoglobin) 
                                      
(%Predicted)
Health 
Care 
Provider 
Global Ratings: 
In your opinion, do you 
think that this patient’s 
cGvHD is mild, moderate or 
severe? 
0=none 
Where would you rate the severity of this patient’s cGvHD 
symptoms on the following scale, where 0 is CGVHD symptoms 
that are not at all severe and 10 is the most severe CGVHD 
symptoms possible: 
0       1       2       3       4       5       6       7       8       9       10
Over the past month would 
you say that this patient’s 
CGVHD is 
+3= Very much better  
+2= Moderately better 
+1= A little better 
  0= About the same 


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1= mild 
2=moderate 
3=severe 
cGvHD symptoms 
 cGvHD 
symptoms  
not at all severe 
           most severe 
       possible 
-1=A little worse 
-2=Moderately worse  
-3=Very much worse 
Karnofsky Performance
Score
Performance Status Scale Definitions (Use Lansky Play Performance for persons < 
16 years old) 
100
Normal no complaints; no evidence of disease 
90
Able to carry on normal activity; minor signs or symptoms of disease 
Able to carry on normal 
activity and to work; no 
special care needed.
80
Normal activity with effort; some signs or symptoms of disease 
70
Cares for self; unable to carry on normal activity or to do active work 
60
Requires occasional assistance but is able to care for most personal needs 
Unable to work; able to live at 
home and care for most 
personal 
needs; 
varying 
amount of assistance needed.
50
Requires considerable assistance and frequent medical care 
40
Disabled; requires special care and assistance 
30
Severely disabled; hospital admission is indicated although death not imminent 
20
Very sick; hospital admission necessary; active supportive treatment necessary 
10
Moribund; fatal processes progressing rapidly 
Unable to care for self; 
requires 
equivalent 
of 
institutional or hospital care; 
disease may be progressing 
rapidly.
0
Dead 


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16.8 APPENDIX H: CALCULATIONS FOR PARTIAL RESPONSE IN CHRONIC GVHD
Organ and Starting Score or Value at Baseline
Partial Response Criterion1
Skin (% of BSA)
> 50
25-50
< 25
e/s ≤ 0.5 and e > 0
s – e ≥ 25 and e > 0
Only CR; no PR possible
Eye (mm Schirmer’s test)
< 5 mm
5-10 mm
e – s ≥ 5 mm and e < LLN
Only CR; no PR possible
Mouth (Schubert Scale 0-15)
> 8
4 – 7 
< 4 
e/s ≤ 0.5 and e > 0
s – e ≥ 4 and e > 0
Only CR; no PR possible
Hematology 
Platelet count
Eosinophil count
≥ 3 X ULN
< 3 X ULN
e – s ≥ 100,000/μL and e < LLN
e/s ≤ 0.5 and e > ULN
Only CR; no PR possible
Gastrointestinal ( 0 -3 scales)
3
2
1
e = 1 or 2
e = 1
Only CR; no PR possible
Liver function
(ALT, alkaline phosphatase and bilirubin) 
≥ 3 X ULN
< 3 X ULN
e/s ≤ 0.5 and e > ULN
Only CR; no PR possible
Abbreviations: s: starting score or value; e: ending score or value; ULN: upper limit of normal; 
LLN: lower limit of normal


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16.9 APPENDIX I: CALCULATIONS FOR PROGRESSION IN CHRONIC GVHD
Organ and Starting Score or Value
Progression Criterion1
Skin (% of BSA)
e – s ≥ 25
Eye (mm Schirmer’s test)
s – e ≥ 5 mm
Mouth (Schubert Scale 0-15)
e – s ≥ 3
Hematology
Platelet count
Eosinophil count
≥ 3 X ULN
< 3 X ULN 
s – e ≥ 50,000/μL and e < LLN
e - s ≥ 3 X ULN 
e - s ≥ 2 X ULN
Gastrointestinal (0 -3 scales)
e – s ≥ 1
Liver function
(ALT, alkaline phosphatase and bilirubin) 
s ≥ 3 X ULN
s < 3 X ULN
e - s ≥ 3 X ULN 
e - s ≥ 2 X ULN 
Lungs (Lung function scale 12 points)2
e - s ≥ 3 
1.  Abbreviations: starting score or value; e: ending score or value; ULN: upper limit of normal; 
LLN: lower limit of normal
2. If the starting lung function score is ≥ 10, progression is defined as ≥ 5% decrease of FEV1 in 
two tests measured at least 2 weeks apart.


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16.10 APPENDIX J: CHRONIC GVHD CUTANEOUS ASSESSMENT WORKSHEET  (ADULT)
Erythematous changes
Moveable-sclerosis/Dermal 
sclerosis 
Non-moveable/subcutaneous 
sclerosis or fasciitis 
% region 
involved 
Multiplier  Total 
BSA 
% region 
involved
Multiplier Total 
BSA 
% region 
involved 
Multiplier Total 
BSA 
Head/neck/scalp 
 
0.09 
 
 
0.09 
 
 
0.09 
 
Anterior torso 
 
0.18 
 
 
0.18 
 
 
0.18 
 
Posterior torso 
 
0.18 
 
 
0.18 
 
 
0.18 
 
L. upper extrem. 
 
0.09 
 
 
0.09 
 
 
0.09 
 
R. upper extrem. 
 
0.09 
 
 
0.09 
 
 
0.09 
 
L. lower extrem. 
(incl. L. buttock) 
 
0.18 
 
 
0.18 
 
 
0.18 
 
R. lower extrem. 
(incl. R. buttock) 
 
0.18 
 
 
0.18 
 
 
0.18 
 
Genitalia 
 
0.01 
 
 
0.01 
 
 
0.01 
 


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Total Erythema                      Total Dermal                     Total Subcut
_________________        ____________________                    ___________   
       Signature                                     Printed Name                                      Date/Time                                 
  


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16.11 APPENDIX K: LEE SYMPTOM SCALE
Not at 
all
Slightly
Moderately
Quite a 
bit
Extremely
SKIN:
a. Abnormal skin color
0
1
2
3
4
b. Rashes
0
1
2
3
4
c. Thickened skin
0
1
2
3
4
d. Sores on skin
0
1
2
3
4
e. Itchy skin
0
1
2
3
4
EYES AND MOUTH:
f. Dry eyes
0
1
2
3
4
g. Need to use eyedrops frequently
0
1
2
3
4
h. Difficulty seeing clearly
0
1
2
3
4
i. Need to avoid certain foods due to 
mouth pain
0
1
2
3
4
j. Ulcers in mouth
0
1
2
3
4
k. 
Receiving 
nutrition 
from 
an 
intravenous line or feeding tube
0
1
2
3
4
BREATHING:
l. Frequent cough
0
1
2
3
4
m. Colored sputum
0
1
2
3
4
n. Shortness of breath with exercise
0
1
2
3
4
o. Shortness of breath at rest
0
1
2
3
4
p. Need to use oxygen
0
1
2
3
4
EATING AND DIGESTION:


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Not at 
all
Slightly
Moderately
Quite a 
bit
Extremely
q. Difficulty swallowing solid foods
0
1
2
3
4
r. Difficulty swallowing liquids
0
1
2
3
4
s. Vomiting
0
1
2
3
4
t. Weight loss
0
1
2
3
4
MUSCLES AND JOINTS:
u. Joint and muscle aches
0
1
2
3
4
v. Limited joint movement
0
1
2
3
4
w. Muscle cramps
0
1
2
3
4
x. Weak muscles
0
1
2
3
4
ENERGY:
y. Loss of energy
0
1
2
3
4
z. Need to sleep more/take naps
0
1
2
3
4
aa. Fevers
0
1
2
3
4
MENTAL AND EMOTIONAL:
bb. Depression
0
1
2
3
4
cc. Anxiety
0
1
2
3
4
dd. Difficulty sleeping
0
1
2
3
4


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16.12 APPENDIX L: POMALIDOMIDE PREGNANCY PREVENTION RISK MANAGEMENT PLANS
This Appendix applies to all patients receiving pomalidomide therapy. The following Pregnancy 
Risk Minimization Plan documents are included in this Appendix: 
1) Pomalidomide Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth 
Control Methods (Appendix M); 
2) Pomalidomide Information Sheet (Appendix N).
1. The Pomalidomide Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable 
Birth Control Methods document (Appendix M) provides the following information:
•
Potential risks to the fetus associated with pomalidomide exposure
•
Definition of Female of Childbearing Potential (FCBP)
•
Pregnancy testing requirements for patients receiving Pomalidomide who are females 
of childbearing potential
•
Acceptable birth control methods for both female of childbearing potential and male 
patients receiving pomalidomide in the study
•
Requirements for counselling of all study patients receiving pomalidomide about 
pregnancy precautions and the potential risks of fetal exposure to pomalidomide
2. The Pomalidomide Information Sheet (Appendix N) will be given to each patient receiving 
pomalidomide study therapy. The patient must read this document prior to starting 
pomalidomide study treatment and each time they receive a new supply of study drug.


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16.13 APPENDIX M: 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 is 
menstruating, amenorrheic from previous medical treatments, under 50 years of age and/or 
perimenopausal and do not qualify for the females not of reproductive potential category.
Criteria for females not of reproductive potential: 
Defined as females who have been in natural menopause for at least 24 consecutive months, or 
who have had a hysterectomy and/or bilateral oophorectomy.
Counselling
For a female of childbearing potential, pomalidomide is contraindicated unless all of the following 
are met (ie, 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 study drug is 
dispensed following a negative pregnancy test
•
She understands the need and accepts to undergo pregnancy testing based on the 
frequency outlined in this protocol (Section 2.2)
•
She acknowledges that she understands the hazards and necessary precautions 
associated with the use of pomalidomide
The investigator must ensure that females of childbearing potential:
•
Comply with the conditions for pregnancy risk minimization, including confirmation 
that she has an adequate level of understanding
•
Acknowledge the aforementioned requirements


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For a female NOT of childbearing potential, pomalidomide is contraindicated unless all of the 
following are met (ie, all females NOT of childbearing potential must be 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 (ie, 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 pregnant 
female or a female of childbearing potential
•
Understand the need for the use of a condom even if he has had a vasectomy, if engaged 
in sexual activity with a pregnant female or a female of childbearing potential.  
Contraception
Females of childbearing potential (FCBP) enrolled in this protocol must agree to use two reliable 
forms of contraception simultaneously or to practice complete abstinence from heterosexual 
contact during the following time periods related to this study: 1) for at least 28 days before starting 
study drug; 2) while participating in the study; 3) during 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:  
•
Highly effective methods:
o
Intrauterine device (IUD)
o
Hormonal (birth control pills, injections, implants)
o
Tubal ligation
o
Partner’s vasectomy
•
Additional effective methods:
o
Male condom
o
Diaphragm
o
Cervical Cap
Because of the increased risk of venous thromboembolism in patients 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.


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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 
study drug.  The first pregnancy test must be performed within 10-14 days prior to the start of 
study drug and the second pregnancy test must be performed within 24 hours prior to the start of 
study drug.  The patient may not receive study drug until the study doctor 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 a pregnant 
female or a female of childbearing potential while participating in the study, during dose 
interruptions and for at least 28 days following study drug discontinuation, even if he has 
undergone a successful vasectomy.  
During study participation and for 28 days following study drug discontinuation 
Female 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.  
•
Counselling about pregnancy precautions and the potential risks of fetal exposure must 
be conducted at a minimum of every 28 days. 
•
If pregnancy or a positive pregnancy test does occur in a study patient, study drug 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.


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Male Patients:
•
Counselling about the requirement for complete abstinence or condom use during 
sexual contact with a pregnant female or a female of childbearing potential and the 
potential risks of fetal exposure to pomalidomide must be conducted at a minimum of 
every 28 days.  
•
If pregnancy or a positive pregnancy test does occur in the partner of a male study 
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 study doctor at the end of treatment.
•
Patients should not donate blood during therapy and for at least 28 days following 
discontinuation of study drug.
•
Male patients should not donate semen or sperm during therapy or for at least 28 days 
following discontinuation of study drug.
•
Only enough study drug for one cycle of therapy may be dispensed with each cycle of 
therapy. 
  


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


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


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16.15 APPENDIX O: MEDICATION DIARY
Today’s date ___________________________
Patient 
Name____________________________ 
Patient 
Study 
ID________________________INSTRUCTIONS TO THE PATIENT:
1.
Complete one form for each cycle.
2.
You will take your dose of pomalidomide each day at approximately the same time.  Pomalidomide 
capsules should be swallowed whole, and should not be broken, chewed or opened. Caregivers who 
are women able to become pregnant should not handle pomalidomide unless wearing gloves. You 
will take ____0.5 mg capsules,  ____1 mg capsules and ____ 2 mg capsules each day.
3.
Record the date, the number of capsules of each size you took, and when you took them.  
4.
If you have any comments or notice any side effects, please record them in the Comments column.
5.
Please bring your pill bottle and this form to your physician when you go for your next appointment.
# of capsules taken
Date
Day
Time of 
daily dose
0.5 
mg
1 mg
2 mg
Comments
1
2
3
4
5
6
7
8
9
10
11
12
13
14
Page 2


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Patient Name____________________________ Patient Study ID________________________
(initials acceptable)
INSTRUCTIONS TO THE PATIENT:
1.
Complete one form for each cycle.
2.
You will take your dose of pomalidomide each day at approximately the same time.  Pomalidomide 
capsules should be swallowed whole, and should not be broken, chewed or opened. Caregivers who 
are women able to become pregnant should not handle pomalidomide unless wearing gloves. You 
will take ____0.5 mg capsules,  ____1 mg capsules and ____ 2 mg capsules each day.
3.
Record the date, the number of capsules of each size you took, and when you took them.  
4.
If you have any comments or notice any side effects, please record them in the Comments column.
5.
Please bring your pill bottle and this form to your physician when you go for your next appointment.
# of capsules taken
Date
Da
y
Time 
of 
daily dose
0.5 
mg
1 mg
2 mg
Comments
15
16
17
18
19
20
21
22
23
24
25
26
27
28
Patient’s 
Signature: 
__________________________________________ 
Date: 
_________________________
Physician’s Office will complete this section:
1. Date patient started protocol treatment___________ Date patient was removed from study 
____________


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2. Patient’s planned daily dose______________   Total number of pills taken this month 
_________________
Physician/Nurse/Data 
Manager’s 
Signature 
_____________________________________________________


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16.16 APPENDIX P: DATA COLLECTION ELEMENTS REQUIRED BY PROTOCOL 
ALL OF THE FOLLOWING ELEMENTS WILL BE RECORDED IN THE C3D DATABASE.
A. PATIENT ENROLLMENT 
Recipient
•
Date of birth, age, sex, race, ethnicity
•
Height
•
Weight
•
Karnofsky Performance Status
•
Date of original diagnosis of the underlying disease (month/year)
•
Diagnosis for which transplant was performed
•
Date and type of transplant
•
Conditioning regimen
•
Acute GVHD yes/no
•
Chronic GVHD date of diagnosis
•
Chronic GVHD classification (late, overlap, classic)
•
Prior systemic therapy for cGVHD
•
Prior therapy for cGVHD
•
Date of Informed Consent signature, consent version and date of registration
•
Baseline History/Physical
•
Baseline Symptoms 
•
Intensity of current immunosupression: None, Mild (single agent prednisone <0.5 
mg/kg/day), Moderate (prednisone >0.5 mg/kg/day and or any single 
agent/modality), High (2 or more agents/modalities +prednisone >0.5 mg/kg/day)
•
Clinician’s impression of activity: Inactive, off systemic therapy or topical 
immunosupression; Inactive, on systemic therapy or topical immunosupression; 
Active, irrespective of the level of current therapy; Highly Active, irrespective of the 
level of current therapy
•
Findings of consultations done at screening
Donor
•
Age at transplant
•
Relationship, sex
•
Degree and type of HLA match (allele or serologic)
•
CMV status


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B.  STUDY DRUG ADMINISTRATION AND RESPONSE FOR EACH COURSE OF 
THERAPY GIVEN
•
Dates study drug given
•
Actual dose given
•
Response assessment 
C.   LABORATORY AND DIAGNOSTIC TEST DATA
•
All Clinical laboratory and diagnostic test results done at screening except diagnostic 
tests which are not specified in the protocol, and if the results are not needed to document 
the start or end of an adverse event that requires reporting.
•
All tests done to document resolution of adverse events
•
Serologies-CMV and HSV
D.  ADVERSE EVENTS
•
All unexpected serious adverse events that are possibly, probably, or definitely related to 
the research 
•
All deaths, except deaths due to progressive disease 
•
All Protocol Violations or Deviations
•
All Unanticipated Problems
E.  CONCOMITANT MEASURES
•
Baseline immunosuppresive medications 
•
Other therapy for recorded adverse events
F. Off study
•
Date and reason for off study
•
Date and cause of death
•
Autopsy findings


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16.17  APPENDIX Q:CHRONIC GVHD COMPOSITE ASSESSMENT SCALE – EVALUATION TOOLS
16.17.1Component 1: Skin
Patient Name: ______________                  Patient MR #: _________________
Date of Assessment: ________ 
1. CAS - Initial assessment 
a.
Extent (% body surface area, BSA) of involvement are estimated for lichenoid, 
sclerotic, and fascial disease.
b. A score 0-3 (none, mild, moderate, severe) are given that directly correlates with BSA 
affected (see table below)
c.
The highest score in any skin sub-type are used to determine the overall stage of 
involvement
•
Check appropriate box in each row
Sub-type
Normal=0
     
MILD=1
MODERATE=2
SEVERE=3
Erythema /
Lichenoid
0
1-25% 
BSA
25 
– 
50%BSA
3 =  > 50% BSA
Sclerosis,
movable
0
1-25% 
BSA
25 
– 
50%BSA
3 = > 50% BSA
Sclerosis, fixed
(fasciitis)
0
1-25% 
BSA
25 
– 
50%BSA
3 = > 50% BSA
Overall stage (max 3): ____
 
_________________        ____________________                    ___________
Signature                                     Printed Name                                      Date/Time          
   
2. Not in CAS - Objective ancillary data (presence or absence)


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3. Not in CAS - Subjective assessments --- Patient Visual Analog Scales
Definitions: Pain due to skin disease from zero (no pain) to 10 (worst imaginable pain) 
Itching is level of discomfort from itching from zero (no itching) to 10 (worst 
imaginable itching)
Clinical severity is patient’s assessment of degree of disease activity on the skin
Pain
(0-10)
Pruritus
(0-10)
Clinical severity
(0-10)
Patient
Physician
Date of 
bx
Clinical findings
Group received
Location 
of bx
Affected/
Unaffected
Bx 
reason
(D, R, 
D/R)*
*D- Diagnostic; R-Research, D/R- Diagnostic/Research.
 
_________________        ____________________                    ___________
Signature                                     Printed Name                                      Date/Time         
Pigment alteration 
(%)
Erosions/
ulcerations
Nail dystrophy
Alopecia
Edema
Xerosis
Present
Absent
Presen
t
Absent
Presen
t
Absent
Presen
t
Absent
Presen
t
Absent
Presen
t
Absent
      %
0 
10
10
1
0
0
Pain
Itching


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16.17.2Component 2: Mouth
1.
CAS – Initial assessment
•
Please, check off the box.
Instrument 
Clinical Sign or 
Symptom
Normal=0
Mild=1
Moderate=2
Severe=3
Oral 
Mucositis 
Rating Scale 
(CAS)
Oral signs of cGVHD
0
1 to 
34
35-69
70-103+
OMRS Score: ______________
Stage: _________________
2.
Biopsy of oral mucosa (please check off the box): 
A.
Research Biopsy (Dr. Hakim’s lab) □ YES □NO
    Size(mm)____
B.
Clinical Biopsy (Pathology) 
□ YES □NO
    Size(mm)____
C.
Minor Salivary Gland
□ YES □NO
3.
Amount of saliva collected in 5 min: ________________
Date: ____/____/____    LIP print name: ___________________________
LIP________________________ Signature: ____________________________


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Schubert Oral Mucositis Rating Scale
Date: ____/____/____    LIP print name:                                                  LIP_______________ 
Signature: ____________________________
______________________________________________________________________________
INSTRUCTIONS: Assess each indicated oral cavity location for the stated clinical 
observation and write in the number corresponding to the rating.
              LIPS
   LABIAL 
MUCOSA
  BUCCAL 
MUCOSA
Lower
Upper
Lower
Upper
Right 
Left
Atrophy
Pseudomembrane
Erythema
Hyperkeratosis
Lichenoid
Ulceration
Edema/Cellulitis
        
                  TONGUE
    PALATE
Dorsal
Later
al 
Ventral
FLOOR 
OF
MOUT
H
Har
d
Soft
  GINGIVA
Atrophy
Pseudomembran
e
Erythema
Hyperkeratosis
Lichenoid
Ulceration
Edema/Cellulitis
          
                Total OMRS Score:  _____  (range:  0 – 273; 
sum all items)
Instructions for Rating:
Atrophy, erythema, hyperkeratosis, lichenoid, and edema
Ulceration 
and Pseudomembrane
Change is rated from normal.
0  =  Normal/No change
               0  =  None
1  =  Mild change
               1  =   0 but  1cm2
2  =  Moderate change
               2  =  1 cm2  but  2 cm2
3  =  Severe change
               3  =   2cm2


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If any area cannot be assessed, circle one of the following:
04  =  Unable to visualize/assess due to severity
09  =  Unable to assess because 
patient is
05  =  Unable to assess because patient is sedated
          not 
available. 
Explain: 
_______________
06 
=Unable 
to 
assess 
because 
patient 
is 
disoriented
________________________________________
07  =  Unable to assess because patient is comatose
10 
 
= 
 
Other. 
Explain: 
______________________
08  =  Unable to assess because patient is unwilling
99  =  Missing
          or unable to cooperate
Check  (  ) type of light source used to visualize the oral cavity:
______  (1)  
Oral water rinse used
____  (1)  Otoscope
___  (2)  Dental Light
_____  (3 )  Other
______  (2)  
Local anesthetic used
Notes:  Patient asked to rate oral pain using the Painometer and to rate dryness verbally (0 
= none to 10= worst):
Oral pain: 
______
Pain on swallowing ______
Dryness in mouth
______
Dryness in throat:
______
Mouth Opening:   
_______ mm    


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Periodontal Screening:
Date: ____/____/____    LIP print name:                                              LIP Signature:____________________________
Time: ____________       
Instrument
Variable Assessed
Mild 
Inflammation=0
.1-1.0
Moderate 
Inflammation=1
.1-2.0
Severe 
Inflammation=
2.1-3.0
Gingival Index
(Harald Löe)
Qualitative change of 
the gingival soft 
tissues
Instrument
Variable Assessed
Excellent 
Plaque 
Control=0
Good 
Plaque 
Control=0.1
-0.9
Fair Plaque 
Control=1.0
-1.9
Poor Plaque 
Control=2.0-
3.0
Plaque Index
(Silness and Löe)
The severity and 
location of the soft 
debris aggregates
Instructions:  
Gingival Index
Upon palpation of the gingiva and running a blunt instrument (periodontal probe) along the 
soft tissue wall of the entrance of the gingival crevice the gingiva is examined and categorized 
the following way:
GI=0:  is the score given to the gingiva the color of which is pale pink to pink.  The surface 
after drying is matt.  The degree of stippling may vary.  The gingival margin may be located 
on the enamel or at various levels apical to the cemento-enamel junction.  Although the margin 
should be thin, the buccal and lingual gingiva may present a rounded termination against the 
tooth, thereby forming the entrance or orifice of the gingival crevice.  The form of the 
interdental gingiva depends on the space and size of the interdental areas.  The tip of the papilla 
should be the most incisally or occlusally located part of the gingiva.  On palpation, the gingival 
should be firm.
GI=1:  is the score given when the gingiva is subject to mild inflammation.  The gingival 
margin is slightly more reddish or bluish-reddish than normal and there is slight edema of the 
margin.  A colorless gingival exudate may be observed or collected at the entrance of the 
crevice.  Bleeding is not provoked.
GI=2:  This is the score for a moderately inflamed gingiva.  The gingiva is red or reddish-blue 
and glazy.  There is enlargement of the margin due to edema.  Bleeding is provoked.
GI=3:  is the score for severe inflammation.  The gingiva is markedly red or reddish-blue and 
enlarged.  There is a tendency to spontaneous bleeding. Ulceration may be seen.
Plaque Index
    PI=0:  This score is given when the gingival area of the tooth surface is literally free of 
plaque.  The surface is tested by running a pointed probe across the tooth surface at the entrance 
of the gingival crevice after the tooth has been properly dried, and if no soft matter adheres to 
the point of the probe, the area is considered clean.


