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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

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.
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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.
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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 KSHVassociated 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.
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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 HIVassociated, 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 61 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 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.
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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. 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.
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12 human subjects protections 12.1

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.
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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.
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12.3 participation of subjects unable

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 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.
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12.4 evaluation of benefits and

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.
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12.4.1 risks to study procedures

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.
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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 65 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.
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12.6 consent and assent process

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.
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manual (non-electronic) signature on electronic

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.
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12.6.1 consent process for adults

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

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).
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13.2 quality assurance and quality

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.
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13.3 conflict of interest policy

The independence of this study from any actual or perceived influence, such as by the pharmaceutical industry, is critical. Therefore, any actual conflict of interest of persons who have a role in the design, conduct, analysis, publication, or any aspect of this trial will be disclosed and managed. Furthermore, persons who have a perceived conflict of interest will be required to have such conflicts managed in a way that is appropriate to their participation in the design and conduct of this trial. The study leadership in conjunction with the National Cancer Institute has established policies and procedures for all study group members to disclose all conflicts of interest and will establish a mechanism for the management of all reported dualities of interest.
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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.
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14 pharmaceutical information 14.1 pomalidomide

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 68 is 19171-19-8. The chemical structure of the active pharmaceutical ingredient (API) is as  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.
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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.
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supply

Celgene Corporation will supply POMALYST® (pomalidomide) through Celgene's Pomalidomide Risk Evaluation and Mitigation Strategy (POMALYST REMS™).
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dosage form

Pomalidomide will be supplied as 1.0 mg, 2.0 mg, 3.0 mg and 4.0 mg capsules for oral administration.
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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.
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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.
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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.
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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.
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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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15 references

1. Krown SE. AIDS-associated Kaposi's sarcoma: pathogenesis, clinical course and treatment. Aids. 1988;2(2):71-80. 2. Chang Y, Cesarman E, Pessin MS, Lee F, Culpepper J, Knowles DM, et al. Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma. Science. 1994;266(5192):1865-9. 3. Uldrick TS, Whitby D. Update on KSHV epidemiology, Kaposi Sarcoma pathogenesis, and treatment of Kaposi Sarcoma. Cancer Lett. 2011;305(2):150-62. 4. Kaposi M. Idiopathic multiple pigmented sarcoma of the skin. CA Cancer J Clin. 1982;1982(32):342-7. 5. Hengge UR, Ruzicka T, Tyring SK, Stuschke M, Roggendorf M, Schwartz RA, et al. Update on Kaposi's sarcoma and other HHV8 associated diseases. Part 2: pathogenesis, Castleman's disease, and pleural effusion lymphoma. Lancet Infect Dis. 2002;2(6):344-52.  
6. Cesarman E, Chang Y, Moore PS, Said JW, Knowles DM. Kaposi's sarcoma-associated herpesvirus-like DNA sequences in AIDS-related body-cavity-based lymphomas. N Engl J Med. 1995;332(18):1186-91. 7. Soulier J, Grollet L, Oksenhendler E, Cacoub P, Cazals-Hatem D, Babinet P, et al. Kaposi's sarcoma-associated herpesvirus-like DNA sequences in multicentric Castleman's disease. Blood. 1995;86(4):1276-80. 8. Uldrick TS, Wang V, O'Mahony D, Aleman K, Wyvill KM, Marshall V, et al. An Interleukin-6-Related Systemic Inflammatory Syndrome in Patients Co-Infected with Kaposi Sarcoma-Associated Herpesvirus and HIV but without Multicentric Castleman Disease. Clin Infect Dis. 2010;51(3):350-8. 9. Teruya-Feldstein J, Zauber P, Setsuda JE, Berman EL, Sorbara L, Raffeld M, et al. Expression of human herpesvirus-8 oncogene and cytokine homologues in an HIV-seronegative patient with multicentric Castleman's disease and primary effusion lymphoma. Lab Invest. 1998;78(12):1637-42. 10. Gao SJ, Kingsley L, Hoover DR, Spira TJ, Rinaldo CR, Saah A, et al. Seroconversion to antibodies against Kaposi's sarcoma-associated herpesvirus-related latent nuclear antigens before the development of Kaposi's sarcoma. N Engl J Med. 1996;335(4):233-41. 11. de Sanjose S, Nieters A, Goedert JJ, Domingo-Domenech E, Fernandez de Sevilla A,
Bosch R, et al. Role of hepatitis C virus infection in malignant lymphoma in Spain. Int J Cancer.  
2004;111(1):81-5. 12. Sitas F, Carrara H, Beral V, Newton R, Reeves G, Bull D, et al. Antibodies against human herpesvirus 8 in black South African patients with cancer. N Engl J Med. 1999;340(24):1863-71. 13. Biggar RJ, Chaturvedi AK, Goedert JJ, Engels EA. AIDS-related cancer and severity of immunosuppression in persons with AIDS. J Natl Cancer Inst. 2007;99(12):962-72. 14. Biggar RJ, Rosenberg PS, Cote T. Kaposi's sarcoma and non-Hodgkin's lymphoma following the diagnosis of AIDS. Multistate AIDS/Cancer Match Study Group. Int J Cancer. 1996;68(6):754-8. 15. Shiels MS, Pfeiffer RM, Hall HI, Li J, Goedert JJ, Morton LM, et al. Proportions of Kaposi sarcoma, selected non-Hodgkin lymphomas, and cervical cancer in the United States occurring in persons with AIDS, 1980-2007. JAMA. 2011;305(14):1450-9. 16. Brown EE, Whitby D, Vitale F, Marshall V, Mbisa G, Gamache C, et al. Virologic, hematologic, and immunologic risk factors for classic Kaposi sarcoma. Cancer. 2006;107(9):2282-90. 17. Guihot A, Dupin N, Marcelin AG, Gorin I, Bedin AS, Bossi P, et al. Low T cell responses to human herpesvirus 8 in patients with AIDS-related and classic Kaposi sarcoma. J Infect Dis. 2006;194(8):1078-88. 18. Bihl F, Mosam A, Henry LN, Chisholm JV, 3rd, Dollard S, Gumbi P, et al. Kaposi's sarcoma-associated herpesvirus-specific immune reconstitution and antiviral effect of combined HAART/chemotherapy in HIV clade C-infected individuals with Kaposi's sarcoma. Aids. 2007;21(10):1245-52. 19. Barozzi P, Bonini C, Potenza L, Masetti M, Cappelli G, Gruarin P, et al. Changes in the immune responses against human herpesvirus-8 in the disease course of posttransplant Kaposi sarcoma. Transplantation. 2008;86(5):738-44.  
20. Engels EA, Biggar RJ, Hall HI, Cross H, Crutchfield A, Finch JL, et al. Cancer risk in people infected with human immunodeficiency virus in the United States. Int J Cancer. 2008;123(1):187-94. 21. Engels EA, Pfeiffer RM, Goedert JJ, Virgo P, McNeel TS, Scoppa SM, et al. Trends in cancer risk among people with AIDS in the United States 1980-2002. Aids. 2006;20(12):164554. 22. Shiels MS, Pfeiffer RM, Gail MH, Hall HI, Li J, Chaturvedi AK, et al. Cancer Burden in the HIV-Infected Population in the United States. J Natl Cancer Inst. 2011. 23. Simard EP, Pfeiffer RM, Engels EA. Cumulative incidence of cancer among individuals with acquired immunodeficiency syndrome in the United States. Cancer. 2011;117(5):1089-96. 24. Shiels MS, Goedert JJ, Engels EA. Recent trends and future directions in human immunodeficiency virus-associated cancer. Cancer. 2010;116(23):5344-7. 25. Mbulaiteye SM, Biggar RJ, Goedert JJ, Engels EA. Immune deficiency and risk for malignancy among persons with AIDS. J Acquir Immune Defic Syndr. 2003;32(5):527-33. 26. Mosam A, Carrara H, Shaik F, Uldrick T, Berkman A, Aboobaker J, et al. Increasing incidence of Kaposi's sarcoma in black South Africans in KwaZulu-Natal, South Africa (19832006). Int J STD AIDS. 2009;20(8):553-6. 27. Stein L, Urban MI, O'Connell D, Yu XQ, Beral V, Newton R, et al. The spectrum of human immunodeficiency virus-associated cancers in a South African black population: Results from a case-control study, 1995-2004. Int J Cancer. 2008. 28. Mbulaiteye SM, Katabira ET, Wabinga H, Parkin DM, Virgo P, Ochai R, et al. Spectrum of cancers among HIV-infected persons in Africa: the Uganda AIDS-Cancer Registry Match Study. Int J Cancer. 2006;118(4):985-90. 29. Sitas F, Newton R. Kaposi's sarcoma in South Africa. J Natl Cancer Inst Monogr. 2001(28):1-4. 30. Moore PS, Gao SJ, Dominguez G, Cesarman E, Lungu O, Knowles DM, et al. Primary characterization of a herpesvirus agent associated with Kaposi's sarcomae. J Virol. 1996;70(1):549-58. 31. Moore PS, Chang Y. Kaposi's sarcoma-associated herpesvirus-encoded oncogenes and oncogenesis. J Natl Cancer Inst Monogr. 1998(23):65-71. 32. Staskus KA, Sun R, Miller G, Racz P, Jaslowski A, Metroka C, et al. Cellular tropism and viral interleukin-6 expression distinguish human herpesvirus 8 involvement in Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. J Virol. 1999;73(5):4181-7. 33. Sun R, Lin SF, Staskus K, Gradoville L, Grogan E, Haase A, et al. Kinetics of Kaposi's sarcoma-associated herpesvirus gene expression. J Virol. 1999;73(3):2232-42. 34. Jenner RG, Alba MM, Boshoff C, Kellam P. Kaposi's sarcoma-associated herpesvirus latent and lytic gene expression as revealed by DNA arrays. J Virol. 2001;75(2):891-902. 35. Della Bella S, Taddeo A, Calabro ML, Brambilla L, Bellinvia M, Bergamo E, et al. Peripheral blood endothelial progenitors as potential reservoirs of Kaposi's sarcoma-associated herpesvirus. PLoS One. 2008;3(1):e1520. 36. Wu W, Vieira J, Fiore N, Banerjee P, Sieburg M, Rochford R, et al. KSHV/HHV-8 infection of human hematopoietic progenitor (CD34+) cells: persistence of infection during hematopoiesis in vitro and in vivo. Blood. 2006;108(1):141-51. 37. Monini P, Colombini S, Sturzl M, Goletti D, Cafaro A, Sgadari C, et al. Reactivation and persistence of human herpesvirus-8 infection in B cells and monocytes by Th-1 cytokines increased in Kaposi's sarcoma. Blood. 1999;93(12):4044-58. 38. Moore PS, Boshoff C, Weiss RA, Chang Y. Molecular mimicry of human cytokine and cytokine response pathway genes by KSHV. Science. 1996;274(5293):1739-44. 39. Ganem D. KSHV and the pathogenesis of Kaposi sarcoma: listening to human biology and medicine. J Clin Invest. 2010;120(4):939-49. 40. Boshoff C, Endo Y, Collins PD, Takeuchi Y, Reeves JD, Schweickart VL, et al. Angiogenic and HIV-inhibitory functions of KSHV-encoded chemokines. Science. 1997;278(5336):290-4. 41. Weiss RA, Whitby D, Talbot S, Kellam P, Boshoff C. Human Herpesvirus Type 8 and Kaposi's Sarcoma. JNCI Monographs. 1998;1998(23):51-4. 42. Wen KW, Damania B. Kaposi sarcoma-associated herpesvirus (KSHV): molecular biology and oncogenesis. Cancer Lett. 2010;289(2):140-50. 43. Neipel F, Albrecht JC, Ensser A, Huang YQ, Li JJ, Friedman-Kien AE, et al. Human herpesvirus 8 encodes a homolog of interleukin-6. J Virol. 1997;71(1):839-42. 44. Nicholas J, Ruvolo VR, Burns WH, Sandford G, Wan X, Ciufo D, et al. Kaposi's sarcoma-associated human herpesvirus-8 encodes homologues of macrophage inflammatory protein-1 and interleukin-6. Nat Med. 1997;3(3):287-92.  
45. Pati S, Foulke JS, Jr., Barabitskaya O, Kim J, Nair BC, Hone D, et al. Human Herpesvirus 8-Encoded vGPCR Activates Nuclear Factor of Activated T Cells and Collaborates with Human Immunodeficiency Virus Type 1 Tat. J Virol. 2003;77(10):5759-73. 46. Arvanitakis L, Geras-Raaka E, Varma A, Gershengorn MC, Cesarman E. Human herpesvirus KSHV encodes a constitutively active G-protein-coupled receptor linked to cell proliferation. Nature. 1997;385(6614):347-50. 47. Aoki Y, Jones KD, Tosato G. Kaposi's sarcoma-associated herpesvirus-encoded interleukin-6. J Hematother Stem Cell Res. 2000;9(2):137-45. 48. Osborne J, Moore PS, Chang Y. KSHV-encoded viral IL-6 activates multiple human IL-6 signaling pathways. Hum Immunol. 1999;60(10):921-7. 49. Bais C, Van Geelen A, Eroles P, Mutlu A, Chiozzini C, Dias S, et al. Kaposi's sarcoma associated herpesvirus G protein-coupled receptor immortalizes human endothelial cells by activation of the VEGF receptor-2/ KDR. Cancer Cell. 2003;3(2):131-43. 50. Emuss V, Lagos D, Pizzey A, Gratrix F, Henderson SR, Boshoff C. KSHV manipulates Notch signaling by DLL4 and JAG1 to alter cell cycle genes in lymphatic endothelia. PLoS Pathog. 2009;5(10):e1000616. 51. Grisotto MG, Garin A, Martin AP, Jensen KK, Chan P, Sealfon SC, et al. The human herpesvirus 8 chemokine receptor vGPCR triggers autonomous proliferation of endothelial cells. J Clin Invest. 2006;116(5):1264-73. 52. Montaner S, Sodhi A, Molinolo A, Bugge TH, Sawai ET, He Y, et al. Endothelial infection with KSHV genes in vivo reveals that vGPCR initiates Kaposi's sarcomagenesis and can promote the tumorigenic potential of viral latent genes. Cancer Cell. 2003;3(1):23-36.  
53. Qin Z, Kearney P, Plaisance K, Parsons CH. Pivotal advance: Kaposi's sarcomaassociated herpesvirus (KSHV)-encoded microRNA specifically induce IL-6 and IL-10 secretion by macrophages and monocytes. J Leukoc Biol. 2010;87(1):25-34. 54. Schwarz M, Murphy PM. Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor constitutively activates NF-kappa B and induces proinflammatory cytokine and chemokine production via a C-terminal signaling determinant. J Immunol. 2001;167(1):505-13. 55. An J, Sun Y, Sun R, Rettig MB. Kaposi's sarcoma-associated herpesvirus encoded vFLIP induces cellular IL-6 expression: the role of the NF-kappaB and JNK/AP1 pathways. Oncogene. 2003;22(22):3371-85. 56. Deng H, Chu JT, Rettig MB, Martinez-Maza O, Sun R. Rta of the human herpesvirus 8/Kaposi sarcoma-associated herpesvirus up-regulates human interleukin-6 gene expression. Blood. 2002;100(5):1919-21. 57. Meduri GU, Stover DE, Lee M, Myskowski PL, Caravelli JF, Zaman MB. Pulmonary Kaposi's sarcoma in the acquired immune deficiency syndrome. Clinical, radiographic, and pathologic manifestations. Am J Med. 1986;81(1):11-8. 58. Niedt GW, Schinella RA. Acquired immunodeficiency syndrome. Clinicopathologic study of 56 autopsies. Arch Pathol Lab Med. 1985;109(8):727-34. 59. Marchio S, Primo L, Pagano M, Palestro G, Albini A, Veikkola T, et al. Vascular endothelial growth factor-C stimulates the migration and proliferation of Kaposi's sarcoma cells. J Biol Chem. 1999;274(39):27617-22. 60. Masood R, Cai J, Zheng T, Smith DL, Naidu Y, Gill PS. Vascular endothelial growth factor/vascular permeability factor is an autocrine growth factor for AIDS-Kaposi sarcoma. Proc Natl Acad Sci U S A. 1997;94(3):979-84.  
61. Skobe M, Brown LF, Tognazzi K, Ganju RK, Dezube BJ, Alitalo K, et al. Vascular endothelial growth factor-C (VEGF-C) and its receptors KDR and flt-4 are expressed in AIDSassociated Kaposi's sarcoma. J Invest Dermatol. 1999;113(6):1047-53.  
62. Ensoli B, Markham P, Kao V, Barillari G, Fiorelli V, Gendelman R, et al. Block of AIDS-Kaposi's sarcoma (KS) cell growth, angiogenesis, and lesion formation in nude mice by antisense oligonucleotide targeting basic fibroblast growth factor. A novel strategy for the therapy of KS. J Clin Invest. 1994;94(5):1736-46. 63. Folpe AL, Veikkola T, Valtola R, Weiss SW. Vascular endothelial growth factor receptor-3 (VEGFR-3): a marker of vascular tumors with presumed lymphatic differentiation, including Kaposi's sarcoma, kaposiform and Dabska-type hemangioendotheliomas, and a subset of angiosarcomas. Mod Pathol. 2000;13(2):180-5. 64. Aoki Y, Jaffe ES, Chang Y, Jones K, Teruya-Feldstein J, Moore PS, et al. Angiogenesis and hematopoiesis induced by Kaposi's sarcoma-associated herpesvirus-encoded interleukin-6. Blood. 1999;93(12):4034-43.  
65. Katano H, Sato Y, Kurata T, Mori S, Sata T. Expression and localization of human herpesvirus 8-encoded proteins in primary effusion lymphoma, Kaposi's sarcoma, and multicentric Castleman's disease. Virology. 2000;269(2):335-44. 66. Oxholm A. Epidermal expression of interleukin-6 and tumour necrosis factor-alpha in normal and immunoinflammatory skin states in humans. APMIS Suppl. 1992;24:1-32.  
67. Ensoli B, Nakamura S, Salahuddin SZ, Biberfeld P, Larsson L, Beaver B, et al. AIDSKaposi's sarcoma-derived cells express cytokines with autocrine and paracrine growth effects.  
Science. 1989;243(4888):223-6. 68. Staskus KA, Zhong W, Gebhard K, Herndier B, Wang H, Renne R, et al. Kaposi's sarcoma-associated herpesvirus gene expression in endothelial (spindle) tumor cells. J Virol. 1997;71(1):715-9. 69. Aoki Y, Yarchoan R, Wyvill K, Okamoto S, Little RF, Tosato G. Detection of viral interleukin-6 in Kaposi sarcoma-associated herpesvirus-linked disorders. Blood.  
2001;97(7):2173-6.  
70. Buonaguro L, Buonaguro FM, Tornesello ML, Beth-Giraldo E, Del Gaudio E, Ensoli B, et al. Role of HIV-1 Tat in the pathogenesis of AIDS-associated Kaposi's sarcoma. Antibiot Chemother. 1994;46:62-72. 71. Krown SE. Highly active antiretroviral therapy in AIDS-associated Kaposi's sarcoma: implications for the design of therapeutic trials in patients with advanced, symptomatic Kaposi's sarcoma. J Clin Oncol. 2004;22(3):399-402. 72. Bower M, Weir J, Francis N, Newsom-Davis T, Powles S, Crook T, et al. The effect of HAART in 254 consecutive patients with AIDS-related Kaposi's sarcoma. AIDS. 2009;23(13):1701-6. 73. Mosam A, Shaik F, Uldrick T, Esterhuizen T, Friedland G, Scadden D, et al. The KAART Trial: a Randomised Controlled Trial of HAART Compared to theCombination of HAART and Chemotherapy in Treatment Naive Patients With HIV-associated Kaposi's Sarcoma (HIV-KS) in KwaZulu-Natal (KZN), South Africa NCT 00380770. 17th Conference on Retroviruses and Opportunistic Infections; San Francisco, CA2010. 74. Nunez M, Saballs P, Valencia ME, Santos J, Ferrer E, Santos I, et al. Response to liposomal doxorubicin and clinical outcome of HIV-1-infected patients with Kaposi's sarcoma receiving highly active antiretroviral therapy. HIV Clin Trials. 2001;2(5):429-37.  
75. Northfelt DW, Dezube BJ, Thommes JA, Miller BJ, Fischl MA, Friedman-Kien A, et al.  
Pegylated-liposomal doxorubicin versus doxorubicin, bleomycin, and vincristine in the treatment of AIDS-related Kaposi's sarcoma: results of a randomized phase III clinical trial. J Clin Oncol. 1998;16(7):2445-51. 76. Wagner D, Kern WV, Kern P. Liposomal doxorubicin in AIDS-related Kaposi's sarcoma: long-term experiences. Clin Investig. 1994;72(6):417-23. 77. James ND, Coker RJ, Tomlinson D, Harris JR, Gompels M, Pinching AJ, et al. Liposomal doxorubicin (Doxil): an effective new treatment for Kaposi's sarcoma in AIDS. Clin Oncol (R Coll Radiol). 1994;6(5):294-6. 78. Bogner JR, Kronawitter U, Rolinski B, Truebenbach K, Goebel FD. Liposomal doxorubicin in the treatment of advanced AIDS-related Kaposi sarcoma. J Acquir Immune Defic Syndr. 1994;7(5):463-8.  
79. Simpson JK, Miller RF, Spittle MF. Liposomal doxorubicin for treatment of AIDSrelated Kaposi's sarcoma. Clin Oncol (R Coll Radiol). 1993;5(6):372-4.  
80. Presant CA, Scolaro M, Kennedy P, Blayney DW, Flanagan B, Lisak J, et al. Liposomal daunorubicin treatment of HIV-associated Kaposi's sarcoma. Lancet. 1993;341(8855):1242-3. 81. Hengge UR, Brockmeyer NH, Baumann M, Reimann G, Goos M. Liposomal doxorubicin in AIDS-related Kaposi's sarcoma [letter]. Lancet. 1993;342(8869):497. 82. Welles L, Saville MW, Lietzau J, Pluda JM, Wyvill KM, Feuerstein I, et al. Phase II trial with dose titration of paclitaxel for the therapy of human immunodeficiency virus-associated Kaposi's sarcoma. J Clin Oncol. 1998;16(3):1112-21. 83. Stebbing J, Wildfire A, Portsmouth S, Powles T, Thirlwell C, Hewitt P, et al. Paclitaxel for anthracycline-resistant AIDS-related Kaposi's sarcoma: clinical and angiogenic correlations. Ann Oncol. 2003;14(11):1660-6. 84. Gill PS, Tulpule A, Espina BM, Cabriales S, Bresnahan J, Ilaw M, et al. Paclitaxel is safe and effective in the treatment of advanced AIDS- related Kaposi's sarcoma. J Clin Oncol. 1999;17(6):1876-83.  
85. Cianfrocca M, Lee S, Von Roenn J, Tulpule A, Dezube BJ, Aboulafia DM, et al.  
Randomized trial of paclitaxel versus pegylated liposomal doxorubicin for advanced human immunodeficiency virus-associated Kaposi sarcoma: evidence of symptom palliation from chemotherapy. Cancer. 2010;116(16):3969-77. 86. Montaner S. Akt/TSC/mTOR activation by the KSHV G protein-coupled receptor: emerging insights into the molecular oncogenesis and treatment of Kaposi's sarcoma. Cell Cycle. 2007;6(4):438-43. 87. Stallone G, Infante B, Grandaliano G, Schena FP, Gesualdo L. Kaposi's sarcoma and mTOR: a crossroad between viral infection neoangiogenesis and immunosuppression. Transpl Int. 2008;21(9):825-32. 88. Stallone G, Schena A, Infante B, Di Paolo S, Loverre A, Maggio G, et al. Sirolimus for Kaposi's sarcoma in renal-transplant recipients. N Engl J Med. 2005;352(13):1317-23. 89. Krown SE. AIDS-associated Kaposi's sarcoma: Is there still a role for interferon alfa? Cytokine Growth Factor Rev. 2007. 90. Krown SE, Lee JY, Lin L, Fischl MA, Ambinder R, Von Roenn JH. Interferon-alpha2b with protease inhibitor-based antiretroviral therapy in patients with AIDS-associated Kaposi sarcoma: an AIDS malignancy consortium phase I trial. J Acquir Immune Defic Syndr. 2006;41(2):149-53.  
91. Krown SE, Aeppli D, Balfour HH, Jr. Phase II, randomized, open-label, communitybased trial to compare the safety and activity of combination therapy with recombinant interferon-alpha2b and zidovudine versus zidovudine alone in patients with asymptomatic to mildly symptomatic HIV infection. HIV Protocol C91-253 Study Team. J Acquir Immune Defic Syndr Hum Retrovirol. 1999;20(3):245-54. 92. Krown SE, Real FX, Cunningham-Rundles S, Myskowski PL, Koziner B, Fein S, et al. Preliminary observations on the effect of recombinant leukocyte A interferon in homosexual men with Kaposi's sarcoma. N Engl J Med. 1983;308(18):1071-6. 93. Little RF, Aleman K, Kumar P, Wyvill KM, Pluda JM, Read-Connole E, et al. Phase 2 study of pegylated liposomal doxorubicin in combination with interleukin-12 for AIDS-related Kaposi sarcoma. Blood. 2007;110(13):4165-71. 94. Yarchoan R, Pluda J, Wyvill K, Aleman K, Rodriguez-Chavez IR, Tosato G, et al. Treatment of AIDS-related Kaposi's sarcoma with interleukin-12: Rationale and preliminary evidence of clinical activty. Critical Review in Immunology. 2007;27(5):401-14.  
95. Little RF, Pluda JM, Wyvill KM, Rodriguez-Chavez IR, Tosato G, Catanzaro AT, et al. Activity of subcutaneous interleukin-12 in AIDS-related Kaposi sarcoma. Blood. 2006;107(12):4650-7. 96. Lupu-Meiri M, Silver RB, Simons AH, Gershengorn MC, Oron Y. Constitutive signaling by Kaposi's sarcoma-associated herpesvirus G- protein-coupled receptor desensitizes calcium mobilization by other receptors. J Biol Chem. 2001;276(10):7122-8. 97. Little RF, Wyvill KM, Pluda JM, Welles L, Marshall V, Figg WD, et al. Activity of Thalidomide in AIDS-Related Kaposi's Sarcoma. J Clin Oncol. 2000;18(13):2593-602.  
98. Fife K, Howard MR, Gracie F, Phillips RH, Bower M. Activity of thalidomide in AIDSrelated Kaposi's sarcoma and correlation with HHV8 titre. Int J STD AIDS. 1998;9(12):751-5.  
99. Ben M'barek L, Fardet L, Mebazaa A, Thervet E, Biet I, Kerob D, et al. A retrospective analysis of thalidomide therapy in non-HIV-related Kaposi's sarcoma. Dermatology. 2007;215(3):202-5.  
100. Rubegni P, Sbano P, De Aloe G, Flori ML, Fimiani M. Thalidomide in the treatment of Kaposi's sarcoma. Dermatology. 2007;215(3):240-4.  
101. Soler RA, Howard M, Brink NS, Gibb D, Tedder RS, Nadal D. Regression of AIDSrelated Kaposi's sarcoma during therapy with thalidomide. Clin Infect Dis. 1996;23(3):501-3; discussion 4-5. 102. Martinez V, Tateo M, Castilla MA, Melica G, Kirstetter M, Boue F. Lenalidomide in treating AIDS-related Kaposi's sarcoma. AIDS. 2011;25(6):878-80. 103. Uldrick TS, Wyvill KM, Kumar P, O'Mahony D, Bernstein W, Aleman K, et al. Phase II Study of Bevacizumab in Patients With HIV-Associated Kaposi's Sarcoma Receiving Antiretroviral Therapy. J Clin Oncol. 2012. 104. Krown SE. Therapy of AIDS-associated Kaposi's sarcoma: targeting pathogenetic mechanisms. Hematol Oncol Clin North Am. 2003;17(3):763-83. 105. Young A. Cardiotoxicity after liposomal anthracyclines. The lancet oncology. 2004;5(11):654. 106. Krown SE, Northfelt DW, Osoba D, Stewart JS. Use of liposomal anthracyclines in Kaposi's sarcoma. Semin Oncol. 2004;31(6 Suppl 13):36-52. 107. Quach H, Ritchie D, Stewart AK, Neeson P, Harrison S, Smyth MJ, et al. Mechanism of action of immunomodulatory drugs (IMiDS) in multiple myeloma. Leukemia. 2010;24(1):22-32.  
108. Corporation C. Investigator's Brochure: Pomalidomide/CC-4047. 14 ed. Summit, NJ2010. 109. Marriott JB, Clarke IA, Dredge K, Muller G, Stirling D, Dalgleish AG. Thalidomide and its analogues have distinct and opposing effects on TNF-alpha and TNFR2 during co-stimulation of both CD4(+) and CD8(+) T cells. Clin Exp Immunol. 2002;130(1):75-84. 110. Kotla V, Goel S, Nischal S, Heuck C, Vivek K, Das B, et al. Mechanism of action of lenalidomide in hematological malignancies. J Hematol Oncol. 2009;2:36. 111. Lacy MQ, Hayman SR, Gertz MA, Short KD, Dispenzieri A, Kumar S, et al. Pomalidomide (CC4047) plus low dose dexamethasone (Pom/dex) is active and well tolerated in lenalidomide refractory multiple myeloma (MM). Leukemia. 2010;24(11):1934-9. 112. Madan S, Lacy M, Dispenzieri A, Gertz M, Buadi F, Hayman SR, et al. Efficacy of Retreatment with Immunomodulatory Compounds In Patients Receiving Initial Therapy for Newly Diagnosed Multiple Myeloma. Blood. 2010;116(21):1964-. 113. Dredge K, Marriott JB, Todryk SM, Muller GW, Chen R, Stirling DI, et al. Protective antitumor immunity induced by a costimulatory thalidomide analog in conjunction with whole tumor cell vaccination is mediated by increased Th1-type immunity. J Immunol. 2002;168(10):4914-9. 114. Schafer PH, Gandhi AK, Loveland MA, Chen RS, Man HW, Schnetkamp PP, et al.  
Enhancement of cytokine production and AP-1 transcriptional activity in T cells by thalidomiderelated immunomodulatory drugs. J Pharmacol Exp Ther. 2003;305(3):1222-32.  
115. Payvandi F, Wu L, Naziruddin SD, Haley M, Parton A, Schafer PH, et al. Immunomodulatory drugs (IMiDs) increase the production of IL-2 from stimulated T cells by increasing PKC-theta activation and enhancing the DNA-binding activity of AP-1 but not NFkappaB, OCT-1, or NF-AT. J Interferon Cytokine Res. 2005;25(10):604-16.  
116. Payvandi F, Wu L, Haley M, Schafer PH, Zhang LH, Chen RS, et al. Immunomodulatory drugs inhibit expression of cyclooxygenase-2 from TNF-alpha, IL-1beta, and LPS-stimulated human PBMC in a partially IL-10-dependent manner. Cell Immunol. 2004;230(2):81-8. 117. Xu W, Celeridad M, Sankar S, Webb DR, Bennett BL. CC-4047 promotes Th1 cell differentiation and reprograms polarized human Th2 cells by enhancing transcription factor Tbet. Clin Immunol. 2008;128(3):392-9.  
118. Galustian C, Meyer B, Labarthe MC, Dredge K, Klaschka D, Henry J, et al. The anticancer agents lenalidomide and pomalidomide inhibit the proliferation and function of T
regulatory cells. Cancer Immunol Immunother. 2009;58(7):1033-45. 119. Schey SA, Fields P, Bartlett JB, Clarke IA, Ashan G, Knight RD, et al. Phase I study of an immunomodulatory thalidomide analog, CC-4047, in relapsed or refractory multiple myeloma. J Clin Oncol. 2004;22(16):3269-76. 120. Gorgun G, Calabrese E, Soydan E, Hideshima T, Perrone G, Bandi M, et al. Immunomodulatory effects of lenalidomide and pomalidomide on interaction of tumor and bone marrow accessory cells in multiple myeloma. Blood. 2010;116(17):3227-37. 121. Lentzsch S, LeBlanc R, Podar K, Davies F, Lin B, Hideshima T, et al. Immunomodulatory analogs of thalidomide inhibit growth of Hs Sultan cells and angiogenesis in vivo. Leukemia. 2003;17(1):41-4. 122. Reddy N, Hernandez-Ilizaliturri FJ, Deeb G, Roth M, Vaughn M, Knight J, et al. Immunomodulatory drugs stimulate natural killer-cell function, alter cytokine production by dendritic cells, and inhibit angiogenesis enhancing the anti-tumour activity of rituximab in vivo. Br J Haematol. 2008;140(1):36-45.  
123. Dredge K, Marriott JB, Macdonald CD, Man HW, Chen R, Muller GW, et al. Novel thalidomide analogues display anti-angiogenic activity independently of immunomodulatory effects. Br J Cancer. 2002;87(10):1166-72. 124. Verhelle D, Corral LG, Wong K, Mueller JH, Moutouh-de Parseval L, Jensen-Pergakes K, et al. Lenalidomide and CC-4047 inhibit the proliferation of malignant B cells while expanding normal CD34+ progenitor cells. Cancer Res. 2007;67(2):746-55. 125. Zhu D, Corral LG, Fleming YW, Stein B. Immunomodulatory drugs Revlimid (lenalidomide) and CC-4047 induce apoptosis of both hematological and solid tumor cells through NK cell activation. Cancer Immunol Immunother. 2008;57(12):1849-59. 126. Shalapour S, Zelmer A, Pfau M, Moderegger E, Costa-Blechschmidt C, van Landeghem FK, et al. The thalidomide analogue, CC-4047, induces apoptosis signaling and growth arrest in childhood acute lymphoblastic leukemia cells in vitro and in vivo. Clin Cancer Res. 2006;12(18):5526-32. 127. Escoubet-Lozach L, Lin IL, Jensen-Pergakes K, Brady HA, Gandhi AK, Schafer PH, et al. Pomalidomide and lenalidomide induce p21 WAF-1 expression in both lymphoma and multiple myeloma through a LSD1-mediated epigenetic mechanism. Cancer Res. 2009;69(18):7347-56. 128. Pal R, Monaghan SA, Hassett AC, Mapara MY, Schafer P, Roodman GD, et al. Immunomodulatory derivatives induce PU.1 down-regulation, myeloid maturation arrest, and neutropenia. Blood. 2010;115(3):605-14. 129. Anderson G, Gries M, Kurihara N, Honjo T, Anderson J, Donnenberg V, et al. Thalidomide derivative CC-4047 inhibits osteoclast formation by down-regulation of PU.1. Blood. 2006;107(8):3098-105. 130. Davies F, Baz R. Lenalidomide mode of action: linking bench and clinical findings. Blood Rev. 2010;24 Suppl 1:S13-9. 131. Davies FE, Raje N, Hideshima T, Lentzsch S, Young G, Tai YT, et al. Thalidomide and immunomodulatory derivatives augment natural killer cell cytotoxicity in multiple myeloma. Blood. 2001;98(1):210-6.  
132. Streetly MJ, Gyertson K, Daniel Y, Zeldis JB, Kazmi M, Schey SA. Alternate day pomalidomide retains anti-myeloma effect with reduced adverse events and evidence of in vivo immunomodulation. Br J Haematol. 2008;141(1):41-51. 133. Infante JR, Jones SF, Bendell JC, Spigel DR, Yardley DA, Weekes CD, et al. A phase I, dose-escalation study of pomalidomide (CC-4047) in combination with gemcitabine in metastatic pancreas cancer. Eur J Cancer. 2011;47(2):199-205. 134. Mesa RA, Pardanani AD, Hussein K, Wu W, Schwager S, Litzow MR, et al. Phase1/-2 study of Pomalidomide in myelofibrosis. Am J Hematol. 2010;85(2):129-30. 135. Tefferi A, Verstovsek S, Barosi G, Passamonti F, Roboz GJ, Gisslinger H, et al. Pomalidomide is active in the treatment of anemia associated with myelofibrosis. J Clin Oncol. 2009;27(27):4563-9. 136. Cooney MM, Nock C, Bokar J, Krishnamurthi S, Gibbons J, Rodal MB, et al. Phase I trial of pomalidomide given for patients with advanced solid tumors. Cancer Chemother Pharmacol. 2012;70(5):755-61. 137. Hsieh MM, Tisdale JF, Rodgers GP, Young NS, Trimble EL, Little RF. Neutrophil count in African Americans: lowering the target cutoff to initiate or resume chemotherapy? J Clin Oncol. 2010;28(10):1633-7. 138. Dunleavy K, Little RF, Pittaluga S, Grant N, Wayne AS, Carrasquillo JA, et al. The role of tumor histogenesis, FDG-PET, and short course EPOCH with dose-dense rituximab (SCEPOCH-RR) in HIV-associated diffuse large B-cell lymphoma. Blood. 2010.  
139. Jacobson MC, Dezube BJ, Aboulafia DM. Thrombotic complications in patients infected with HIV in the era of highly active antiretroviral therapy: a case series. Clin Infect Dis. 2004;39(8):1214-22. 140. Copur AS, Smith PR, Gomez V, Bergman M, Homel P. HIV infection is a risk factor for venous thromboembolism. AIDS Patient Care STDS. 2002;16(5):205-9. 141. Rasmussen LD, Dybdal M, Gerstoft J, Kronborg G, Larsen CS, Pedersen C, et al. HIV and risk of venous thromboembolism: a Danish nationwide population-based cohort study. HIV Med. 2011;12(4):202-10. 142. Musselwhite LW, Sheikh V, Norton TD, Rupert A, Porter BO, Penzak SR, et al. Markers of endothelial dysfunction, coagulation and tissue fibrosis independently predict venous thromboembolism in HIV. AIDS. 2011;25(6):787-95. 143. Pliquett RU, Schofer H, Asbe-Vollkopf A, Hauser IA, Scheuermann EH, Kachel HG. Posttransplant Kaposi sarcoma and risk for deep venous thrombosis: a case-control study. Transplantation. 2011;91(4):e21-2. 144. O'Mahony D, Gandjbakche A, Hassan M, Vogel A, Yarchoan R. Imaging techniques for Kaposi's sarcoma. J HIV Ther. 2008;13(3):65-71. 145. Gandjbakhche A, Vogel A, Amyot F, Chernomordik V, Hassan M, Demos S, et al. Noninvasive Multimodality Imaging Techniques to Assess Kaposi's Sarcoma. Conf Proc IEEE Eng Med Biol Soc. 2005;1:694-6. 146. Rajkumar SV. Treatment of multiple myeloma. Nat Rev Clin Oncol. 2011;8(8):479-91. 147. McCarthy PL, Owzar K, Anderson KC, Hofmeister CC, Hurd DD, Hassoun H, et al. Phase III Intergroup Study of Lenalidomide Versus Placebo Maintenance Therapy Following Single Autologous Hematopoietic Stem Cell Transplantation (AHSCT) for Multiple Myeloma: CALGB 100104. Blood. 2010;116(21):37-.  
148. Attal M, Lauwers Vc, Marit G, Caillot D, Facon T, Hulin C, et al. Maintenance Treatment with Lenalidomide After Transplantation for MYELOMA: Final Analysis of the IFM 2005-02. Blood. 2010;116(21):310-. 149. Marshall V, Martro E, Labo N, