Clinical trial NCT01495598
Conditions: Kaposi Sarcoma Sarcoma, Kaposi
Keywords: Human Herpesvirus-8/HHV8 Immune Modulation CC-4047 IMiD Kaposi Sarcoma
Sponsor: National Cancer Institute (NCI)
Start date: 2012-01-10; Completion date: 2022-05-17
Enrollment: 28 participants; Allocation: NON_RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
Background:

\- Pomalidomide is a drug that can treat cancer through several mechanisms. It is taken by mouth (orally). Pomalidomide can help treat cancer by blocking certain factors that promote tumor growth or by stimulating the immune system to attack tumor cells. It also prevents the growth of new blood vessels that help cancer grow. Researchers want to see if pomalidomide can treat Kaposi sarcoma, a rare and potentially fatal skin cancer. Because Kaposi sarcoma may be associated with human immunodeficiency virus (HIV) infection, researchers want to test the drug in people with and without HIV infection.

Objectives:

\- To see if pomalidomide is a safe and effective treatment for Kaposi sarcoma in people with or without HIV.

Eligibility:

* Individuals at least 18 years of age who have Kaposi sarcoma.
* Participants may or may not have HIV infection.

Design:

* Potential participants will be screened with a medical history and physical exam. Blood and saliva samples will be taken and a chest X-ray will be performed. A skin biopsy of a Kaposi sarcoma lesion may be performed if one has not already been done. Other imaging studies may be performed if needed.
* Participants will take pomalidomide capsules every day for 3 weeks, followed by a 1-week break. These 28 days are one cycle of treatment.
* Participants will have up six cycles of treatment, unless the lesions completely resolve sooner. If there are signs of improvement after six cycles but the lesions are not completely gone, up to another six cycles of treatment may be given.
* Treatment will be monitored with frequent blood tests and other studies including photograph and other imaging of skin lesions.
* Participants will have regular follow-up visits for 5 years after stopping treatment....

Detailed description:
Background:

Kaposi Sarcoma (KS) is an incurable, multicentric angioproliferative tumor that most frequently involves the skin. It is seen most frequently in people with human immunodeficiency virus (HIV) or other forms of immune compromise. Current therapies are limited by toxicities, including cumulative cardiotoxicity, while effective oral agents, agents deliverable in resource-limited settings, and agents deliverable long-term for relapsing disease are all lacking.

Objective:

The primary objective of this study is to:

Assess the safety, tolerability and pharmacokinetics of pomalidomide in subjects with Kaposi sarcoma, whether HIV associated or not.

Eligibility:

* Age greater than or equal to 18 years
* Measurable, pathologically confirmed KS
* Any HIV status; HIV-associated KS subjects must be receiving and able to comply with highly active antiretroviral therapy (HAART) and have achieved an HIV viral load \<10,000 copies/mL
* Hematologic and biochemical parameters within prespecified limits at baseline
* Willing to use effective birth control, as defined in the full protocol
* For subjects enrolled in the anti-tumor activity assessment phase, if KS is HIV-associated it must be increasing despite HAART and HIV suppression for greater than or equal to 2 months, or stable despite HAART for greater than or equal to 3 months
* No symptomatic pulmonary or visceral KS
* No specific KS therapy within 4 weeks (6 weeks if that therapy was bevacizumab)
* Neither pregnant nor breast feeding

Design:

This is an open label single agent phase I/II study of pomalidomide in patients with KS. In the phase I portion, up to six subjects will initially be treated with pomalidomide 5mg daily for 21 days of a 28 day cycle. Subject to toxicity evaluation, this dosage may be deescalated to 3mg daily for 21 days of a 28 day cycle in a second cohort of up to six subjects. If either dose proves tolerable, the study will proceed to the phase II portion, and additional subjects to a goal of 15 HIV positive and 10 HIV negative subjects evaluable for response will be added at the highest tolerable dose to gain preliminary information on activity.

Arms: arm 1: Up to six subjects will initially be treated with for 21 days of a 28 day cycle arm 2: 15 human immunodeficiency virus (HIV) positive and 10 HIV negative subjects evaluable for response will be treated with Pomalidomide 5mg daily for 21 days of a 28 day cycle
Interventions: intervention 1: Pomalidomide
Intervention descriptions: intervention 1: 5 mg by mouth (p.o.) for 21 of 28 days

Protocol documents:
Prot_SAP_000.pdf: 
Abbreviated Title: Pomalidomide in Kaposi sarcoma 
Version Date: 11/19/2021
 
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Abbreviated Title:
Pomalidomide in Kaposi sarcoma
NIH Protocol #: 
12-C-0047 
Celgene Tracking Number: PO-KS-NCI-0050
Version Date: 
11/19/2021
NCT#:
NCT01495598
Title: A Phase I/II Study of the Safety, Pharmacokinetics and Efficacy of Pomalidomide (CC-
4047) in the Treatment of Kaposi Sarcoma in Individuals with or without HIV.
NCI Principal Investigator: Robert Yarchoan, MD
HIV/AIDS Malignancy Branch
CCR, NCI, NIH
10 Center Drive, Room 6N106
Bethesda, MD 20892-1868
Tel: 240-760-6075
Email: robert.yarchoan@nih.gov 
Investigational Agents: 
Drug Name:
Pomalidomide (CC-4047)
IND Number:
113751
Sponsor:
Center for Cancer Research
Manufacturer:
Celgene Corporation
Supplier
Celgene Corporation
Commercial agents: None


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PRÉCIS
Background
Kaposi Sarcoma (KS) is an incurable, multicentric angioproliferative tumor that most frequently 
involves the skin. It is seen most frequently in people with HIV or other forms of immune 
compromise. Current therapies are limited by toxicities, including cumulative cardiotoxicity, 
while effective oral agents, agents deliverable in resource-limited settings, and agents deliverable 
long-term for relapsing disease are all lacking.
Objective 
The primary objective of this study is to:

Assess the safety, tolerability and pharmacokinetics of pomalidomide in subjects with 
Kaposi sarcoma, whether HIV associated or not.
Eligibility 
•
Age ≥18 years
•
Measurable, pathologically confirmed KS
•
Any HIV status; HIV-associated KS subjects must be receiving and able to comply with 
HAART and have achieved an HIV viral load <10,000 copies/mL
•
Hematologic and biochemical parameters within prespecified limits at baseline
•
Willing to use effective birth control, as defined in the full protocol
•
For subjects enrolled in the anti-tumor activity assessment phase, if KS is HIV-associated it 
must be increasing despite HAART and HIV suppression for ≥2months, or stable despite 
HAART for ≥3months
•
No symptomatic pulmonary or visceral KS
•
No specific KS therapy within 4 weeks (6 weeks if that therapy was bevacizumab)
•
Neither pregnant nor breast feeding
Design
This is an open label single agent phase I/II study of pomalidomide in patients with KS. In the 
phase I portion, up to six subjects will initially be treated with pomalidomide 5mg daily for 21 
days of a 28 day cycle. Subject to toxicity evaluation, this dosage may be deescalated to 3mg 
daily for 21 days of a 28 day cycle in a second cohort of up to six subjects. If either dose proves 
tolerable, the study will proceed to the phase II portion, and additional subjects to a goal of 15 
HIV positive and 10 HIV negative subjects evaluable for response will be added at the highest 
tolerable dose to gain preliminary information on activity.


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TABLE OF CONTENTS
PRÉCIS............................................................................................................................................2
TABLE OF CONTENTS ................................................................................................................3
STATEMENT OF COMPLIANCE ................................................................................................5
1
INTRODUCTION ...................................................................................................................5
1.1
Study Objectives ...............................................................................................................5
1.2
Background and Rationale................................................................................................5
2
ELIGIBILITY ASSESSMENT AND ENROLLMENT .......................................................16
2.1
Eligibility Criteria ...........................................................................................................16
2.2
Research Eligibility Evaluation ......................................................................................19
2.3
Participant Registration and Status Update Procedures..................................................20
3
STUDY IMPLEMENTATION .............................................................................................20
3.1
Study Design...................................................................................................................20
3.2
Drug Administration .......................................................................................................25
3.3
Dose Modifications.........................................................................................................26
3.4
Study Calendar................................................................................................................31
3.5
Cost and Compensation ..................................................................................................38
3.6
Criteria for Removal from Protocol Therapy and Off Study Criteria.............................38
4
CONCOMITANT MEDICATIONS/MEASURES...............................................................39
4.1
Concurrent Therapies......................................................................................................39
4.2
Supportive Care...............................................................................................................40
5
BIOSPECIMEN COLLECTION...........................................................................................41
5.1
Correlative and Pharmacokinetic Studies for Research..................................................41
5.2
Sample Storage, Tracking and Disposition.....................................................................47
6
DATA COLLECTION AND EVALUATION .....................................................................50
6.1
Data Collection ...............................................................................................................50
6.2
Response Criteria ............................................................................................................51
6.3
Toxicity Criteria..............................................................................................................54
7
NIH REPORTING REQUIREMENTS/DATA AND SAFETY MONITORING PLAN.....55
7.1
Definitions.......................................................................................................................55
7.2
OHSRP Office of Compliance and Training / IRB Reporting........................................55
7.3
NCI Clinical Director Reporting.....................................................................................55
7.4
NIH Required Data and Safety Monitoring Plan............................................................55
8
SPONSOR PROTOCOL/SAFETY REPORTING................................................................56
8.1
Definitions.......................................................................................................................56
8.2
Assessment of Safety Events ..........................................................................................57
8.3
Reporting of Serious Adverse Events .............................................................................58
8.4
Safety Reporting Criteria to the Pharmaceutical Collaborators......................................58
8.5
Reporting Pregnancies ....................................................................................................59
8.6
Regulatory Reporting for Studies Conducted Under CCR-Sponsored IND...................60
9
CLINICAL MONITORING..................................................................................................60
10
STATISTICAL CONSIDERATIONS ..................................................................................60
10.1
Demographic diversity ................................................................................................60
10.2
Age Exclusion .............................................................................................................61
10.3
Accrual Timeline.........................................................................................................61
10.4
Statistical Analyses......................................................................................................61


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11
COLLABORATIVE AGREEMENTS..................................................................................63
12
HUMAN SUBJECTS PROTECTIONS................................................................................64
12.1
Rationale For Subject Selection ..................................................................................64
12.2
Participation of Children .............................................................................................64
12.3
Participation of Subjects Unable to Give Consent ......................................................64
12.4
Evaluation of Benefits and Risks/Discomforts ...........................................................65
12.5
Risks and Benefits Analysis........................................................................................65
12.6
Consent and Assent Process and Documentation........................................................66
13
REGULATORY AND OPERATIONAL CONSIDERATIONS..........................................66
13.1
Study Discontinuation and Closure.............................................................................66
13.2
Quality Assurance and Quality Control ......................................................................67
13.3
Conflict of Interest Policy ...........................................................................................67
13.4
Confidentiality and Privacy.........................................................................................68
14
PHARMACEUTICAL INFORMATION .............................................................................68
14.1
Pomalidomide..............................................................................................................68
15
REFERENCES ......................................................................................................................71
16
APPENDICES .......................................................................................................................81
16.1
Appendix 1: Pomalidomide Risks of Fetal Exposure, Pregnancy Testing Guidelines 
and Acceptable Birth Control Methods .....................................................................................81
16.2
Appendix 2: Pomalidomide Education and Counseling Guidance Document............84
16.3
Appendix 3: Pomalidomide Information Sheet for Patients Enrolled in Clinical 
Research Studies........................................................................................................................87
16.4
Appendix 4: Performance Status Scales......................................................................89
16.5
Appendix 5: HAMB KS Response Flowsheet ............................................................90
16.6
Appendix 6: Functional Assessment of Quality of Life (v.4) Assessment tool (English 
Version)92
16.7
Appendix 7: Functional Assessment of Quality of Life (v.4) Assessment tool (Spanish 
Version)96
16.8
Appendix 8: Patient Drug Administration Diary ......................................................101
16.9
Appendix 9: Calculation of Creatinine Clearance.....................................................102


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STATEMENT OF COMPLIANCE
The trial will be carried out in accordance with International Conference on 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:

Assess the safety, tolerability and pharmacokinetics of pomalidomide at an oral dose 
regimen of 5mg once daily for 21 days of a 28 day cycle in subjects with Kaposi sarcoma, 
whether HIV associated or not, or in the case that the initial dosing schedule of 
pomalidomide is not tolerated, assess the safety, tolerability and pharmacokinetics of 
pomalidomide at 3mg daily for 21 days of a 28 day cycle.
1.1.2
Secondary Objectives:

Explore in a preliminary manner the antitumor effect of pomalidomide at whichever of the 
dosing schedules described above is determined to be tolerable

Assess the variation in pomalidomide pharmacokinetics in relation to common antiretroviral 
agents, especially potentially nephrotoxic agents such as tenofovir

Assess changes in quality of life in subjects receiving pomalidomide

Explore in a preliminary manner the safety, tolerability and antitumor effect of a second 
course of pomalidomide in patients who manifest KS requiring therapy after deriving 
clinical benefit from initial treatment with pomalidomide.
1.2
BACKGROUND AND RATIONALE
1.2.1
Kaposi Sarcoma and Kaposi sarcoma-associated herpesvirus
1.2.1.1
Epidemiology
Kaposi Sarcoma (KS) is a multicentric angioproliferative tumor that most frequently involves the 
skin but may also involve lymphatic channels and nodes, and viscera including the lungs and 
gastrointestinal tract(1). It is now known to be caused by Kaposi sarcoma herpesvirus (KSHV, 


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also called human herpesvirus 8 [HHV-8])(2). It is remarkable for its tendency to progress or 
regress based on host immune factors(3). KS was originally described by Moritz Kaposi in 1872 
as an indolent tumor usually seen in elderly men in the Mediterranean (now called classical 
KS)(4), but the tumor also exists in endemic form in Africa (often in women and in younger 
patients, and perhaps more clinically aggressive) and in immunosuppressed populations, 
including transplant recipients and persons with HIV (epidemic KS)(5). 
In addition to KS, KSHV is established as the causative agent of primary effusion lymphoma 
(PEL), a distinct form of multicentric Castleman disease (KSHV-MCD)(2, 6, 7), and a newly-
described inflammatory syndrome, the KSHV inflammatory cytokine syndrome (KICS)(8). 
While most common in HIV-infected individuals, each of these tumors has also been reported in 
other immunosuppressed and older individuals(9). KSHV is a necessary, but not sufficient, cause 
of KS. Indeed, in the absence of cofactors such as HIV infection or iatrogenic 
immunosuppression, the risk of developing KSHV-associated diseases among KSHV-infected 
individuals is relatively low: only about 1 in 400 to 1 in 1500 KSHV-infected individuals 
develop KS, with the incidence increasing with age (likely in response to waning cellular 
immunity)(10-12). In contrast, in the absence of effective antiretroviral treatment, as many as 1 
in 2 patients co-infected with HIV and KSHV will develop KS(13, 14). In the US, up to 80% of 
cases of KS occur in people with HIV/AIDS(15). 
Supporting the role of host immune factors in KS pathogenesis, the risk of KS development is 
strongly associated with defects in cellular immunity(3). Decreasing CD4 cell count is associated 
with increasing risk of KS in both AIDS-associated KS and classic KS(13, 16). Furthermore, 
KSHV infected patients with KS have been shown to have decreased KSHV-specific CD4 
responses when compared to HIV/KSHV co-infected individuals without KS (17). Response to 
therapy has been associated with increases in both absolute CD4 count and KSHV-specific T-
cell responses in treatment naive patients with HIV-associated KS(18), as well as in organ 
transplant recipients whose KS regressed with reduction in immunosuppression(19).
The incidence of KS in developed countries declined markedly with effective antiretroviral 
therapies, falling gradually through the 1990s following the development of nucleoside inhibitors 
for HIV and then dramatically after the introduction of highly active combination antiretroviral 
regimens (HAART)(13, 20-25). In sub-Saharan Africa, where the prevalence of both HIV and 
KSHV is very high and widespread access to HAART is still limited, KS remains one of the 
most common tumors(26-29).
1.2.1.2
Pathogenesis
KSHV is a large (165kB) double-stranded DNA virus which, like Epstein-Barr virus (EBV), is a 
member of the gammaherpesvirus family(2, 30). Like all herpesviruses, KSHV infection exhibits 
both latent and lytic phases, distinguished by their viral gene expression patterns(31-33). 
Latency, with extremely limited gene expression, is established in endothelial cells and B-
lymphocytes(34). Following lytic activation via the lytic switch gene RTA, the full complement 
of viral encoded genes is expressed, and host cellular machinery is redirected to the manufacture 
and assembly of progeny virions(35-37).
KSHV is notable for its molecular piracy of genes homologous to cellular regulatory genes(38, 
39) and its modulation of cellular survival, angiogenic and immune regulatory pathways(40, 41). 
Many of the genes expressed in latency are directed to these ends, including ORF K9/vIRF-1 and 
ORF K11.5/vIRF-2, which inhibit interferon signaling and ORF16/vBcl-2, an inhibitor of 


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apoptosis(31, 42). Similarly, genes expressed in lytic stage include a viral homolog of human 
interleukin-6, called viral IL-6 (encoded by ORF K2) and a constitutively active G-protein 
coupled receptor (vGPCR) encoded by ORF74(43-46). Viral IL-6 functions both as a B-cell 
survival factor and a promotor of angiogenesis(47, 48) while vGPCR is constitutively active and 
modulates a range of cellular processes with immunomodulatory and additional pro-angiogenic 
functions(45, 49). Its pro-angiogenic functions are mediated via stabilization of hypoxia 
inducible factor-1α (HIF-1α) and induction of vascular endothelial growth factor-A (VEGF-A) 
and basic fibroblast growth factor (bFGF) (45, 49-52). Additional virally encoded pro-
angiogenic factors include three macrophage inflammatory proteins (viral MIP-1, -2, and -3)(44). 
KSHV also modulates the host cell response through induction of host cytokines including 
human IL-6 and IL-10 (the latter via viral non-coding microRNAs(53)) and TNF-α, among 
others(54-56).
While there are no suitable in vitro or animal models of KS, studies of KS tissue and KSHV-
infected cell lines suggest that, in the absence of effective host immunological control of the 
virus, these factors contribute the pathogenesis of KS(41). KS tumors are notable for the 
proliferation of pathognomonic abnormal spindle cells, mixed inflammatory infiltrates, and the 
formation of aberrant, leaky vascular channels(57, 58). Most of the spindle cells in KS lesions 
contain KSHV, and express vascular epithelial growth factor receptor type 2 (VEGFR-2) and 
VEGF-R3 (Flt-4)(59-63). Moreover, spindle cells derived from KS patients have been shown to 
proliferate in response to VEGF, VEGF-C (a ligand for VEGF-R3) and bFGF(59, 62). The 
inflammatory infiltrate is composed largely of KSHV-uninfected cells including B-
lymphocytes(64, 65). Lesions consequently are characterized by high local expression of TNF-α 
and hIL-6 (from both KSHV-infected and uninfected inflammatory cells), while in severe cases 
pro-inflammatory cytokine abnormalities are detectable even systemically(8, 66, 67). 
Most of the spindle cells in KS lesions contain KSHV in a latent form, while a smaller number of 
cells express KSHV lytic gene products(68). The role of the interplay of lytic and latently 
infected cells in KS tumor tissue is the subject of ongoing investigation(32, 69). However, it is 
hypothesized that production and induction of pro-angiogenic and inflammatory factors by the 
few cells undergoing lytic KSHV replication together with pro-survival and pro-angiogenic 
signaling in latently infected cells are critical(67). Activation of KSHV via vGPCR/ORF74 is 
considered to play a central role in this process(54). Intermittent lytic cycles may also contribute 
to viral and tumor persistence and to internal dissemination of KS lesions, by allowing the 
infection of additional host cells. 
1.2.1.3
Therapies
In patients with HIV-associated KS, HAART is a cornerstone of management. It appears that 
HIV infection can promote the development of KS in a variety of ways, including 
immunosuppression, cytokine dysregulation, and direct effects of HIV in enhancing spindle cell 
proliferation and KSHV cellular infection(13, 16, 18, 70, 71). Institution of HAART alone can 
alone lead to KS regression, and may be sufficient therapy in some cases, presumably through its 
effect on these factors(18, 72, 73). Remissions are most likely to occur in patients who have not 
previously received antiretroviral therapy, those with effective HIV suppression and associated 
immune reconstitution, and those who have limited disease(18, 72). Patients with KS who are 
already receiving effective HAART are much less likely to respond to continued antiretroviral 
therapy alone(71). Regardless of the extent of KS, HAART improves durability of response and 
overall survival in patients with HIV-associated KS. Hence, for those patients who do not 


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respond to HAART alone or who are felt to need additional specific KS therapy, HAART should 
accompany specific KS therapy.
In patients with symptomatic visceral disease, advanced cutaneous or lymphatic involvement, or 
disease whose response to HAART is unsatisfactory, additional systemic therapy with cytotoxic 
agents is indicated. First line cytotoxic therapy in the United States generally comprises 
liposomal doxorubicin (as the liposomal preparation likely improves delivery to the lesions), 
based on phase III studies with liposomal preparations of doxorubicin and daunorubicin 
conducted prior to widespread availability of HAART. These demonstrated overall response 
rates of approximately 46-75%, superior to those seen with combination chemotherapy, and good 
tolerability(74-81). Paclitaxel is also FDA-labeled for use in KS, based on phase II studies 
conducted by HAMB investigators and others(82-84). In a recently-published multicenter study 
comparing liposomal doxorubicin with paclitaxel conducted by the AIDS Malignancy 
Consortium, overall response rates were similar for each agent (46% versus 56%, 
respectively)(85). However, the paclitaxel arm was characterized by somewhat hematologic and 
gastrointestinal toxicity and a higher proportion of patients failing to complete therapy.  
Standard approaches to therapy for patients with non-HIV-associated KS are not well defined. 
For patients whose KS is associated with iatrogenic immunosuppression, for example following 
solid organ transplantation, reduction in immunosuppression or substitution with mTOR pathway 
inhibitors such as rapamycin/sirolimus (which inhibit vGPCR downstream signaling through 
PI3K/AKT(86, 87)) should be considered in the first instance, with cytotoxic therapy reserved 
for advanced or refractory disease(88). In classical KS that requires treatment, liposomal 
doxorubicin is again commonly used as first line therapy in the United States.
In addition to HAART, several other immune modulatory approaches have shown evidence of 
benefit in KS. In both the pre-HAART and HAART eras(89-91), studies with interferon-α 
showed moderate clinical activity, with response rates of 38-42% in highly immunosuppressed 
cohorts, albeit associated with significant toxicity including constitutional symptoms and 
cytopenias(92). More recently, HAMB investigators have reported studies with interleukin-12 
both alone and in combination with cytotoxic chemotherapy). Overall response rates were 71% 
with IL-12 alone at doses from 300-620ng/kg, and 83% when used initially in combination with 
liposomal doxorubicin followed by a consolidation phase with IL-12 monotherapy(93-95). We 
have also observed a partial response to IL-2 in a single patient with non-HIV-associated KS 
(Uldrick and Yarchoan, personal communication), an observation that may in part be explained 
by indirect inhibition of vGPCR via IP-10/CXCL10 modulation(54, 96).
HAMB investigators and others have also previously explored the activity of the oral 
immunomodulatory agent thalidomide in patients with KS, with or without HIV. These studies 
were largely conducted prior to the introduction of HAART. In the HAMB study of HIV-
associated KS, 47% (8) patients achieved a partial response, and an additional 12% (2) had stable 
disease(97). Notably however, in the HAMB cohort the median dose utilized was high: up to 
1000mg, median 500mg, compared with the standard dose in multiple myeloma of 200mg daily. 
Clinical toxicities were correspondingly relatively severe, including sedation and depression. 
Another group demonstrated somewhat lower response rates (35% partial responses) at a dose of 
100mg daily, in a similar patient cohort(98). Toxicities were similar to those seen in the HAMB 
cohort. A retrospective case series of 11 patients with non-HIV-related Kaposi's sarcoma, 
including one renal transplant recipient, three patients (27%) achieved a partial response and 4 
(36%) had a stable disease; several discontinued therapy early due to peripheral neuropathy(99). 


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Other case reports and small series have also reported activity(100, 101). More recently, the 
thalidomide derivative lenalidomide has been reported to have clinical activity in a case series of 
three patients with HIV-associated KS(102).
Direct targeting of dysregulated angiogenesis has also shown therapeutic efficacy in KS. HAMB 
is also investigating the vascular endothelial growth factor (VEGF) pathway inhibitors 
bevacizumab and sorafenib. For bevacizumab as a single agent, the overall response rate was 
31%, with minimal toxicity(103) (also, Uldrick and Yarchoan, personal communication). These 
agents remain the subject of investigation, including the ongoing HAMB study of bevacizumab 
in combination with liposomal doxorubicin followed by bevacizumab maintenance in patients 
with severe KS (study 09-C-0130) and the HAMB phase 1 study of sorafenib in patients with 
limited KS (study 06-C-0083).
Notwithstanding the availability of these agents, there is a substantial unmet clinical need for 
novel, effective and readily deliverable agents for KS(104). Each of the established therapies, 
while effective, has important limitations. In particular, there is a lack of effective oral agents; 
the tolerability of available immune modulatory agents is poor(89, 97); and the most effective 
cytotoxic agents (liposomal doxorubicin and daunorubicin) exhibit cumulative 
cardiotoxicity(105). The latter is particularly significant given that KS commonly recurs: one 
year progression free survival following initial therapy is approximately 70% and patients often 
have to be treated, at least intermittently, for years. This significantly limits the utility of 
anthracyclines in the many patients with recurrent or refractory disease(106). Importantly too, 
with the exception of HAART, no effective agent for KS is both tolerable and readily deliverable 
within the existing health infrastructure to affected populations in resource-limited areas such as 
sub-Saharan Africa. The development of effective anti-KS agents that are safely deliverable 
orally even in resource limited settings could assist in addressing this significant global health 
problem.
1.2.2
Immunomodulatory derivatives of thalidomide
Immunomodulatory derivatives of thalidomide (IMiDs), including pomalidomide (CC-4047) and 
lenalidomide (CC-5013) are structural derivatives of thalidomide, itself a glutamic acid 
derivative(107). Pomalidomide is derived by the addition of an amino group to the fourth carbon 
of the phthaloyl ring of thalidomide (see also Section 14.1)(108). This class of compounds share 
activities including modifying immune system function and angiogenesis, while differing in 
potency and other pharmacologic properties. The derivatives were selected with the aim of 
optimizing the parent compound’s anti-angiogenic and (primarily) TNF-α inhibitory actions 
while minimizing its toxicities, particularly neurotoxicities(109). 
The mechanisms of action of IMiDs are diverse, and likely vary in differing tissue and tumor 
types(107, 110). For pomalidomide, these include effects on T and NK cell function and profiles, 
cytokine regulation, inflammation, and angiogenesis. Its immunomodulatory effects, particularly 
T cell and NK activation and anti-TNF-α activities, are several-fold more potent than 
thalidomide or lenalidomide: for example it is up to 50,000 times more potent than thalidomide 
in its inhibition of TNF-α(107, 109). Conversely, the anti-angiogenic properties of all three 
agents appear approximately equivalent in vitro models(107, 108). Compared with thalidomide, 
pomalidomide and lenalidomide also exhibit enhances direct tumor anti-proliferative activity and 
ability to disrupt tumor-microenvironment interactions(107). Importantly too, pomalidomide 
may have activity in patients previously treated with other members of the class(111, 112).


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1.2.3
Pomalidomide
1.2.3.1
Mechanisms of Action
Pomalidomide augments T cells responsiveness and proliferation by several mechanisms, 
leading to increased production of IL-2 and interferon-γ (IFN-γ) (113-116). It enhances CD4- and 
CD8-positive T cell co-stimulation, associated with increased tyrosine phosphorylation of CD28 
on T cells and activation of the PI3-K signaling pathway, and enhances transcriptional activity of 
activated protein-1 (AP-1), a key driver of IL-2(109), (113-116). This T cell reprogramming is 
mediated at least in part by induction of the transcription factor T-bet(117). In addition, T 
regulatory (Treg) cell expansion and FOXP3 expression on Tregs are inhibited without affecting 
survival or apoptosis, or Treg expression of IL-10 or TGF-β(118). Th1 cytokine production is 
also enhanced. These effects were confirmed in vivo in patients with multiple myeloma treated 
with pomalidomide, who showed increased CD45RO expression on CD4- and CD8-positive T 
cells, with a concomitant decrease in CD45RA, together with increased IL-2 and IL-12 levels: all 
consistent with activation of T cells and monocytes(119).
The immunomodulatory activity of pomalidomide also includes inhibition of pro-inflammatory 
cytokine and chemokine production by peripheral blood mononuclear cells (PBMCs) (114-116). 
Key effects include inhibition of TNF-α, IL-1β, IL-6, monocyte chemoattractant protein-1 
(MCP-1), and macrophage inflammatory protein-1α (MIP-1α) (108, 116, 120). IL-2 production 
is enhanced from both CD4- and CD8-positive T cells, independent of T cell proliferation(115). 
RANTES (regulated upon activation, normal T cell expressed, and secreted) production is 
inhibited(108). IL-10 and IL-12 production may be augmented or inhibited, depending on the 
cell type and other factors; production from PBMCs appears to be inhibited, while T-cell 
production is augmented(108, 115) (116, 120). Pomalidomide exhibited additional anti-
inflammatory effects through inhibition of cyclooxygenase-2 (COX-2) and reduction in TNF-α 
production from LPS stimulated monocytes(116).
Pomalidomide effects on angiogenesis have been demonstrated in in vitro models of endothelial 
sprout formation and vessel migration and other systems(121, 122). In both rat aorta and human 
umbilical artery explants, pomalidomide caused inhibition of microvessel formation and in a 
human umbilical vein endothelial cell (HUVEC) tube formation, in a dose dependent 
manner(108, 123). Pomalidomide also inhibited HIF-1α expression in HUVECs(123). It also 
significantly inhibited endothelial cell invasion through fibronectin coated membranes towards 
VEGF, bFGF, transforming growth factor-α (TGF-α) and TNF-α in cell migration assays(108).
In myeloma, NHL, ALL, breast, non-small cell lung cancer and Namalwa tumor cell lines (the 
latter being hematopoetic cells with one copy of chromosome 5 deleted), pomalidomide 
demonstrated inhibition of cellular proliferation(121, 124-126). The mechanisms of this effect 
likely include induction of cyclin dependent kinase (CDK) inhibitors p21, p27 and p15, resulting 
in G0/G1 cell cycle arrest(108, 127), together with down-regulation of nuclear factor (NF) kB 
and early growth response genes-1 and 2 (Erg-1 and -2), PU.1 and SPARC (secreted protein 
activated and rich in cysteine) (108, 128, 129). In addition, direct tumor cell killing was 
exhibited by mechanisms thought to involve NK cell activation(122, 130, 131). Pomalidomide 
enhanced killing of chronic myeloid leukemia and multiple myeloma cell lines in PBMC co-
culture systems, while this effect was blocked by NK cell depletion, cyclosporine A 
administration, and IL-2 blockade(125). Similar effects have been observed in different systems 
with prostate cancer, NHL and ovarian tumor cell lines(108). 


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1.2.3.2
Animal Studies
Animal studies with pomalidomide have been conducted in mice, rats, rabbits and monkeys. In 
all cases, pomalidomide was rapidly observed following oral administration, while renal 
excretion of metabolites was the predominant route of clearance(108). In both rodent models, 
whether by oral or intravenous (IV) administration there were no deaths and no significant 
clinical effects in doses up to 2000mg/kg orally and up to 50mg/kg IV. For rats undergoing 
continuous oral dosing for 90 days at up to 1500mg/kg daily the no-observable adverse event 
level (NOAEL) was 1500mg/kg daily. In cynomolgus monkeys, an ongoing study at up to 
1mg/kg daily orally showed adverse effects at the highest dose level including cutaneous and 
deep tissue abscesses, with increased white cell counts (but not neutropenia) and 
hypoalbuminemia. Since monkeys were the most sensitive species in the toxicology program, the 
NOAEL of 0.2mg/kg daily was used to calculate the human equivalent dose of 0.06mg/kg daily 
for continuous oral doing (4mg for a 60 kilogram person). No significant or cardiac or 
respiratory safety concerns were apparent in rodents, dogs or monkeys, and pomalidomide was 
not mutagenic in bacterial or mammalian mutagenesis assays.
Pomalidomide, like other IMiDs, may cause fetal malformations. In preclinical studies, in 
pregnant rabbits (the species most sensitive to the teratogenic effects of thalidomide) who were 
administered pomalidomide at doses from 10 to 250mg/kg daily, external and cardiac 
malformations were observed. A relationship was noted between increasing pomalidomide dose 
and both the frequency of occurrence of each type of malformation and the number of fetuses 
affected(108).
1.2.3.3
Pharmacology
The pharmacokinetics of pomalidomide were characterized in healthy male subjects at doses 
from 1 to 50mg (single administration)(108). Following oral dosing, there was moderately rapid 
absorption with a Cmax that was less than dose proportional occurring at a median tmax of 2.5 to 6 
hours post dose. After reaching Cmax, plasma concentrations of pomalidomide declined in an 
apparent biphasic manner. The systemic exposure of pomalidomide, as determined from the area 
under the plasma concentration time curve (AUC0-tz and AUC0-∞) increased in an approximately 
dose proportional manner. The T1/2 ranged from 8.2 to 10.8 hours, with no apparent dose-related 
trend. Excretion was urinary, predominantly as metabolites. These characteristics were very 
similar to those seen in a separate phase 1b study in subjects with multiple myeloma119.
Pomalidomide did not inhibit CYP 1A2, 2B6, 2C8, 2C19, 2D6, 2E1 or 3A4/5 activity in human 
liver microsomes in vitro (IC50>30 µM; <10% inhibition at 30 µM)(108). Treatment of cultured 
hepatocytes with up to 3 µM pomalidomide twice daily for three consecutive days caused no 
changes in any of the CYP enzyme activities examined (1A2, 2B6, 2C9, 2C19 and 3A4/5). 
Hence pomalidomide is not likely to cause drug/drug interactions due to enzyme inhibition or 
induction when co-administered with CYP substrates.
1.2.3.4
Clinical Studies
Four completed studies in humans have been conducted with pomalidomide as a single agent in 
various malignancies(108, 119, 132); in addition there is one completed study in combination 
with dexamethasone in multiple myeloma (111) and one additional study in combination with 
gemcitabine in patients with pancreatic cancer (133). Two studies in myelofibrosis have also 
been completed(134, 135). In addition, studies are ongoing in small cell lung cancer, 
miscellaneous solid tumors (combined) and non-malignant conditions including myelofibrosis, 


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chronic graft-versus host disease and sickle cell disease, with over 250 patients enrolled to date. 
In consideration of adverse events, it should be emphasized that dose and schedule vary 
substantially between studies: in particular, there is variation in whether pomalidomide is 
administered using continuous dosing (with arbitrarily-distinguished 28 day ‘cycles’) or cyclic 
dosing (21 days followed by a 7 day ‘rest’ period to complete a 28 day cycle, as is used with 
lenalidomide). 
In the first-in-human phase 1 study, 30 healthy male subjects received single doses of 
pomalidomide, escalated from 1 to 50mg(108). Adverse events were mild or moderate in all 
cases, with no grade 3/4 events. There were no clinically significant laboratory abnormalities in 
any subject. A mild, dose related decline in CD4-positive T cells was observed, greatest at the 
50mg dose level.
In the phase 1b study in 24 patients with relapsed or refractory multiple myeloma(119), 24 
patients received a dose-escalating regimen of oral pomalidomide, administered continuously 
with arbitrarily defined 28 day cycles and commencing at a dose of 1mg daily (escalated to 2, 5, 
and 10mg). Dose limiting toxicities were assessed during the first four weeks of therapy. The 
most common drug-related toxicity was neutropenia, with grade 3/4 neutropenia occurring in 14 
patients overall and increasing in a dose dependent manner. One deep venous thrombosis was 
observed in the DLT assessment timeframe, though this was probably due to unrelated 
melanoma developing in a groin lymph node, and three additional subjects developed 
thromboses after 4, 9 and 11 months of therapy respectively. No other severe (grade 3/4) non-
hematologic toxicity was observed. Hematologic toxicity was less severe after the initial cycle, 
with the median time to grade 3/4 neutropenia in those experiencing this event being 3 weeks on 
therapy. The maximum tolerated dose in this population was 2mg daily continuous dosing.
A second arm of the phase 1b study (reported separately(132)) utilized the same dose levels 
(1mg escalated to 2, 5, and 10mg) but in an alternate-daily dosing schedule, again continuously 
for a 28 day ‘cycle’. A further 24 patients were enrolled. The most common drug-related toxicity 
was again neutropenia, which was grade 3 in 6 of 17 patients (35%) treated at or below the 5mg 
dose level (with no grade 4 toxicity at these levels), and grade 4 in three patients, all at the 10mg 
alternate daily dose level. No other serious possibly drug-related adverse events were reported. 
The maximum tolerated dose in this population was therefore 5mg alternate daily. 
Similarly in the separate phase 2 study in combination with dexamethasone, the major toxicities 
were hematologic(111). This enrolled 34 patients with relapsed or refractory patients all of 
whom were refractory to the related compound lenalidomide. Grade 3 or 4 hematologic toxicity 
occurred in 13 patients (38%), consisting of neutropenia in 10 patients (29%), anemia in 4 
patients (12%) and thrombocytopenia in 3 (9%). The most common grade 3/4 non-hematologic 
toxicity was fatigue in 3 patients (9%).  No thrombotic complications were seen. Interestingly, 
this combination was active even in lenalidomide-refractory patients: the overall response rate 
was 47%, including 3 very good partial responses, with a median response duration of nine 
months. 
Two further small phase 2 studies of pomalidomide as a single agent in solid tumors have been 
completed. In 44 patients with advanced prostate cancer, receiving 1 or 2mg of pomalidomide 
daily using a continuous dosing regimen, only one serious (grade 3/4) possibly drug-related 
adverse event was reported, acute renal impairment(108). Other adverse events were grade 1/2 
only. Significant neutropenia was not observed, though there was a trend to lower neutrophil 


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counts at the higher dose, suggesting a significant difference in toxicities and tolerability in non-
hematologic malignancies. In the next study of 7 patients with advanced soft tissue sarcomas, 
subjects received 7mg of pomalidomide daily continuous dosing, for a relatively short duration 
(median treatment duration 49 days, median 2 cycles of therapy)(108). Leukopenia (including 
one grade 4 event), neutropenia including febrile neutropenia (none worse than grade 3) and 
anemia (none worse than grade 3) were the only serious adverse events reported, though the 
majority of subjects experienced some decline in hematologic indices.
One completed study examined pomalidomide in combination with an established cytotoxic 
agent in pancreatic cancer using a dose escalating design(133). In this study, 23 patients received 
2 to 10mg of pomalidomide daily for 21 days of a 28 day cycle, in combination with gemcitabine 
1000mg/m2 days 1, 8 and 15. Patients were not heavily pretreated, and the median ECOG 
performance status (PS) was zero (in 87% of those enrolled). Adverse events included 
neutropenia (grade 3/4 in 38% of cycles), deep venous thrombosis (22%) and anemia (9%); the 
investigators note that gemcitabine as a single agent is also associated with substantial 
hematotoxicity, and that the thrombotic risk in pancreatic cancer is significantly elevated. No 
other severe (grade 3/4) non-hematologic drug-related toxicity was observed. The maximum 
tolerated dose of pomalidomide in combination with gemcitabine was 10 mg daily for 21 of 28 
days. 
Interim analysis of a further dose-escalating study of pomalidomide alone in advanced solid 
tumors has been presented in abstract form(136). In its initial form, patients of any PS with 
“adequate organ function” and any number of prior regimens were eligible. Dosing was 
continuous, with arbitrarily defined 28 day cycles. Using these inclusion criteria, adverse events 
were relatively severe: at the 3mg daily dose level, they included grade 4 neutropenia, pulmonary 
embolus, gastrointestinal bleeding, and an infection resulting in death. Following amendment to 
limit ECOG PS to ≤1 and prior regimens to fewer than three, no dose limiting toxicities were 
reported at either the 3 or 4mg daily dosing levels. At the 5mg level, dose limiting neutropenia 
was observed, and the cohort is presently being expanded at the 4mg daily continuous dose level.
Based on these studies, the major serious adverse events appear to be reversible dose and 
schedule dependent hematotoxicity (most notably neutropenia with anemia and 
thrombocytopenia less frequent) and deep venous thrombosis (assessment of the frequency of 
which is complicated by high underlying rates of thrombosis in the malignancies studied), with 
other adverse events less common and generally mild. Patients with solid tumors were able to 
tolerate substantially higher total doses than those with hematologic malignancies. Prior 
cytotoxic exposure and patient PS also appear to influence the frequency and severity of adverse 
events. Cyclic or alternate daily dosing may reduce the severity of hematopoietic side effects 
while maintaining similar total dose delivery (for example, use of 5mg 21/28 days rather than 
4mg continuously)(132-134). Significant neurotoxicity (whether sedation, peripheral neuropathy, 
or otherwise) has not been observed. Serious adverse events reported to the sponsor from the 
ongoing studies mentioned above have been consistent with those published(108). In light of the 
teratogenic effects observed in preclinical studies, all human studies have used stringent 
contraceptive guidelines.


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1.2.4
Pomalidomide in Kaposi Sarcoma
1.2.4.1
Rationale
The development of novel IMiDs presents an opportunity to extend prior investigations of 
thalidomide in KS and potentially address the ongoing clinical needs outlined above(104), 
potentially with reduced toxicity. The AIDS Malignancy Consortium is currently undertaking a 
complementary phase 1/2 study with the related compound lenalidomide (NCT01057121) in the 
United States, while the French National Agency for Research on AIDS and Viral Hepatitis is 
planning a phase 2 study of lenalidomide in France (NCT01282047). Unlike the present study, 
these are each restricted to patients with HIV-associated KS. Given the emerging evidence from 
other tumor types that patients refractory to thalidomide or lenalidomide may respond to 
pomalidomide, establishing the tolerability and activity, if any, of both lenalidomide and 
pomalidomide could significantly expand therapeutic options for patients with KS, whether HIV-
associated or not.
Taken together, the current understanding of the pathogenesis of KS and the activities of 
pomalidomide in pre-clinical models and other tumor types suggest several possible mechanisms 
of activity for pomalidomide in KS (Figure 1). In particular, inhibition of TNF-α, IL-6 and IL-
10; induction of IL-2 and IL-12; T cell co-stimulation and inhibition of T regulatory activity; and 
inhibition of pro-angiogenic factors including bFGF and VEGF are each rational targets in KS, 
and each are modulated by pomalidomide. The mechanism of the observed responses to 
thalidomide in HIV-associated KS remains to be fully elucidated; notably though, in the HAMB 
study of thalidomide, TNF-α levels decreased significantly from baseline in this cohort, while we 
did not observe statistically significant changes in serum bFGF, VEGF, or IL-6 (T cell activation 
and KSHV-specific T cell responses were not assessed in this study)(97).
Figure 1: Possible Modes of Action of Pomalidomide in KS
1.2.4.2
Special Considerations and Dosing


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The dose for exploration in KS has been determined with consideration of the special 
characteristics particularly of patients with HIV-associated KS. Patients with uncomplicated KS 
(whether HIV-associated or not) rarely if ever exhibit significant marrow involvement(1). Hence 
the initial dosing here is derived from solid tumor studies. The present study will also be 
restricted to patients with limited disease and good performance status, factors which also appear 
to reduce the incidence of severe hematotoxicity with pomalidomide. However, patients with 
HIV not infrequently exhibit mild cytopenias (predominantly anemia), and benign ethnic 
neutropenia is also common in this population(137). We therefore selected a cyclic regimen to 
allow a period of hematopoietic regeneration prior to repeat dosing, and a starting dose (5mg for 
21 of 28 days) which is well within the current tolerated range in solid tumor patients. This is 
slightly lower in total dose delivered per cycle than a 4mg continuous regimen. Should this prove 
more toxic than expected, the dose will be de-escalated to 3mg for 21 of 28 days, which is within 
the current tolerated range in patients with hematologic malignancies (intermediate in total dose 
delivered per cycle between a 2mg continuous regimen and a 5mg alternate daily regimen, both 
of which were tolerated in patients with multiple myeloma). It should be noted that advances in 
HIV therapy and supportive care have allowed the safe delivery in this population of even 
markedly hematotoxic regimens, including paclitaxel and EPOCH(82),(138). 
The baseline thrombotic risk associated with KS is not well-established, while HIV infection is 
established as a thrombotic risk factor (particularly when poorly controlled or associated with 
comorbidities)(139-141). These factors play an important part in estimating the potential risk of 
thrombosis with pomalidomide therapy. One case series in the pre-HAART era, of patients with 
relatively severe KS, reported an increased incidence of thrombosis in limbs affected by 
KS(141). This has not been confirmed, and in more recent studies of thrombotic risk in patients 
with HIV, KS has not emerged as an independent risk factor(139, 142) (also, Musselwhite and 
Sereti, personal communication). One case-control study in post-transplant KS showed an 
increased occurrence of DVT in KS cases, but the small number of cases and long time elapsed 
between KS and DVT (over 2 years) raise the possibility that this finding was coincidental(143). 
No thromboses were seen in either of the phase 2 studies of thalidomide in KS(97, 98, 143). 
Nonetheless, it would not be unexpected that the peripheral venous stasis and endothelial damage 
that may be seen in patients with extensive KS, combined with effects of HIV in those with HIV-
associated disease, could elevate thrombotic risk. Thromboprophylaxis will therefore be 
employed for all subjects.
Two recent randomized studies of the related compound lenalidomide used as maintenance 
therapy in multiple myeloma have reported an increased number of malignancies in the 
lenalidomide arm(144, 145). In both studies, the most commonly reported malignancies were 
myelodysplastic syndromes and myeloid leukemias. Notably, there is an elevated baseline risk of 
these malignancies in multiple myeloma as well as with the use of alkylating agents that are used 
in this patient population. The impact of this and other possible confounding factors including 
increased survival in the treatment arms and ascertainment of malignancies in the control arms 
are currently being evaluated(146). Individuals with HIV are generally not at high risk of 
developing myeloid malignancies, but do incur a 10-1000 fold elevated risk of 
lymphoproliferative disorders and lymphoma, where IMiDs may have a therapeutic benefit(20, 
25). Given the uncertainty surrounding these observations and these characteristic of the 
proposed study population, the impact (if any) of pomalidomide on the risk of subsequent 
malignancies is unknown, and it is possible that the net effect will be protective. Subjects will be 


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followed for five years following completion of therapy, with surveillance for second 
malignancies comprising part of this follow up.
Importantly for patients with HIV-associated KS, pomalidomide is not anticipated to cause or be 
affected by drug-drug interactions due to inhibition or induction when co-administered with 
cytochrome P450 substrates(108). As many antiretrovirals do affect the P450 system this is a 
potential advantage to the use of pomalidomide, particularly in resource-limited settings where 
the choice of antiretroviral regimens may be limited. It is also therefore not expected that the use 
of differing HAART regimens will have a clinically significant impact on subjects, and for 
practical reasons and to improve generalizability they will not be standardized. As a practical 
matter, the variation in HAART regimens is not great: approximately 85% of HAMB patients are 
in any case on regimens incorporating the same nucleoside reverse transcriptase inhibitor 
backbone (tenofovir/emtricitabine), and in approximately 65% of patients this is used in 
combination with the non-nucleoside reverse transcriptase inhibitor efavirenz. The remainder of 
patients receive a variety of protease inhibitor regimens with a minority (approximately 5%) on 
other, deep salvage regimens (Polizzotto and Yarchoan, personal communication). It is possible 
however, given the dependence on renal excretion, that pomalidomide levels may be affected by 
potentially nephrotoxic antiretrovirals (such as tenofovir), and this will be explored.
2
ELIGIBILITY ASSESSMENT AND ENROLLMENT
2.1
ELIGIBILITY CRITERIA
2.1.1
Inclusion Criteria
2.1.1.1
Age ≥18 Years.
2.1.1.2
Any HIV status.
2.1.1.3
Kaposi sarcoma pathologically confirmed by Department of Pathology, Clinical Center, 
National Institutes of Health.
2.1.1.4
At least five measurable KS lesions with no previous local radiation, surgical or 
intralesional cytotoxic therapy that would prevent response assessment for that lesion.
2.1.1.5
ECOG Performance Status ≤2
2.1.1.6
Life expectancy ≥6 months
2.1.1.7
For patients with HIV-associated KS:
2.1.1.7.1 Must be receiving, and adherent to, a HAART regimen consistent with current 
clinical guidelines.
2.1.1.7.2 Must have been receiving HAART for at least one month.
2.1.1.7.3 Must have achieved an HIV VL <10,000 copies/mL.
2.1.1.8
The following hematological parameters:
2.1.1.8.1 Hemoglobin ≥10 g/dL
2.1.1.8.2 Platelets ≥75,000 cells/mm3
2.1.1.8.3 Absolute neutrophil count (ANC) ≥1000 cells/mm3
2.1.1.9
The following biochemical parameters:
2.1.1.9.1 Estimated or measured creatinine clearance ≥45mL/minute (see Appendix 9 for 
estimation of creatinine clearance)
2.1.1.9.2 Serum alanine aminotransferase (ALT) ≤2.5 x upper limit of normal


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2.1.1.9.3 Serum aspartate aminotransferase (AST) ≤ 2.5 x upper limit of normal
2.1.1.9.4 Bilirubin ≤ 1.5x upper limit of normal unless the patient is receiving protease 
inhibitor therapy (e.g. indinavir, ritonavir, nelfinavir, or atazanavir) known to be 
associated with increased bilirubin, in which case total bilirubin ≤7.5 mg/dL with 
direct fraction ≤ 0.7 mg/dL.
2.1.1.10 Females of childbearing potential (FCBP) as defined in Appendix 1 must have a 
negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 
14 days prior to and again within 24 hours before 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 subjects must be counseled at a minimum of every 28 days about 
pregnancy precautions and risks of fetal exposure. See Section 16.1 Appendix 1, Risks 
of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control 
Methods, and also Section 16.2, Appendix 2: Pomalidomide Education and 
Counseling Guidance Document.
2.1.1.11 All study participants must agree to be registered into the mandatory POMALYST 
REMS™ program, and be willing and able to comply with the requirements of the 
POMALYST REMS™ program.
2.1.1.12 Females of reproductive potential must be willing to adhere to the scheduled pregnancy 
testing as required in the POMALYST REMS™ program.
2.1.1.13 Able to take aspirin 81mg daily or if intolerant of aspirin, able to take a substitute 
thromboprophylaxis such as low molecular weight heparin at a thromboprophylactic 
dose (such as enoxaparin 0.5mg/kg once daily).
2.1.1.14 Willing and able to give informed consent.
2.1.1.15 For subjects with HIV-associated entered after a tolerable dose has been determined, 
KS lesions must be either:
2.1.1.15.1 Increasing despite HAART and HIV suppression below the limit of detection (48 
copies/mL) in the two months prior to screening or
2.1.1.15.2 Stable despite HAART for at least three months. Stable disease must be 
symptomatic (examples of symptomatic disease include disease associated with 
pain, edema, psychological distress and/or social withdrawal).
This is to gain preliminary information about pomalidomide activity without 
confounding due to HAART initiation.
2.1.2
Exclusion Criteria
2.1.2.1
Symptomatic pulmonary KS.
2.1.2.2
Symptomatic visceral KS (except for non-ulcerating disease restricted to the oral 
cavity).
2.1.2.3
Specific KS therapy, including cytotoxic chemotherapy but not including HAART, 
within the past 4 weeks (6 weeks if the therapy was bevacizumab).


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2.1.2.4
Use of other anticancer treatments or agents within the past 4 weeks (6 weeks if the 
therapy was a monoclonal antibody).
2.1.2.5
History of malignant tumors other than KS, unless:
2.1.2.5.1 In complete remission for ≥1 year from the time response was first documented or 
2.1.2.5.2 Completely resected basal cell carcinoma or
2.1.2.5.3 In situ squamous cell carcinoma of the cervix or anus.
2.1.2.6
 History of infection meeting any of the following criteria:
2.1.2.6.1 Any infection that would be scored as grade 4 by CTCAE that occurred within six 
weeks of study screening.
2.1.2.6.2 Any infection that would be scored as grade 3 by CTCAE that occurred within 
two weeks of study screening.
2.1.2.6.3 History of fungal and mycobacterial infections, unless at least six weeks has 
passed since the completion of induction antimicrobial therapy. Patients may be 
receiving consolidation therapy for infections of these types.
2.1.2.7
Any abnormality that would be scored as a ≥grade 3 toxicity by CTCAE, except:
2.1.2.7.1 Obesity is not considered an abnormality for the purposes of eligibility 
assessment unless in the opinion of the Principal Investigator or Lead Associate 
Investigator its clinical consequences in a particular subject places the subject at 
unacceptable risk if they were to participate in the study or confounds the ability 
to interpret data from the study.
2.1.2.7.2 Lymphopenia
2.1.2.7.3 Asymptomatic hyperuricemia, hypophosphatemia, or creatine kinase (CK) 
elevations
2.1.2.7.4 Direct manifestations of KS
2.1.2.7.5 Direct manifestations of HIV infection, except for neurologic or cardiac 
manifestations
2.1.2.7.6 Direct manifestations of HIV therapy, except for neurologic or cardiac 
manifestations.
2.1.2.8
History of venous or arterial thromboembolism, unless:
2.1.2.8.1 Line-related thrombosis without embolus occurring ≥1 year prior to screening.
2.1.2.8.2 Complications resulting from atherosclerotic coronary artery disease, peripheral 
vascular disease, or cerebrovascular disease (including infarction) are not 
considered exclusion criteria unless in the opinion of the Principal Investigator or 
Lead Associate Investigator their clinical consequences in a particular subject 
places the subject at unacceptable risk if they were to participate in the study or 
confounds the ability to interpret data from the study.
2.1.2.9
Known drug-related, inherited, or acquired procoagulant disorder including prothrombin 
gene mutation 20210, antithrombin III deficiency, protein C deficiency, protein S 
deficiency and antiphospholipid syndrome but not including heterozygosity for the Factor 
V Leiden mutation or the presence of a lupus anticoagulant in the absence of other criteria 
for the antiphospholipid syndrome.
2.1.2.10 Pregnancy


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2.1.2.11 Breast feeding (if lactating, must agree not to breast feed while taking pomalidomide).
2.1.2.12 Prior therapy with pomalidomide.
2.1.2.13 Known hypersensitivity to thalidomide, lenalidomide or pomalidomide. including prior 
development of erythema nodosum if characterized by a desquamating rash while 
taking thalidomide, lenalidomide or pomalidomide.
2.1.2.14 Any condition, including the presence of laboratory abnormalities, which in the opinion 
of the Principal Investigator or Lead Associate Investigator places the subject at 
unacceptable risk if they were to participate in the study or confounds the ability to 
interpret data from the study.
2.2
RESEARCH ELIGIBILITY EVALUATION
Potential subjects will be evaluated by a HAMB physician investigator for protocol eligibility. 
Baseline evaluation will include a complete medical history, review of systems, and physical 
examination including documentation of the presence and extent of any KS lesions.
2.2.1
Clinical Examination
2.2.1.1
Complete medical history 
2.2.1.2
Comprehensive physical examination.
2.2.2
Clinical Laboratory Data 
(studies performed in Clinical Center Department of Laboratory Medicine except HIV, HBV and 
HCV viral load monitoring performed in Clinical Center Blood Bank)
2.2.2.1
CBC with differential and reticulocyte count
2.2.2.2
Acute care panel (Sodium, Potassium, Chloride, CO2, Creatinine, Glucose, and Urea 
Nitrogen)
2.2.2.3
Mineral panel (Phosphorus, Magnesium, Albumin, and Calcium)
2.2.2.4
Hepatic panel (Alkaline Phosphatase, ALT, AST, Total Bilirubin, and Direct Bilirubin)
2.2.2.5
C-reactive protein
2.2.2.6
Creatine kinase, uric acid, LDH, amylase and lipase
2.2.2.7
APTT, PT, thrombin time (TT), fibrinogen, D-dimer
2.2.2.8
Lymphocyte phenotype TBNK (requires simultaneous CBC and automated differential)
2.2.2.9
HIV Western blot (unless prior lab evaluation by Department of Laboratory Medicine, 
Clinical Center, NIH shows that the patient is HIV infected)
2.2.2.10 HIV viral load if HIV seropositive by Western Blot
2.2.2.11 RPR
2.2.2.12 Tuberculosis testing by PPD or interferon gamma release assay (Quantiferon Gold)
2.2.2.13 Urinalysis.
2.2.3
Pregnancy Testing
2.2.3.1
Urine and serum β-hCG (female subjects only). Must follow pregnancy testing 
requirements as outlined in the POMALYST REMS™ program.  


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2.2.4
Radiographic studies 
2.2.4.1
Chest X-ray.
2.2.4.2
If clinically indicated, a Chest CT may be performed where necessary to assess 
abnormal chest x-ray findings or unexplained respiratory symptoms.
2.2.4.3
Endoscopic studies may be performed when clinically indicated to evaluate and measure 
visceral KS. Such studies are indicated where there are symptoms suggestive of KS 
involvement at the site (including but not limited to hemoptysis, melena, unexplained 
dyspnea) and/or findings on Chest CXR or computer tomography which could represent 
visceral KS. Studies may include bronchoscopy, upper and/or lower gastrointestinal 
endoscopy. Evaluation is not required in the absence of symptoms or imaging 
abnormalities.
2.2.5
KS Tumor Biopsy 
2.2.5.1
Where pathological tissue for confirmation of the diagnosis has not already been 
obtained, biopsy of skin or other involved tissue will be performed.
2.2.5.2
Where diagnostic biopsies are obtained, the specimens will be handled as follows:
2.2.5.2.1 Place sufficient tissue for diagnostic purposes directly into formalin and submit to 
Laboratory of Pathology for histopathology and immunohistochemistry including 
KSHV-LANA and KSHV-vIL-6.  
2.2.5.2.2 Additional research tests may be performed on the screening tissue biopsy only 
where the patient has enrolled on study 01-C-0038 (Collection of Blood, Bone 
Marrow, Tumor, or Tissue Samples from Patients with HIV Infection, KSHV 
Infection, Viral-related Pre-Malignant Lesions, and/or Cancer). See Section 
5.1.2.3.1  for handling and prioritization instructions.  
2.3
PARTICIPANT REGISTRATION AND STATUS UPDATE PROCEDURES
Registration and status updates (e.g., when a participant is taken off protocol therapy and when a 
participant is taken off-study) will take place per CCR SOP ADCR-2, CCR Participant 
Registration & Status Updates found here. 
3
STUDY IMPLEMENTATION
3.1
STUDY DESIGN
This is an open label single agent study of pomalidomide in patients with KS, whether HIV 
associated or not. 
3.1.1
Study Schema
Phase I Dose-establishment component:


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Phase II Antitumor activity assessment component
3.1.2
Dose Limiting Toxicity
For purposes of defining the toxic dose and as a basis of discussion for off-study criteria, the 
following is the definition of dose-limiting toxicity (DLT). It should be noted that neither pre-
existing manifestations of HIV infection, nor of therapy for HIV infection, nor of KS (including 
bleeding from KS) will be considered dose-limiting. Dose limiting toxicities will be assessed 
over the first 8 weeks (2 cycles) of drug administration.
If a patient meets the criteria defined below, they will be considered as having dose-limiting 
toxicity.
3.1.2.1
Any grade 4 toxicity not including lymphopenia, CD4 lymphopenia, neutropenia, 
anemia and bilirubin or CK elevation that is at least possibly due to pomalidomide and 
is not attributable to HIV, its therapy or KS. 
3.1.2.2
For lymphopenia, CD4 lymphopenia, neutropenia, or anemia and bilirubin or CK 
elevation additional restrictions apply to better separate drug effects from 
manifestations of HIV and/or its therapy. For these parameters, the definition of dose-
limiting toxicity is as follows: 
3.1.2.2.1 For lymphopenia and CD4 counts, a decrease that (1) represents a grade 4 
toxicity; (2) represents a 80% decrease from the entry value; (3) occurs in a 
patient with controlled HIV (<1,000 copies/mL); and (4) represents a 50 cell/mm3 
decrease from entry will be considered dose-limiting if found to be present on two 
successive determinations. If a CD4 count meets the numerical criteria on one 
determination, it should be repeated at the next possible visit to see if it is 
confirmed.
3.1.2.2.2 Neutropenia will only be considered dose-limiting if grade 4 for 14 days or more 
(including with G-CSF administration) or if grade 4 febrile neutropenia occurs.
3.1.2.2.3 Anemia will only be considered dose limiting if grade 4 and other causes are not 
identified (for example, antiretroviral therapy with agents such as zidovudine).


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3.1.2.2.4 For patients on HIV protease inhibitors who manifest hyperbilirubinemia, an 
increase total bilirubin of ≥5.0 mg/mL over baseline with an increase in indirect 
bilirubin of ≥4.5 mg/ml over baseline is considered dose-limiting. This is because 
bilirubin is frequently elevated in patients receiving these medications. This does 
not apply to patients whose HAART regimen does not include a protease 
inhibitor.
3.1.2.2.5 Grade 4 creatine kinase (CK) elevations will not be considered dose-limiting if it 
is determined that this is at least possibly due to recent exercise or trauma. This is 
because it is our experience that some KS patients and HIV-infected patients on 
clinical trials develop substantially increased CK levels from exercise or trauma.
3.1.2.3
Any grade 3 toxicity that is at least possibly due to pomalidomide and is not 
attributable to HIV, its therapy, or KS with the following restrictions:
3.1.2.3.1 Those toxicities excluded above in section 3.1.2.2
3.1.2.3.2 Grade 3 thrombocytopenia will only be considered dose limiting if grade 3 for 14 
days or more (all grade 4 thrombocytopenia will be considered dose limiting).
3.1.2.3.3 Grade 3 asymptomatic hyperuricemia or hypophosphatemia will not be 
considered dose limiting, as these are often caused by HIV infection or 
antiretroviral therapy.
3.1.2.3.4 Grade 3 amylase elevations will not be considered dose-limiting if it is 
determined that it is not of pancreatic origin. 
3.1.2.3.5 For rash, grade 3 toxicity is considered dose-limiting only if it does not decrease 
to grade 1 within 4 weeks off therapy; if it recurs on re-challenge with 
pomalidomide; or if it is erythema nodosum characterized by a desquamating 
rash.
3.1.2.3.6 For hypertension, grade 3 toxicity is considered dose limiting where systolic 
blood pressure of ≥160 mm Hg or diastolic blood pressure of ≥100 mm Hg is not 
controlled with antihypertensive medications (all grade 4 hypertension will be 
considered dose limiting).
3.1.2.4
Any arterial or deep venous thrombembolic event or a second superficial 
thromboembolic event that is at least possibly due to pomalidomide.
3.1.2.5
Inability to deliver pomalidomide on at least 50% of scheduled days during the first two 
cycles of therapy as a result of toxicity that is probably or definitely attributable to 
pomalidomide will be considered dose limiting. Delivery interruptions not related to 
pomalidomide (for example, due to unrelated intercurrent illness, patient personal 
emergencies, or other exigencies) will not be considered for this criterion. 
3.1.3
Dose De-escalation
Up to six subjects will initially be treated with pomalidomide at dose level 1, 5mg PO daily for 
21 days followed by 7 days ‘rest’ to complete the 28 day cycle.  Subject to toxicity evaluation 
(Section 3.1.2), this dosage may be deescalated to dose level minus 1, 3mg PO daily for 21 days 
followed by 7 days ‘rest’ to complete the 28 day cycle in a second cohort of up to six subjects.
A dose will be considered as toxic if two or more of the subjects entered at that dose level 
develop a DLT within the first 8 weeks (2 cycles) of drug administration. This time period has 
been selected, in line with prior HAMB studies, as in the great majority of cases KS will require 


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at least 8 weeks of treatment. The tolerated dose will be defined as the highest dose level 
administered as part of the protocol where 0 or 1 of 6 subjects experience a dose limiting toxicity 
within the first 8 weeks of drug administration.
If it is determined that a dose is toxic then subjects in that group who have not experienced a 
DLT or off-therapy criterion will be dropped to the next lower level. In the case that the lowest 
predetermined dose is determined to be toxic, all subjects will cease therapy unless in the interim 
the protocol has been amended by seeking IRB approval to include an additional lower dose 
level. 
3.1.4
Antitumor Activity Assessment
If either dose proves tolerable, additional subjects will be added at the highest tolerable dose to 
gain preliminary information on activity, to a goal of 15 HIV positive and 10 HIV negative 
subjects evaluable for response. Only subjects who complete at least two cycles of therapy will 
be considered evaluable for response. For subjects in the anti-tumor activity assessment phase 
whose KS is HIV-associated, more stringent entry criteria will apply to be considered evaluable 
for response (Section 2.1.1.15); all subjects with non-HIV-associated KS who complete at least 
two cycles of therapy will be considered evaluable for response.
In the absence of off-therapy criteria, therapy will continue for 24 weeks (6 cycles of 4 weeks 
each). Subjects who, in the opinion of the investigators, are continuing to derive benefit may 
continue on therapy for up to an additional 24 weeks (6 additional cycles). Examples of derived 
benefit to be used in consideration of possible additional therapy include, but are not limited to, 
the following:
3.1.4.1
Achievement of partial response from baseline (Section 6.2) with evidence of continuing 
disease improvement on therapy
3.1.4.2
Achievement of stable disease (Section 6.2) in subjects whose disease was progressing at 
baseline
3.1.4.3
Improvement in tumor-associated edema or pain (objective as measured by limb 
circumference, or subjective as measured by analgesia or diuretic requirements) 
3.1.4.4
Improvement in quality of life measures, such as KS-associated impairment of activity 
or mobility or social withdrawal.
Up to two subjects at each dose level who are removed from study prior to the completion of 8 
weeks of therapy for reasons other than drug toxicity, whether in the dose establishment phase or 
antitumor activity assessment phase, may be replaced at the discretion of the Principal 
Investigator or Lead Associate Investigator.
3.1.5
Phase 2 (Expansion Cohort)
As of 06/28/2012, the first six patients completed the first 8 weeks of therapy without DLTs. 
Hence, the planned Phase I dose assessment phase has been completed, establishing that 5mg 
pomalidomide for 21 of 28 days is tolerable in this population. This is therefore the dose to be 
used for Phase II response assessment. 
3.1.6
Option of Second Course of Pomalidomide (effective with Amendment D version date: 
01/22/2013)
Following completion of the initial course of pomalidomide therapy (up to 48 weeks), subjects 
(from the Phase 1 or 2 portion of the study) who again manifest KS requiring therapy while not 


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taking pomalidomide within the study follow up period (5 years) may be considered for an 
additional course of therapy at the Phase 2 dose of 5mg 21 of 28 days, so long as each of the 
following criteria apply:
3.1.6.1
The subject achieved a tumor response (complete or partial) or derived other clinical 
benefit from their initial course of therapy (examples of clinical benefit being given in 
Section 3.1.4.2-3.1.4.4)
3.1.6.2
The KS present is progressing while not taking pomalidomide and either symptomatic 
(for example with pain, edema) or causing psychological distress) 
3.1.6.3
The eligibility criteria described in Section 2.1 are again met at the time of 
consideration of an additional course of therapy, and no exclusion criteria are present 
except that item 2.1.2.12 (prior therapy with pomalidomide) will not apply. Screening 
evaluations described in Section 2.2. will be repeated at the time of consideration of an 
additional course of therapy.
3.1.6.4
Interval administration of other therapies for KS (local or systemic) will not preclude 
consideration of a second course of pomalidomide within the protocol, so long as the 
above criteria are met.
3.1.6.5
Drug administration, evaluations, and off-therapy criteria and correlative studies for the 
optional second course of therapy parallel those described for the initial course, except 
that pharmacokinetic studies and optional on-therapy research biopsies will not be 
performed for the second course. These evaluations are detailed in Section 3.4.2, 
“Optional Second Treatment Course Study Calendar”.
In the absence of off-therapy criteria, the second course of therapy will continue for 24 weeks (6 
cycles of 4 weeks each). Subjects who, in the opinion of the investigators, are continuing to 
derive benefit may continue on the second course therapy for up to an additional 24 weeks (6 
additional cycles). Thus the maximal duration of pomalidomide therapy that may be 
administered within the protocol is 96 weeks (two courses of 48 weeks each); though in most 
cases the amount administered will be considerably less.
3.2
DRUG ADMINISTRATION
3.2.1
Pomalidomide
3.2.1.1
Pomalidomide will be dispensed through a qualified healthcare professional (including 
but not limited to, nurses, pharmacists and physicians).  These healthcare professionals 
will be trained by Celgene in requirements specific to counseling of subjects.  Once 
trained these healthcare staff will counsel subjects prior to medication being dispensed 
to ensure that the subject has complied with all requirements including use of birth 
control and pregnancy testing (FCBP) and that the subject understands the risks 
associated with pomalidomide.  This step will be documented with a completed 
Education and Counseling Guidance Document (Appendix 2) and no drug will be 
dispensed until this step occurs. Counseling includes verification with the patient that 
required pregnancy testing was performed and results were negative. A Pomalidomide 
Information Sheet (Appendix 3) will be supplied with each medication dispensed.
Subjects will be counseled regarding pomalidomide risks of fetal exposure, pregnancy 
testing guidelines and acceptable birth control methods (Appendix 1) prior to 
commencement of therapy and at least every 28 days while on therapy. In addition, the 


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‘Pomalidomide Education and Counseling Guidance Document’ (Appendix 2) will be 
completed prior to each dispensing of study drug by a clinical investigator with the 
subject, and the subject will be provided with a copy of the ‘Pomalidomide Information 
Sheet for Patients Enrolled in Clinical Research Studies’ (Appendix 3).
3.2.1.2
Pomalidomide will be self-administered on an outpatient basis at the assigned dose once 
daily. Subjects will be instructed to take pomalidomide at approximately the same time 
every morning. Subjects should fast (water to drink only) for at least 2 hours prior to 
taking a dose to at least 30 minutes post-dose of pomalidomide. A light breakfast (such 
as tea without sugar and dry toast) may be taken in the morning but must be completed 
at least 2 hours prior to taking a morning dose. Sugary and fatty foods should be 
avoided prior to taking the medication doses. 
3.2.1.3
Subjects will keep a daily diary recording pomalidomide administration including the 
time of administration, and any clinical toxicity or other observations made during the 
cycle (Appendix 8). This will be used as only an aide memoire for subjects. The 
clinical research team will maintain the primary source record of events including 
toxicities.
3.2.1.4
Thromboprophylaxis with aspirin 81mg or an acceptable alternative agent will continue 
throughout therapy (days 1-28 of each cycle), as described in Section 4.1.2.
3.2.1.5
 Treatments and corresponding evaluations may be rescheduled to the closest day 
possible without constituting a protocol violation (e.g. for Federal holidays or 
unforeseen circumstances such as travel difficulties, snow closures and the like).
3.2.1.6
Only enough pomalidomide for one cycle of therapy will be supplied to the patient 
each cycle.
3.2.1.7
Pomalidomide capsules should be swallowed whole, and should not be broken, chewed 
or opened.  
3.2.1.8
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.
3.2.1.9
Subjects who take more than the prescribed dose of pomalidomide should be instructed 
to seek emergency medical care if needed and contact study staff immediately. 
3.2.2
Special Handling Instructions
Females of childbearing potential should not handle or administer pomalidomide unless they are 
wearing gloves.
3.2.3
Record of administration
Accurate records will be kept of all study drug administration (including dispensing and dosing) 
will be made in the source documents. 
3.3
DOSE MODIFICATIONS
All treatment modifications should be discussed with the senior clinical investigators on the 
study. Dose modification guidelines apply to the Phase 1 and Phase 2 portions of the study as 
well as the Second Optional Course of Therapy.
For Phase 1: Subjects who are enrolled on the initial (5mg) dose level who experience a DLT not 
including a thromboembolic event that resolves to grade 1 (or the grade they had at entry) within 


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28 days and continue to have KS may be considered for further therapy at the 3mg dose level if 
they continue to have KS requiring therapy. Response assessment for any such patients is 
described in Section 10.4.
Table 1: Dose Modification of Pomalidomide
Event
Action
Resumption of Therapy
Neutropenia.  ANC 500 to 
<1000 cells/mm³ (CTCAE 
Grade 3)
*If observed during cycle (day 2 of cycle 
onward) therapy may continue with additional 
weekly CBCs. If observed day 1 of new cycle, 
therapy should be held. Consider G-CSF. 
(filgrastim) 5mcg/kg/daily SC rounded by ±10% 
to use the most economical combination of 
available products (commercial vials contain 300 
mcg or 480 mcg). Pegylated filgrastim should 
not be used. Pomalidomide should not be 
administered during G-CSF treatment or within 
24 hours after a G-CSF dose.
CBCs should be evaluated weekly and a 
new cycle of treatment may commence 
at the same dose level on or after day 29 
once ANC ≥1000 cells/mm³.
Neutropenia. 
ANC 
<500 
cells/mm³. (CTCAE Grade 4)
*Suspend or hold pomalidomide. Administer G-
CSF (filgrastim) 5mcg/kg/daily SC rounded by 
±10% to use the most economical combination 
of available products (commercial vials contain 
300 mcg or 480 mcg). Pegylated filgrastim 
should not be used. Pomalidomide should not be 
administered during G-CSF treatment or within 
24 hours after a G-CSF dose.
CBCs should be evaluated weekly and a 
new cycle of treatment may commence 
at the same dose level on or after day 29 
once ANC ≥1000 cells/mm³ so long as 
criteria for a DLT are not met.


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Event
Action
Resumption of Therapy
Febrile Neutropenia. ANC 
<1000 cells/mm³ with a 
single temperature >38.3°C 
or T≥38°C for more than one 
hour.
Suspend or hold pomalidomide. Supportive care 
including intravenous antibiotics as outlined in 
Section 4.2.2. Administer G-CSF (filgrastim) 
5mcg/kg/daily SC rounded by ±10% to use the 
most economical combination of available 
products (commercial vials contain 300 mcg or 
480 mcg). Pegylated filgrastim should not be 
used. Pomalidomide should not be administered 
during G-CSF treatment or within 24 hours after 
a G-CSF dose.
CBCs should be evaluated weekly and a 
new cycle of treatment may commence 
at the same dose level on or after day 29 
once ANC ≥1000 cells/mm³ so long as 
criteria for a DLT are not met.
Thrombocytopenia.: platelet 
count 25,000 to <50,000 
cells/mm³. (CTCAE Grade 3)
If observed during cycle (day 2 of cycle 
onward), pomalidomide may continue with 
additional weekly CBCs. If observed day 1 of 
new cycle, pomalidomide should be held. Hold 
thromboprophylaxis until platelet count ≥ 50000 
cells/mm³.
CBCs should be evaluated weekly and a 
new cycle of treatment may commence 
at the same dose level on or after day 29, 
once platelet count ≥ 50000 cells/mm³ so 
long as criteria for a DLT are not met.
Thrombocytopenia: platelet 
count < 25,000 cells/mm³ 
(CTCAE Grade 4)
Discontinue therapy.  Consider platelet 
transfusion if Plt ≤10000 cells/mm³, bleeding or 
risk factors for bleeding present as outlined in 
Section 4.2.4. Hold thromboprophylaxis until 
platelet count ≥ 50,000 cells/mm³.
Not to resume
Anemia. Hb <8.0 g/dL 
(CTCAE Grade 3)
Consider red cell transfusion if symptomatic, or 
as required to maintain Hb ≥10.0g/L during 
therapy.
Pomalidomide may continue at the same 
dose level once Hb ≥10.0g/L so long as 
criteria for a DLT are not met. 


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Event
Action
Resumption of Therapy
Thromboembolic events 
(first episode of superficial 
venous thrombosis)
Suspend or hold pomalidomide.
On or after day 29 and following 
documentation of complete resolution 
(e.g. by ultrasonography) at the same 
dose level.
Thromboembolic events 
(Arterial, deep venous, or 
second episode of superficial 
venous thrombosis)
Discontinue therapy. 
Not to resume.
Infection at any site 
(≥CTCAE Grade 3) at least 
possibly attributable to 
pomalidomide
Suspend or hold Pomalidomide.
On or after day 29 and following 
documentation of resolution to ≤CTCAE 
Grade 1 at the same dose level. Therapy 
may resume during oral antibiotic 
consolidation therapy if there is no 
clinical or laboratory evidence of active 
infection.
CK elevation at least 
possibly attributable to 
pomalidomide (≥ CTCAE 
Grade 3)
Hold pomalidomide for a maximum of 2 weeks. 
Encourage increased oral fluid intake and 
avoidance of strenuous physical activities. 
Administer intravenous fluid if CK >10,000 
U/L. 
Resume therapy at the same dose level 
once resolution to ≤CTCAE Grade 2. 
Permanently discontinue if not at 
≤CTCAE Grade 2 after a total of 3 
weeks off drug (including the time off 
drug during the last week of the cycle) or 
if CK rises again to grade 4 and it is not 
possibly attributable to excess exercise 
or to trauma.
Any other DLT of CTCAE 
Grade 3 at least possibly 
attributable to pomalidomide
Suspend or hold pomalidomide.
On or after day 29 and following 
resolution to ≤CTCAE Grade 1 at the 
same dose level (see Section 3.5).


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Event
Action
Resumption of Therapy
Any other DLT of CTCAE 
Grade 4 at least possibly 
attributable to pomalidomide
Discontinue therapy. 
Not to resume (see section 3.3).
*At the discretion of the investigators, subjects who experience grade 3 or 4 neutropenia requiring G-CSF during a 
cycle as described below may receive G-CSF 5mcg/kg/daily SC rounded by ±10% to use the most economical 
combination of available products during the ‘rest’ days of subsequent cycles to minimize recurrent neutropenia.


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3.4
STUDY CALENDAR
3.4.1
Initial Treatment Course Calendar
First 
Cycle
Second and 
Third 
Cycles
Fourth 
and 
Later 
Cycles
Post Therapy
Evaluation
Screen
Pre 
Therapy1
Day 
1
Day 
15
Day 
1
Day 
15
Day 1
Day 
29 
Final 
Cycle
28 ± 
7 
days 
later
History and physical2
X
X
X
X
X
X
X
Clinical Labs3
X
X
X
X
X
X
X
X
Pregnancy Test4
X
X
X
X
X
X
X
Pomalidomide 
Education and 
Counseling5
X
X
X
X
HIV Western blot 
X
Chest X-ray
X
Electrocardiogram
X
KS Response 
Evaluation
KS Tumor 
Measurements
X
X
X
X
KS Tumor 
Photography6
X
X
X
X
KS Non-invasive 
Tumor Imaging 6
X
X
X
X
Tumor Biopsies7
X
X
X
Quality of Life 
Assessment8
X
X
X
Pharmacokinetics9
X
X
Adverse Event 
Monitoring
X
X
KSHV VL (PBMCs 
and saliva), viral IL-6, 
human cytokines10
X
X
X
X
KSHV Immune 
Response Assays11
X
X
Monocyte and T cell 
activation and 
subsets11
X
X
X
HIV VL (Single Copy 
Research Assay)12
X
X
X
X
X
X


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1 Pre-therapy studies will be performed after screening and enrollment, and at least 48 hours 
before commencement of therapy.
2 Includes current medications and ECOG performance status
3 See Section 2.2.2 for screening labs, 3.4.3 for baseline labs, 3.4.4 for on treatment labs and 
3.4.5 for post treatment labs. Note as described in Section 3.4.4, day 8, 15 and 22 of cycle 1 and 
Day 15 of cycles 2 and 3 are limited laboratory toxicity checks only. Laboratory toxicity checks 
may be performed by the patient’s primary care physician through a certified outside laboratory 
with results to be provided to NCI investigators, for patients living at a distance from the 
Clinical Center.
4 In females of child-bearing potential (FCBP), as defined in Appendix 1. Urine and serum β-
HCG will be performed within 14 days prior to starting pomalidomide, again within 24 hours of 
starting pomalidomide, and then performed weekly for the first 28 days of study participation 
and then every 28 days while on study, at study drug discontinuation, and at day 28 following 
study drug discontinuation. If menstrual cycles are irregular, the pregnancy testing must occur 
weekly for the first 28 days and then every 14 days while on study, at study discontinuation, and 
at days 14 and 28 following study drug discontinuation.
5All patients must be counseled about pregnancy precautions, risks of fetal exposure and other 
risks.  The counseling must be done on Day 1 of each cycle (or at a minimum of every 28 days) 
and at drug discontinuation. See Appendix 1: Pomalidomide Risks of Fetal Exposure, Pregnancy 
Testing Guidelines and Acceptable Birth Control Methods and: Appendix 2 Pomalidomide 
Education and Counseling Guidance Document.
6 Pre-therapy, day one of subsequent cycles until the sixth cycle and then (for patients receiving 
more than six cycles) day one of odd-numbered cycles (beginning with Cycle 7) and again at the 
end of first course of therapy.
7 Pathological confirmation of diagnosis in Department of Pathology, Clinical Center, National 
Institutes of Health is required for eligibility screening, and may be undertaken using a recent 
biopsy from an outside institution if available. In this case, an additional research biopsy at 
baseline is optional. Research biopsy day one of cycle three (only) is optional. Diagnostic and 
research biopsy at end of first course of therapy is optional. Optional on-therapy research 
biopsies will not be performed for subjects receiving a second course of therapy.
8 Pre-therapy, day one of cycle four, and end of first course of therapy.
9 See Section 5.1.1.2  for full pharmacokinetic studies schedule. Not to be performed for subjects 
receiving a second course of therapy. 
10 At each collection: 1 yellow top tube for PBMCs; 1 blue top tube for saliva; 2 red top tubes for 
viral IL-6; 3 green top tubes for cytokines; 2 yellow top tubes for storage
11 Repeated day one of cycle four and 28±7 days following the end of the first course of therapy
12Only in HIV infected subjects whose HIV VL is undetectable by conventional assays.
As noted in Section 3.2.1.5, with the exception of pharmacokinetics, treatments and 
corresponding evaluations may be rescheduled to the closest day possible without constituting a 
protocol violation (e.g. for Federal holidays or unforeseen circumstances such as travel 
difficulties, snow closures and the like).


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3.4.2
Optional Second Treatment Course Calendar
First Cycle
Second and 
Third 
Cycles
Fourth 
and Later 
Cycles
Post Therapy
Evaluation
Pre 
Therapy1
Day 
1
Day 
15
Day 
1
Day 
15
Day 1
Day 29 
Final 
Cycle
28 ± 7 
days 
later
History and physical2
X
X
X
X
X
X
X
Clinical Labs1
X
X
X
X
X
X
X
X
Pregnancy Test3
X
X
X
X
X
X
X
Pomalidomide Education 
and Counseling4
X
X
X
X
HIV Western blot 
X
Chest X-ray
X
Electrocardiogram
X
KS Response Evaluation:
KS Tumor Measurements
X
X
X
X
KS Tumor Photography5
X
X
X
X
KS Non-invasive Tumor 
Imaging5
X
X
X
X
Tumor Biopsies6
Not performed for second course
Quality of Life 
Assessment7
X
X
X
Pharmacokinetics8
Not performed for second course
Adverse Event 
Monitoring
X
X
KSHV VL (PBMCs and 
saliva), viral IL-6, human 
cytokines9
X
X
X
X
KSHV Immune Response 
Assays10
X
X
Monocyte and T cell 
activation and subsets10
X
X
X
HIV VL (Single Copy 
Research Assay)11
X
X
X
X
X
X


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1 Pre-therapy studies will be performed at least 2 days before commencement of second course of 
therapy.
2 Includes current medications and ECOG performance status
3 In females of child-bearing potential (FCBP), as defined in Appendix 1. Urine and serum β-HCG 
will be performed within 14 days prior to starting pomalidomide, again within 24 hours of starting 
pomalidomide, and then performed weekly for the first 28 days of study participation and then 
every 28 days while on study, at study drug discontinuation, and at day 28 following study drug 
discontinuation. If menstrual cycles are irregular, the pregnancy testing must occur weekly for the 
first 28 days and then every 14 days while on study, at study discontinuation, and at days 14 and 
28 following study drug discontinuation.
4 All patients must be counseled about pregnancy precautions, risks of fetal exposure and other 
risks.  The counseling must be done on Day 1 of each cycle (or at a minimum of every 28 days) 
and at drug discontinuation. See Appendix 1: Pomalidomide Risks of Fetal Exposure, Pregnancy 
Testing Guidelines and Acceptable Birth Control Methods and: Appendix 2Pomalidomide 
Education and Counseling Guidance Document.
5 Pre-therapy, day one of subsequent cycles until the sixth cycle and then (for patients receiving 
more than six cycles) day one of odd-numbered cycles (beginning with Cycle 7) and again at the 
end of second course of therapy.
6 Research biopsies will not be performed for subjects receiving a second course of therapy.
7 Pre-therapy, day one of cycle four, and end of second course of therapy.
8 Pharmacokinetics will not be performed for subjects receiving a second course of therapy.
9 At each collection: 1 yellow top tube for PBMCs; 1 blue top tube for saliva; 2 red top tubes for 
viral IL-6; 3 green top tubes for cytokines; 2 yellow top tubes for storage
10 Repeated day one of cycle four and 28±7 days following the end of second course of therapy. 
11 Only in HIV infected subjects whose HIV VL is undetectable by conventional assays.
As noted in Section 3.2.1.5, treatments and corresponding evaluations may be rescheduled to the 
closest day possible without constituting a protocol violation (e.g. for Federal holidays or 
unforeseen circumstances such as travel difficulties, snow closures and the like).
3.4.3
Baseline Studies
Screening clinical laboratory and radiographic studies may be used for baseline evaluation 
provided they were obtained within 14 days of study enrollment or within 28 days of first dose of 
therapy, except baseline CBC and acute care, mineral and hepatic panel and (for females) a 
pregnancy test is required within 24 hours prior to first dose of therapy. CBC, acute care, mineral 
and hepatic panels, and pregnancy test repeated within 24 hours of first dose must continue to 
meet eligibility criteria (Sections 2.1.1.8 to 2.1.1.10) for the subject to commence therapy. 
Pharmacokinetics studies must be performed day one of cycle one. Correlative studies must be 
performed pre-therapy (for Immune Activation and KSHV Immune Response Assays) or day 1 
of cycle one (for Cytokine, Angiogenesis and Virologic Studies) as specified in Section 5.1.2. 
3.4.3.1
Clinical Examination
3.4.3.1.1 Complete medical history 
3.4.3.1.2 Comprehensive physical examination
3.4.3.2
Clinical Laboratory Data
3.4.3.2.1 CBC with differential and reticulocyte count 


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3.4.3.2.2 Acute care panel (Sodium, Potassium, Chloride, CO2, Creatinine, Glucose, and 
Urea Nitrogen)
3.4.3.2.3 Mineral panel (Phosphorus, Magnesium, Albumin, and Calcium)
3.4.3.2.4 Hepatic panel (Alkaline Phosphatase, ALT, AST, Total Bilirubin, and Direct 
Bilirubin)
3.4.3.2.5 C-reactive protein
3.4.3.2.6 Creatine kinase, uric acid, LDH, amylase and lipase
3.4.3.2.7 Thyroid stimulating hormone (TSH)
3.4.3.2.8 APTT, PT, thrombin time (TT), fibrinogen, D-dimer
3.4.3.2.9 Lymphocyte phenotype TBNK (requires simultaneous CBC and automated 
differential)
3.4.3.2.10 HIV viral load if HIV seropositive by Western Blot
3.4.3.2.11 EBV viral load if seropositive
3.4.3.2.12 CMV viral load if seropositive
3.4.3.2.13 Hepatitis A antibody screen 
3.4.3.2.14 Hepatitis B antibody screen (HBV S Ag, HBV S Ab, HBV core Ab) and viral 
load if there is evidence of past or current infection
3.4.3.2.15 Hepatitis C antibody screen and HCV viral load
3.4.3.2.16 RPR
3.4.3.2.17 Tuberculosis testing by PPD or interferon gamma release assay (Quantiferon 
Gold)
3.4.3.3
Pregnancy Testing
3.4.3.4
Urine and serum β-hCG (female subjects only)
3.4.3.5
Electrocardiogram (EKG)
3.4.3.6
Pharmacokinetic Studies (see Section 5.1.1)
3.4.3.7
Correlative Studies (see Section 5.1.2)
3.4.3.8
Baseline assessment for response evaluation (see Sections 6.2.1 and 6.2.2)
3.4.4
Treatment Phase Studies
Clinical examination and clinical laboratory evaluation will be repeated each cycle, except for 
additional clinical assessment on day 15 of cycle one and additional laboratory toxicity checks 
on day 15 of cycle one, two and three (see Section 3.4). Laboratory toxicity checks may be 
performed by the patient’s primary care physician through a certified outside laboratory with 
results to be provided to NCI investigators, for patients living at a distance from the Clinical 
Center.
3.4.4.1
Clinical Examination
Evaluation will be repeated on or immediately before day 1 of each cycle, and on day 15 of cycle 
1. Objective signs, relevant positive and negative findings on history and examination, and 
clinical toxicities will be evaluated and recorded each visit.
3.4.4.2
Clinical Laboratory Data
3.4.4.2.1 Evaluations will be repeated on or immediately before day 1 of each cycle.


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3.4.4.2.2 CBC with differential and reticulocyte count 
3.4.4.2.3 Acute care panel (Sodium, Potassium, Chloride, CO2, Creatinine, Glucose, and 
Urea Nitrogen)
3.4.4.2.4 Mineral panel (Phosphorus, Magnesium, Albumin, and Calcium)
3.4.4.2.5 Hepatic panel (Alkaline Phosphatase, ALT, AST, Total Bilirubin, and Direct 
Bilirubin)
3.4.4.2.6 C-reactive protein
3.4.4.2.7 Creatine kinase, uric acid, LDH, amylase and lipase
3.4.4.2.8 Thyroid stimulating hormone (TSH)
3.4.4.2.9 APTT, PT, thrombin time (TT), fibrinogen, D Dimer
3.4.4.2.10 HIV viral load if HIV seropositive
3.4.4.2.11 Lymphocyte phenotype TBNK (requires simultaneous CBC and automated 
differential)
3.4.4.2.12 EBV viral load if seropositive
3.4.4.2.13 CMV viral load if seropositive
3.4.4.2.14 HBV viral load if evidence of past or current infection
3.4.4.2.15 HCV viral load if evidence of past or current infection.
3.4.4.3
Additional Clinical Laboratory Toxicity Check
3.4.4.3.1 Evaluations will be repeated on day 15 of cycles one, two and three only. Results 
from these evaluations will be used to determine if dose adjustments are required 
for subsequent days of the cycle (as outlined in Table 1).
3.4.4.3.2 CBC with differential and reticulocyte count 
3.4.4.3.3 Acute care panel (Sodium, Potassium, Chloride, CO2, Creatinine, Glucose, and 
Urea Nitrogen)
3.4.4.3.4 Mineral panel (Phosphorus, Magnesium, Albumin, and Calcium)
3.4.4.3.5 Hepatic panel (Alkaline Phosphatase, ALT, AST, Total Bilirubin, and Direct 
Bilirubin)
3.4.4.4
Pregnancy Testing
In females of child-bearing potential (FCBP) urine and serum β-HCG will be performed weekly 
for the first 28 days of study participation and then every 28 days while on study, at study drug 
discontinuation, and at day 28 following study drug discontinuation. If menstrual cycles are 
irregular, the pregnancy testing must occur weekly for the first 28 days and then every 14 days 
while on study, at study discontinuation, and at days 14 and 28 following study drug 
discontinuation.
3.4.4.5
Correlative Studies (see section 5.1.2)
3.4.4.6
Response evaluation (see sections 6.2.1 and 6.2.2)
3.4.5
Post-treatment Evaluation
Subjects will be reviewed at day 29 of their final cycle, and further evaluated for short term 
toxicity a further 28 days (±7 days) after completion of the final cycle. Objective signs, relevant 
positive and negative findings on history and examination, and clinical toxicities will be 


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37
evaluated and recorded each visit. If any drug toxicity remains at the follow-up evaluation, 
subjects will be followed as medically indicated until the toxicity stabilizes or resolves. 
3.4.5.1
Clinical Examination
3.4.5.2
Clinical Laboratory Data
3.4.5.2.1 CBC with differential and reticulocyte count 
3.4.5.2.2 Acute care panel (Sodium, Potassium, Chloride, CO2, Creatinine, Glucose, and 
Urea Nitrogen)
3.4.5.2.3 Mineral panel (Phosphorus, Magnesium, Albumin, and Calcium)
3.4.5.2.4 Hepatic panel (Alkaline Phosphatase, ALT, AST, Total Bilirubin, and Direct 
Bilirubin)
3.4.5.2.5 C-reactive protein
3.4.5.2.6 Creatine kinase, uric acid, LDH, amylase and lipase
3.4.5.2.7 Thyroid stimulating hormone (TSH)
3.4.5.2.8 APTT, PT, thrombin time (TT), fibrinogen, D Dimer
3.4.5.2.9 HIV viral load if HIV infected
3.4.5.2.10 Lymphocyte phenotype TBNK (requires simultaneous CBC and automated 
differential)
3.4.5.2.11 EBV viral load if seropositive
3.4.5.2.12 CMV viral load if seropositive
3.4.5.2.13 HBV viral load if evidence of past or current infection
3.4.5.2.14 HCV viral load if evidence of past or current infection.
3.4.5.3
Pregnancy Testing
In females of child-bearing potential (FCBP) urine and serum β-HCG will be performed at study 
drug discontinuation, and at day 28 following study drug discontinuation. If menstrual cycles are 
irregular, the pregnancy testing must occur at study drug discontinuation, and at days 14 and 28 
following study drug discontinuation.
3.4.5.4
Correlative Studies (see section 5.1.2)
3.4.5.5
Response Evaluation (see sections 6.2.1 and 6.2.2) 
3.4.5.6
Long-term follow up
Subjects will be clinically evaluated every 3 months for the first 6 months after completion of 
therapy, then every six months to a total of two years after therapy, and then annually to a total 
of five years after completion of therapy to evaluate for disease progression and the development 
of secondary malignancies. CBC, Acute care, mineral and hepatic panels, HIV VL if HIV 
infected, and Lymphocyte phenotype TBNK will be rechecked or, if performed by primary care 
in the community, outside results will be reviewed. 
For subjects who receive an additional course of pomalidomide, clinical evaluation will be for 
five years following the completion of the first course of therapy including a minimum of two 
years following the completion of the second course of therapy in any case where follow up 
would otherwise be completed in less than two years after the second course. The visit schedule 
will be increased as follows to be: every 3 months for the first 6 months after completion of the 


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38
second course of therapy, then every six months to a total of two years after the second course of 
therapy, and then annually to a total of five years after completion of the first course of therapy.
During follow-up visits, KS lesions will be assessed, and if patients have not received additional 
systemic therapy for KS (except for antiretroviral therapy), disease progression will be assessed.  
For patients who have received other therapies or have previously progressed, this information as 
well as the status of their KS lesions will be recorded at the time of the visit (without necessarily 
assessing disease progression).
The time of the visits may be accelerated or delayed somewhat if need be because of difficulty 
scheduling, etc. This follow up will be in parallel with primary care provision in the community.
If patients cannot or refuse to come in for follow-up visits, an attempt will be made to obtain data 
on the patient's general status, their KS treatment, the status of their KS, and secondary 
malignancies from their primary care providers in the community, and this will not constitute a 
protocol deviation.  For this protocol, "secondary malignancies" will be defined as all new 
malignancies, whether or not they have been previously reported as associated with 
pomalidomide.  It will include malignancies known to be associated with KSHV or HIV 
infection. 
3.5
COST AND COMPENSATION 
3.5.1
Costs
NIH does not bill health insurance companies or participants for any research or related clinical 
care that participants receive at the NIH Clinical Center.  If some tests and procedures performed 
outside the NIH Clinical Center, participants may have to pay for these costs if they are not covered 
by insurance company.  Medicines that are not part of the study treatment will not generally be 
provided or paid for by the NIH Clinical Center.    
3.5.2
Compensation
Participants will not be compensated on this study.
3.5.3
Reimbursement 
The NCI will cover the costs of some expenses associated with protocol participation.  Some of 
these costs may be paid directly by the NIH and some may be reimbursed to the 
participant/guardian as appropriate.  The amount and form of these payments are determined by 
the NCI Travel and Lodging Reimbursement Policy.   
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 28 days (±7 days) following the last dose of therapy.
3.6.1
Off-Therapy
3.6.1.1
Any toxicity which is grade 4 and a dose limiting toxicity as defined in Section 3.1.2 at 
least possibly related to pomalidomide.
3.6.1.2
Any toxicity which is grade 3 and a dose limiting toxicity as defined in Section 3.1.2 at 
least possibly related to pomalidomide that does not resolve within 28 days to either 
grade 1 or the grade the patient had at entry.


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3.6.1.3
Development of deep venous or arterial thrombosis, whether symptomatic or not, or 
development of a second on-study superficial venous thrombosis.
3.6.1.4
Pregnancy.
3.6.1.5
Achievement of pathologically confirmed complete remission.
3.6.1.6
Completion of six cycles of therapy (unless continuing to derive clinical benefit, as 
described in Section 3.1.4, in which case up to 12 cycles may be administered).
3.6.1.7
Clinically significant progressive disease compared with the tumor baseline for the 
current course of therapy by NCI-HAMB modified ACTG KS response criteria, 
sustained for eight weeks and not attributed to immune reconstitution syndrome. As KS 
may wax and wane, and improvements may be seen despite an initial period of 
progression, physician investigators may continue therapy through the first 6 cycles, 
despite meeting formal criteria for progressive disease, as long as disease progression is 
not clinically significant. Such cases must be discussed with the Principal Investigator 
and study subject. Clinically significant progression includes all symptomatic visceral 
disease and disease which is organ- or life-threatening.
3.6.1.8
ECOG performance status ≥3.
3.6.1.9
Significant non-adherence to protocol therapy or HAART (the latter only in subjects 
with HIV-associated KS).
3.6.1.10 Inability to achieve HIV viral control, defined as failure to maintain an HIV VL 
<10,000 copies/mL persisting on at least two successive determinations at least four 
weeks apart and persisting despite optimization of HAART regimen. If a change in 
HAART regimen is required, a further period of up to eight weeks to assess the effect of 
this change on HIV VL is allowable.
3.6.1.11 Subject requests to be withdrawn from active therapy
3.6.1.12 Subjects may be taken off therapy at the discretion of the Principal Investigator 
3.6.2
Off Study Criteria
3.6.2.1
Subjects may be taken off study at the discretion of the Principal Investigator.
3.6.2.2
Subjects may withdraw from the study as a matter of personal preference.
3.6.2.3
Subject has completed the study follow-up period
3.6.2.4
Death
.
4
CONCOMITANT MEDICATIONS/MEASURES
4.1
CONCURRENT THERAPIES
4.1.1
Antiretroviral therapy
4.1.1.1
HIV infected subjects must be receiving, and adherent to, HAART.
4.1.1.2
Referring physicians may manage this component of care while liaising with study 
physician investigators, at the discretion of the Principal Investigator or Lead Associate 
Investigator.


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4.1.1.3
Recommended combination therapy will be based on Department of Health and Human 
Services Guidelines for treatment of HIV infection. However, patients may have 
extenuating circumstances requiring deviation from these guidelines.
4.1.2
Thromboprophylaxis
4.1.2.1
Subjects will receive thromboprophylaxis for the duration of pomalidomide therapy 
(including ‘rest’ days), ceasing 28 days following the last cycle of pomalidomide.
4.1.2.2
Recommended thromboprophylaxis is aspirin 81mg PO once daily.
4.1.2.3
In subjects intolerant of the above, an appropriate alternate regimen may be used. 
Alternatives include but are not limited to enoxaparin 0.5mg/kg to a maximum of 40mg 
SC once daily Enoxaparin dose may be rounded to accommodate available commercial 
prefilled syringes with. Enoxaparin may also be considered in subjects with additional 
thrombotic risk factors, such as immobility or significant KS-associated edema. Patients 
receiving therapeutic anticoagulation for another indication (for example atrial 
fibrillation), whether with warfarin, enoxaparin, or another agent, may continue that 
agent in lieu of thromboprophylaxis.
4.1.2.4
Neither aspirin nor low molecular weight heparin will be administered when platelet 
count <50,000 cells/mm3.
4.1.3
Pneumocystis jiroveci (PCP) prophylaxis
4.1.3.1
Pneumocystis jiroveci prophylaxis is indicated if the CD4 count is ≤ 200cells/µL and 
for patients with a history of PCP infection. 
4.1.3.2
Recommended therapy is trimethoprim/sulfamethoxazole DS PO three times weekly. 
4.1.3.3
In patients intolerant of the above, an appropriate alternate regimen may be used. 
Alternatives include but are not limited to dapsone 50–100 mg PO daily or 100 mg PO 
twice weekly; atovaquone 1500 mg PO daily; aerosolized pentamidine monthly.
4.1.4
Mycobacterium avium complex (MAC) prophylaxis
4.1.4.1
Consider for patients whose CD4 cells are below 50-75/mm3, and for those with historic 
CD4 nadir ≤75/mm3.
4.1.4.2
Recommend azithromycin 1200 mg once weekly, but other agents are acceptable.
4.1.5
Contraindicated Therapies
4.1.5.1
Corticosteroids may be given only if the Principal Investigator or a physician Associate 
Investigator approves them. In general, except for physiologic replacement, 
corticosteroids (including topical preparations) should be avoided wherever possible, as 
they can have adverse effects on KS.
4.1.5.2
Radiation therapy is contraindicated for patients receiving therapy on protocol, as the 
effects of radiation therapy in combination with pomalidomide in patients with KS are 
unknown.
4.2
SUPPORTIVE CARE
4.2.1
General Principles of Supportive Care
Medications may be administered as clinically indicated, or at the discretion of the Principal 
Investigator, with the exception of other specific therapies for KS


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4.2.2
Febrile Neutropenia
Subjects who develop febrile neutropenia will be hospitalized and treated with appropriate 
broad-spectrum intravenous antibiotics. See Section 3.3 for treatment modifications and 
guidelines for filgrastim use pertaining to neutropenia.
4.2.3
Anemia
If subject develops symptomatic anemia, or if the hemoglobin falls below 8.0 mg/dL transfusion 
may be considered. Appropriate evaluation for etiology of the anemia, including but not limited 
to pomalidomide, HIV and its therapy, should be initiated.
4.2.4
Thrombocytopenia
Thrombocytopenia should be treated conservatively. In the absence of bleeding or a planned 
invasive procedure, platelet transfusions should be given for a platelet count below 10,000/mm3. 
For subjects with risk factors for bleeding, including fever, platelet transfusion may be 
considered for platelet counts below 20,000/mm3. If invasive procedures are planned or the 
patient develops bleeding, platelet transfusions should be administered in accordance with 
standard of practice, usually maintaining a platelet count > 50,000/mm3. 
4.2.5
Opportunistic Infections
Subjects who develop opportunistic infections, including but not limited to pneumocystis jiroveci 
pneumonia, mycobacterial diseases, cytomegalovirus (CMV), and fungal infections will be 
treated using standard regimens. All opportunistic infections will be discussed with the Principal 
Investigator. Consultation with the Infectious Disease Service is mandatory for subjects 
diagnosed with mycobacterium tuberculosis.
4.2.6
Nutritional Assessment and Psychological Support
4.2.6.1
HIV and KS may compromise nutritional status. Careful attention will be paid to 
nutritional status, and consultation with nutrition healthcare workers to optimize caloric 
intake will be undertaken as necessary. 
4.2.6.2
The chronic, incurable and potentially life-threatening nature of this disease and the 
stigmatizing nature of visible lesions is a profound psychological stressor. All such 
subjects on the study will be informed of and encouraged to see a NIH Social Worker 
for evaluation and support.
5
BIOSPECIMEN COLLECTION
5.1
CORRELATIVE AND PHARMACOKINETIC STUDIES FOR RESEARCH.
Correlative studies to be performed during treatment with pomalidomide include assessment of 
changes in tumor blood flow by non-invasive imaging techniques(147, 148); assessment of 
changes in systemic cytokines and angiogenic factors including IL-1β, IL-2, IL-5, human IL-6, 
viral IL-6, IL-8, IL-10, IL-12, IFN-γ, TNF-α, VEGF-A, IP-10/CXCL-10 and RANTES; 
assessment of changes in HIV and KSHV viral loads (VL), including changes in HIV VL 
occurring below the conventional limit of detection; assessment of biochemical changes in KS 
tumor tissues (including the Notch ligands Dll1, Dll3, Dll4, Jag1 and Jag2; the Notch receptors 
Notch1,2, 3 and 4; Notch intracellular domain (ICD); the Notch target genes Hey1 and Hey2; the 
transcription factors ZEB1, ZEB2, Slug and snail; EphrinB2 and EphB receptors; and markers of 


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42
NFkB activation [p65, p50IkBalpha and IKK1]); and preliminary assessment of changes in 
immunologic parameters, including monocyte activation, T-cell activation and subsets, and anti-
KSHV specific T-cell immune responses.  Correlative assays may be performed in batches.
5.1.1
Pharmacokinetic studies 
Pharmacokinetic studies will be performed during the first course of therapy at the time of first 
dose (day one to two of cycle one), and be repeated at steady state (day 15 to 16 of cycle one). 
5.1.1.1
Pharmacokinetic sample collection and analysis will be carried out in all enrolled 
subjects. For determination of pomalidomide pharmacokinetics, serial venous blood 
samples (6mL sodium heparin tube) will be obtained before and after drug 
administration on day 1 of cycle 1 (first administration) and day 15 of cycle 1 (steady 
state). The following time points for collection will be used: pre-dose, 1, 2, 3, 4, 6, 8, 
24, according to the following table, in order to capture a fair estimate of the Cmax and 
terminal elimination phase. 
5.1.1.2
Pharmacokinetic Sample Schedule for Pomalidomide (times as close as feasible to those 
specified):
Cycle
Day
PK Sampling
Scheduled Time
Tube
1
1
Pomalidomide
Pre-dose
1
1
1
Pomalidomide
1 hour after dose
2
1
1
Pomalidomide
2 hours after dose
3
1
1
Pomalidomide
3 hours after dose
4
1
1
Pomalidomide
4 hours after dose
5
1
1
Pomalidomide
6 hours after dose
6
1
1
Pomalidomide
8 hours after dose
7
1
2
Pomalidomide
24 hours after dose
8
1
15
Pomalidomide
Pre-dose
9
1
15
Pomalidomide
1 hour after dose
10
1
15
Pomalidomide
2 hours after dose
11
1
15
Pomalidomide
3 hours after dose
12
1
15
Pomalidomide
4 hours after dose
13
1
15
Pomalidomide
6 hours after dose
14


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Cycle
Day
PK Sampling
Scheduled Time
Tube
1
15
Pomalidomide
8 hours after dose
15
1
16
Pomalidomide
24 hours after dose
16
5.1.1.3
Handling of Pharmacokinetic Samples
5.1.1.3.1 The Blood Processing Core (BPC) (Figg Laboratory. 5A-09, 301-594-6131 or 
301-402-3622) will coordinate sample collection, processing and pharmacokinetic 
analysis. Research nurses will give the lab 24 hours advance notice on PK blood 
draws.
5.1.1.3.2 The date, planned time and exact draw time and cycle day of collection for each 
specimen will be recorded on a pharmacokinetic form containing the study 
number and unique patient identifier. The exact time of draw and cycle timepoint 
will be recorded by research or floor nurses on the blood tube label.
5.1.1.3.3 Research nurses will page 102-11964 (Figg laboratory) immediately prior to 
blood draw. Blood will be drawn into green-top tubes to which 0.1% hydrochloric 
acid has been added. These will be supplied in capped tubes by the Figg 
laboratory to the clinical team prior to the patient starting treatment. After 
drawing, blood samples must be thoroughly mixed for drug stability and placed 
immediately on wet ice for transport to the Figg laboratory.
5.1.1.3.4 Samples will then be centrifuged within 30 minutes of collection, for 10 minutes at 
2000g (4°C), and plasma supernatants will be transferred to individually labeled 
tubes, barcoded, anonymized, and stored at -80 °C until analysis. Patient data will 
be entered into a secure and encrypted LabSamples database maintained by the 
Clinical Pharmacology Program, Office of the Clinical Director.
5.1.1.3.5 An ultra high pressure liquid chromatography-tandem mass spectrometry analytical 
method will be used to quantify pomalidomide plasma concentrations.
5.1.1.3.6 Pharmacokinetic parameters calculated by noncompartmental analysis will be the 
maximum plasma concentration (Cmax), the time at Cmax (Tmax), the Cmax at steady-
state (Cmax ss), Tmax ss, apparent clearance (CL/F), and the apparent volume of 
distribution (Vss/F), the area under the plasma concentration time curve on day 1 
extrapolated to infinity (AUC0-∞) and at steady state (AUC0-24), terminal 
elimination half-life (T1/2). The study will include exploratory population 
pharmacokinetic correlative analysis of drug-interaction effects on pomalidomide 
plasma exposure for subjects on antiretroviral medications.
5.1.2
Correlative Studies
5.1.2.1
Sample Collection
5.1.2.1.1 Correlative Cytokine, Angiogenesis and Virologic Studies 
Evaluations will occur on day 1 of each cycle as well as on day 29 of the final cycle. There will 
also be an additional pre-therapy collection for single copy HIV VL.
5.1.2.1.1.1 KSHV viral load in peripheral blood mononuclear cells 
One yellow top tube (send to Whitby laboratory)


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5.1.2.1.1.2 KSHV viral load in saliva
One blue top conical polypropylene tube (no additive) of saliva obtained with 
Scope® mouthwash (BD Falcon® Ref 353070) (send to Whitby laboratory).
5.1.2.1.1.3 viral IL-6, human IL-6, human IL-10, IL-1β, IL-5 IL-8, IL-12, IFN-γ, TNF-α, 
RANTES and IP-10/CXCL-10 
Two red top tubes (send to Leidos Biomedical Research Inc., Frederick)
5.1.2.1.1.4 Measurement of VEGF, FGF-2, Dll4/Notch and Ephrinb2/Ephb2 
Three sodium heparin green top tubes (send for storage to Leidos Biomedical 
Research Inc. Frederick)
5.1.2.1.1.5 Single copy HIV VL (only in patients with HIV infection) 
One 6mL lavender top (EDTA) tubes for measurement of single copy HIV 
VL.  Send to Leidos Biomedical Research Inc., Frederick to be frozen at -
40°C. These samples will be transferred to the Maldarelli laboratory when 
ready for batched testing. Samples will be run only in patients whose HIV VL 
by conventional techniques is approaching or below the limit of detection. 
5.1.2.1.1.6 Two yellow top tubes (send for storage to  Leidos Biomedical Research Inc., 
Frederick).
5.1.2.1.2 Immune Activation and KSHV Immune Response Assays
Studies will be performed on one occasion pre-therapy (to be after screening and enrollment and 
at least 2 days before commencement of therapy and repeated 28 days (±7 days) after completion 
of the final cycle. Monocyte and T-cell Activation and Subset assays only will also be repeated 
day 1 of cycle 4. If a fresh monocyte sample is planned and the Sereti laboratory is unable to 
receive the fresh monocyte sample on the day of a planned draw (for example due to staff illness, 
equipment failures, or other exigencies) the fresh monocyte sample may be drawn on the next 
available cycle or run from frozen specimens without constituting a protocol deviation; for the 
pre-therapy draw samples may be drawn any day prior to drug administration up to and including 
cycle 1 day 1.
If immune activation studies and KSHV immune response assays have been performed on a 
subject as part of the HAMB Tissue Procurement study (01-C-0038) within 14 days of enrolment 
on 12-C-0047, then at the discretion of the Principal Investigator or Lead Associate Investigator 
the samples drawn under 01-C-0038 may be used for the pomalidomide pre-therapy baseline and 
this draw does not need to be repeated pre-therapy. In these cases, the investigator will confirm 
that the patient gave consent for future use of specimens when the consent for 01-C-0138 was 
signed.
5.1.2.1.2.1  KSHV Serology, KSHV miRNA Typing and KSHV-specific T-cell 
Responses
Performed in the laboratory of Dr. Denise Whitby, NCI-Frederick.
Serology and miRNA Typing will be performed at the pre-therapy draw only.
Samples for KSHV-specific T-cell Responses will be stored and performed in 
batches with paired samples from individual subjects assayed together for 
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Send 34mL blood in four yellow top (ACD) tubes to Leidos Biomedical 
Research Inc., Frederick for storage prior to transfer to Whitby laboratory.
5.1.2.1.2.2  Monocyte and T-cell Activation and Subset Assays
Performed in the laboratory of Dr. Irini Sereti, NIAID.
As of amendment E, fresh monocyte studies from EDTA samples will not be 
performed. Monocyte studies will be performed from frozen sodium heparin 
samples.
T-cell studies will be stored and performed in batches with paired samples 
from individual subjects assayed together for consistency: send 40mL blood in 
green top (sodium heparin) tubes to Leidos Biomedical Research Inc., 
Frederick for storage.
5.1.2.2
Description of Studies
5.1.2.2.1 Human Cytokine Assays
Human multiplex inflammatory cytokine ELISA (Meso-Scale Discovery, Gaithersburg, MD: 
Cat.# K15008), human IL-5 ELISA (Cat.# K111AJA), VEGF ELISA (Cat.# K111BMA), 
RANTES (Cat.# K111BFA) and IP-10/CXCL-10 (Cat.# K111AVA) will be performed in the 
AIDS Monitoring Laboratory, Leidos Biomedical Research Inc., Frederick.
5.1.2.2.2 Viral IL-6 Assay
Performed in the laboratory of Dr. Robert Yarchoan, using a modification of the method 
previously described by our group(69).
5.1.2.2.3 KSHV Serology, KSHV Viral Load, and KSHV Specific T-cell Responses
Performed in the laboratory of Dr. Denise Whitby, Leidos Biomedical Research Inc., Frederick, 
using methods previously described by her group(19),(149-151).
5.1.2.2.4 HIV Viral Load Single Copy Assay
Performed in the laboratory of Dr Frank Maldarelli, NCI, using real-time reverse transcriptase-
initiated PCR assays previously described by his group(152).
5.1.2.2.5 Monocytes and T-cell Activation, Stimulation and Subset Assays
Performed in the laboratory of Dr Irini Sereti, NIAID.  Assays of monocyte activation and T cell 
polyclonal stimulation and activation, including HLA DR/38/Ki67/PD-
1/CD57/Ro/CD27/FoxP3/CD25 will be performed by flow cytometry.
5.1.2.2.6 Systemic Angiogenesis Assays
Performed in the laboratory of Dr. Giovanna Tosato, NCI.  Assays of FGF-2, Dll4/Notch and 
Ephrinb2/Ephb2 will be performed by ELISA and/or Western blot on blood samples.
5.1.2.2.7 KS Tissue Angiogenesis and Signaling Assays
Performed in the laboratory of Dr. Giovanna Tosato, NCI.
Assays of the Notch ligands Dll1, Dll3, Dll4, Jag1 and Jag2; the Notch receptors Notch1,2, 3 and 
4; Notch intracellular domain (ICD); the Notch target genes Hey1 and Hey2; the transcription 
factors ZEB1, ZEB2, Slug and snail; EphrinB2 and EphB receptors; and markers of NFkB 
activation p65, p50IkBalpha and IKK1 will be performed using mRNAs for quantitative PCR, 
Westerns blots, and immunohistochemistry for confocal microscopy.
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Performed in the laboratory of Dr Joseph Ziegelbauer, HAMB, CCR, NCI.  After cell separation, 
cells will be lysed to extract RNA and protein. These samples will be analyzed using quantitative 
PCR, gene expression arrays and Western blots with a focus on KSHV miRNA target genes.
5.1.2.3
KS Tumor Biopsies
5.1.2.3.1 From screening material
If additional research tests are to be performed on the screening biopsy (see 
Section 2.2.5.2.2), please divide the specimen remaining after sufficient tissue for 
diagnostic purposes has been submitted to Laboratory of Pathology in formalin 
for histopathology and immunohistochemistry and distribute in the priority 
indicated in Section 5.1.2.3.3.
5.1.2.3.2 Additional optional biopsies:
5.1.2.3.2.1 On therapy biopsy
Where there is cutaneous disease, an optional biopsy for research purposes may 
be performed during the treatment phase on day one of cycle three (or day 28 of 
cycle two if this is more convenient). A 2-3mm cutaneous punch biopsy only will 
be obtained.  Where an on-treatment research biopsy is obtained, the specimens 
will be handled as follows, in this priority:
Place sufficient tissue for diagnostic purposes directly into formalin and submit 
to Laboratory of Pathology for histopathology and immunohistochemistry 
including KSHV-LANA and KSHV-vIL-6.
Divide the remainder and provide to the 1. Tosato laboratory (fresh, on gauze 
damp but not wet with saline, at 4°C) for tissue expression of Dll4/Notch, 
Jag1/Notch, Jag2/Notch, Notch ICD (intracellular domain), Hey1/Hey2 and 
EphrinB/EphB, and markers of NFkB activation (including p65, p50IkBalpha, 
IKK1)
5.1.2.3.2.2 Post-therapy biopsy
Additional optional 6 mm cutaneous punch biopsies may be performed in one or 
both of the following two circumstances if clinically indicated: after therapy has 
been completed, if clinically indicated and subject to patient agreement, to 
confirm clinical complete response; or during therapy to document progressive 
disease if there is clinical uncertainty about new lesions. Where such biopsies are 
obtained, the specimens will be handled as follows, in this priority:
Place sufficient tissue for diagnostic purposes directly into formalin and submit 
to Laboratory of Pathology for histopathology and immunohistochemistry 
including KSHV-LANA and KSHV-vIL-6.
Divide the remainder and distribute in the priority indicated in Section 5.1.2.3.3
5.1.2.3.3 Distribution of Biopsy Material
1. Tosato laboratory (fresh, on gauze damp but not wet with saline, at 4°C) for tissue 
expression of Dll4/Notch, Jag1/Notch, Jag2/Notch, Notch ICD (intracellular 
domain), Hey1/Hey2 and EphrinB/EphB, and markers of NFkB activation 
(including p65, p50IkBalpha, IKK1)
2. Whitby laboratory (frozen, on dry ice or trizol) for KSHV gene expression


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3. Ziegelbauer laboratory (fresh, on saline-soaked gauze, at 4°C) for KSHV RNA and 
protein expression analysis with a focus on KSHV miRNAs and miRNA target 
gene evaluation
4. For any residual tissue, freeze as soon as possible for storage at -40°C and send via 
messenger to the AIDS Monitoring Laboratory (AML), Leidos Biomedical 
Research Inc., at NCI-Frederick (see Section 5.2).
5.1.2.4
Biospecimens for storage 
Assays will be performed in batches with the exception of monocyte functional assays and 
pharmacokinetic testing. Samples for the batched correlative studies above will be sent via 
messenger to the AIDS Monitoring Laboratory (AML), Leidos Biomedical Research Inc. in the 
NCI-Frederick (See Section 5.2) for storage until assays are performed.  Collection schedule and 
sample requirements are given in Section 3.4, and Section 5.1.2.1.
5.2
SAMPLE STORAGE, TRACKING AND DISPOSITION 
It is understood that per the NCI policy regarding the Requirements for the Research Use of 
Stored Human Specimens and Data, prospective NIH IRB approval and continuing IRB 
oversight must be obtained for research involving identified or coded samples or data where 
investigators can identify the source. This policy applies to research protocols where the 
remaining research activities are limited to data analysis and to the subsequent research use of 
specimens or data previously collected under a now terminated protocol. The following 
guidelines describe how these principles apply to this specific protocol.
AIDS Monitoring Laboratory, Science Applications International Corporation

Many samples on this study will be processed and stored in the AIDS Monitoring 
Laboratory (AML) run by Leidos Biomedical Research Inc. in the NCI-Frederick 
facility located with Fort Detrick. The samples are stored under code, and the 
information linking these unique codes to the subjects is kept on the AML database. 
The laboratory informatics system conforms to NIH Information Technology Security 
Requirements and NIH Protection of Human Research Subjects Guidelines. All 
laboratory staff is trained to adhere to NIH Information Technology Security 
Requirements and NIH Protection of Human Research Subjects Guidelines. 
Computers used to access inventory systems require username and password for 
login. The laboratory database is housed in a secure, protected environment and 
backups are performed routinely. Access to specimen information, clinical data, and 
stored specimens is limited to approved laboratory staff and the investigator in charge 
of the study (or individuals authorized by the investigator).
Specimen Withdrawal for Research Purposes

The protocol team will inform the AML staff when tests are to be run with the 
specimens, and the samples used for testing will be tracked by the AML. This 
information will in turn be shared with the protocol team. The research nurse on the 
study will be in charge of tracking this information for the protocol team.
Specimens Sent to the Whitby Laboratory

Some of the specimens are sent to the laboratory of Dr. Denise Whitby, also in Leidos 
Biomedical Research Inc., in the NCI-Frederick facility located with Fort Detrick. 
This is a locked laboratory, and a log is kept of the specimens and when they are 


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utilized. The samples sent are coded by the protocol research team and have no 
patient identifiers. They are logged in by Dr. Whitby’s laboratory and are run in batch 
when enough specimens are collected. Records are kept when the specimens are used 
for analysis.
Denise Whitby PhD
 Leidos Biomedical Research Inc., Frederick 
50 Boyles St, Building 535, Room 428A
Frederick, MD
301-846-5828
Specimens Sent to the Yarchoan Laboratory

A limited number of samples are sent to Dr. Yarchoan’s laboratory. This is a locked 
laboratory, and a log is kept of the specimens and when they are utilized. 
Robert Yarchoan, MD
Building 10, Room 5A25
Bethesda, MD
301-402-3630 
Specimens Sent to the Tosato Laboratory

A limited number of samples are sent to Dr. Tosato’s laboratory. This is a locked 
laboratory, and a log is kept of the specimens and when they are utilized. The samples 
sent are coded by the protocol research team and have no patient identifiers. They are 
logged in by Dr. Tosato’s laboratory and are run in batch when enough specimens are 
collected. Records are kept when the specimens are used for analysis.
Giovanna Tosato, MD
Building 37, Room 4124
Convent Drive
Bethesda, MD
301-594-9596
Specimens Sent to the Ziegelbauer Laboratory

A limited number of samples are sent to Dr. Ziegelbauer’s laboratory. This is a locked 
laboratory, and a log is kept of the specimens and when they are utilized. The samples 
sent are coded by the protocol research team and have no patient identifiers. They are 
logged in by Dr. Ziegelbauer’s laboratory and are run in batch when enough 
specimens are collected. Records are kept when the specimens are used for analysis.
Joseph Ziegelbauer, PhD
Building 10, Room 5A21
10 Center Dr
Bethesda, MD
301-594-6634
Specimens Sent to the Maldarelli Laboratory

A limited number of samples are sent to Dr. Maldarelli’s laboratory. This is a locked 
laboratory, and a log is kept of the specimens and when they are utilized. The samples 
sent are coded by the protocol research team and have no patient identifiers. They are 
logged in by Dr. Maldarelli’s laboratory and are run in batch when enough specimens 
are collected. Records are kept when the specimens are used for analysis.


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Frank Maldarelli, MD
Building 10, 5A06
10 Center Dr
Bethesda, MD
301-435-8019
Specimens Sent to the Sereti Laboratory

A limited number of samples are sent to Dr. Sereti’s laboratory. This is a locked 
laboratory, and a log is kept of the specimens and when they are utilized. The samples 
sent are coded by the protocol research team and have no patient identifiers. They are 
logged in by Dr. Sereti’s laboratory and are run in batch when enough specimens are 
collected. Records are kept when the specimens are used for analysis.
Irini Sereti, MD
Building 10, 11B07
10 Center Dr
Bethesda, MD
301-496-5533
Clinical Testing of Stored Specimens

Clinical testing of all samples will be one in accordance to the protocol. The protocol 
team will inform the AML staff when tests are to be run with the specimens, and the 
samples used for testing will be tracked by the AML. This information will in turn be 
shared with the protocol team. The research nurse on the study will be in charge of 
tracking this information for the protocol team.
Clinical Center Processing and Storage of Clinical Specimens

Many routine samples and a sample of the biopsy specimens are sent to the 
Laboratory of Pathology (CCR), Department of Laboratory Medicine, and 
Department of Transfusion Medicine at the NIH Clinical Center. These samples will 
be handled according to the procedures of these departments. Results for clinical 
testing are generally available via the CRIS electronic medical record.
Co-enrollment on 01-C-0038

If subjects have co-enrolled on study 01-C-0038 (Collection of Blood, Bone Marrow, 
Tumor, or Tissue Samples from Subjects with HIV Infection, KSHV Infection, Viral-
related Pre-Malignant Lesions, and/or Cancer), then the samples may also be tested 
under the specifications of that study. Similarly, if subjects have co-enrolled on other 
studies approved by the NIH Intramural IRB that call for maintaining and testing the 
samples, then they may be transferred to those studies.
Handling of Specimens at Study Termination

At the termination of the protocol, if subjects have co-enrolled on study 01-C-0038 
(Collection of Blood, Bone Marrow, Tumor, or Tissue Samples from Patients with 
HIV Infection, KSHV Infection, Viral-related Pre-Malignant Lesions, and/or Cancer), 
then the samples will be transferred to that study unless the patient requests that this 
not occur. Also, if subjects have co-enrolled on other studies approved by the NIH 
Intramural IRB that call for maintaining the samples, then they will be maintained on 
those protocols. Otherwise, the unused samples will be destroyed.
Loss or Destruction of Samples


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
The Principal Investigator will record any loss or unanticipated destruction of the 
samples as a deviation. Reporting will be per the requirements of Section 7.2.
6
DATA COLLECTION AND EVALUATION 
6.1
DATA COLLECTION
Members of the HIV/AIDS Malignancy Branch clinical research team will collect data on 
study subjects according to the Schedule of Evaluations outlined in Section 3.4. Complete 
records will be maintained on each patient including supplementary information obtained 
from outside laboratories, radiology reports, or physician’s records. These will serve as 
the primary source material that forms the basis for the research record. The primary 
source documentation will assure the following: 

The patient satisfied each eligibility criterion.

Signed informed consent was obtained prior to registration and treatment. 

Treatment was given according to protocol or any protocol violations documented 
and justified. 

Toxicity and response were assessed according to protocol.

Drug accountability records were kept on each patient. 
Clinical data will be coded for database entry. Data will be stored in the CCR C3D 
clinical trials database. Dr. Robert Yarchoan, the Principal Investigator, will be 
responsible for the protocol. 
The PI will be responsible for overseeing entry of data into an in-house password 
protected electronic system (C3D) and ensuring data accuracy, consistency and 
timeliness. The principal investigator, associate investigators/research nurses and/or a 
contracted 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 28 days (±7 days) after removal from study treatment or 
until off-study, whichever comes first.
An abnormal laboratory value will be recorded in the database as an AE only 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 
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Loss or destruction of data: Should we become aware that a major breach in our plan to protect 
subject confidentiality and trial data has occurred, this will be reported expeditiously per 
requirements in Section 7.2.1.
6.2
RESPONSE CRITERIA
While the evaluation of the response of KS to an agent or regimen is difficult to grade by means 
of commonly used oncologic definitions, in an effort to standardize the evaluation of therapy 
against KS, the AIDS Clinical Trial Group Oncology Committee has devised a set of staging and 
response definitions for KS. We will use a modification of these criteria to assess responses, 
which is consistent with the criteria used in our previous KS studies. It should be noted that there 
is some observer variability in the evaluation of the number, size, nodularity, and color of 
lesions, and this must be taken into account when measurements are interpreted.
For the purposes of this study, patients should be evaluated at baseline and re-evaluated 
for response on day 1 of every cycle or every other cycle depending on study (see 
sections 6.2.1 and 6.2.2 below) and at the end of treatment.  
For assessment of response, only patients who complete at least two cycles of therapy are 
evaluable.
For evaluation of less than complete responses in subjects with more than 50 lesions at 
entry, only the previously selected 1 - 3 representative areas that contain at least 20 
lesions will be considered. However, complete responses still require the absence of any 
detectable disease over the entire body (i.e. not confined to the representative areas).
6.2.1
Methods of Evaluation for Measurable Disease
6.2.1.1
KS Tumor Photography
Baseline whole body photographs will be obtained upon entry into the study. At this time, 5 
lesions (hereafter called marker lesions), representative of the patient’s disease and, if possible, 
located on separate areas of the body will be selected. These marker lesions should be lesions 
that have never been treated with local therapies such as radiation therapy or intralesional 
injections. An attempt will be made to distribute the “marker” lesions between the representative 
areas (described below in section 6.2.1.3.1) and the rest of the body.  Detailed photographs of 
these lesions will be obtained with a metric rule beside them. 
After baseline, photography will be repeated day one of the first six cycles; for any patients 
receiving more than six cycles, photography will be repeated on alternate cycles (on odd-
numbered cycles, starting with cycle 7) thereafter. Photography will also be performed on day 29 
of the final cycle.
For subjects receiving a second course of pomalidomide (Section 3.1.6), a new tumor baseline 
will be determined immediately prior to commencement of the second course as described 
above. Documentation of extent of disease and response to therapy will follow the same schema 
described for the initial course of therapy, with all comparisons made against this new baseline. 
6.2.1.2
Documentation of Marker Lesions
The size, color and nodularity of the marker lesions will be recorded on Day 1 of each cycle and 
on day 29 of the final cycle. Documentation will depend on the number of lesions.
6.2.1.3
Documentation of Extent of Disease


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6.2.1.3.1 Subjects with 50 or more KS lesions: for subjects with 50 or more lesions at entry, 
between 1 and 3 representative areas will be selected at baseline and these will be 
used for each subsequent evaluation. Representative areas are sections of the body 
(e.g. the back, a leg, an arm, etc.), which contain at least 20 KS lesions. The total 
number of lesions in these representative areas will be counted and a record made 
of whether they are flat or raised. If, in the course of treatment, a single lesion 
breaks up into 2 or more smaller lesions whose area does not extend beyond the 
boundary of the initial lesion, these lesions will still be counted as single lesions 
for the purpose of assessing total numbers in defining a response to therapy. 
After baseline, the number of lesions within the representative areas will be counted at 
the completion of each cycle.
6.2.1.3.2 Subjects with fewer than 50 KS lesions: for subjects with less than 50 lesions at 
entry, the total number of lesions will be counted and a record made of whether 
they are flat or raised.
After baseline, the number of lesions within the representative areas will be counted at 
the completion of each cycle.
6.2.1.3.3 Additional studies for visceral KS involvement: additional studies, including but 
not limited to, gastrointestinal endoscopy and bronchoscopy will be performed at 
entry where clinically indicated, based on clinical evaluation of the patient.
6.2.1.4
KS Tumor Non-invasive Imaging
Evaluation of the vascularity in KS will be performed using 3 non-invasive modalities: laser 
Doppler imaging, multi-spectral imaging, and infrared thermal imaging.  Imaging will use the 
modalities previously explored in study 01-C-0158(144, 145). A target lesion of KS as well as 
normal skin will be identified and recorded for follow-up studies. The target lesion will also be 
measured and photographed. These are correlative studies performed in parallel with tumor 
response assessment, and are not considered in the evaluation of KS response by modified 
ACTG criteria.
After baseline, imaging will be repeated on day one of the first six cycles; and for any patients 
receiving more than six cycles, imaging will be repeated on alternate cycles (on odd-numbered 
cycles, starting with cycle 7) thereafter. Imaging will also be performed on day 29 of the final 
cycle.
For subjects receiving a second course of pomalidomide (Section 3.1.6), a new tumor baseline 
will be determined immediately prior to commencement of the second course as described 
above. Documentation of extent of disease and response to therapy will follow the same schema 
described for the initial course of therapy, with all comparisons made against this new baseline. 
6.2.1.5
KS tumor biopsies 
See section 5.1.2.3
6.2.2
Quality of Life Evaluation
Quality of life assessment will be performed using the Functional Assessment of HIV 
Questionnaire(153) (see also www.facit.org), adapted with the inclusion of three additional 
questions directed at specific assessment of KS impact on quality of life developed for a prior 
AIDS Malignancy Consortium study in KS(85) (


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Appendix 6 [English] and Appendix 7 [Spanish]). The questionnaire will be self-administered 
by subjects in an environment providing visual and auditory privacy and free from distractions.  
Questionnaires will be administered at baseline, on day 1 of cycle 4 and 28 days after the 
completion of the final cycle.
For subjects who are not fluent in English or Spanish, where an approved translated version of 
the FAHI questionnaire for the patient’s first language is available from the Functional 
Assessment of Chronic Illness Therapy group (www.facit.org/questionnaires) these may be used 
in place of the questionnaire in 
Appendix 6 and Appendix 7. Where a suitable questionnaire is not available, the English 
version may be used only with the assistance of an approved translator.
For subjects whose written literacy in the language of FAHI questionnaire administration is 
questionable, the questionnaire may be administered orally with the verbal and recording 
assistance of an approved translator or member of the study clinical team.
For subjects receiving a second course of pomalidomide (Section 3.1.6), a new quality of life 
baseline will be determined immediately prior to commencement of the second course as 
described above. Questionnaires will be administered immediately prior to commencement of the 
second course, on day 1 of cycle 4 of the second course, and 28 days after the completion of the 
final cycle of the second course. Comparisons will be made to the new baseline.
6.2.3
Response Criteria
Complete Response: 

The absence of any detectable residual disease, including tumor associated edema, 
persisting for at least 4 weeks.

For subjects with pigmented macular skin lesions persisting after apparent complete 
response, a biopsy of at least one representative lesion is required to document the 
absence of malignant cells. If a lesion has not been biopsied, the patient may be classified 
as having a clinical CR.

For subjects with visceral disease, the diagnostic radiologic or endoscopic study should 
be repeated if not medically contraindicated and found to be negative for evidence of 
disease. If such procedures are medically contraindicated but the patient has no clinical 
evidence of visceral disease, the patient may be classified as having a clinical CR.
Clinical Complete Response:

The absence of any detectable residual disease, including tumor associated edema, 
persisting for at least 4 weeks.

For subjects with pigmented macular skin lesions persisting after apparent complete 
response, if a representative lesion has not been biopsied.
For subjects with visceral disease, the diagnostic radiologic or endoscopic study should be 
repeated if not medically contraindicated and found to be negative for evidence of disease. If 
such procedures are medically contraindicated but the patient has no clinical evidence of visceral 
disease, the patient may be classified as having a clinical CR.
Partial Response


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
No progressive disease (see below and noting, that single lesions which split up into 2 or 
more smaller lesions during the course of treatment will still be counted as one); no new 
lesions occurring in previously uninvolved areas of the body; no new visceral sites of 
involvement or the appearance or worsening of tumor-associated edema or effusions and:

A 50% or greater decrease in the number and/or size of previously existing lesions lasting 
for at least 4 weeks or

Complete flattening of at least 50% of all previously raised lesions (i.e., 50% of all 
previously nodular or plaque-like lesions become macular) lasting for at least 4 weeks or

A 50% decrease in radiologically measurable visceral lesions sustained without evidence 
of re-growth for at least 4 weeks or

A 50% decrease in radiologically measurable visceral lesions sustained without evidence 
of re-growth for at least 4 weeks or

Subjects who otherwise meet the criteria for a CR but still have residual tumor-associated 
edema or effusions will be classified as having a PR.
Progressive Disease

For those criteria that involve measurement of lesions in the clinic, the designation of 
progression should be made, when feasible, only when the criteria below have been met 
in two measurements spaced at least 1 week apart. For the assignment of progressive 
disease for the primary outcome analysis, progression will be defined in comparison to 
baseline measurements.

An increase of 25% or more over baseline in the number of lesions and/or the size (sum 
of the products of the largest perpendicular diameters) of the marker lesions or

A change in character from macular to plaque-like or nodular of at least 25% of the 
lesions or

New visceral sites of involvement or progression of visceral disease or

The development of new or increasing tumor-associated edema or effusion that lasts at 
least 1 week and interferes with the patient’s normal activities.

Clarification:  There is a certain variability in the measurement of KS lesions, and this 
becomes particularly problematic if patients have very few lesions. To mitigate against 
this effect, if the cutaneous burden of KS is at any time 8 or less lesions, progressive 
disease will require the development of at least 2 new lesions. Similarly, if the cutaneous 
burden of KS is at any time 8 or less nodular lesions, progressive disease will require the 
development of at least 2 new nodular lesions.
Stable Disease

Any tumor measurement not meeting the criteria for Complete Response, Partial 
Response, or Progressive Disease.
Overall Response 

Overall response rate is the sum of complete responses, clinical complete responses, and 
partial responses.


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6.3
TOXICITY CRITERIA
The following adverse event management guidelines are intended to ensure the safety of 
each patient while on the study. Adverse events occurring during the study will be graded 
according to the NCI Common Terminology Criteria for Adverse Events version 4.0 
(CTCAE v4.0) at: 
http://ctep.info.nih.gov/protocolDevelopment/electronic_applications/ctc.htm
Toxicity Attribution

The Principal Investigator or physician Associate Investigator will meet at least 
weekly to discuss adverse events, and document the relationship of the protocol 
intervention to each adverse event by assigning attribution per adverse event at time 
of clinical evaluation. Attribution will be rated as follows:
o Unrelated: the adverse event is clearly not related to the investigational agents.
o Unlikely related: the adverse event is doubtfully related to the investigational 
agents.
o Possibly related: the adverse event may be related to the investigational agents.
o Probably related: the adverse event is likely related to the investigational agents.
o Definitely related: the adverse event is clearly related to the investigational agents
7
NIH REPORTING REQUIREMENTS/DATA AND SAFETY MONITORING PLAN
7.1
DEFINITIONS
Please refer to definitions provided in Policy 801: Reporting Research Events found here.
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 here. 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 here. 
7.3
NCI CLINICAL DIRECTOR REPORTING
Problems expeditiously reported to the OHSRP in iRIS will also be reported to the NCI Clinical 
Director.  A separate submission is not necessary as reports in iRIS will be available to the 
Clinical Director.
In addition to those reports, all deaths that occur within 30 days after receiving a research 
intervention should be reported via email to the Clinical Director unless they are due to 
progressive disease.  
To report these deaths, please send an email describing the circumstances of the death to Dr. 
Dahut at NCICCRQA@mail.nih.gov within one business day of learning of the death.


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7.4
NIH REQUIRED DATA AND SAFETY MONITORING PLAN
7.4.1
Principal Investigator/Research Team 
The clinical research team will meet on a regular basis (weekly) 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.
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.


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
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).
8.1.4
Severity
The severity of each Adverse Event will be assessed utilizing the CTCAE version 4.
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.


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For timeframe of recording adverse events, please refer to Section 6.1 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 
and instructions can be found at: 
https://ccrod.cancer.gov/confluence/display/CCRCRO/Forms+and+Instructions.
8.4
SAFETY REPORTING CRITERIA TO THE PHARMACEUTICAL COLLABORATORS 
All events listed below must be reported in the defined timelines to OSROSafety@mail.nih.gov. 
CCR OSRO will send all reports to the manufacturer as described below.
Serious adverse events (SAE) are defined above. If any SAE is required to be reported to 
the sponsor according to Section 8.1.2 (i.e. within 28 days of receiving drug or assessed 
as being possibly related to drug administration), the sponsor should inform Celgene of 
the SAE within 1 business day of being aware of the event. This must be documented on 
a Celgene SAE form or FDA 3500A or MEDWATCH form. This form must be 
completed and supplied to Celgene within 24 hours/1 business day. The initial report 
must be as complete as possible, including an assessment of the causal relationship 
between the event and the investigational product(s), if available. Information not 
available at the time of the initial report (e.g., an end date for the adverse event or 
laboratory values received after the report) must be documented on a follow-up 
MEDWATCH. A final report to document resolution of the SAE is required. The 
Celgene tracking number (PO-KS-NCI-0050) and the institutional protocol number 
should be included on SAE reports (or on the fax cover letter) sent to Celgene. A copy of 
the fax transmission confirmation of the SAE report to Celgene should be attached to the 
SAE and retained with the patient records.
All adverse experience reports must include the patient number, age, sex, weight, severity 
of reaction (mild, moderate, severe), relationship to study drug (probably related, 
unknown relationship, definitely not related), date and time of administration of test 
medications and all concomitant medications, and medical treatment provided.  The 
investigator is responsible for evaluating all adverse events to determine whether criteria 
for “serious” and as defined above are present. The Investigator must keep copies of all 
AE information, including correspondence with Celgene and the IRB/EC on file for 
records retention information).  The investigator is responsible for reporting adverse 
events to Celgene as described below.


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In addition, if secondary malignancies that do not fall under the criteria for expedited 
reporting in section 7.2.1 are reported to the sponsor, the sponsor should inform Celgene 
of the malignancy within 7 working days of receiving the report using the same forms.
8.4.1
IND Annual Reports to Celgene
As the FDA has granted an IND number, it is a requirement of 21 CFR 312.33, that an annual 
report is provided to the FDA within 60-days of the IND anniversary date. 21 CRF 312.33 
provides the data elements that are to be submitted in the report. The Annual Report should be 
filed in the study's Regulatory Binder, and a copy provided to Celgene Corporation as a 
supporter of this study as follows.
Celgene Corporation
Attn: Medical Operations
300 Connell Dr. Suite 6000 
Berkeley Heights, NJ 07922 
Tel: (908) 673-9000
8.5
REPORTING PREGNANCIES
Pregnancies and suspected pregnancies (including a positive pregnancy test regardless of age or 
disease state) of a female subject occurring while the subject is on investigational product (IP), or 
within 28 days of the subject’s last dose of IP, are considered immediately reportable events. IP is 
to be discontinued immediately. The pregnancy, suspected pregnancy, or positive pregnancy test 
must be reported to the Sponsor within 24 hours, and the Sponsor will report this to Celgene Drug 
Safety within one business day by facsimile, or other appropriate method, using the Pregnancy 
Initial Report Form, or approved equivalent form. The Investigator will follow the female subject 
until completion of the pregnancy and up to 1 year to monitor the baby, and must notify CCR and 
the CCR in turn will notify Celgene Drug Safety immediately about the outcome of the pregnancy 
(either normal or abnormal outcome) using the Pregnancy Follow-up Report Form, or approved 
equivalent form. 
Celgene Drug Safety Contact Information:
Celgene Corporation
Global Drug Safety and Risk Management   
Connell Corporate Park 
300 Connell Dr. Suite 6000 
Berkeley Heights, NJ 07922
Fax: (908) 673-9115
e-mail: drugsafety@celgene.com
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://ccrod.cancer.gov/confluence/display/CCRCRO/Forms+and+Instructions.


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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 (spontaneous miscarriage, elective termination, ectopic 
pregnancy, normal birth, or congenital abnormality) 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 (spontaneous miscarriage, elective termination, ectopic pregnancy, normal birth, 
or congenital abnormality) occurring from the date of the first dose until 28 days after the last 
dose should, if possible, be followed up and documented.
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.
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 study endpoints; adherence to the protocol, regulations, 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.
This trial will be monitored by personnel employed by an 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. 


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10 STATISTICAL CONSIDERATIONS
10.1 DEMOGRAPHIC DIVERSITY
Subjects from both genders and all racial/ethnic groups are eligible for this study if they 
meet the eligibility criteria. Outreach efforts will be made to extend accrual to a 
representative population. 
It should be noted that in the US, KSHV seroprevalence is relatively low in females 
with or without HIV infection. However, recent HAMB studies have increasingly 
accrued female immigrants from Africa and transgendered persons.
10.2 AGE EXCLUSION
Patients under the age of 18 will be excluded. KSHV infection and its complications including 
KS and HIV infection are each very rare in North American children, making it unlikely that 
pediatric cases of KS will be seen.
10.3
 ACCRUAL TIMELINE
As the subjects being evaluated for toxicity may or may not be evaluable for response as part of 
the stringent eligibility response cohort, after an amendment to evaluate HIV positive and HIV 
negative patients in separate cohorts, the study may require enrolling from 25 to 40 subjects, 
depending on the final dose level and the number of those evaluated for toxicity that may also be 
evaluable for response. 
It is anticipated that ten to twelve patients per year may enroll onto this trial. In order to allow for 
the possibility of a very small number of inevaluable subjects, the accrual ceiling will be set at 40 
subjects. Accrual is expected to be completed within two to three years.
HAMB has an established cohort of KSHV-seropositive subjects, most with KS or a history of 
KS through protocol 01-C-0193 and other ongoing studies of KS, KSHV-MCD and KSHV-
associated lymphoma as well as a referral base in the HIV and infectious disease community 
which together provide a population to support projected accrual. Accrual will be regularly 
reviewed against projections, and consideration given to additional promotional activities should 
it fall short of projections.
10.4
 STATISTICAL ANALYSES
An initial toxicity assessment phase of the trial will be conducted in which up to six subjects will 
be treated with pomalidomide at 5mg daily for 21 days of a 28 day cycle. If two or more subjects 
experience a DLT within the first two cycles (eight weeks), then up to six subsequent subjects 
will be treated at 3 mg daily for 21 days of a 28 day cycle. The highest dose at which zero or one 
of six subjects experience a DLT during the first two cycles (eight weeks) will be used to 
determine potential clinical activity. 
Once the dose for assessment of clinical activity is determined, two expansion cohorts will be 
established to investigate response rate. These will be established with the goal of enrolling ten 
evaluable HIV negative patients, and fifteen evaluable HIV positive patients. Where KS is HIV-
associated, these latter subjects will have somewhat more stringent entry criteria with respect to 
KS not responding to HAART to enable a better assessment of any anti-tumor activity 
uncomplicated by tumor responses associated with HAART initiation (inclusion criterion 
2.1.1.15 above). Subjects treated at the dose chosen for assessment during the toxicity 


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assessment phase who met these additional eligibility criteria at study entry will be considered 
evaluable for response for this part of the study, in the appropriate cohort. 
There are two circumstances under which an individual subject’s dose could be de-escalated: 
first if two other subjects on the same dose level experience a DLT (Section 3.1.3), and second if 
the subject experiences a non-thromboembolic DLT on the higher dose level which resolves 
within 28 days (Section 3.3). In either instance, if the subject is evaluable they will be considered 
part of the initial (higher) dose cohort for the purposes of evaluating response. 
At the dose for assessment of clinical activity, two cohorts of patients will be evaluated 
according to their HIV status as follows:
Of the ten evaluable subjects enrolled in the HIV negative expansion cohort, the probability of 
three or more responding (complete responders plus partial responders) is 83.3% if the true 
probability of a response is 40%, and 7.0% if the true probability of a response is 10%. Thus, 
obtaining at least three subjects with a response in the ten HIV negative evaluable subjects is 
more likely to be consistent with a ≥40% true response rate than with a ≤10% true response rate. 
This outcome (three or more responders) will be considered sufficiently positive for further 
investigation of the agent in this group. 
Of the fifteen evaluable subjects enrolled in the HIV positive expansion cohort, the probability of 
four or more responding (complete responders plus partial responders) is 90.9% if the true 
probability of a response is 40%, and 5.6% if the true probability of a response is 10%. Thus, 
obtaining at least four subjects with a response in the 15 evaluable HIV positive subjects is more 
likely to be consistent with a ≥40% true response rate than with a ≤10% true response rate. This 
outcome (four or more responders) will be considered sufficiently positive for further 
investigation of the agent in this group. As of the submission of amendment G, fifteen evaluable 
subjects in the HIV positive expansion cohort have been accrued to address the primary question 
of assessing the anti-tumor effect of pomalidomide in those patients. The responses for these 15 
subjects will be reported together with the 7 subjects enrolled to date in the HIV negative 
expansion cohort.  The protocol allows for accrual up to 18 HIV (+) patients and 10 HIV (-) 
patients. As the endpoint for activity has been reached for the HIV (+) patients at this time, the 
initial analysis describing the activity of pomalidomide in KS will include only patients entered 
up until this time. Any additional subjects accrued after this point in either cohort (up to 3 in 
each cohort) will be primarily evaluated for correlative endpoints; they will also be included in 
any description of long term clinical outcomes at a later point.
At the conclusion of the trial, the response rates from the two cohorts will be compared and if 
they are sufficiently similar (p>0.30 by a two-tailed Fisher’s exact test), in addition to being 
reported separately, they can be pooled together and also reported in that manner. Also, after the 
all patients have been evaluated for response, 95% confidence intervals will be formed about the 
response rate in both cohorts, as well as together, if sufficiently similar. The maximum 
confidence interval widths would be +/-32% with 10 patients, +/-26% with 15 patients, and +/-
20% with 25 patients. 
To allow for the possibility of different accrual rates between these two cohorts in this rare 
disease, up to an additional three subjects may be accrued to the evaluable HIV positive cohort 
(for a maximum of eighteen) in the case that ten evaluable HIV negative subjects have not yet 
been accrued at the time that accrual of evaluable HIV positive subjects reaches fifteen. In the 


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event that 16 to 18 HIV positive patients are enrolled, 4 or more responders will still be needed 
to be considered sufficiently positive for further investigation.
Response rates will be estimated for pomalidomide. Survival analysis will be performed using 
Kaplan-Meier methods. Progression-free survival will be defined as the time from Day 1 of a 
given intervention until progression requiring a change in therapy. Event-free survival will be 
defined as the time from Day 1 of a given intervention until progression requiring a change in 
therapy or death as a result of any cause. All results will be carefully reported in the context of 
the limited size of the study.
For those subjects who obtain a clinical complete or partial response or clinical benefit from 
initial treatment with pomalidomide, and subsequently again manifest KS requiring therapy 
while not receiving pomalidomide, an additional course of treatment with pomalidomide may be 
offered as described in Section 3.1.6. Based on responses seen at the time of this amendment 
(January 2013) and our experience with treatment of KS, it is anticipated that approximately 3-6 
subjects will potentially be eligible for and receive an additional course of therapy, but this 
estimate will be refined as further subjects are enrolled and become assessable for response. The 
scientific objective of this cohort will be to explore the safety and tolerability of a second course 
of pomalidomide in patients who had previously benefited from the agent: this exploration will 
comprise a secondary objective for the protocol overall. As a further objective, tumor response 
rates in this cohort will also be evaluated with exploratory intent; and virologic and immunologic 
correlative studies will be performed for comparison with those obtained during the first 
treatment course. For those subjects treated with this additional course, a new tumor baseline will 
be taken, and the subsequent response to treatment from this baseline will be determined. The 
fraction of the patients who receive the extra course who respond to treatment (complete 
responders plus partial responders) will be determined and estimated along with a 95% 
confidence interval. The results obtained following this subsequent treatment will be presented 
separately from those for the initial treatment.
Each of the correlative analyses will be evaluated with exploratory intent, using non-parametric 
methods generally, and without formal adjustment for multiple tests performed. Results will be 
presented in the context of a hypothesis generating study.
11 COLLABORATIVE AGREEMENTS
Pomalidomide will be provided to the investigators under a Co-operative Research and 
Development Agreement (CRADA) between Celgene Corporation and the National Cancer 
Institute; CRADA #2719. Therefore, the following obligations apply to the use of pomalidomide 
in this study, and to the data generated herein.
Pomalidomide may not be used outside the scope of the CRADA, nor can pomalidomide be 
transferred or licensed to any party not participating in activities specified in the CRADA. 
Celgene data regarding pomalidomide are confidential and proprietary to Celgene and shall be 
maintained as such by the investigators. The protocol documents for studies utilizing 
investigational agents contain confidential information and should not be shared or distributed 
without the permission of the NCI. If a copy of this protocol is requested by a patient 
participating on the study or a patient’s family member, the individual should sign a 
confidentiality agreement. 


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For data generated from the CRADA, the producing Party will retain sole ownership of and title 
to all copies of CRADA Data produced solely by its employee(s). The Parties agree to exchange 
all data and materials generated from the study. 
The CRADA Parties are encouraged to make publicly available the results of their research and 
development activities.  Before either Party submits a paper or abstract for publication or 
otherwise intends to publicly disclose information about a CRADA Subject Invention, CRADA 
Data, or CRADA Materials, the other Party will have thirty (30) days to review proposed 
manuscripts and three (3) days to review proposed abstracts to assure that Confidential 
Information is protected.  Either Party may request in writing that the proposed publication or 
other disclosure be delayed for up to thirty (30) additional days as necessary to file a Patent 
Application.
12 HUMAN SUBJECTS PROTECTIONS 
12.1 RATIONALE FOR SUBJECT SELECTION
The protocol is designed for analysis of adult subjects with measurable KS. KSHV infection in 
the US is associated with certain ethnic and behavioral groups, including African immigrants and 
men who have sex with men (MSM)(154-157); most of the women who have participated in 
previous HAMB studies of KSHV-associated diseases have been immigrants from Africa. KS 
and other KSHV-associated diseases are much more common in subjects with intercurrent 
immunodeficiencies, including HIV, and it is anticipated that the majority of study participants 
will be drawn from these groups. Including both HIV-infected and HIV-uninfected individuals 
may enable a greater understanding of the similarities and differences of pomalidomide safety, 
toxicity and response in these groups.
Strategies for recruitment will include announcements on www.clinicaltrials.gov, letters to 
referring physicians, targeting HIV providers and those who provide primary care to the African 
immigrant community, and AIDS treatment bulletins. 
12.2 PARTICIPATION OF CHILDREN
As noted in Section 10.2, KSHV-associated disease is extremely rare in children in North 
America. It is also known that KS may have a markedly different presentation and natural history 
in pediatric populations, perhaps representing biologically distinct disease variants. Furthermore, 
as approved therapies are available for KS and the proposed therapies have uncertain efficacy, 
and the risk to a vulnerable population appears excessive in the absence of preliminary estimates 
of benefit. For these reasons, subjects <18 years old will be excluded from the study. If the 
therapy appears beneficial, a risk/benefit assessment will be made for the potential enrollment of 
children, and if it appears reasonable to do so, consideration for amending the protocol to allow 
enrollment of children will be made.
12.3 PARTICIPATION OF SUBJECTS UNABLE TO GIVE CONSENT
Adults unable to give consent are excluded from enrolling in the protocol.  However, it is 
possible that subjects enrolled in the protocol may permanently lose the capacity to consent for 
themselves during the course of this study. In the event this occurs, the subjects will remain in 
the study because there is a prospect of direct benefit. 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 


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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 to assess ongoing capacity of the subjects and to identify an LAR, as needed.
Please see Section 12.6.1 for consent procedure.
12.4 EVALUATION OF BENEFITS AND RISKS/DISCOMFORTS
The investigational nature and objectives of this study, the procedures and treatments involved 
and their attendant risks and discomforts, potential benefits, and potential alternative therapies 
will be carefully explained to the patient or the patient’s surrogate, and a signed informed 
consent document will be obtained.
While the study is performed based on background data suggesting that pomalidomide may be of 
benefit to patients with KS, there is no assurance that this will be the case and it is quite possible 
that there may be no direct benefit to the patient volunteers on this study. The potential benefit is 
that the protocol therapy may result in control of KS and resolution of symptoms in those 
patients to whom it is administered. 
The potential risk for patients receiving treatment is that the protocol therapy may be toxic, 
ineffective, or both. In addition, the study requires multiple, sometimes invasive, evaluations. 
The time commitment and potential morbidity associated with tumor biopsy and blood sampling 
is a potential risk and discomfort to study participants.
Biopsies are an important part of this study. Up to three optional, sequential biopsies will be 
obtained from each patient over the course of protocol participation. The material obtained will 
be used to evaluate for the correlative endpoints, and may be used to guide future studies in this 
disease. Refusal to undergo biopsy will not result in removal from study.
12.4.1 Risks to Study Procedures
12.4.1.1 Blood sampling
Side effects of blood draws include pain and bruising, lightheadedness, and rarely, fainting.
12.4.1.2 Medical photography
No physical risks are associated with these procedures.
12.5 RISKS AND BENEFITS ANALYSIS
The risks to individual study subjects are reasonable in relation to the anticipated benefits. This 
protocol explores an agent with a strong preclinical rationale in KS, and which is a derivative of 
another agent (thalidomide) that was shown to have promising clinical activity in our prior study 
in KS. Pomalidomide has an acceptable toxicity profile at similar or higher doses to that used 
here in studies in other solid tumors (and a better toxicity profile than thalidomide when directly 
compared), and promising clinical activity in other solid tumors and hematologic malignancies. 
Potential therapeutic benefits include limitation of cumulative anthracycline dosing, more rapid 
tumor regression, and additional therapeutic options for patients for difficult to manage and 
chronic KS. The risks include potential toxicities of pomalidomide alone or in combination with 
HIV and its therapies and additional studies associated with participation in a clinical study. The 


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major alternative for patients with limited KS is to receive FDA approved agents outside of a 
clinical study, or not to receive any KS-directed therapy. The comparative risks and benefits are 
acceptable for an early phase clinical study, when compared to the alternatives for patients with 
limited KS.
12.6 CONSENT AND ASSENT PROCESS AND DOCUMENTATION
The informed consent document will be provided as a physical or electronic document to the 
participant or consent designee(s) as applicable for review prior to consenting.  A designated 
study investigator will carefully explain the procedures and tests involved in this study, and the 
associated risks, discomforts and benefits. In order to minimize potential coercion, as much time 
as is needed to review the document will be given, including an opportunity to discuss it with 
friends, family members and/or other advisors, and to ask questions of any designated study 
investigator. A signed informed consent document will be obtained prior to entry onto the study.
The initial consent process as well as re-consent, when required, may take place in person or 
remotely (e.g., via telephone or other NIH approved remote platforms used in compliance with 
policy, including HRPP Policy 303) per discretion of the designated study investigator and with 
the agreement of the participant/consent designee(s).  Whether in person or remote, the privacy 
of the subject will be maintained. Consenting investigators (and participant/consent designee, 
when in person) will be located in a private area (e.g., clinic consult room). When consent is 
conducted remotely, the participant/consent designee will be informed of the private nature of 
the discussion and will be encouraged to relocate to a more private setting if needed.  
Consent will be documented with required signatures on the physical document (which includes 
the printout of an electronic document sent to participant) or as described below, with a manual 
(non-electronic) signature on the electronic document. When required, witness signature will be 
obtained similarly as described for the investigator and participant.
Manual (non-electronic) signature on electronic document:
When a manual signature on an electronic document is used for the documentation of consent 
at the NIH Clinical Center, this study will use the following to obtain the required signatures:

Adobe platform (which is not 21 CFR Part 11 compliant); or,  

iMedConsent platform (which is 21 CFR Part 11 compliant)
During the consent process, participants and investigators will view individual copies of the 
approved consent document on screens at their respective locations (if remote consent); the 
same screen may be used when in the same location but is not required.  
Both the investigator and the participant will sign the document using a finger, stylus or mouse. 
Note: Refer to the CCR SOP PM-2, Obtaining and Documenting the Informed Consent Process 
for additional information (e.g., verification of participant identity when obtaining consent 
remotely) found here.
12.6.1 Consent Process for Adults Who Lack Capacity to Consent to Research Participation
For participants addressed in section 12.3, an LAR will be identified consistent with Policy 403 
and informed consent obtained from the LAR, as described in Section 12.6.


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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, 
investigator, funding agency, the Investigational New Drug (IND sponsor 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
The 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 Conference 
on Harmonisation Good Clinical Practice (ICH GCP), and applicable regulatory requirements 
(e.g., Good Laboratory Practices (GLP), Good Manufacturing Practices (GMP)). 
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 


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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 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 NIH.
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 
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
Description
Pomalidomide, 4-amino-2-(2,6-dioxo-3-piperidyl)isoindoline-1’-one)-1,3-dione, belongs to the 
IMiDs class of compounds. The Chemical Abstract Service (CAS) registry number for CC-4047 


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is 19171-19-8. The chemical structure of the active pharmaceutical ingredient (API) is as 
follows: 
Pomalidomide has an asymmetric carbon atom and can therefore exist as the optically active 
forms S (-) and R (+). Pomalidomide is being developed as a racemate.
Mechanism of Action
Pomalidomide is a novel member of a class of pharmaceutical compounds known as 
immunomodulatory drugs (IMiDs). It 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. The pharmacodynamic properties of pomalidomide are of potential 
therapeutic benefit in the treatment of several human tumors. 
Supply
Celgene Corporation will supply POMALYST® (pomalidomide) through Celgene’s 
Pomalidomide Risk Evaluation and Mitigation Strategy (POMALYST REMS™). 
Dosage Form
Pomalidomide will be supplied as 1.0 mg, 2.0 mg, 3.0 mg and 4.0 mg capsules for oral 
administration.
Packaging
Pomalidomide will be shipped to the pharmacy at the study site in individual bottles. Bottles will 
contain a sufficient number of capsules to last for one cycle of dosing. Study drug must be 
dispensed in the original packaging with the label clearly visible. 
Labeling
Pomalidomide investigational supplies are dispensed to the patients in individual bottles of 
capsules. Each bottle will identify the contents as study medication. In addition, the label will 
bear Celgene’s name, quantity contained and the standard caution statement as follows: Caution: 
New drug - Limited by Federal law to investigational use. Pomalidomide should not be handled 
by FCBP unless wearing gloves. 
The study drug label must be clearly visible.  Additional labels must not cover the Celgene label.
Receipt of Study Drug
The Investigator or designee is responsible for taking an inventory of each shipment of study 
drug received, and comparing it with the accompanying study drug accountability form. The 
Investigator will verify the accuracy of the information on the form, sign and date it, retain a 
copy in the study file, and return a copy to Celgene or its representative.


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Storage
At the study site, all investigational study drugs will be stored in a locked, safe area to prevent 
unauthorized access.
The study drug should be stored at room temperature away from direct sunlight and protected 
from excessive heat and cold.
Unused Study Drug Supplies
Celgene will instruct the Investigator on the return or destruction of unused study drug. If any 
study drug is lost or damaged, its disposition should be documented in the source documents. 
Study drug supplies will be retained at the clinical site pending instructions for disposition by 
Celgene. Patients will be instructed to return any unused capsules to the study site. 
Drug Dispensing Requirements
Pomalidomide (POMALYST®) will be provided to research subjects for the duration of their 
participation in this trial at no charge to them or their insurance providers.  Pomalidomide will be 
provided in accordance with the Celgene Corporation’s POMALYST REMS™ program.  Per the 
standard POMALYST REMS™ program requirements, all physicians who prescribe 
pomalidomide for research subjects enrolled into this trial, and all research subjects enrolled into 
this trial, must be registered in and must comply with all requirements of the POMALYST 
REMS™ program.  
Drug will be shipped on a per patient basis by the contract pharmacy to the clinic site 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.


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16 APPENDICES
16.1 APPENDIX 1: POMALIDOMIDE RISKS OF FETAL EXPOSURE, PREGNANCY TESTING 
GUIDELINES AND ACCEPTABLE BIRTH CONTROL METHODS
Risks Associated with Pregnancy
Pomalidomide was found to be teratogenic in a developmental study in rabbits. Pomalidomide is 
an analogue of thalidomide. Thalidomide is a known human teratogen that causes severe life-
threatening human birth defects. If Pomalidomide is taken during pregnancy, it may cause birth 
defects or death to an unborn baby.
Criteria for females of childbearing potential (FCBP)
This protocol defines a female of childbearing potential as a sexually mature woman who:
1. has not undergone a hysterectomy or bilateral oophorectomy or
2. has not been naturally postmenopausal (amenorrhea following cancer therapy does not 
rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at 
any time in the preceding 24 consecutive months).
Counseling
For a female of childbearing potential, pomalidomide is contraindicated unless all of the 
following are met (i.e., all females of childbearing potential must be counseled concerning the 
following risks and requirements prior to the start of pomalidomide study therapy): 

She understands the potential teratogenic risk to the unborn child

She understands the need for effective contraception, without interruption, 28 days before 
starting study treatment, throughout the entire duration of study treatment, dose 
interruption and 28 days after the end of study treatment

She should be capable of complying with effective contraceptive measures

She is informed and understands the potential consequences of pregnancy and the need to 
notify her study doctor immediately if there is a risk of pregnancy

She understands the need to commence the study treatment as soon as study drug is 
dispensed following a negative pregnancy test

She understands the need and accepts to undergo pregnancy testing based on the 
frequency outlined in this protocol

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
For a female NOT of childbearing potential, pomalidomide is contraindicated unless all of the 
following are met (i.e., all females NOT of childbearing potential must be counselled concerning 
the following risks and requirements prior to the start of pomalidomide study therapy): 

She acknowledges that she understands the hazards and necessary precautions associated 
with the use of pomalidomide


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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 counseled concerning the following risks and requirements prior to the start of 
pomalidomide study therapy):

Understand the potential teratogenic risk if engaged in sexual activity with a pregnant 
female or a female of childbearing potential

Understand the need for the use of a condom even if he has had a vasectomy, if engaged 
in sexual activity with a pregnant female or a female of childbearing potential. 
Contraception
Females of childbearing potential (FCBP) enrolled in this protocol must agree to use two reliable 
forms of contraception simultaneously or to practice complete abstinence from heterosexual 
contact during the following time periods related to this study: 1) for at least 28 days before 
starting study drug; 2) while participating in the study; 3) dose interruptions; and 4) for at least 
28 days after study treatment discontinuation. 
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:

Intrauterine device (IUD)

Hormonal (birth control pills, injections, implants)

Tubal ligation

Partner’s vasectomy
Additional effective methods:

Male condom

Diaphragm

Cervical Cap
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:


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83
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. 

Counseling about pregnancy precautions and the potential risks of fetal exposure must be 
conducted at a minimum of every 28 days. 

If pregnancy or a positive pregnancy test does occur in a study patient, study drug must 
be immediately discontinued.

Pregnancy testing and counseling must be performed if a patient misses her period or if 
her pregnancy test or her menstrual bleeding is abnormal. Study drug treatment must be 
discontinued during this evaluation.

Females must agree to abstain from breastfeeding during study participation and for at 
least 28 days after study drug discontinuation.
Male Patients:

Counseling about the requirement for complete abstinence or condom use during sexual 
contact with a pregnant female or a female of childbearing potential and the potential 
risks of fetal exposure to pomalidomide must be conducted at a minimum of every 28 
days. 

If pregnancy or a positive pregnancy test does occur in the partner of a male study 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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16.2 APPENDIX 2: POMALIDOMIDE EDUCATION AND COUNSELING GUIDANCE DOCUMENT
To be completed prior to each dispensing of study drug.
Protocol Number: ____________________________________________
Patient Name (Print): __________________ DOB: _____/_____/_____ (mm/dd/yyyy)
(Check the appropriate box to indicate risk category)
Female ☐
If female, check one:
☐ FCBP (Female of childbearing potential): sexually mature female who: 1) has not 
undergone a hysterectomy (the surgical removal of the uterus) or bilateral 
oophorectomy (the surgical removal of both ovaries) or 2) has not been naturally 
postmenopausal (amenorrhea following cancer therapy does not rule out 
childbearing potential) for at least 24 consecutive months (i.e., has had menses at 
any time during the preceding 24 consecutive months)
☐ NOT FCBP
Male ☐
Do not dispense study drug if:
•
The patient is pregnant.
•
No pregnancy tests were conducted for a FCBP.
•
The patient states she did not use TWO reliable methods of birth control 
(unless practicing complete abstinence of heterosexual contact) at least 28 
days prior to therapy, during therapy and during dose interruption.
FCBP:
1.   I verified that the required pregnancy tests performed are negative.
2.   I counseled FCBP regarding the following:
•
Potential risk of fetal exposure to pomalidomide:  If pomalidomide is taken 
during pregnancy, it may cause birth defects or death to any unborn baby. 
Females are advised to avoid pregnancy while taking pomalidomide. The 
teratogenic potential of pomalidomide in humans cannot be ruled out. FCBP 
must agree not to become pregnant while taking pomalidomide. 
•
Using TWO reliable methods of birth control at the same time or complete 
abstinence from heterosexual contact [at least 28 days prior to therapy, during 
therapy , during dose interruption and 28 days after discontinuation of study 
drug].
•
That even if she has amenorrhea she must comply with advice on 
contraception  
•
Use of one highly effective method and one additional method of birth control 
AT THE SAME TIME. The following are examples of highly effective and 
additional effective methods of contraception:  
•
Highly effective methods:
•
Intrauterine device (IUD)
•
Hormonal (birth control pills, injections, implants)


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•
Tubal ligation
•
Partner’s vasectomy
•
Additional effective methods:
•
Male condom
•
Diaphragm
•
Cervical Cap
•
Pregnancy tests before and during treatment, even if the patient agrees not to 
have reproductive heterosexual contact. Two pregnancy tests will be 
performed prior to receiving study drug, one within 10-14 days and the second 
within 24 hours of the start of study drug.
•
Frequency of pregnancy tests to be done:
•
Every week during the first 28 days of this study and a pregnancy test 
every 28 days during the patient’s participation in this study if menstrual 
cycles are regular or every 14 days if cycles are irregular.  
•
If the patient missed a period or has unusual menstrual bleeding. 
•
When the patient is discontinued from the study and at day 28 after study 
drug discontinuation if menstrual cycles are regular. If menstrual cycles are 
irregular, pregnancy tests will be done at discontinuation from the study 
and at days 14 and 28 after study drug discontinuation.
•
Stop taking study drug immediately in the event of becoming pregnant and to 
call their study doctor as soon as possible. 
•
NEVER share study drug with anyone else.
•
Do not donate blood while taking study drug and for 28 days after stopping 
study drug.
•
Do not breastfeed a baby while participating in this study and for at least 28 
days after study drug discontinuation.
•
Do not break, chew, or open study drug capsules.
•
Return unused study drug to the study doctor.
3.    Provide Pomalidomide Information Sheet to the patient.
FEMALE NOT OF CHILDBEARING POTENTIAL (NATURAL MENOPAUSE 
FOR AT LEAST 24 CONSECUTIVE MONTHS, A HYSTERECTOMY, OR 
BILATERAL OOPHORECTOMY):
1.
I counseled the female NOT of childbearing potential regarding the following:
•
Potential risk of fetal exposure to pomalidomide (Refer to item #2 in FCBP)
•
NEVER share study drug with anyone else.
•
Do not donate blood while taking study drug and for 28 days after stopping 
study drug.
•
Do not break, chew, or open study drug capsules
•
Return unused study drug capsules to the study doctor.
2.
Provide Pomalidomide Information Sheet to the patient.
MALE:


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86
1.
I counseled the Male patient regarding the following:
•
Potential study drug fetal exposure to pomalidomide (Refer to item #2 in 
FCBP).
•
To engage in complete abstinence or use a condom when engaging in sexual 
contact (including those who have had a vasectomy) with a pregnant female or 
a female of childbearing potential,  while taking study drug, during dose 
interruptions and for 28 days after stopping study drug.
•
Males should notify their study doctor when their female partner becomes 
pregnant and female partners of males taking study drug should be advised to 
call their healthcare provider immediately if they get pregnant
•
NEVER share study drug with anyone else.
•
Do not donate blood while taking study drug and for 28 days after stopping 
study drug.
•
Do not donate semen or sperm while taking study drug and for 28 days after 
stopping study drug.
•
Do not break, chew, or open study drug capsules.
•
Return unused study drug capsules to the study doctor.
2.   Provide Pomalidomide Information Sheet to the patient.
Investigator/Counselor Name (Print): ____________________
 (circle applicable)
Investigator/Counselor Signature: _______________________ 
Date: _____/_____/_____
(circle applicable)
Maintain a copy of the Education and Counseling Guidance Document in the patient 
records.


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


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88
If you are a female not of childbearing potential:
In order to ensure that an unborn baby is not exposed to pomalidomide, your study doctor will 
confirm that you are not able to become pregnant.
If you are a male:
The effect of pomalidomide on sperm development is not known and has not been studied. The 
risk to the fetus in females of child bearing potential whose male partner is receiving 
pomalidomide is unknown at this time. 
Male patients must either not have any sexual relations with a female who can become 
pregnant or a pregnant female or must use a condom during sexual intercourse with a 
pregnant female or a female that can become pregnant (including those who have had a 
vasectomy):
•
While you are taking pomalidomide 
•
During dose interruptions of pomalidomide 
•
For 28 days after you stop taking pomalidomide  
Male patients should not donate sperm or semen while taking pomalidomide and for 28 days 
after stopping pomalidomide. 
If you suspect that your partner is pregnant any time during the study, you must immediately 
inform your study doctor. The study doctor will report all cases of pregnancy to Celgene 
Corporation.
Pomalidomide restrictions in sharing pomalidomide and donating blood:
•
Do not share pomalidomide with other people. It must be kept out of the reach of 
children and should never be given to any other person.
•
Do not give blood while you take pomalidomide and for 28 days after stopping 
pomalidomide. 
•
Do not break, chew, or open pomalidomide capsules.
•
You will be supplied with no more than one cycle of pomalidomide 
•
Return unused pomalidomide capsules to your study doctor.
Additional information is provided in the informed consent form and you can ask your study 
doctor for more information.


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89
16.4 APPENDIX 4: PERFORMANCE STATUS SCALES
ECOG Performance Status
Karnofsky Performance Status
Grade
Description
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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16.5 APPENDIX 5: HAMB KS RESPONSE FLOWSHEET


Abbreviated Title: Pomalidomide in Kaposi sarcoma 
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91


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92
16.6 APPENDIX 6: FUNCTIONAL ASSESSMENT OF QUALITY OF LIFE (V.4) ASSESSMENT TOOL 
(ENGLISH VERSION)
Below is a list of statements that other people with your illness have said are important. 
Please circle or mark one number per line to indicate your response as it applies to the 
past 7 days.
1. PHYSICAL WELL-BEING
Not at 
all
A little 
bit
Some-
what
Quite a 
bit
Very 
much
GP1
I have a lack of energy
0
1
2
3
4
GP2
I have nausea
0
1
2
3
4
GP3
Because of my physical condition, I have trouble 
meeting the needs of my family
0
1
2
3
4
GP4
I have pain
0
1
2
3
4
GP5
I am bothered by side effects of treatment
0
1
2
3
4
GP6
I feel ill
0
1
2
3
4
GP7
I am forced to spend time in bed
0
1
2
3
4
B1
I have been short of breath
0
1
2
3
4
B8
I am bothered by a change in weight
0
1
2
3
4
BMT6
I get tired easily
0
1
2
3
4
HI7
I feel fatigued
0
1
2
3
4
HI12
I feel weak all over
0
1
2
3
4
L2
I have been coughing
0
1
2
3
4


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93
2. EMOTIONAL WELL-BEING/LIVING WITH HIV
Not at 
all
A little 
bit
Some-
what
Quite a 
bit
Very 
much
GE1
I feel sad
0
1
2
3
4
GE4
I feel nervous
0
1
2
3
4
GE5
I worry about dying
0
1
2
3
4
GE6
I worry that my condition will get worse
0
1
2
3
4
HI1
I am unhappy with my appearance
0
1
2
3
4
HI2
It is hard to tell other people about my infection
0
1
2
3
4
HI4
I worry about spreading my infection
0
1
2
3
4
HI5
I am concerned about what the future holds for 
me
0
1
2
3
4
B7
I worry about the effects of stress on my illness
0
1
2
3
4
HI10
I am embarrassed by my illness
0
1
2
3
4
3. LIVING WITH KS
Not at 
all
A little 
bit
Some-
what
Quite a 
bit
Very 
much
HKS1
Pain has interfered with my normal work or 
activities
0
1
2
3
4
HKS2
I am satisfied with my physical appearance
0
1
2
3
4
HKS3
I have had swelling in my face, arms, or legs
0
1
2
3
4


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4. FUNCTIONAL AND GLOBAL WELL-BEING
Not at 
all
A little 
bit
Some-
what
Quite a 
bit
Very 
much
GF1
I am able to work (including work at home)
0
1
2
3
4
GF2
My work (including work at home) is fulfilling
0
1
2
3
4
GF3
I am able to enjoy life
0
1
2
3
4
GF4
I have accepted my illness
0
1
2
3
4
GF5
I am sleeping well
0
1
2
3
4
GF6
I am enjoying the things I usually do for fun
0
1
2
3
4
GF7
I am content with the quality of my life right now
0
1
2
3
4
GE2
I am satisfied with how I am coping with my 
illness
0
1
2
3
4
GE3
I am losing hope in the fight against my illness
0
1
2
3
4
B4
I feel sexually attractive
0
1
2
3
4
C6
I have a good appetite
0
1
2
3
4
HI6
I feel motivated to do things
0
1
2
3
4
HI11
I am hopeful about the future
0
1
2
3
4


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5. SOCIAL WELL-BEING
Not at 
all
A little 
bit
Some-
what
Quite a 
bit
Very 
much
GS1
I feel close to my friends
0
1
2
3
4
GS2
I get emotional support from my family
0
1
2
3
4
GS3
I get support from my friends
0
1
2
3
4
GS4
My family has accepted my illness
0
1
2
3
4
GS5
I am satisfied with my family communication 
about my illness
0
1
2
3
4
GS6
I feel close to my partner (or the person who is 
my main support)
0
1
2
3
4
HI3
I have people to help me if I need it
0
1
2
3
4
Q1
Regardless of your current level  of sexual activity, please answer the following question.
If you prefer not to answer it, please mark this box ☐ and go to the next section.
GS7
I am satisfied with my sex life
0
1
2
3
4
6. COGNITIVE FUNCTIONING
Not at 
all
A little 
bit
Some-
what
Quite a 
bit
Very 
much
L1
My thinking is clear
0
1
2
3
4
HI8
I have trouble concentrating
0
1
2
3
4
HI9
I have trouble remembering things
0
1
2
3
4


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96
16.7 APPENDIX 7: FUNCTIONAL ASSESSMENT OF QUALITY OF LIFE (V.4) ASSESSMENT TOOL 
(SPANISH VERSION)
A continuación encontrará una lista de afirmaciones que otras personas con su misma 
enfermedad consideran importantes. Marque un solo número por línea para indicar la 
respuesta que corresponde a los últimos 7 días.
1. ESTADO FÍSICO GENERAL DE SALUD
Nada
Un poco
Algo
Mucho
Much-
ísimo
GP1
Me falta energía
0
1
2
3
4
GP2
Tengo náuseas
0
1
2
3
4
GP3
Debido a mi estado físico, tengo dificultad para 
atender a las necesidades de mi familia
0
1
2
3
4
GP4
Tengo dolor
0
1
2
3
4
GP5
Me molestan los efectos secundarios del 
tratamiento
0
1
2
3
4
GP6
Me siento enfermo(a)
0
1
2
3
4
GP7
Tengo que pasar tiempo acostado(a)
0
1
2
3
4
B1
Me ha faltado el aire para respirar
0
1
2
3
4
B8
Me molestan los cambios de peso
0
1
2
3
4
BMT6
Me canso fácilmente
0
1
2
3
4
HI7
Me siento agotado(a)
0
1
2
3
4
HI12
Siento debilidad en todo el cuerpo
0
1
2
3
4
L2
He estado tosiendo
0
1
2
3
4


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2. ESTADO EMOCIONAL/VIVIENDO CON VIH
Nada
Un 
poco
Algo
Mucho
Much-
ísimo
GE1
Me siento triste
0
1
2
3
4
GE4
Me siento nervioso(a)
0
1
2
3
4
GE5
Me preocupa morir
0
1
2
3
4
GE6
Me preocupa que mi enfermedad empeore
0
1
2
3
4
HI1
Estoy descontento(a) con mi apariencia 
personal
0
1
2
3
4
HI2
Me cuesta trabajo hablar de mi enfermedad 
con otras personas
0
1
2
3
4
HI4
Temo contagiar mi enfermedad a otras 
personas
0
1
2
3
4
HI5
Estoy preocupado(a) por lo que me pueda 
pasar
0
1
2
3
4
B7
Me preocupan las consecuencias del estrés 
(la tensión) en mi enfermedad
0
1
2
3
4
HI10
Mi enfermedad me da vergüenza
0
1
2
3
4


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3. VIVIENDO CON KS
Nada
Un 
poco
Algo
Mucho
Much-
ísimo
HKS1
El dolor interfiere con mi trabajo normal y 
mis actividades
0
1
2
3
4
HKS2
Estoy satisfecho con mi apariencia fisica
0
1
2
3
4
HKS3
He tenido inchazon en la cara, brazos o 
piernas
0
1
2
3
4
4. ESTADO GENERAL DE FUNCIONAMIENTO
Nada
Un 
poco
Algo
Mucho
Much-
ísimo
GF1
Puedo trabajar (incluya trabajo en el hogar)
0
1
2
3
4
GF2
Me satisface mi trabajo (incluya trabajo en el 
hogar)
0
1
2
3
4
GF3
Puedo disfrutar de la vida
0
1
2
3
4
GF4
He aceptado mi enfermedad
0
1
2
3
4
GF5
Duermo bien
0
1
2
3
4
GF6
Disfruto con mis pasatiempos de siempre
0
1
2
3
4
GF7
Estoy satisfecho(a) con mi calidad de vida 
actual
0
1
2
3
4
GE2
Estoy satisfecho(a) de cómo estoy 
enfrentando mi enfermedad
0
1
2
3
4


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GE3
Estoy perdiendo las esperanzas en la lucha 
contra mi enfermedad
0
1
2
3
4
B4
Me siento físicamente atractivo(a)
0
1
2
3
4
C6
Tengo buen apetito
0
1
2
3
4
HI6
Me siento motivado(a) para hacer cosas
0
1
2
3
4
HI11
Tengo esperanzas para el futuro
0
1
2
3
4
5. AMBIENTE SOCIAL
Nada
Un 
poco
Algo
Mucho
Much-
ísimo
GS1
Me siento cercano(a) a mis amistades
0
1
2
3
4
GS2
Recibo apoyo emocional por parte de mi 
familia
0
1
2
3
4
GS3
Recibo apoyo por parte de mis amistades
0
1
2
3
4
GS4
Mi familia ha aceptado mi enfermedad
0
1
2
3
4
GS5
Estoy satisfecho(a) con la manera en que se 
comunica mi familia acerca de mi 
enfermedad
0
1
2
3
4
GS6
Me siento cercano(a) a mi pareja (o a la 
persona que es mi principal fuente de apoyo)
0
1
2
3
4
HI3
Tengo quien me ayude, si lo necesito
0
1
2
3
4


Abbreviated Title: Pomalidomide in Kaposi sarcoma 
Version Date: 11/19/2021
 
100
Q1
Sin importar su nivel actual de actividad sexual, conteste a la siguiente pregunta. Si prefiere no 
contestarla, marque esta casilla ☐ y continúe con la siguiente sección.
GS7
Estoy satisfecho(a) con mi vida sexual
0
1
2
3
4
6. ACTIVIDAD MENTAL
Nada
Un 
poco
Algo
Mucho
Much-
ísimo
L1
Pienso con claridad
0
1
2
3
4
HI8
Tengo dificultad para concentrarme
0
1
2
3
4
HI9
Tengo dificultad para recordar las cosas
0
1
2
3
4


Abbreviated Title: Pomalidomide in Kaposi sarcoma 
Version Date: 11/19/2021
 
101
16.8 APPENDIX 8: PATIENT DRUG ADMINISTRATION DIARY
Patient Name _________________________________ Study ID __________________
Please complete this form and return to the research nurse or doctor every cycle
You will take:      Pomalidomide        Dose: ___________
DAY
DATE
TIME  TAKEN
COMMENTS (side effects or missed doses)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
Rest Day
23
Rest Day
24
Rest Day
25
Rest Day
26
Rest Day
27
Rest Day
28
Rest Day
Patient Signature:____________________________________


Abbreviated Title: Pomalidomide in Kaposi sarcoma 
Version Date: 11/19/2021
 
102
16.9 APPENDIX 9: CALCULATION OF CREATININE CLEARANCE
1. Calculation: Cockcroft-Gault formula for creatinine clearance estimation:
Males: CrCl (estimated) =(140-age) * (weight)/(sCr * 72)
Females: CrCl (estimated) =(140-age) * (weight * 0.85)/(sCr * 72)
Notes: 
CrCl (estimated): estimated creatinine clearance rate in mL/min
Age in years
Weight in kilograms (lean or actual body weight, whichever is less)
sCr:serum creatinine in mg/dl
Estimated creatinine clearance should not be used in the following circumstances:
-altered protein intake (vegetarian diet, creatine supplements)
-altered muscle mass (malnutrition, wasting, amputation)
-in such cases, a 24-hour urine collection for measured creatinine clearance 
should be obtained
2. Calculation: 24 hour Creatinine Clearance
Males and Females: CrCl=(uCr * uV) / (sCr *1440)
Notes: 
CrCl: Creatinine clearance in ml/min
sCr: serum creatinine in mg/dl
uCr: urine creatinine in mg/dl
uV: 24 hour urine volume in ml
1440: number of minutes in 24 hours
3. Calculation: Lean Body Weight
Males: Lean Body Weight = (1.10 x Weight(kg)) - 128 ( Weight2/(100 x Height(m))2)
Females: Lean Body Weight= (1.07 x Weight(kg)) - 148 ( Weight2/(100 x Height(m))2)

ICF_001.pdf: 
PATIENT IDENTIFICATION
Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (1)
Version Date: 11/29/2021
Page 1 of 19
CC pre rCR ICF template v. 12.01.20
MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
PRINCIPAL INVESTIGATOR: Robert Yarchoan, M.D.
STUDY TITLE:
A Phase I/II Study of the Safety, Pharmacokinetics and 
Efficacy of Pomalidomide (CC-4047) in the Treatment of 
Kaposi Sarcoma in Individuals With or Without HIV
STUDY SITE:
NIH Clinical Center
Cohort: 
Standard 
Consent Version:  
11/29/2021 
WHO DO YOU CONTACT ABOUT THIS STUDY? 
PI: 
Robert Yarchoan, M.D.
Phone: 240-760-6075
            
E-Mail: Robert.Yarchoan@nih.gov
This consent form describes a research study and is designed to help you decide if you would like 
to be a part of the research study.  
The remaining document will now describe the research study in more detail.  This information 
should be considered before you make your choice. Members of the study team will talk with you 
about the information in this document. Some people have personal, religious, or ethical beliefs 
that may limit the kinds of medical or research interventions in which they would want to 
participate. Take the time you need to ask any questions and discuss this study with NIH staff, and 
with your family, friends, and personal health care providers.
If the individual being asked to participate in this research study is not able to give consent for 
themselves, you, as the Legally Authorized Representative, will be their decision-maker and you 
are being asked to give permission for this person to be in this study. For the remainder of this 
document, the term “you” refers to you as the decision-maker and/or the individual being asked to 
participate in this research.  
IT IS YOUR CHOICE TO TAKE PART IN THE STUDY
You may choose not to take part in this study for any reason. If you join this study, you may change 
your mind and stop participating in the study at any time and for any reason. In either case, you 
will not lose any benefits to which you are otherwise entitled. However, to be seen at the NIH, you 
must be taking part in a study or are being considered for a study. If you do choose to leave the 
study, please inform your study team to ensure a safe withdrawal from the research.  
WHY IS THIS STUDY BEING DONE?
This is a research study to gain information on the use of an anti-cancer medicine called 
pomalidomide (also called CC-4047) in people with Kaposi sarcoma (KS), whether or not the 
Kaposi sarcoma is associated with acquired immunodeficiency syndrome (AIDS) or human 
IRB NUMBER: 12C0047
IRB APPROVAL DATE: 11/30/2021


PATIENT IDENTIFICATION
Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (1)
Version Date: 11/29/2021
Page 2 of 19
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MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
immunodeficiency virus (HIV) infection.  We would like to obtain information on the side effects 
and blood levels of pomalidomide in people with KS. In addition, the study will look for any 
evidence of a beneficial effect of treatment with pomalidomide on the KS lesions or the quality of 
life of individuals with KS, but this is not the primary purpose of the study. The use of 
pomalidomide in KS is experimental. Pomalidomide (CC-4047) is a medicine taken by mouth 
(orally). It belongs to a group of medicines called immunomodulatory drugs (IMiDs) that is in the 
same family of drugs as thalidomide.  The effects of drugs in this class include modifying or 
regulating the functioning of the immune system, and they also have effects on the body’s 
production of new blood vessels. Pomalidomide is chemically similar to two other medicines, 
thalidomide and lenalidomide, and both of those medicines have been approved by the Food and 
Drug Administration (FDA), the USA drug approval agency, for treatment of patients with a blood 
cancer called multiple myeloma. The effects of pomalidomide on the immune system and on blood 
vessels may be beneficial in KS, as it acts against some of the factors that are thought to be 
important in the development and growth of KS. However, this has not been proven. The related 
drug thalidomide has been used in people with KS, and has been shown to have beneficial effects 
on the lesions in some subjects.  However, thalidomide has not at this time been approved by the 
Food and Drug Administration for treatment of KS.
Why are you being asked to take part in this study?
You are being asked to take part in this study so that we may evaluate this new medicine in people, 
like yourself, who have Kaposi sarcoma, whether or not the KS is related to AIDS or HIV infection.
How many people will take part in this study? 
We plan to enroll between 25 and 40 subjects in this study.
Description of Research Study
If you consent to participate in this study, you will take pomalidomide tablets each day for three 
weeks (21 days), followed by a one week (7 day) “rest” from the tablets. Together these three 
weeks taking medicine and one rest week are called a “cycle” of therapy. Pomalidomide therapy 
will continue for six cycles (six months) unless your KS completely disappears in less time or you 
have unacceptable side effects from the pomalidomide. If you still have KS at the end of the six 
cycles but it seems that your KS is improving, you may be able to continue pomalidomide for up 
to an additional six cycles. The time period described above is called the initial (or first) course. 
After you finish the initial course of therapy with pomalidomide, we will continue to follow you 
for an additional 5 years with infrequent visits and communication with your primary care doctor 
to monitor for any late side effects or toxicity from pomalidomide and to follow the course of your 
KS. 
If during this time you again develop KS that requires treatment, you may be able to receive a 
second (optional) course of therapy with pomalidomide. This would be considered if your KS 
improved with the initial course of therapy and if you and your physician consider that a second 
(optional) course would be appropriate. If you did receive this second course, it would again be 
for six cycles (six months) unless the KS disappears in less time or you have unacceptable side 
effects from the pomalidomide. If in the second course you still have KS at the end of six cycles 
but it seems that your KS is improving you may be able to continue pomalidomide for up to an 
additional six cycles.
IRB NUMBER: 12C0047
IRB APPROVAL DATE: 11/30/2021


PATIENT IDENTIFICATION
Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (1)
Version Date: 11/29/2021
Page 3 of 19
CC pre rCR ICF template v. 12.01.20
MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
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
Before you begin the study, you will be evaluated by a physician investigator, as well as other 
members of the research team for eligibility to participate in the study.  We will discuss your 
medical history in detail and draw blood from a vein to perform laboratory tests to help determine 
whether you are eligible to participate. You will also have a chest X-ray to make sure that you are 
eligible to participate and to document whether KS affects your lungs. We will also need a small 
sample of tissue (biopsy) from a KS lesion in order to confirm your diagnosis.  If you have already 
had a biopsy, we will work with you to have the biopsy sent to pathologists at the NCI for review.  
If you have not have not had a biopsy, we will arrange for a biopsy to confirm the diagnosis of KS. 
If you undergo a biopsy at NIH for diagnostic reasons, we may use a portion of that tissue for 
research purposes as well.  If the reason you are having a biopsy is for your medical care, we will 
not take additional tissue unless you give us permission to do so.  Rather, the amount of the tissue 
taken will be defined by the medically indicated procedure. 
Depending on your symptoms and the results of your chest X-ray and blood tests, we may perform 
additional tests to determine where in the body you may have KS lesions.  These tests could include 
CT scans or the examination of the lungs or gastrointestinal tract with an endoscope (a flexible 
instrument to examine the interior of the organ). We will discuss these tests and the reasons they 
are required if you need to have them.  These scans would be done for your clinical care, not for 
the research.
Before you start pomalidomide, we will also ask that you complete a paper questionnaire asking 
about the effects of your illness on your day-to-day activities and mood (together called quality of 
life).  You be asked to repeat the same questionnaire once more while you are taking 
pomalidomide, and again after you stop taking the medicine.
During the study
During the initial course of the study (and the second optional course, if applicable), you will 
receive pomalidomide at a dose of 5 mg. You will take pomalidomide tablets by mouth every day 
for the first three weeks of a four week cycle. There is one rest week before starting the next cycle. 
Pomalidomide should be taken each morning at approximately the same time.  You should fast 
(drink water only) for at least two hours before and at least 30 minutes after taking pomalidomide.  
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.
All subjects will take either a “baby” aspirin or another medicine to reduce the chance of blood 
clotting. Those with HIV will also be required to be on combination antiretroviral (anti-HIV) 
medications. In addition, all subjects 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.
During the first cycle of therapy, we will conduct studies to measure the levels of pomalidomide 
in your blood at two time points: first the day you start taking the medicine, and again after you 
IRB NUMBER: 12C0047
IRB APPROVAL DATE: 11/30/2021


PATIENT IDENTIFICATION
Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (1)
Version Date: 11/29/2021
Page 4 of 19
CC pre rCR ICF template v. 12.01.20
MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
have been taking the medicine for 2 weeks. On those days, you will have blood drawn immediately 
before you take the pomalidomide tablets, again at 1, 2, 3, 4, 6 and 8 hours after taking the tablets, 
and once more 24 hours after taking the tablets (the next morning). You do not need to be in 
hospital overnight for these blood draws. Each of these blood draws is less than 1½ teaspoons of 
blood.  A small catheter (plastic tube) may be placed in your vein so that you do not have to have 
a new needle put into your vein for each of the blood draws.
You will be evaluated throughout the study to record any changes in your KS lesions and to ensure 
that you are not experiencing any intolerable side effects.  During the first cycle of therapy, you 
will be evaluated by a physician prior to therapy, as well as two weeks later, to answer any 
questions you may have and to ensure that you are tolerating the therapy. On subsequent cycles, a 
physician will evaluate you on the day you start the pomalidomide and you will have further blood 
tests on that day. The blood tests include counts of blood cells, tests of blood chemistry and, for 
people with HIV, tests of HIV viral load and CD4 counts. For the first cycle you will have blood 
tests each week, and for the second and third cycles only, you will also have blood tests two weeks 
into the cycle to ensure you are tolerating the therapy. During clinic visits you will be asked 
questions to help us determine how well you are tolerating the treatment and a physical 
examination will be performed. Every four weeks while you are receiving the pomalidomide, you 
will also have an assessment of your KS lesions.  If you have more than 50 KS lesions on your 
skin, then this assessment will focus on only a portion of your body. You will also have 
photographs taken of your lesions.  In addition, three experimental non-invasive imaging studies 
will be performed. None of these will treat the KS or make it improve, and we do not believe that 
any of them will harm your skin.  The three methods are called:
1) Laser Doppler imaging: 
The laser light used for the laser Doppler can harm your eyes if you stare at it directly, but 
precautions will be taken so that you will not stare at it. Laser Doppler imaging takes about 3 
minutes to perform on each lesion.  It uses a low power laser beam that scans across the skin lesion 
being measured.  The instrument does not touch your skin. You may be asked to have a blood 
pressure cuff put on your arm and have laser Doppler imaging performed before and after the cuff 
is inflated for a short time (generally less than thirty seconds). In standard practice, a similar 
machine is used to measure how deeply severe burns affect the skin and to assess allergic responses 
in the skin. However, its use in Kaposi’s sarcoma is experimental.  The purpose of this 
experimental use is to attempt to measure the amount of blood flow through the blood vessels in 
the Kaposi’s sarcoma lesions.
2) Multi-spectral imaging:
The multi-spectral imaging exam should take about 2 minutes to perform on each lesion. It uses 
principles of the way hemoglobin absorbs light.  Hemoglobin is a protein in the blood that carries 
oxygen to your tissues.  The light on the multi-spectral imaging instrument is absorbed differently 
depending on whether the hemoglobin has oxygen attached to it or not.  This will allow an estimate 
to be made regarding the total blood volume, and how much of it is carrying oxygen or not.
3) Infrared thermal imaging: 
IRB NUMBER: 12C0047
IRB APPROVAL DATE: 11/30/2021


PATIENT IDENTIFICATION
Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (1)
Version Date: 11/29/2021
Page 5 of 19
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MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
The thermal imaging takes about a minute to perform on each lesion. It uses a special camera to 
take digital infrared pictures of your skin. This enables us to form a picture of the temperature of 
your KS lesions and thus assess the blood flow in the Kaposi’s sarcoma lesions. 
The conventional photography and experimental imaging studies will be performed before the first 
cycle and then repeated after each of the first six cycles; if you receive more than six cycles the 
studies will be repeated every other cycle after the first six (on the odd-numbered cycles, starting 
with cycle 7); and the studies will be repeated again after the last cycle of therapy.
Throughout the study, we will be collecting samples from you in order to conduct additional 
research studies described below.  A few days before you begin taking pomalidomide we will 
collect approximately 80 mL of blood (a little more than five tablespoons).  Starting from day of 
cycle one, we will collect a sample of saliva and approximately 80-90mL of blood on the first day 
of each cycle and the last day of the final cycle (day 29).  There will be additional collection of 
approximately 40-50 mL (around 3 tablespoons) of blood on the first day of cycles 1 and 4 and the 
fifteenth day of cycle 1.  On the fifteenth days of cycle two and three there will be draws of 8ml 
(half a tablespoon) only. Finally, at your post therapy visit which will occur approximately 4 weeks 
after you have completed your final cycle, we will collect an additional 120mL (8 tablespoons) of 
blood.   
We will use these samples to test for the levels of the virus that causes KS (KSHV), HIV levels if 
you are HIV positive, and the levels of a number of blood chemicals called cytokines that can tell 
us how your body and your immune system are responding to the pomalidomide.   
In addition to collecting blood and saliva for research, we will ask you for permission to collect 
one biopsy for research while you are taking pomalidomide.  Before your third cycle, you will be 
asked if you are willing to have a skin (lesion) biopsy for special research studies evaluating the 
effect of pomalidomide on your KS lesions. Additional biopsies may be taken for clinically 
indicated purposes. For example, when it appears that all of the KS is gone, a biopsy helps 
determine if there is any KS that remains, or if it is in fact completely gone. Another example is if 
new lesions appear while you are on therapy and they are suspicious for KS, a biopsy can be taken 
to determine if KS is present in the new lesion (s). These biopsies may also be used for special 
research studies, but their main purpose would be to determine the status of the KS. You may 
refuse to have the research biopsy or any of the clinical biopsies and continue to participate on the 
study.
When you are finished taking the drugs (treatment)
When you are finished taking the drugs, we will continue to follow you in clinic for up to five 
years to make sure that your KS does not return or get worse and to assess for any late side effects 
from the pomalidomide.
If during this time you again develop KS that requires treatment and you along with your physician 
agree that you may benefit from a second (optional) course of therapy with pomalidomide, you 
will be evaluated throughout the second course in the same manner and at the same frequency as 
described above, with two exceptions: blood levels of pomalidomide will not be tested during the 
second course and the skin biopsies for research will not be repeated during the second course. 
The purpose of these evaluations is to record any changes in your KS lesions and to ensure that 
you are not experiencing any intolerable side effects.
IRB NUMBER: 12C0047
IRB APPROVAL DATE: 11/30/2021


PATIENT IDENTIFICATION
Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (1)
Version Date: 11/29/2021
Page 6 of 19
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MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
Study Chart
This chart outlines what will happen if you choose to participate:
Birth Control
Pregnancy:
Screening for Eligibility

Medical History and Physical Exam

Review of Biopsy

Blood Tests

Chest X-Ray and EKG
Treatment
Therapy: 
Pomalidomide tablets each day for three weeks (21 days), followed by a 
one week (7 day) “rest” from the tablets
Monitoring: 
Review of side effects
Physical Exam
Blood Tests
Tumor measurements and photography
Research:
Blood and saliva samples
Additional biopsy (optional)
Non-invasive imaging 
Stop treatment:
Completion of six to twelve cycles of therapy
Progressive KS or complete resolution of KS
Patient preference
After Treatment

Research blood and saliva samples

Additional biopsy (optional)

Clinic visit every 3-6 months for first 2 years after therapy and then 
every year for up to 5 years

May potentially receive a second course of pomalidomide (6-12 
months) if KS again requires treatment, and if there was a benefit 
from the first course.
IRB NUMBER: 12C0047
IRB APPROVAL DATE: 11/30/2021


PATIENT IDENTIFICATION
Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (1)
Version Date: 11/29/2021
Page 7 of 19
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MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
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.
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 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.
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. 
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. 
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 (FCBP), 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. 
IRB NUMBER: 12C0047
IRB APPROVAL DATE: 11/30/2021


PATIENT IDENTIFICATION
Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (1)
Version Date: 11/29/2021
Page 8 of 19
CC pre rCR ICF template v. 12.01.20
MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
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 participating in this study

during dose interruptions

and  for at least 28 days after discontinuation from the study   
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 
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 
IRB NUMBER: 12C0047
IRB APPROVAL DATE: 11/30/2021


PATIENT IDENTIFICATION
Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (1)
Version Date: 11/29/2021
Page 9 of 19
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MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
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 are discontinued from 
the study and at day 28 after discontinuation from the study if your menstrual cycles are regular.  
If your menstrual cycles are irregular, you will have pregnancy tests when you are discontinued 
from the study and at days 14 and 28 after discontinuation from the study.
You must not breastfeed a baby while you are participating in this study and for at least 28 days 
after you have stopped 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 
have been discontinued from the study. 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 and 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 have been discontinued from this 
study, 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 have been discontinued from the study, even if you have had a 
successful vasectomy.  You must tell your doctor if you have sex with a female of childbearing 
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 have been discontinued from the study. 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, 
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. In addition, you will receive any 
new information during the course of the study concerning significant treatment findings from this 
IRB NUMBER: 12C0047
IRB APPROVAL DATE: 11/30/2021


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study or others (good or bad) that may affect your willingness to continue your participation. 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 (CC-4047):
Pomalidomide (CC-4047) has been studied in healthy volunteers and in patients with cancer of the 
blood and other organs of the body, including Kaposi sarcoma, 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 12 May 2014, there were 11 
completed clinical studies and 44 ongoing studies using pomalidomide, and the risks below are 
drawn from reports from these patients. 
The side effects that patients had after starting the study drug in completed and ongoing studies 
are noted below.  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 a consequence of 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.
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.
The side effects listed below are grouped as follows:  1) side effects reported in 10-46% of patients; 
2) side effects reported in 1-10% of patients; and 3) other important side effects.
1) Side effects reported in 10-46% of patients participating in Celgene-sponsored clinical studies 
with pomalidomide included:

Neutropenia (low white blood cell count) with or without infection

Thrombocytopenia (low platelet count) 

Anemia (a decrease in your red blood cells which carry oxygen) 

Fever 

Constipation

Diarrhea (loose stool)

Decreased appetite 

Nausea 

Fatigue (tiredness) 
IRB NUMBER: 12C0047
IRB APPROVAL DATE: 11/30/2021


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
Headache

Dizziness

Dyspnea (shortness of breath) 

Cough 

Edema (swelling) 

Rash

Dry skin and itch

Muscle aches or cramps 
2) Side effects reported in 1 to 10% of patients participating in Celgene-sponsored clinical studies 
with pomalidomide included:

Infection

Respiratory infection (sinus or lung infection)

Pharyngitis (inflammation of the throat) 

Vomiting

Abnormal shaking

Pain in chest, back, joints or limbs (arms or legs)

Paraesthesia (skin tingling) 

Hypoaesthesia (decreased sensitivity to touch) 

Abnormal blood test results 

Confusion

Blurry vision 

Hypothyroidism (abnormal thyroid tests, sometimes causes fatigue, constipation, dry skin 
or cold intolerance)
3) Other important side effects reported in patients participating in Celgene-sponsored clinical 
studies with pomalidomide that are considered important enough for you to be made aware of 
include: 

New cancers (including acute myeloid leukemia (AML) (a cancer of the bone marrow 
which affects your white blood cells, adrenal carcinoma (cancer of the adrenal gland), 
bladder transitional cell carcinoma (cancer of the urinary bladder), renal cell carcinoma 
(kidney cancer), myelodysplastic syndrome (MDS:  a group of diseases that affect your 
blood and bone marrow), skin cancers and thyroid cancer 

Inflammation of your lungs 

Renal failure (kidneys not working correctly)
IRB NUMBER: 12C0047
IRB APPROVAL DATE: 11/30/2021


PATIENT IDENTIFICATION
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Deep vein thrombosis (DVT) and pulmonary embolism (PE)
Medications in the same family of medications as pomalidomide have demonstrated an increased 
risk of DVT (blood clot in a larger blood vessel) and PE (a blood clot in or around the lungs) in 
some subjects with certain medical conditions.  You will receive either a “baby” aspirin or another 
medicine to reduce the chance of blood clotting while you are receiving pomalidomide.
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, females who are able to become pregnant and males who are able to father 
a child, should not touch or handle the pomalidomide capsules. 
We do not know if pomalidomide has any effect on your being able to have a child in the future, 
please speak with your doctor about family planning options for the future.
You must agree to abstain from donating blood or sperm while taking pomalidomide (even if you 
temporarily stop your medication) for at least 1 week after the last dose of pomalidomide.
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 inform the study 
physician or a member of the research team immediately. Please also let your study physician 
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. 
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 study drug.  In some cases, side effects can be serious, 
long-lasting or may never go away.
You should talk to your study physician about any side effects that you have while taking part in 
the study. 
Optional Biopsies 
A punch skin biopsy will be performed.  Prior to the biopsy, you will receive local anesthesia 
through a small injection into the area of skin surrounding the biopsy site. One quarter-centimeter 
samples of KS will be removed with a needle during the skin biopsy. 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 biopsies.  The biopsy to be performed is exclusively for research purposes 
and will not benefit you.  It might help other people in the future
You will be given the opportunity to decide whether you want to have the tumor biopsy at the time 
of the procedure. 
IRB NUMBER: 12C0047
IRB APPROVAL DATE: 11/30/2021


PATIENT IDENTIFICATION
Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (1)
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Risks from blood draws
Side effects of blood draws include pain and bruising in the area where the needle was placed, 
lightheadedness, and rarely, fainting and infection.
Risks from medical Photography
There are no risks associated with medical photography.
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 cannot predict whether 
you will benefit directly from taking part in this study, although the knowledge gained from this 
study may help others in the future who have cancer.  This study may lead to an increase in 
understanding of this particular approach to therapy of KS, and possibly better treatments based 
on results from this study for patients in the future. Potential benefits to you could include 
shrinking of your KS or lessening of your symptoms, such as pain and swelling, which are caused 
by KS. However, it is possible that you will not receive any benefit from participating.
Alternative Approaches or Treatments
What other choices do I have if I do not take part in this study? 
Options for standard therapy of KS includes local administration of treatment to the lesions (if they 
are not too numerous or too spread out) and systemic therapies that treat the whole body.  
Sometimes, patients with HIV or AIDS-related KS improve with effective antiretroviral (anti-
HIV) therapy alone, without needing additional therapy specifically for the KS.  If a trial of 
antiretroviral (anti-HIV) therapy without specific KS therapy seems reasonable in your case, the 
study physicians will make this recommendation.   Also, some patients with mild KS that is not 
troubling them can be observed without specific treatment.
Local therapies include radiation therapy, which can help KS so long as the area to treat is not too 
large and has a good blood supply and good potential for healing. A gel that you can rub on your 
skin called panretin has also been approved by the US Food and Drug Administration for use in 
KS, and again is mainly used for small lesions.  In addition, for small lesions, some types of 
chemotherapy can be injected directly into the lesions.  Sometimes, very small lesions can be 
frozen off using liquid nitrogen or treated with laser therapy. 
Patients with KS lesions on multiple parts of their body or different areas of their skin can be 
treated with systemic therapies. The Food and Drug Administration has approved two systemic 
therapies for KS, both of which are types of cytotoxic cancer chemotherapy given through the 
veins: liposomal anthracyclines (liposomal doxorubicin and liposomal daunorubicin) and 
paclitaxel. Other systemic therapy options include other cancer chemotherapy drugs, and 
interferon alpha (an immune modifying drug which is injected under the skin). 
Severe KS or KS that is symptomatic and involves the vital organs, such as the lungs or intestines, 
usually requires chemotherapy given systemically through the veins for treatment.  If your KS 
requires this type of treatment, then the investigators on this study will inform you of this, and tell 
you that it would be inappropriate to treat you on this experimental study.  
IRB NUMBER: 12C0047
IRB APPROVAL DATE: 11/30/2021


PATIENT IDENTIFICATION
Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
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CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
A reasonable approach to consider rather than entry onto this research study would be to undergo 
standard therapy with one of the treatment approaches mentioned above, and the investigators at 
the NCI who explain the research protocol will also explain your standard medical treatment 
options to you.
Sometimes people with advanced HIV infection and severe KS decide that they would rather have 
no treatment at all, other than to be kept as comfortable as possible.  The study physicians will 
discuss this issue with you if it appears to be a reasonable approach for you.  The study physicians 
will provide their opinion on your prospects for benefit with standard medical treatment.
We encourage you to ask any question you have about your condition.  If at any time you feel that 
you have not been able to ask questions or do not understand any issue, we urge you to contact 
any member you chose on the research team, so that your questions and concerns can be addressed.
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 instructions given to you by your study doctors and nurses, 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 to that point may still be provided to Celgene Corporation 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.
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. 
IRB NUMBER: 12C0047
IRB APPROVAL DATE: 11/30/2021


PATIENT IDENTIFICATION
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NIH-2977 (4-17)
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CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
The National Institutes of Health and the research team for this study have participated in the 
development of pomalidomide to be used in certain diseases caused by the KSHV. Also, the 
National Institutes of Health and the research team for this study have developed a product (an 
assay for viral interleukin-6) being used in this study. This means it is possible that the results of 
this study could lead to payments to NIH. By law, the government is required to share such 
payments with the employee inventors. You will not receive any money from the development of 
this drug or the assay.
In addition, the National Institutes of Health and the research team for this study are using a drug 
(pomalidomide) developed by Celgene Corporation through a joint study with your researchers 
and the company. The company also provides financial support for this study.
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 they 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 for use in making 
clinical decisions.  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.
PAYMENT
Will you receive any type of payment for taking part in this study?
You will not receive any payment for taking part in this study. 
REIMBURSEMENT
Will you receive reimbursement or direct payment by NIH as part of your participation?
On this study, the NCI will reimburse the cost for some of your expenses such as those for hotel, 
travel, meals.  Some of these costs may be paid directly by the NIH and some may be reimbursed 
after you have paid. The amount and form of these payments are determined by the NCI Travel 
and Lodging Reimbursement Policy.  You will be given a summary of the policy which provides 
more information.
IRB NUMBER: 12C0047
IRB APPROVAL DATE: 11/30/2021


PATIENT IDENTIFICATION
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CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
If your travel to the NIH Clinical Center (e.g. flight, hotel) is arranged and paid for by the NIH, 
the agency making the reservations and their representatives will have access to your identifiable 
information.
COSTS
Will taking part in this research study cost you anything? 
NIH does not bill health insurance companies or participants for any research or related clinical 
care that you receive at the NIH Clinical Center. 

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.
CLINICAL TRIAL REGISTRATION AND RESULTS REPORTING
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.
CONFIDENTIALITY PROTECTIONS PROVIDED IN THIS STUDY  
Will your medical information be kept private? 
We will do our best to make sure that the personal information in your medical record will be kept 
private.  However, we cannot guarantee total privacy.  Organizations that may look at and/or copy 
your medical records for research, quality assurance, and data analysis include:

The NIH and other government agencies, like the Food and Drug Administration (FDA), 
which are involved in keeping research safe for people.

National Institutes of Health Intramural Institutional Review Board

Qualified representatives from Celgene Corporation, the pharmaceutical company who 
produces Pomalidomide.
The researchers conducting this study and the NIH follow applicable laws and policies to keep 
your identifying information private to the extent possible.  However, there is always a chance 
that, despite our best efforts, your identity and/or information about your participation in this 
research may be inadvertently released or improperly accessed by unauthorized persons.
IRB NUMBER: 12C0047
IRB APPROVAL DATE: 11/30/2021


PATIENT IDENTIFICATION
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MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
In most cases, the NIH will not release any identifiable information collected about you without 
your written permission.  However, your information may be shared as described in the section of 
this document on sharing of specimens and data, and as further outlined in the following sections.    
Further, the information collected for this study is protected by NIH under a Certificate of 
Confidentiality and the Privacy Act. 
Certificate of Confidentiality
To help us protect your privacy, the NIH Intramural Program has received a Certificate of 
Confidentiality (Certificate). With this certificate, researchers may not release or use data or 
information about you except in certain circumstances.  
NIH researchers must not share information that may identify you in any federal, state, or local 
civil, criminal, administrative, legislative, or other proceedings, for example, if requested by a 
court.  
The Certificate does not protect your information when it:  
1. is disclosed to people connected with the research, for example, information may be used 
for auditing or program evaluation internally by the NIH; or 
2. is required to be disclosed by Federal, State, or local laws, for example, when information 
must be disclosed to meet the legal requirements of the federal Food and Drug 
Administration (FDA); 
3. is for other research;
4. is disclosed with your consent. 
The Certificate does not prevent you from voluntarily releasing information about yourself or your 
involvement in this research. 
The Certificate will not be used to prevent disclosure to state or local authorities of harm to self or 
others including, for example, child abuse and neglect, and by signing below you consent to those 
disclosures. Other permissions for release may be made by signing NIH forms, such as the Notice 
and Acknowledgement of Information Practices consent.
Privacy Act
The Federal Privacy Act generally protects the confidentiality of your NIH medical records we 
collect under the authority of the Public Health Service Act.  In some cases, the Privacy Act 
protections differ from the Certificate of Confidentiality.  For example, sometimes the Privacy Act 
allows release of information from your medical record without your permission, for example, if 
it is requested by Congress. Information may also be released for certain research purposes with 
due consideration and protection, to those engaged by the agency for research purposes, to certain 
federal and state agencies, for HIV partner notification, for infectious disease or abuse or neglect 
reporting, to tumor registries, for quality assessment and medical audits, or when the NIH is 
involved in a lawsuit.  However, NIH will only release information from your medical record if it 
is permitted by both the Certificate of Confidentiality and the Privacy Act.
POLICY REGARDING RESEARCH-RELATED INJURIES  
The NIH 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 
IRB NUMBER: 12C0047
IRB APPROVAL DATE: 11/30/2021


PATIENT IDENTIFICATION
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NIH-2977 (4-17)
File in Section 4: Protocol Consent (1)
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MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
research-related injuries will be provided by the NIH, the NIH Clinical Center, or the Federal 
Government. However, you have the right to pursue legal remedy if you believe that your injury 
justifies such action.
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, Robert 
Yarchoan, MD, Robert.yarchoan@nih.gov, at 240-760-6075. You may also call the NIH Clinical 
Center Patient Representative at 301-496-2626, or the NIH Office of IRB Operations at 301-402-
3713, if you have a research-related complaint or concern.
CONSENT DOCUMENT 
Please keep a copy of this document in case you want to read it again.
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IRB APPROVAL DATE: 11/30/2021


PATIENT IDENTIFICATION
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MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
Adult Research Participant: I have read the explanation about this study and have been given the opportunity 
to discuss it and to ask questions. I consent to participate in this study.
Signature of Research Participant
Print Name of Research Participant
Date
Legally Authorized Representative (LAR) for an Adult Unable to Consent: I have read the explanation 
about this study and have been given the opportunity to discuss it and to ask questions. I am legally authorized 
to make research decisions on behalf of the adult participant unable to consent and have the authority to provide 
consent to this study. As applicable, the information in the above consent was described to the adult participant 
unable to consent who agrees to participate in the study.
Signature of LAR
Print Name of LAR
Date
Investigator:
Signature of Investigator
Print Name of Investigator
Date
Witness should sign below if either: 
1. A short form consent process has been used to enroll a non-English speaking subject or
2. An oral presentation of the full consent has been used to enroll a blind or illiterate subject
Signature of Witness*
Print Name of Witness
Date
*NIH ADMINISTRATIVE SECTION TO BE COMPLETED REGARDING THE USE OF AN 
INTERPRETER:
An interpreter, or other individual, who speaks English and the participant’s preferred language facilitated
the administration of informed consent and served as a witness. The investigator obtaining consent may not 
also serve as the witness.
An interpreter, or other individual, who speaks English and the participant’s preferred language facilitated
the administration of informed consent but did not serve as a witness. The name or ID code of the person 
providing interpretive support is:
.
IRB NUMBER: 12C0047
IRB APPROVAL DATE: 11/30/2021