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PI=1:  This score is given when no plaque can be observed in situ by the unarmed eye, but 
when the plaque is made visible on the point of the probe after this has been moved across the 
tooth surface at the entrance of the gingival crevice. 
PI=2:  This score is given when the gingival area is covered with a thin to moderately thick 
layer of plaque.  The deposit is visible to the naked eye.
PI=3:  Heavy accumulation of soft matter, the thickness of which fills out the niche produced 
by the gingival margin and the tooth surface.  The interdental area is stuffed with soft debris.
Scoring For both indices, scores are given for distal, buccal, mesial and lingual surfaces.  The scores are 
added together and divided by the number of surfaces scored (4), and then divided by the number of teeth 
scored (6).  This is your Gingival Index or Plaque Index score.
VISUAL ANALOG SCALE FOR XEROSTOMIA
Date: ____/____/____    LIP print name:                                          LIP Signature:____________________________


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NUMERIC RATING SCALES (0-10) FOR ORAL PAIN, SENSITIVITY, AND DRYNESS 
ORAL PAIN/SENSITIVITY
On a 0 to 10 scale, how SENSITIVE or PAINFUL was your mouth at its WORST in the past 
month?     Please circle the number.
0
1
2
3
4
5
6
7
8
9
10
No sensitivity
            Worst 
sensitivity
ORAL DRYNESS
On a 0 to 10 scale, how DRY is your mouth at its WORST in the past month? Please circle 
the number.
0
1
2
3
4
5
6
7
8
9
10
No dryness
Worst dryness
Global Scale
Compared to one month ago, what is the overall condition of your mouth? Please circle.
Much worse
A little worse
Same
A little better
Much better
LIP Print Name:                                            LIP Signature:_____________________________
Date of Evaluation:________


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ORAL HEALTH IMPACT PROFILE (OHIP-14)
Date: ____/____/____    LIP print name:                                                   LIP 
Signature:______________________________
#
Because of problems with your teeth, 
denture or mouth have you…
Never (0)
Hardly 
ever (1)
Occasionally 
(2)
Often 
(3)
Very 
Often 
(4)
1
Had trouble pronouncing words
 
 
 
 
 
2
Felt sense of taste has worsened
 
 
 
 
 
3
Had painful aching in the mouth
 
 
 
 
 
4
Found it uncomfortable to eat any foods
 
 
 
 
 
5
Have been self-conscious
 
 
 
 
 
6
Felt tense
 
 
 
 
 
7
Had an unsatisfactory diet
 
 
 
 
 
8
Had to interrupt meals
 
 
 
 
 
9
Found it difficult to relax
 
 
 
 
 
10
Have been a bit embarrassed
 
 
 
 
 
11
Have been irritable with other people
 
 
 
 
 
12
Had difficulty doing usual jobs
 
 
 
 
 
13
Felt life in general was less satisfying
 
 
 
 
 
14
Have been totally unable to function
 
 
 
 
 
Total ________________________________


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16.17.3Component 3: Vaginal/Vulvar
16.17.3.1
Vaginal/Vulvar-Initial assessment form
Note: patient won't be referred if less than 16
Patient Name: ______________                  Patient MR #: _________________
Date of Assessment: ________ 
1. CAS – Initial assessment
Please, check all boxes that pertain
NORMAL=0
MILD=1
MODERATE=2
SEVERE=3
Vulva OR Vagina
     
Vulva
Vulva
Severe Vulva OR Vagina
Erythema around 
openings of 
vestibular glands
OR
Erosions on flat 
surfaces most 
notable on 
vulva
OR
Vulvar architectural 
changes such as 
nearly complete 
resorption of the labia 
minora and clitoral 
agglutination
OR
Generalized 
erythema / edema 
of vulva including 
vestibule 
OR
Fissures in 
vulvar folds 
(e.g. interlabial 
sulci; 
fourchette)
OR
Vaginal synechiae 
including shortened 
vagina
OR
No symptoms
Periurethral or 
other patchy 
erythema
OR
Increased 
friability of 
vulvar mucosa
Hematocolpos
OR


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NORMAL=0
MILD=1
MODERATE=2
SEVERE=3
Introital stenosis
OR
Leukokeratosis 
(r/o HPV)
Myofascial 
pain/spasm of levator 
or pelvic floor 
muscles
Overall stage (determined by most severe finding): __________
2. Not in CAS – Gynecologic history
Reason for BMT::_______________________________________________________
Type of BMT:__________________________________________________________
Date(s) of BMT:________________________________________________________
Current immunosuppressive medications:
______________________________________________________________________
3. Menstrual history: 
     How old were you when you first had a period? _______________________
     Were your periods regular before you had your BMT?  Yes/No 
    Are you still getting periods?   Yes/No
  When was your last menstrual period? ______________________________


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    Did your BMT or other treatment affect your periods?  Yes/No
       If yes, how?   Less frequent/ More frequent/ Stopped
Describe________________________________________________________
 
4. Hormone use:
Did you use hormones after your BMT?  Yes/No 
     If yes, which ones (Check all that apply) 
5. Combined hormones
Birth control pills:  
     Yes / No        Dates:_____________________
Prempro:
 
      Yes / No       Dates:_____________________
Estradiol/prog (FemHRT) Yes / No       Dates:_____________________
Estrodiol/test (Estratest)  Yes / No       Dates:_____________________
Other: _______________________       Dates: ____________________
6. Menopausal hormones – estrogens:
Estrogen oral pill:              Yes/No     Dates: _________________________
Estrogen topical cream:   Yes/No     Dates: _________________________
Estrogen vaginal pill:        Yes/No    Dates: _________________________
Estrogen patch:                 Yes/No    Dates: _________________________
Estrogen ring:                    Yes/No    Dates: _________________________
Other: _______________________   Dates: _________________________
7. Menopausal hormones – progesterone:
Progesterone:                     Yes/No     Dates: ________________________
Provera:                               Yes/No     Dates: ________________________
Other: _______________________     Dates: ________________________
 


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Are you currently taking hormones?  Yes/No     
Specify _________________________________________________________
Any contraindications to hormone use?  Yes/No     
Specify _________________________________________________________
8. Gynecologic surgery history:
Have you ever had gynecology surgery?  Yes/No
           Specify what surgery and year ______________________________________
 
Do you still have a uterus?  Yes/No 
Do you still have your ovaries?  Yes/No 
 
9. Pap smear history: 
Have you ever had an abnormal pap?  Yes/No; if yes, when?_____________
 
What was done?  _________________________________________________    
 
When was your last pap smear? ____________________________________
 
Was it normal or abnormal? ________________________________________
10. STD history:
Have you ever been told you have had any of the following?
Chlamydia:          Yes/No
Gonorrhea:          Yes/No
Genital herpes:   Yes/No
Warts or HPV:     Yes/No


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Dysplasia:           Yes/No
 
11. Obstetric history:
Have you ever been pregnant?              Yes/No   How many times? ________
12. Sexual history:
Have you ever been sexually active?   Yes/No
Are you sexually active currently?        Yes/No
Have you had intercourse since your transplant? Yes/No
Describe __________________________________________________________ 
13. Not in CAS - Questions addressing pain when the vulva is touched
 Do you have pain when nothing is touching the vulva?   Yes/No
 
Do you have vulvar pain or burning when you urinate?   Yes/No
           If yes, is this when the urine touches the vulva?              Yes/No
           If yes, does the pain makes you want to urinate?             Yes/No
 Do you have vulvar pain or burning when you: 
Insert a tampon:                                  Yes/No/NA                                             
Wear tight jeans or pants:                  Yes/No/NA
When you ride a bike:                         Yes/No/NA
During foreplay:                                  Yes/No/NA 
When the penis touches the vulva:   Yes/No/NA
 
Does the vulvar pain prevent or interrupt intercourse?    Yes/No/NA
Do you have pain with deep penetration of the penis?     Yes/No/NA
Have you been told there is scarring in the vagina?         Yes/No/NA


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Do you think there is scarring in the vagina?                    Yes/No/unknown
__________________        ____________________                    ____________    
               Signature                          Printed Name                                      Date          


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16.17.3.2
   Vaginal/Vulvar-follow-up form 
1.   CAS – Initial assessment                  
•
Please check all boxes that pertain
NORMAL=0
MILD=1
MODERATE=2
SEVERE=3
Vulva OR Vagina
Vulva
Vulva
Severe Vulva OR Vagina
Erythema around 
openings of 
vestibular glands
OR
Erosions on flat 
surfaces most 
notable on 
vulva
OR
Vulvar architectural 
changes such as 
nearly complete 
resorption of the 
labia minora and 
clitoral agglutination
OR
Generalized 
erythema / 
edema of vulva 
including 
vestibule 
OR
Fissures in 
vulvar folds 
(e.g. interlabial 
sulci; 
fourchette)
OR
Vaginal synechiae 
including shortened 
vagina
OR
Periurethral or 
other patchy 
erythema
OR
Increased 
friability of 
vulvar mucosa
Hematocolpos
OR
Introital stenosis
OR
No symptoms
Leukokeratosis 
(r/o HPV)
Myofascial 
pain/spasm of levator 
or 
pelvic 
floor 
muscles
Overall stage (determined by most severe finding): __________


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2. Not in CAS – Gynecologic follow-up
History and Clinical course since last visit ________________________________
______________________________________________________________________________
______________________________________________________________________________
______________________________________________________
Current systemic immunosuppressive medications _________________________
______________________________________________________________________________
______________________________________________________________
•
Have you used topical temovate on the vulva since your last visit? Yes / No       
Describe use and effect _______________________________________________
____________________________________________________________________
•
Have you used hormone therapy since your last visit?  Yes / No     
Specify _________________________________________________________
Describe use and effect _______________________________________________
Pap smear: 
 
•
When was your last pap smear? ____________________________________
 
•
Was it normal or abnormal? ________________________________________
 
Sexual history:
•
Have you been sexually active since your last visit?   Yes / No
•
If yes, was it painful?   
Yes / No   
•
Did you have pain after intercourse?  
Yes / No    
•
If yes, How long did the pain last?_________
Any other comments:________________________________________________
________________________________________________________________
Do you have pain when nothing is touching the vulva?   Yes / No/ NA
 
Do you have vulvar pain or burning when you urinate?   Yes / No/ NA


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           If yes, is this when the urine touches the vulva?              Yes / No/ NA
           If yes, does the pain makes you want to urinate?             Yes / No/ NA
 
Do you have vulvar pain or burning when you: 
                                                
• Wear tight jeans or pants:                  Yes / No/ NA
• When you ride a bike:                         Yes / No/ NA
• During foreplay:                                  Yes / No / NA
• When the penis touches the vulva:   Yes / No/ NA
      Since the last visit:
•
Does the vulvar pain prevent or interrupt intercourse?    Yes / No/ NA
•
Do you have pain with deep penetration of the penis?     Yes / No/ NA
•
Have you been told there is scarring in the vagina?         Yes / No/ NA
•
Do you think there is scarring in the vagina?                    Yes / No/ unknown
RECOMMENDATIONS: __________________________________________________            
______________________________________________________________________
__________________        ____________________                    ____________    
               Signature                          Printed Name                                      Date                                         


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16.17.4 Component 3: Function  
Description
There are standard ranges for all tests. Every joint has an established range of motion (ROM). 
For example, the normal ROM for shoulder flexion is 180 degrees, each quartile is 45 degrees. If 
the shoulder can be put through 125 degrees it is 75% of normal. Similar is for grip strength (in 
Kg or pounds of pressure) and for walk time. The velocity is established based on norms for age 
and sex. For example if 18 feet/second, if divided by 4 and gets quartiles. 
Patient Name: ______________                  Patient MR #: _________________
Date of Assessment: ________ 
Assessed: Yes/No      
Assessed Partially: Yes/No      
Reason if “No”: age restriction
1. CAS – Initial Assessment
•
PLEASE ASSESS in according to age restrictions for each parameter
•
Please, check off the appropriate box 
                                 Musculoskeletal findings
Parameter
NORMAL=0
     
MILD=1
MODERATE=2
SEVERE=3
ROM*
Assess 
if patient ≥ 4
0-25%
26-50%
51-75%
>75%
grip strength*
Assess 
if patient ≥ 6
0-25%
26-50%
51-75%
I.
>
75%
walk velocity*
Assess 
if patient ≥ 6
0-25%
26-50%
51-75%
II.
>
75%
HAP*
Assess 
if patient ≥ 16
>81
73-81
61-72
<61


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* Reduction in maximal performance
Overall stage (max3): __________
Total score (max 12): __________
** Please provide the actual result of reduction in maximal performance
*** Please provide the actual result as % of predicted
__________________        ____________________                    ____________    
       Signature                                     Printed Name                                      Date                                         
Parameter
Actual Number**
% of predicted***
ROM
Trial 1
Trial 2
Trial 3
Average
Right
grip strength
Dominant Hand
R       L
Circle One
Left
walk velocity
Total Distance Walked in 2 Minutes: 
  ______    feet walked in 2 minutes
 ______    feet walked in 6 minutes 
                                           
MAS
AAS
HAP


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2. P-ROM


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3. Occupational Therapy 
1. CAS outcome measures:
Dx:  ________________________________
Date of transplant: __________________________
Date of evaluation:______________________________   
Timepoint:________________________________
Instrumental Activities of Daily Living:  
Frenchay Activities Index:________________
Activity Card Sort:______________________
Basic Self Care:
Barthel Index:_______________
Motor Function:
 Disabilities of the Arm Hand and Shoulder (DASH) score :___________________
 Manual Abilities Measure: ______________
Grooved Peg board
1. Total time dominant hand: _____________________________seconds 
2. Total time non dominant hand:_____________________________seconds 
Recommendations:
Date of Evaluation:                             __LIP 
Signature:_________________________/phone::301-451-7502


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2. Manual Ability Measure (MAM-36)
Patient ID: -------------------------
Today's Date: -----
Age:  
_
Sex: --- Highest Level of Education:  
_
Race
(White, African American, American Indian, Asian-Pacific, Mixed Races, Don't 
know)
Are you Hispanic?    
Yes,   
No
Are you currently employed? If so, what is your occupation Gob title)?
If not, what was your occupation before you were diagnosed with your current condition?
What is your diagnosis for coming to the clinic? 
_
How long ago were you diagnosed with this condition? 
_
Do you have any other medical problems that affect the use of your hands?
If you have had hand surgery, or if you have surgery scheduled, please indicate the 
date(s) and what was/will be done:
Which is your dominant hand?
Right  
,
Left  
, Ambidextrous  
, Don't know  
Which hand(s) has limited function or hand use?  Both_, Right  , Left  
,
Do you live alone now?
Yes         No  
, with 


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INSTRUCTIONS:
Please circle one response regarding how easy or how hard it is for you to 
perform the following tasks.
Easy (4) =I can do the activity  without  any problem.
A little hard (3) = I usually  do the task myself,  although  it takes longer or more effort now 
than before (i.e., before having current  diagnosis/condition/disability). Sometimes, there is pain 
or discomfort when I do the task.
Very hard (2)  = It is very hard for me to do the task and I usually ask others to do it for me 
unless no one is around.
Cannot do (1)  =I am unable to do the task all by myself.
Almost Never do (0) =I have not done and almost will never do the task, even though  I think I 
can do it.
Task
Easy
A little 
hard
Very hard Cannot do Never do
Eat a sandwich
4
3
2
1
0
Drink a glass of water
4
3
2
1
0
Pick up a half-full  water pitcher
4
3
2
1
0
Use a spoon or fork
4
3
2
1
0
Butter bread (Put butter or jam on
4 
3
2
1
0
Cut meat on a plate with a knife
4
3
2
1
0
Squeeze  toothpaste
4
3
2
1
0
Brush teeth 
:
4
3
2
1
0
Brush or comb hair 
4
3
2
1
0
Wash hands
4
3
2
1
0
Wring a towel '
4
3
2
1
0
Zip pants
4
3
2
1
0
Zip a jacket 
4
3
2
1
0
Button clothes 
4
3
2
1
0
Fasten a clothes  snap or hook
4
3
2
1
0
Cut nails with a nail clipper
4
3
2
1
0
Tie shoes with laces
4
3
2
1
0


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l
Task
Easy
A little 
hard
Very hard Cannot do Never do
Use a remote  control
4
3
2
1
0
Key in telephone numbers
4
3
2
1
0
Turn door knob to open a door 
4
3
2
1
0
Turn key to open a lock
4
3
2
1
0
Carry a shopping bag with a hand     
loop
4
3
2
1
0
Open a previously-opened wide- 
mouth jar (jam, pickle)
4
3
2
1
0
Open a previously-unopened  carton 
box (milk, cereal)
4
3
2
1
0
Pour liquid from a bottle into a glass
4
3
2
1
0
Open a medicine bottle with child- 
proof top
4
3
2
1
0
Open an envelope without a letter 
Opener
4
3
2
1
0
Peel vegetables or fruits
4
3
2
1
0
Count money (bills and coins)
4
3
2
1
0
Take things out of a wallet (bills, 
papers, credit cards)
4
3
2
1
0
Write 3 to 4 sentences legibly
4
3
2
1
0
Tum pages of a book
4
3
2
1
0
Use a hammer or screwdriver
4
3
2
1
0
Fold clothes after laundering
4
3
2
1
0
Take a CD/DVD out of its case and put 
it onto a player/drive
4
3
2
1
0


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3. Human Activity Profile
Instructions
•
Please check each activity according to these directions:
•
Check Column 1 ("Still Doing This Activity") if:
•
You completed the activity unassisted the last time you had the need or opportunity to do 
so.
•
Check Column 2 ("Have Stopped Doing This Activity") if:
•
You have engaged in the activity in the past, but you probably would not perform the activity 
today even if the opportunity should arise.
•
Check Column 3 ("Never Did This Activity") if:
•
You have never engaged in the specific activity.
  Human Activity Profile Test
Still doing         D
this activity
Have stopped         
doing  this activity 
Never did 
this activity
1.  Getting in and out of chairs 
      or bed (without assistance)
    
2.  Listening to the radio
3.  Reading books, magazines or newspapers
4.  Writing (letters, notes)
5.  Working at a desk or table
6.  Standing (for more than one minute) 
7.  Standing (for more than five minutes)
8.  Dressing or undressing (without assistance)
9.  Getting clothes from 
      drawers or closets
10. Getting in or out of a car
      (without assistance)
11. Dining at a restaurant


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  Human Activity Profile Test
Still doing         D
this activity
Have stopped         
doing  this activity 
Never did 
this activity
12. Playing cards/table games
13. Taking a bath (no assistance needed)
14. Putting on shoes, stockings or socks
      (no assistance needed)
15. Attending a movie, play, church 
      event or sports activity
16. Walking 30 yards (27 meters)
17. Walking 30 yards (non-stop)
18. Dressing/undressing (no rest
      or break needed)
19.Using public transportation or
     driving a car  (100 miles or less)
20. Using public transportation or
      driving a car (99 miles or more)
21. Cooking your own meals
22. Washing or drying dishes
23. Putting groceries on shelves
24. Ironing or folding clothes
25. Dusting/polishing furniture
      or polishing cars
26. Showering
27. Climbing six steps
28. Climbing six steps (non-stop)
29. Climbing nine steps
30. Climbing 12 steps


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  Human Activity Profile Test
Still doing         D
this activity
Have stopped         
doing  this activity 
Never did 
this activity
31. Walking ½ block on level ground
32. Walking ½ block on
       level ground (non-stop)
33. Making a bed (not changing sheets)
34. Cleaning windows
35. Kneeling, squatting to do light work
36. Carrying a light load of groceries
37. Climbing nine steps (non-stop)
38. Climbing 12 steps (non-stop)
39. Walking ½ block uphill
40. Walking ½ block uphill (non-stop) 
41. Shopping (by yourself)
42. Washing clothes (by yourself)
43. Walking one block on level  
       ground  
44. Walking two blocks on level 
       ground
45. Walking one block on level 
      ground (non-stop)
46. Walking two blocks on level 
      ground (non-stop)
47. Scrubbing (floors, walls or cars)
48. Making beds (changing sheets)


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  Human Activity Profile Test
Still doing         D
this activity
Have stopped         
doing  this activity 
Never did 
this activity
49. Sweeping
50. Sweeping (five minutes 
      non-stop)
51. Carrying a large suitcase or 
       bowling (one line)
52. Vacuuming carpets
53. Vacuuming carpets 
      (five minutes non-stop)
54. Painting (interior/exterior)
55. Walking six blocks on level    
       ground
56. Walking six blocks on level 
       ground (non-stop)
57. Carrying out the garbage
58. Carrying a heavy load
       of groceries
59. Climbing 24 steps
60. Climbing 36 steps
61. Climbing 24 steps (non-stop)
62. Climbing 36 steps (non-stop)
63. Walking one mile
64. Walking one mile (non-stop)
65. Running 110 yards (100 meters)
      or playing softball/baseball


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  Human Activity Profile Test
Still doing         D
this activity
Have stopped         
doing  this activity 
Never did 
this activity
66. Dancing (social)
67. Doing calisthenics or aerobic
      dancing (5 minutes non-stop)
68. Mowing the lawn (power mower,
      but not a riding mower)
69. Walking two miles
70. Walking two miles (non-stop)
71. Climbing 50 steps
72. Shoveling, digging or spading
73. Shoveling, digging or spading
      (five minutes non-stop)
74. Climbing 50 steps (non-stop)
75. Walking three miles or golfing
       18 holes without a riding cart
76. Walking three miles (non-stop)
77. Swimming 25 yards
78. Swimming 25 yards (non-stop)
79. Bicycling one mile
80. Bicycling two miles
81. Bicycling one mile (non-stop)
82. Bicycling two miles (non-stop)
83. Running or jogging ¼ mile
84. Running or jogging ½ mile


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  Human Activity Profile Test
Still doing         D
this activity
Have stopped         
doing  this activity 
Never did 
this activity
85. Playing tennis or racquetball
86. Playing basketball (game play)
87. Running or jogging ¼ mile (non-stop)
88. Running or jogging ½ mile (non-stop)
89. Running or jogging one mile
90. Running or jogging two miles
91. Running or jogging three miles
92. Running or jogging one mile in 
      12 minutes or less
93. Running or jogging two miles
      in 20 minutes or less
94. Running or jogging three
      miles in 30 minutes or less


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16.17.5Component 4: Eyes
Patient Name: 
Patient MR#:
Date of Assessment:  
Assessed: Yes 
No 
Age Restriction
Reason if "NO":
1.
CAS - Initial assessment
PLEASE ASSESS if  patient is 9 years old and older
Please Check off the boxes (grade the worst eye)
 1+ = few separated spots
2+ = many separated spots
3+ = confluent spots
None = 0
Mild = 1
Moderate = 2
Severe = 3
Schirmer's without
Anesthesia
> 10 mm
Schirmer's without
Anesthesia
7 to 10 mm
Schirmer's without
Anesthesia
3 to 6 mm
Schirmer's without
Anesthesia
< 3 mm
X
No 
punctate 
keratopath
Mild 
punctate 
keratopathy
Moderate 
punctate 
keratopathy
Severe 
punctate 
keratopathy
X
Grade 0
No 
conjunctival 
disease
X
Grade 1 
conjunctival 
hyperemia 
occuring on 
the bulbar or 
palpebral 
conjuctiva.
Grade 2
palpebral conjunctival 
fibrovascular changes 
occuring along the superior 
border of the upper eyelid, or 
the lower border of the tarsal 
plate of the lower eyelid, with 
or without conjuctival 
epithelial sloughing, 
involving < 25 % of the total 
surface area
OR
Grade 3
palpebral conjunctival 
fibrovascular changes 
occuring along the superior 
border of the upper eyelid, or 
the lower border of the tarsal 
plate of the lower eyelid, 
involving 25 to 75 % of
Grade 3
> 75 % of the 
total surface 
area with or 
without a 
cicatricial 
entropion.


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Schirmer’s without Anesthesia: 
Rt eye____ mm     Lf eye____mm 
Schirmer’s with Anesthesia*: 
Rt eye____ mm     Lf eye____mm
Overall Stage (max 3) :------ 
Total Score (max 9): ---------
2.
.Not in CAS - Ocular Symptoms
Dryness
Redness
Irritation
None
Mild
Moderate
Severe
None
Mild
Moderate
Severe
None
Mild
Moderate
Severe
Right 
Eye
X
X
X
Left 
Eye
X
X
X
3.
Not in CAS - Recommended therapy:
Recommended Therapy
None
Ocular 
lubrication
topical restasis 
or
topical 
corticosteroids
Punctual 
occlusion
Other
X
X
X
discussed ASED and scleral 
contact lenses
4.
Composite Assessment Scale:
Test
Grade 0 
(none)
Grade 1 
(mild)
Grade 2 
(moderate)
Grade 3 
(severe)
Schirmer’s Tear 
Test (without 
Anesthesia)
> 10 mm
7-10 mm
3-6 mm
< 3 mm
Punctate 
Keratopathy
None
1+ = few 
separated spots
2+ = many 
separated spots
3+ = confluent 
spots


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Conjunctival 
Inflammation 
and Scarring
(see scheme 
below)
No conjunctival 
disease
Grade 1
Grade 2 or 3
Grade 4
Examined by:  ----------------------------------------------------          -----------------------------------
                                                                                                           Date
 
__________________        ____________________                    ____________   
Signature                                    Printed Name                                      Date
16.18   APPENDIX R: CHRONIC GVHD COMPOSITE ASSESSMENT SCALE BARTHEL INDEX 
SCORE
Patient Name:________________________  MR #:________________________
Rater Name:  _________________________  Date:  _______________________
Activity
Score
Ratings
Feeding
  0=unable
  5=needs help cutting, spreading butter, etc., or requires modified  diet
10= independent 
Bathing
  0=dependent
  5=independent
Grooming
  0=needs help with personal care
  5=independent with face/hair/teeth/shaving (implements provided)


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Dressing
  0=dependent
  5=needs help but can do about half unaided
10= independent (including buttons, zippers, laces, etc.)
Bowels
  0=incontinent (or needs to be given enemas)
  5=occasional accidents 
10= continent
Bladder
  0=incontinent, or catherized and unable to manage alone
  5=occasional accidents 
10= continent
Toilet Use
  0=dependent 
  5=needs some help, but can do something alone
10= independent (on and off, dressing and wiping)
Transfers (Bed 
to chair and Back) 
  0=Unable, no sitting balance 
  5=major help (one or two people, physical), can sit
10=Minor help (verbal or physical)
15=independent
Mobility  (on 
level surfaces)  
  0=Immobile < 50 yards) 
  5=wheelchair independent, including corners>50 yards
10=walks with help of one person (verbal or physical)>50 yards
15=independent (may use any aid; for example cane or walker)>50 yards 
Stairs
  0=unable 
  5=needs help (verbal, physical, carrying aid)
10= independent  
Total Score: (0-100) ________________ 
______________________
____________________________
       ______________
Signature:    
Printed Name:
Date:  


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16.19 APPENDIX S: CHRONIC GVHD COMPOSITE ASSESSMENT SCALE FRENCHAY ACTIVITIES 
INDEX
Patient Name:________________________MR #:________________________
Rater Name:  _________________________  Date:  _______________________
In the last 3 months, how often have you undertaken:
Task 
Number
Task Description: Domestic Chores
Score
Ratings:  
0=Never
1= Less than once a week
2=1-2 times per week
3=Most days
1.
Preparing main meals
2.
Washing up after meals
Subtotal Domestic Chores : (__/6)
In the last 3 months, how often have you undertaken:
Task Number
Task Description: Leisure/work
Score
Ratings:  
0=Never
1= 1-2 times in 3 months 
2= 3-12 times in 6 months
3=At least weekly
3.
Washing clothes
4.
Light Housework
5.
Heavy Housework
6.
Local Shopping
7.
Social Occasions
8.
Walking outside for >15 minutes
9.
Actively pursuing a hobby
10.
Driving a car/going on bus


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Subtotal Leisure/Work: (____/24)
In the last 6 months how often have you undertaken:
Task 
Number
Task Description: Outdoor 
Score
Ratings: 
11.
Travel outing/car ride
0=Never
1=1-2 times in 6 months
2=3-12 times in 6 months
3= at last weekly
12.
Gardening
0=Never
1=Light
2=Moderate
3=Heavy/All necessary
13.
Household Maintenance
0=Never
1=Light
2=Moderate
3=Heavy/All necessary
14.
Reading Books
0=None
1=1 in 6 months
2=Less than 1 in 2 weeks
3= More than 1 every 2 weeks
15.
Gainful Work
0=None
1=Up to 10 hours/week
2=10-30 hours/week
3=Over 30 hours/week
Subtotal Outdoor:    (___/15)
Total Score:  _____/45
______________________
____________________________
       ______________
Signature:    
Printed Name:
Date:  


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Revised guidelines for using the Frenchay Activities Index
The aim is to record activities which require some initiative from the patient. It is important to 
concentrate upon the patient’s actual frequency of activity over the recent past, not distant past 
performance nor potential performance. One activity can only score on one item.
Specific item information:
1. Needs to play a substantial part in the organization, preparation and cooking of main 
meal. Not just making snacks or reheating prepared food.
2. Must do all or share equally, e.g. washing or wiping and putting away. Not just rinsing an 
occasional item.
3. Organization of washing and drying clothes, whether in washing machine, or by hand or 
at laundromat. Sharing task equally, e.g. loading, unloading, hanging, folding.
4. Dusting, polishing, ironing, tidying small objects or bedclothes. Anything heavier is 
included in item 5.
5. All heavier housework including changing beds, cleaning floors, fires and windows, 
vacuuming, moving chairs, etc. 
6. Playing a substantial role in organizing and buying groceries, whether small or large 
amounts. Must go to the shop and not just push a cart. Can include collection of pension 
or going to the Post Office. 
7. Going out to clubs, church activities, cinema, theatre, drinking, to dinner with friends, 
etc. May be transported there, provided patient takes an active part once arrived. Includes 
social activities at home, initiated by the patient, e.g. visits from family or friends not 
where main purpose is to provide care.
8. Sustained walking for at least 15 minutes (allowed short stops for breath). About one 
mile. Can include walking to do shopping, provided walks far enough.
9. Must require some ‘active’ participation and thought, e.g. propagating or caring for 
houseplants, knitting, painting, games, sports (not just watching sport on television). Can 
be mental activities, e.g. reading specialist magazines, doing the stocks and shares or 
window shopping for pleasure. 
10. Must drive a car (not just be a passenger), or get to a bus/coach and travel on it 
independently.
11. Coach or rail trips or car rides to some place for pleasure. Not for a routine ‘social outing’ 
(i.e. shopping, going to local friends). Must involve some organization and decision-
making by the patient. Excludes trips organized passively by institutions unless patient 
exercises choice on whether to go. The common factor is travel for pleasure. Holidays 
within the six months are divided into days per month e.g. a 7-day holiday equals 1 or 2 
days per month.
12. Gardening outside:
a.
Light = occasional weeding or sweeping paths
b. Moderate = regular weeding, raking, pruning, etc.
c.
Heavy = all necessary work including heavy digging.
13. Household maintenance:
a.
Light = repairing small items, replacing lamp lightbulb or plug
b. Moderate = spring cleaning, hanging a picture, routine car maintenance
c.
Heavy = painting/decorating, most necessary household/car maintenance.


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14. Must be full-length books, not periodicals, magazines or newspapers. Can be talking books.
15. Work for which the patient is paid, not voluntary work. The time worked should be averaged 
out over six months. For example, one month working for 18 hours/week over the six-month 
period would be scored as ‘up to 10 hours/week’.


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16.20 APPENDIX T: QUALITY OF LIFE ASSESSMENTS (OBTAINED AT BASELINE THEN 
YEARLY)


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Today’s Date: ________________________
MR#/Name: ________________________


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B. CHRONIC GVHD ACTIVITY ASSESSMENT-PATIENT SELF REPORT
Symptoms
Please rate how severe the following 
symptoms have been in the last seven 
days.  Please fill in the circle below from 0 
(symptom has not been present) to 10 
(the symptom was as bad as you can 
imagine it could be) for each item.
Not                                                                                                                                             As Bad As You
Present                                                                                                                                         Can Imagine
   
  0               1            2            3             4            5            6            7            8             9         10
Your skin itching at its WORST?
O
O
O
O
O
O
O
O
O
O
O
Your mouth dryness at its WORST?
O
O
O
O
O
O
O
O
O
O
O
Your mouth pain at its WORST?
O
O
O
O
O
O
O
O
O
O
O
Your mouth sensitivity at its WORST?
O
O
O
O
O
O
O
O
O
O
O
What is your main complaint with regard to your eyes?
Eyes
Please rate how severe is this eye symptom, between 0 
(not at all severe) and 10 (most severe):
0    1     2     3     4     5     6     7     8      9    10
Vulvovaginal Symptom
(females only)
Do you have any burning, pain or discomfort in the area 
of your vagina, vulva or labia?  
OR
Do you have any discomfort or pain with sexual 
intercourse?
o
Yes
o
No
o
Not applicable
Patient Global Ratings:
1. Overall, do you think that your chronic graft versus host disease is mild, moderate or severe?
1= mild
2=moderate
3=severe
2. Please circle the number indicating how severe your chronic graft versus host disease symptoms are, where 0 is cGvHD 
symptoms that are not at all severe and 10 is the most severe chronic GvHD symptoms possible.
          0         1           2           3           4           5           6           7           8            9           10
cGvHD symptoms                                                                                                                                       Most severe cGvHD                                                                                         
not at all severe                                                                                                                                                    symptoms                                                                                               
                                                                                                                                                                                possible
3. Compared to a month ago, overall would you say that your cGvHD symptoms are:
+3= Very much better
+2= Moderately better
+1=A little better
 0= About the same
-1=A little worse
-2=Moderately worse
-3=Very much worse


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Attach copies of:
Adults (persons 18 years or older):
Children/Adolescents (persons 17 years or younger):
-Lee cGvHD Symptom Scale 
-Lee cGvHD Symptom Scale (persons 8-12 years old may
-Human Activity Profile
                                 complete with help of the health care professional)  
-SF036
                -ASK-p38 Activities Scale for Kids
-FACT-BMT 
-VARNI-Generic and Disease Specific Inventory
Today’s Date: ________________________
MR#/Name: ________________________


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C. Human Activity Profile
Instructions
•
Please check each activity according to these directions:
•
Check Column 1 ("Still Doing This Activity") if:
•
You completed the activity unassisted the last time you had the need or opportunity to do 
so.
•
Check Column 2 ("Have Stopped Doing This Activity") if:
•
You have engaged in the activity in the past, but you probably would not perform the activity 
today even if the opportunity should arise.
•
Check Column 3 ("Never Did This Activity") if:
•
You have never engaged in the specific activity.
  Human Activity Profile Test
Still doing          
this activity
Have stopped         
doing this activity  
Never did 
this activity
1.  Getting in and out of chairs 
      or bed (without assistance)
    
2.  Listening to the radio
3.  Reading books, magazines or newspapers
4.  Writing (letters, notes)
5.  Working at a desk or table
6.  Standing (for more than one minute) 
7.  Standing (for more than five minutes)
8.  Dressing or undressing (without assistance)
9.  Getting clothes from 
      drawers or closets
10. Getting in or out of a car
      (without assistance)


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  Human Activity Profile Test
Still doing          
this activity
Have stopped         
doing this activity  
Never did 
this activity
11. Dining at a restaurant
12. Playing cards/table games
13. Taking a bath (no assistance needed)
14. Putting on shoes, stockings or socks
      (no assistance needed)
15. Attending a movie, play, church 
      event or sports activity
16. Walking 30 yards (27 meters)
17. Walking 30 yards (non-stop)
18. Dressing/undressing (no rest
      or break needed)
19.Using public transportation or
     driving a car  (100 miles or less)
20. Using public transportation or
      driving a car (99 miles or more)
21. Cooking your own meals
22. Washing or drying dishes
23. Putting groceries on shelves
24. Ironing or folding clothes
25. Dusting/polishing furniture
      or polishing cars
26. Showering
27. Climbing six steps
28. Climbing six steps (non-stop)
29. Climbing nine steps


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  Human Activity Profile Test
Still doing          
this activity
Have stopped         
doing this activity  
Never did 
this activity
30. Climbing 12 steps
31. Walking ½ block on level ground
32. Walking ½ block on
       level ground (non-stop)
33. Making a bed (not changing sheets)
34. Cleaning windows
35. Kneeling, squatting to do light work
36. Carrying a light load of groceries
37. Climbing nine steps (non-stop)
38. Climbing 12 steps (non-stop)
39. Walking ½ block uphill
40. Walking ½ block uphill (non-stop) 
41. Shopping (by yourself)
42. Washing clothes (by yourself)
43. Walking one block on level  
       ground  
44. Walking two blocks on level 
       ground
45. Walking one block on level 
      ground (non-stop)
46. Walking two blocks on level 
      ground (non-stop)
47. Scrubbing (floors, walls or cars)


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  Human Activity Profile Test
Still doing          
this activity
Have stopped         
doing this activity  
Never did 
this activity
48. Making beds (changing sheets)
49. Sweeping
50. Sweeping (five minutes 
      non-stop)
51. Carrying a large suitcase or 
       bowling (one line)
52. Vacuuming carpets
53. Vacuuming carpets 
      (five minutes non-stop)
54. Painting (interior/exterior)
55. Walking six blocks on level    
       ground
56. Walking six blocks on level 
       ground (non-stop)
57. Carrying out the garbage
58. Carrying a heavy load
       of groceries
59. Climbing 24 steps
60. Climbing 36 steps
61. Climbing 24 steps (non-stop)
62. Climbing 36 steps (non-stop)
63. Walking one mile
64. Walking one mile (non-stop)


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  Human Activity Profile Test
Still doing          
this activity
Have stopped         
doing this activity  
Never did 
this activity
65. Running 110 yards (100 meters)
      or playing softball/baseball
66. Dancing (social)
67. Doing calisthenics or aerobic
      dancing (5 minutes non-stop)
68. Mowing the lawn (power mower,
      but not a riding mower)
69. Walking two miles
70. Walking two miles (non-stop)
71. Climbing 50 steps
72. Shoveling, digging or spading
73. Shoveling, digging or spading
      (five minutes non-stop)
74. Climbing 50 steps (non-stop)
75. Walking three miles or golfing
       18 holes without a riding cart
76. Walking three miles (non-stop)
77. Swimming 25 yards
78. Swimming 25 yards (non-stop)
79. Bicycling one mile
80. Bicycling two miles
81. Bicycling one mile (non-stop)
82. Bicycling two miles (non-stop)


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  Human Activity Profile Test
Still doing          
this activity
Have stopped         
doing this activity  
Never did 
this activity
83. Running or jogging ¼ mile
84. Running or jogging ½ mile
85. Playing tennis or racquetball
86. Playing basketball (game play)
87. Running or jogging ¼ mile (non-stop)
88. Running or jogging ½ mile (non-stop)
89. Running or jogging one mile
90. Running or jogging two miles
91. Running or jogging three miles
92. Running or jogging one mile in 
      12 minutes or less
93. Running or jogging two miles
      in 20 minutes or less
94. Running or jogging three
      miles in 30 minutes or less
Today’s Date: ________________________
MR#/Name: ________________________


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D. Disabilities of the Arm, Shoulder and Hand. 


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Today’s Date: ________________________
MR#/Name: ________________________


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E. PRO-CTCAE for Pomalidomide
As individuals go through treatment for their cancer they sometimes experience different 
symptoms and side effects.   
For each question, please check or mark an X in the one box that best describes your experiences 
over the past 7 days…
FATIGUE, TIREDNESS OR LACK OF ENERGY
What was the SEVERITY of your FATIGUE, TIREDNESS, OR LACK OF ENERGY at its 
WORST?
Ο  None
Ο Mild
Ο Moderate
Ο Severe
Ο Very severe
How much did FATIGUE, TIREDNESS, OR LACK OF ENERGY at its WORST 
INTERFERE with your usual or daily activities?
Ο Not at all
Ο A little bit
Ο Somewhat
Ο Quite a bit
Ο Very much
NUMBNESS OR TINGLING IN YOUR HANDS OR FEET
What was the SEVERITY of your NUMBNESS OR TINGLING IN YOUR HANDS OR 
FEET at its WORST?
Ο None
Ο Mild
Ο Moderate
Ο Severe
Ο Very severe
How much did NUMBNESS OR TINGLING IN YOUR HANDS OR FEET INTERFERE 
with your usual or daily activities?
Ο Not at 
all
Ο A little bit
Ο Somewhat
Ο Quite a bit
Ο Very much
 PAIN
How OFTEN did you have PAIN?
Ο Never
Ο Rarely
Ο Occasionally
Ο Frequently
Ο Almost constantly
What was the SEVERITY of your PAIN at its WORST?
Ο None
Ο Mild
Ο Moderate
Ο Severe
Ο Very severe
How much did PAIN INTEREFERE with your usual or daily activities?
Ο Not at 
all
Ο A little 
bit
Ο Somewhat
Ο Quite a bit
Ο Very much


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CONSTIPATION
What was the SEVERITY of your CONSTIPATION at its WORST?
Ο None
Ο Mild
Ο Moderate
Ο Severe
Ο Very severe
PROBLEMS WITH CONCENTRATION
What was the SEVERITY of your PROBLEMS WITH CONCENTRATON at their WORST?
Ο None
Ο Mild
Ο Moderate
Ο Severe
Ο Very severe
How much did PROBLEMS WITH CONCENTRATION INTERFERE with your usual or 
daily activities?
Ο Not at all
Ο A little bit
Ο Somewhat
Ο Quite a bit
Ο Very much
TREMORS
How OFTEN did you have TREMORS?
Ο Never
Ο Rarely
Ο Occasionally
Ο Frequently
Ο Almost 
constantly
What was the SEVERITY of your TREMORS at their WORST?
Ο None
Ο Mild
Ο Moderate
Ο Severe
Ο Very severe
OTHER SYMPTOMS
Do you have any other symptoms that you wish to report?
Ο Yes
Ο No
Please list any other symptoms:
1.
What was the severity of this symptom at its WORST?
O  None  O Mild  O Moderate  O Severe  O Very Severe
2.
What was the severity of this symptom at its WORST?
O  None  O Mild  O Moderate  O Severe  O Very Severe
3.
What was the severity of this symptom at its WORST?


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O  None  O Mild  O Moderate  O Severe  O Very Severe
Today’s Date: ________________________
MR#/Name: ________________________

ICF_004.pdf: 
MEDICAL RECORD 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
• 
Adult Patient or 
• Parent, for Minor Patient 
INSTITUTE: 
National Cancer Institute 
STUDY NUMBER: 
12-C-0197 
PRINCIPAL INVESTIGATOR: 
Steven Pavletic, MD 
STUDY TITLE:  
A Randomized Phase 2 Single-Center Study of Pomalidomide for Chronic GvHD 
 
 
Continuing Review Approved by the IRB on 11/13/17 
Amendment Approved by the IRB on 10/25/18  (J) 
 
                  Date Posted to the Web: 10/31/18 
Standard 
PATIENT IDENTIFICATION 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
• 
Adult Patient or 
• Parent, for Minor Patient 
NIH-2514-1 (07-09) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent (1) 
 
 
INTRODUCTION 
We invite you to take part in a research study at the National Institutes of Health (NIH). 
First, we want you to know that: 
Taking part in NIH research is entirely voluntary.  
You may choose not to take part, or you may withdraw from the study at any time.  In 
either case, you will not lose any benefits to which you are otherwise entitled.  However, 
to receive care at the NIH, you must be taking part in a study or be under evaluation for 
study participation. 
You may receive no benefit from taking part.  The research may give us knowledge that 
may help people in the future. 
Second, some people have personal, religious or ethical beliefs that may limit the kinds of 
medical or research treatments they would want to receive (such as blood transfusions).  If you 
have such beliefs, please discuss them with your NIH doctors or research team before you agree 
to the study. 
Now we will describe this research study.  Before you decide to take part, please take as much 
time as you need to ask any questions and discuss this study with anyone at NIH, or with family, 
friends or your personal physician or other health professional.   
Why is this study being done?  
This study is being done to gain information on the use of an experimental medicine called 
pomalidomide (also called CC-4047) in people with chronic graft-versus-host disease (GvHD). 
We would like to obtain information on the efficacy of pomalidomide in people with chronic 
GvHD. Although pomalidomide has been already used in humans in cluding patients with 
chronic GvHD we will also look for any evidence of the side effects of treatment.  
Pomalidomide is taken by mouth. It works by modifying the body’s immune response. The 
effects of pomalidomide on the immune system may be beneficial in chronic GvHD. However, 
this has not been proven.  Pomalidomide is chemically similar to the drug thalidomide, which 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER: 
12-C-0197 
CONTINUATION: page 2 of 17 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (10-84) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
 
has been shown to have beneficial effects in some people with chronic GvHD. However, 
thalidomide has not been approved by the Food and Drug Administration (FDA) for treatment of 
chronic GvHD. 
Why are you being asked to take part in this study? 
You are being asked to take part in this study because you have moderate or severe chronic 
GvHD that is not controlled by standard medicines such as corticosteroids or other treatments.    
How many people will take part in this study?  
We plan to enroll up to 35 subjects in this study. 
Description of Research Study 
In this study, we are studying the efficacy of different doses (high or low) of pomalidomide and 
their effect on chronic GvHD. The doses being studied are 0.5 mg and 2 mg per day. After you 
are accepted for this study and you choose to take part, you will be "randomized" into one of the 
two treatment groups (called “arms”). Randomization means that you are put into a group by 
chance. A computer program will place you in one of the treatment arms. Neither you nor your 
doctor can choose the treatment arm you will be in. All patients in the study will receive 
pomalidomide, just at different doses over time depending on their assigned treatment arm. 
You will take pomalidomide capsules once a day in 4-week periods called cycles. All patients 
will start receiving the same dose of pomalidomide (0.5 mg). Patients in the 0.5 mg (low dose) 
treatment arm will stay at this same daily dose till the end of the study. Patients in the 2 mg 
treatment arm (high dose) will have their dose increased by 0.5 mg every two weeks until the 2 
mg dose is reached. Pomalidomide has been given to humans at these doses before, but you will 
be still watched carefully for any side effects. 
Pomalidomide therapy will continue for 6 cycles (6 months) unless your GvHD gets worse or 
you have unacceptable side effects from the pomalidomide. If your GvHD has improved at the 
end of the 6 cycles, you may be able to continue pomalidomide for up to 6 more cycles. 
A detailed description of what will happen if you take part in this study, as well as a list of 
potential risks and discomforts associated with participation in the study are listed below. 
What will happen if you take part in this research study?   
Before you begin the study 
You will need to have examinations, tests and procedures to see if you qualify for the study.  
Many of these tests are performed as part of your regular medical care or during the prior 
treatments for your GvHD. You will be asked to sign a separate consent describing the tests you 
will need to have done. In order for you to enroll in the Study you must follow the requirements 
of POMALYST REMS™ program. 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER: 
12-C-0197 
CONTINUATION: page 3 of 17 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (10-84) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
 
After all of these examinations are performed we determine you are eligible for the trial, you will 
be asked to sign this informed consent agreeing to participate in this research study. 
During the study 
During the study, you will take pomalidomide capsules by mouth every day. Pomalidomide 
should be taken at about the same time each day. Pomalidomide capsules should be swallowed 
whole, and should not be broken, chewed or opened. Patients are instructed to fast (water or clear 
fluids only) for at least 2 hours prior to taking a dose to at least 1 hour post-dosing.  
Pomalidomide should not be swallowed concurrently with other allowed medications while on-
study. 
You will be asked to complete a medication diary and to return any unused study drug and empty 
bottles to the clinic at each visit. 
If you are taking other medications that increase the risk of blood clotting or you have other risk 
factors for blood clotting, you will take aspirin or another medicine to reduce the chance of blood 
clotting. All patients taking pomalidomide must follow strict guidelines for prevention of 
pregnancy. This is because there is a risk of harm to a fetus if pregnancy occurs while taking 
pomalidomide. These guidelines are outlined in the section on birth control below. 
Standard procedures being done because you are in this study; these may be done more 
often because you are in the study: 
• Clinic visit, which will include a medical history, physical exam, and measurement of 
weight and vital signs every 2 weeks during the first 3 cycles, then at the beginning of 
every cycle, and when you stop taking pomalidomide 
• Assessment of your GvHD, including questions about your symptoms, before you start 
pomalidomide, every 3 months while you are taking pomalidomide, and when you stop 
taking pomalidomide 
• Blood draws for laboratory tests every 2 weeks during the first 3 cycles, then at the 
beginning of every cycle, and when you stop taking pomalidomide 
• Urine tests before starting pomalidomide, every 3 months while you are taking 
pomalidomide, and when you stop taking pomalidomide 
• Non-invasive imaging such as CT scans (a computerized x-ray examination) or MRI (an 
examination using magnetic field and radio waves) before starting pomalidomide and as 
medically necessary 
• Lung function test every 3 months while you are taking pomalidomide, and when you 
stop taking pomalidomide 
• EKG (a recording of the heart’s electrical activity) and echocardiogram (an examination 
of your heart using sound waves) at the time of starting the study, monthy first three 
months, at six months and as medically necessary 
• Pregnancy tests if you are a woman who is able to become pregnant, weekly during the 
first cycle, then every 28 days if you have regular periods or every 14 days if your 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER: 
12-C-0197 
CONTINUATION: page 4 of 17 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (10-84) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
 
periods are irregular. We will provide a pregnancy test kit for you to use at home for the 
weeks you are not here at the NIH. 
• As part of the evaluations for this study and of your graft-versus-host disease you will see 
specialists in dermatology (skin disease) and dentistry prior to study entry. You will see 
specialists in rehabilitation medicine, occupational therapy, ophthalmology (eyes) and 
gynecology (if female) up to two weeks after study entry. You will also see these 
specialists at 3-6 month intervals while you are on this study. 
 
Tests and procedures that are either being tested in this study or being done to see how 
the drug is affecting your body: 
 
• Blood draws to measure the levels of pomalidomide in your blood on the day you start 
pomalidomide, every 2 weeks for the first 3 months, then monthly until the 6-month visit. 
Each of these blood draws requires less than 2/3 teaspoons of blood (3 mL).   
• Other blood samples will be collected for research at the same time points, about 50 mL 
(10 tea spoons of blood) except at the study beginning and after 3 and 6 months of 
therapy when a larger blood draw will be performed, about 20 teaspoons of blood (100 
mL).  
• You will be asked to give a sample of mouth saliva up to 10 cc (two teaspoons) before 
start of the therapy and at the end at six months or at permanently stopping pomalidomide 
therapy     
• We would like your permission to collect biopsies (removal of a small bit of tissue for 
examination under a microscope) from your skin and mouth before starting 
pomalidomide and after 6 months or at permanently stopping the pomalidomide to study 
the effect of pomalidomide on immune response in these tissues.  
• Photographs of your body cGVHD manifestations before starting the study and after 6 
months or at permanently stopping pomalidomide    
When you are finished taking the drugs (treatment) 
When you are finished taking the drugs, we will continue to follow you for up to 2 years after 
you first started taking pomalidomide. The follow-up will include a clinic visit 3 months after 
your last dose of pomalidomide, and a phone call or visit to your regular doctor 1 and 2 years 
from the date you first started taking pomalidomide. 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER: 
12-C-0197 
CONTINUATION: page 5 of 17 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (10-84) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
 
Study Chart 
This chart outlines what will happen if you choose to participate: 
 
 
 
 
 
 
↓ 
 
 
 
 
 
 
 
 
 
 
↓ 
 
 
Screening for Eligibility 
• Medical history and physical exam 
• Blood tests 
• Chest CT scan 
• Lung function test 
• EKG and echocardiogram 
• Pregnancy testing 
Treatment 
Therapy:  
Pomalidomide capsules by mouth once each day 
Monitoring:  
Review of side effects 
Medical history and physical exam 
Assessment of GvHD 
Blood and urine tests 
Non-invasive imaging 
Lung function testing 
EKG and echocardiogram 
Pregnancy testing and pregnancy prevention counseling 
Research: 
Blood, saliva, urine samples,  
Biopsies (optional) 
Stop treatment: 
Completion of 6 to 12 cycles of therapy 
Progressive GvHD 
 
Patient preference 
Unacceptable toxicity 
Other medical reasons 
After Treatment 
• Follow-up for up to 2 years after the first dose of 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER: 
12-C-0197 
CONTINUATION: page 6 of 17 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (10-84) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
 
Birth Control 
Pregnancy: 
Pomalidomide was found to cause birth defects in an experimental study in animals.  
Pomalidomide is related to thalidomide.  Thalidomide is known to cause severe life-threatening 
human birth defects. Pomalidomide is therefore considered to have the potential to cause birth 
defects in humans.  If pomalidomide is taken during pregnancy, it may cause birth defects or 
death to an unborn baby.  Females must not become pregnant while taking pomalidomide.  
In order to participate in this study, you must register into and follow the requirements of 
the POMALYST REMS™ program of Celgene Corporation.  This program provides 
education and counseling on the risks of fetal exposure, blood clots and reduced blood 
counts.  You will be required to receive counseling, follow the pregnancy testing and birth 
control requirements of the program that are appropriate for you and take surveys 
regarding your compliance with the POMALYST REMS™ program.   
 
In addition, all patients taking pomalidomide must follow guidelines for prevention of 
pregnancy. This is because there is a risk of harm to a fetus if pregnancy occurs while taking 
pomalidomide. These guidelines are outlined below. 
Note:  By signing this consent you confirm that you understand and agree to receive counseling 
and to comply with the pregnancy precaution requirements of the POMALYST REMS™ 
program. 
Screening: 
• Pregnancy test, if applicable: If you are a female of childbearing potential, you will be 
required to have two negative pregnancy tests: the first test within 10-14 days before 
starting pomalidomide and the second test within 24 hours before your first dose of 
pomalidomide. 
• For the purposes of this study, a female of childbearing potential is a 
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 for 
at least 24 consecutive months (i.e., has had menses at any time during the 
preceding 24 consecutive months) 
  
Pomalidomide is an analogue of thalidomide. Thalidomide is a known to cause severe life-
threatening human birth defects. If pomalidomide is taken during pregnancy, it may cause birth 
defects or death to an unborn baby. Females are advised to avoid pregnancy while taking 
pomalidomide. You have been informed that the risk of birth defects is unknown. If you are 
female, you agree not to become pregnant while taking pomalidomide.  


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER: 
12-C-0197 
CONTINUATION: page 7 of 17 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (10-84) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
 
Females:   
If you are a female, you must not be pregnant.   
You will be considered not of child bearing potential if you meet the following criteria: 
• Absence of menstrual periods (natural menopause) for the past 24 consecutive months or  
• Have had a hysterectomy (the surgical removal of the uterus) or both ovaries surgically 
removed  
If you do not meet these criteria, you will be considered a female of child bearing potential. If 
there is ANY chance that you can become pregnant, you must follow the guidelines below. 
If you ARE a female of childbearing potential, you will not be able to participate in this research 
study unless you have had two negative pregnancy tests, one within 10-14 days and one within 
24 hours of starting pomalidomide.  
In addition, with your doctor’s knowledge and approval, you agree to use TWO reliable forms of 
birth control or practice complete abstinence from heterosexual intercourse during the following 
time periods related to this study: 
• For at least 28 days before starting pomalidomide  
• While taking pomalidomide 
• During dose interruptions 
• And for at least 28 days after you stop taking pomalidomide    
You agree to inform the investigator immediately if:  
• You have any reason to suspect you are pregnant 
• You find that circumstances have changed and that there is a risk of becoming pregnant 
• You have stopped using the approved forms of TWO reliable birth control methods 
• You must talk to your doctor before changing any birth control methods 
• The following methods of birth control are considered acceptable birth control methods:  
Highly Effective Methods 
Additional Effective Methods 
Intrauterine device (IUD)  
Latex condom 
Hormonal (birth control pills, injections, implants) 
Diaphragm 
Tubal ligation   
Cervical Cap 
Partner’s vasectomy 
Special Note: Certain HIV-protease inhibitors, griseofulvin, modafinil, pencillins, rifampin, 
rifabutin, phenytoin, carbamazepine, or certain herbal supplements such as St. John’s Wort may 
reduce the effectiveness of hormonal contraceptives during and up to one month after 
discontinuation of these concomitant therapies. 
Therefore, females of childbearing potential requiring treatment with one or more of these drugs 
must choose ONE non-hormonal method as the highly effective method of birth control (IUD, 
tubal ligation, partner’s vasectomy) along with ONE of the additional effective methods (latex 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER: 
12-C-0197 
CONTINUATION: page 8 of 17 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (10-84) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
 
condom, diaphragm, cervical cap) or abstain from heterosexual contact while taking 
pomalidomide. 
You must use at least one highly effective method and one additional effective method of birth 
control AT THE SAME TIME. However, your doctor may recommend that you use two barrier 
methods for medical reasons. 
If you have sex without using TWO reliable methods of birth control, or if for any reason you 
think you may be pregnant, you must IMMEDIATELY stop taking pomalidomide and tell your 
doctor. 
You will have pregnancy tests before and during treatment, even if you agree not to have 
reproductive heterosexual intercourse. You will have a pregnancy test done by the doctor every 
week during the first 28 days of this study. You will then have a pregnancy test every 28 days 
during your participation in this study if your menstrual cycles are regular or every 14 days if 
your cycles are irregular. You will also have a pregnancy test if you miss your period or have 
unusual menstrual bleeding. In addition, you will have pregnancy tests when you stop taking 
pomalidomide and at day 28 after you stop taking pomalidomide if your menstrual cycles are 
regular. If your menstrual cycles are irregular, you will have pregnancy tests when you stop 
taking pomalidomide and at days 14 and 28 after you stop taking pomalidomide. 
You must not breastfeed a baby while you are participating in this study and for at least 28 days 
after you stop taking pomalidomide.  
You must NEVER share pomalidomide (or other study drugs) with someone else. You must 
NEVER donate blood while you are participating in this study and for at least 28 days after you 
stop taking pomalidomide. You will be counseled at least every 28 days and at discontinuation 
from the trial about not sharing pomalidomide (and other study drugs), the potential risks of fetal 
exposure, and abstaining from blood donations. 
If you have any reason to suspect you are pregnant, you must IMMEDIATELY stop taking 
pomalidomide and tell your doctor. If you have a positive pregnancy test while participating in 
this study, you must IMMEDIATELY stop taking pomalidomide and tell your study doctor. If 
you have a positive pregnancy test within 28 days after you stop taking pomalidomide, you must 
IMMEDIATELY tell your doctor.  
Study subjects who become pregnant will be monitored throughout the pregnancy and will 
continue to be monitored for 30 days after delivery (premature delivery, aborted fetus, full-term 
pregnancy, or no longer pregnant). 
Males:  
You have been informed about the risk of birth defects and you agree to use a latex condom 
every time you have sex with a female of childbearing potential while you are participating in 
this study and for at least 28 days after you stop taking pomalidomide, even if you have had a 
successful vasectomy. You must tell your doctor if you have sex with a female of childbearing 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER: 
12-C-0197 
CONTINUATION: page 9 of 17 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (10-84) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
 
potential without using a latex condom or if you think for any reason your partner may be 
pregnant. 
You must NEVER share pomalidomide (or other study drugs) with someone else. You must 
NEVER donate blood, sperm, or semen while you are participating in this study and for at least 
28 days after you stop taking pomalidomide. You will be counseled at least every 28 days 
regarding abstaining from donating blood, sperm, or semen; birth control requirements; not 
sharing pomalidomide (and other study drugs); and the potential risks of fetal exposure. 
Risks or Discomforts of Participation 
What side effects or risks can I expect from being in this study? 
There is always a risk involved in taking any drugs, but you will be carefully monitored for any 
problems and you are encouraged to report anything that is bothering you. There may be risks or 
side effects of the study drug that are unknown or cannot be predicted at this time. You should 
not hesitate to report anything that upsets you or may be troubling you to your study physician or 
member of the study team, even if you do not think it is connected to taking the study drug.   
If you have any questions you should contact the study physician or member of the study team. 
You will receive any new information during the course of the study concerning significant 
treatment findings from this study or others (good or bad) that may affect your willingness to 
continue. In addition to the risks of the study drug, pomalidomide, described below, you may 
experience discomfort associated with blood draws and tissue biopsies (whether clinically 
indicated or related to research) while participating in the study. 
Risks of pomalidomide: 
Pomalidomide has been studied in healthy volunteers and in patients with cancer of the blood 
and other organs of the body, as well as in patients with other diseases. As with any other 
experimental treatment, there may be side effects or risks associated with pomalidomide, some 
of which are not yet known. As of March 1, 2011, about 517 patients participating in Celgene-
sponsored studies had taken pomalidomide, and the risks below are drawn from reports from 
these patients.  
The side effects that patients had after starting pomalidomide in completed and ongoing studies 
are noted below. Your health care team may give you medicines to help lessen or treat side 
effects. Many side effects go away soon after you stop taking the study drug. In some cases, side 
effects can be serious, long-lasting or may never go away, or can cause death. It is not yet 
possible to know for certain which of the reported side effects are directly due to pomalidomide 
itself. As pomalidomide is being studied as a treatment for serious diseases, some of the reported 
conditions could be from the disease itself, or other pre-existing diseases, or other drugs the 
patient may have been taking. It should not therefore be assumed that all the side effects listed 
below were caused by pomalidomide. 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER: 
12-C-0197 
CONTINUATION: page 10 of 17 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (10-84) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
 
Pomalidomide can cause a decrease in the number of white blood cells, red blood cells, platelets, 
and/or neutrophils (a type of white blood cell). White blood cells are cells of your immune 
system. In some patients, a decrease in blood cells can be serious and may require you to stop 
treatment. A decrease in white blood cells and/or neutrophils may lead to fever and/or a life-
threatening infection. The red blood cells carry oxygen to your organs. A decrease in red blood 
cells can lead to fatigue or feeling tired. A decrease in platelets may lead to bleeding and require 
stopping treatment. Other laboratory values may become abnormal, as well. 
Side effects reported as serious at least once are bolded. 
Likely (reported in more 
than 10% of patients) 
Less Likely (reported in 5 to 
10% of patients) 
Rare but Serious (reported in less 
than 5% of patients) 
• Low white blood cell 
count  
• Constipation 
• Nausea  
• Skin rashes  
• Fatigue or tiredness 
• Shortness of breath 
• Lung infection 
• Cough  
• Dizziness 
• Muscle aches or pains 
• Skin tingling 
• Fever 
• Low platelet count 
• Inflammation of the 
throat 
• Skin itching 
• Swelling 
• Diarrhea (loose stool) 
• Muscle cramps  
• Headache  
• Pain in chest, back, 
joints, arms or legs 
• Dry skin and itch 
• Decreased sensitivity to 
touch 
• Fever and infection when the 
white blood cell count is low 
• Decrease in red blood cells, 
which carry oxygen 
• Severe infection of the 
bloodstream 
• Urinary tract infection 
• Dehydration (too little fluids in 
the body) 
• Too much calcium in the blood 
• Kidneys not working correctly 
• Cancer of the white blood 
cells, adrenal gland, bladder, 
kidney, or thyroid 
• Confusion 
• Blood clot in the veins or lung 
• Atrial fibrillation (when the 
top of your heart quivers 
instead of beating)  
Deep vein thrombosis and pulmonary embolism 
Medications in the same family of medications as pomalidomide have shown an increased risk of 
deep vein thrombosis (blood clot in a larger blood vessel) and pulmonary embolism (a blood clot 
in or around the lungs) in some subjects with certain medical conditions. If you are at increased 
risk for blood clots due to certain medical conditions or other medications you may be taking, 
you will receive either aspirin or another medicine to reduce the chance of blood clotting while 
you are receiving pomalidomide. 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER: 
12-C-0197 
CONTINUATION: page 11 of 17 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (10-84) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
 
Reproductive Risks 
As indicated in the section on birth control, pomalidomide is related to thalidomide, a drug 
known to cause severe life-threatening human birth defects. If pomalidomide is taken during 
pregnancy, it may cause birth defects or death to an unborn baby.   
Additional precautions 
Other than the patient, women who are able to become pregnant and men who are able to father a 
child should not touch or handle the pomalidomide capsules.  
While in this study, if any physician or healthcare provider, other than your study physician, 
prescribes medication(s) for you for another condition or reason, or you are taking any over-the-
counter medications, vitamins, herbal, holistic or homeopathic remedies, please tell the study 
doctor or a member of the research team immediately. Please also let your study doctor know all 
of your present and past diseases and allergies. This is important because a possible interaction 
with some medications, vitamins, and remedies may cause serious side effects, and/or may still 
be unknown.  
Biopsies 
Optional punch skin and oral biopsies will be performed. Prior to the biopsy, you will receive 
local anesthesia through a small injection into the area of skin or mouth mucosa surrounding the 
biopsy site. Samples will be removed with a needle during the biopsy (size of the pencil eraser). 
You may require a stitch after the biopsy. Risks of the biopsy include local oozing of blood or 
discomfort. Infection is a rare complication of skin/oral biopsies. The biopsies to be performed 
are exclusively for research purposes and will not benefit you. They might help other people in 
the future. The decision to participate in this part of the research is optional, and no matter what 
you decide to do, it will not affect your care. Your permission for this will be obtained at the 
time of the biopsy. 
Potential Benefits of Participation 
Are there benefits to taking part in this study?  
No benefit can be promised to you for your participation in this study. We do not know if you 
will receive personal medical benefit directly from taking part in this study, although the 
knowledge gained from this study may help others in the future who have chronic GvHD. This 
study may lead to an increase in understanding of pomalidomide as therapy for chronic GvHD, 
and possibly better treatments based on results from this study for patients in the future. Potential 
benefits to you could include improvement in your GvHD or lessening of your symptoms that 
are caused by your GvHD. However, it is possible that you will not receive any benefit from 
participating. 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER: 
12-C-0197 
CONTINUATION: page 12 of 17 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (10-84) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
 
Alternative Approaches or Treatments 
What other choices do I have if I do not take part in this study?  
Instead of being in this study, you have these options: 
• Getting treatment or care for GvHD without being in a study 
• Taking part in another study 
• Getting comfort care, also called palliative care. This type of care helps reduce pain, 
tiredness, appetite problems and other problems caused by GvHD. It does not treat the 
GvHD directly. Instead, it tries to improve how you feel. Comfort care tries to keep you 
as active and comfortable as possible. 
Please talk to your doctor about these and other options. 
 
Stopping Therapy  
Your doctor may decide to stop your therapy for the following reasons: 
• if he/she believes that it is in your best interest 
• if your disease worsens or comes back during treatment 
• if you have side effects from the treatment that your doctor thinks are too severe 
• if new information shows that another treatment would be better for you 
• if you do not follow the treatment plan, including steps to prevent getting pregnant 
and protecting others from pomalidomide 
If this occurs, you will be informed of the reason therapy is being stopped. 
You can stop taking part in the study at any time. However, if you decide to stop taking part in 
the study, we would like you to talk to the study doctor and your regular doctor first. 
If you decide at any time to withdraw your consent to participate in the trial, we will not collect 
any additional medical information about you. However, according to FDA guidelines, 
information collected on you up until that point may still be provided to Celgene or designated 
representatives. If you withdraw your consent and leave the trial, any samples of yours that have 
been obtained for the study and stored at the NCI can be destroyed upon request. However, any 
samples and data generated from the samples that have already been distributed to other 
researchers or placed in the research databases cannot be recalled and destroyed. 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER: 
12-C-0197 
CONTINUATION: page 13 of 17 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (10-84) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
 
Research Subject’s Rights 
What are the costs of taking part in this study?  
If you choose to take part in the study, the following will apply, in keeping with the NIH policy: 
• 
You will receive study treatment at no charge to you. This may include 
surgery, medicines, laboratory testing, x-rays or scans done at the 
Clinical Center, National Institutes of Health (NIH), or arranged for you 
by the research team to be done outside the Clinical Center, NIH if the 
study related treatment is not available at the NIH.  
• 
There are limited funds available to cover the cost of some tests and 
procedures performed outside the Clinical Center, NIH.  You may have 
to pay for these costs if they are not covered by your insurance company. 
• 
Medicines that are not part of the study treatment will not be provided or 
paid for by the Clinical Center, NIH. 
• 
Once you have completed taking part in the study, medical care will no 
longer be provided by the Clinical Center, NIH. 
Will my medical information be kept private? 
We will do our best to make sure that the personal information in you medical record will be 
kept private.  However, we cannot guarantee total privacy.  Your personal information may be 
given out if required by law.  If information from this study is published or presented at scientific 
meetings, your name and other personal information will not be used.  Organizations that may 
look at and/or copy your medical records for research, quality assurance, and data analysis 
include: 
• The National Cancer Institute (NCI) and other government agencies, like the Food and 
Drug Administration (FDA), involved in keeping research safe for people. 
• Regulatory agencies in the United States 
• NCI Institutional Review Board 
• Qualified representatives from Celgene, the pharmaceutical company who produces 
pomalidomide. 
• In order to obtain pomalidomide free of charge from Celgene, your name, address, phone, 
date of birth and the fact that you are participating in this trial will be disclosed to 
Celgene and its agents or vendors that supply pomalidomide and administer the 
POMALYST REMS™ program.  By signing this consent form you agree to this 
disclosure. 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER: 
12-C-0197 
CONTINUATION: page 14 of 17 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (10-84) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required 
by U.S. Law. This Web site will not include information that can identify you. At most, the Web 
site will include a summary of the results.  You can search this Web site at any time. 
Certificate of Confidentiality  
To help us protect your privacy, we have obtained a Certificate of Confidentiality. The 
researchers can use this Certificate to legally refuse to disclose information that may identify you 
in any federal, state, or local civil, criminal, administrative, legislative, or other proceedings, for 
example, if there is a court subpoena. The researchers will use the Certificate to resist any 
demands for information that would identify you, except as explained below. 
You should also know that there are several circumstances in which the Certificate does not 
provide coverage. These include when information:  
• will be used for auditing or program evaluation internally by the NIH; or  
• must be disclosed to meet the legal requirements of the federal Food and Drug 
Administration (FDA).  
• is necessary for your medical treatment and you have consented to this disclosure;  
• is for other research.  
In addition, identifiable, sensitive information protected by this Certificate cannot be admissible 
as evidence or used for any purpose in any action, suit, or proceeding without your consent.  
You should understand that a Certificate of Confidentiality does not prevent you or a member of 
your family from voluntarily releasing information about yourself or your involvement in this 
research. If an insurer, employer, or other person obtains your written consent to receive research 
information, then the researchers will not use the Certificate to withhold that information. 
The Certificate of Confidentiality will not protect against the required reporting by hospital staff 
of information on suspected child abuse, reportable communicable diseases, and/or possible 
threat of harm to self or others. 
Conflict of Interest 
The National Institutes of Health (NIH) reviews NIH staff researchers at least yearly for conflicts 
of interest.  This process is detailed in a Protocol Review Guide. You may ask your research 
team for a copy of the Protocol Review Guide or for more information.  Members of the research 
team who do not work for NIH are expected to follow these guidelines but they do not need to 
report their personal finances to the NIH. 
Members of the research team working on this study may have up to $15,000 of stock in the 
companies that make products used in this study.  This is allowed under federal rules and is not a 
conflict of interest.  


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER: 
12-C-0197 
CONTINUATION: page 15 of 17 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (10-84) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
 
The National Institutes of Health and the research team for this study are using pomalidomide, 
developed by Celgene.  This means it is possible that the results of this study could lead to 
payments to NIH scientists and to the NIH.  By law, government scientists are required to 
receive such payments for their inventions.  You will not receive any money from the 
development of pomalidomide.  
Use of Specimens and Data for Future Research 
To advance science, it is helpful for researchers to share information they get from studying 
human samples.  They do this by putting it into one or more scientific databases, where it is 
stored along with information from other studies. A researcher who wants to study the 
information must apply to the database and be approved.  Researchers use specimens and data 
stored in scientific databases to advance science and learn about health and disease.   
We plan to keep some of your specimens and data that we collect and use them for future 
research and share them with other researchers. We will not contact you to ask about each of 
these future uses.  These specimens and data will be stripped of identifiers such as name, address 
or account number, so that it may be used for future research on any topic and shared broadly for 
research purposes. Your specimens and data will be used for research purposes only and will not 
benefit you.  It is also possible that the stored specimens and data may never be used.  Results of 
research done on your specimens and data will not be available to you or your doctor.  It might 
help people who have cancer and other diseases in the future.   
If you do not want your stored specimens and data used for future research, please contact us in 
writing and let us know that you do not want us to use your specimens and/or data.  Then any 
specimens that have not already been used or shared will be destroyed and your data will not be 
used for future research. However, it may not be possible to withdraw or delete materials or data 
once they have been shared with other researchers. 


MEDICAL RECORD 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
• 
Adult Patient or 
• Parent, for Minor Patient 
STUDY NUMBER: 
12-C-0197 
CONTINUATION: page 16 of 17 pages 
 
PATIENT IDENTIFICATION 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
(Continuation Sheet) 
• 
Adult Patient or 
• Parent, for Minor Patient 
NIH-2514-1 (07-09) 
P.A.:  09-25-0099 
 
File in Section 4:  Protocol Consent 
 
 
OTHER PERTINENT INFORMATION 
1. 
Confidentiality.  When results of an NIH research study are reported in medical journals 
or at scientific meetings, the people who take part are not named and identified.  In most cases, 
the NIH will not release any information about your research involvement without your written 
permission.  However, if you sign a release of information form, for example, for an insurance 
company, the NIH will give the insurance company information from your medical record.  This 
information might affect (either favorably or unfavorably) the willingness of the insurance 
company to sell you insurance. 
The Federal Privacy Act protects the confidentiality of your NIH medical records.  However, you 
should know that the Act allows release of some information from your medical record without 
your permission, for example, if it is required by the Food and Drug Administration (FDA), 
members of Congress, law enforcement officials, or authorized hospital accreditation 
organizations. 
2. 
Policy Regarding Research-Related Injuries.  The Clinical Center will provide short-
term medical care for any injury resulting from your participation in research here.  In general, 
no long-term medical care or financial compensation for research-related injuries will be 
provided by the National Institutes of Health, the Clinical Center, or the Federal Government.  
However, you have the right to pursue legal remedy if you believe that your injury justifies such 
action. 
3. 
Payments.  The amount of payment to research volunteers is guided by the National 
Institutes of Health policies.  In general, patients are not paid for taking part in research studies at 
the National Institutes of Health.  Reimbursement of travel and subsistence will be offered 
consistent with NIH guidelines. 
4. 
Problems or Questions.  If you have any problems or questions about this study, or 
about your rights as a research participant, or about any research-related injury, contact the 
Principal Investigator, Steven Pavletic, M.D., Building 10, Room 4-3130, Telephone: 240-760-
6174. You may also call the Clinical Center Patient Representative at (301) 496-2626. If you 
have any questions about the use of your specimens and data for future research studies, you may 
also contact the Office of the Clinical Director, Telephone:  240-760-6070. 
5.  
Consent Document.  Please keep a copy of this document in case you want to read it 
again. 
 
 
 
 
 


MEDICAL RECORD 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
• 
Adult Patient or 
• Parent, for Minor Patient 
STUDY NUMBER: 
12-C-0197 
CONTINUATION: page 17 of 17 pages 
 
PATIENT IDENTIFICATION 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
(Continuation Sheet) 
• 
Adult Patient or 
• Parent, for Minor Patient 
NIH-2514-1 (07-09) 
P.A.:  09-25-0099 
 
File in Section 4:  Protocol Consent 
 
 
 
 
COMPLETE APPROPRIATE ITEM(S) BELOW: 
A. Adult Patient’s Consent 
B. Parent’s Permission for Minor Patient. 
I have read the explanation about this study 
and have been given the opportunity to discuss 
it and to ask questions.  I hereby consent to 
take part in this study. 
I have read the explanation about this study 
and have been given the opportunity to discuss 
it and to ask questions.  I hereby give 
permission for my child to take part in this 
study.   
(Attach NIH 2514-2, Minor’s Assent, if 
applicable.) 
 
  
  
 
 
 
Signature of Adult Patient/ 
Legal Representative 
Date 
Signature of Parent(s)/ Guardian Date 
 
 
Print Name 
 
 
Print Name 
C. Child’s Verbal Assent (If Applicable) 
The information in the above consent was described to my child and my child agrees to 
participate in the study. 
 
  
  
 
Signature of Parent(s)/Guardian 
Date 
Print Name 
THIS CONSENT DOCUMENT HAS BEEN APPROVED FOR USE  
NOVEMBER 13, 2017 THROUGH November 12, 2018. 
 
 
 
 
 
 
 
 
Signature of Investigator 
Date 
Signature of Witness 
Date 
 
 
Print Name 
 
 
Print Name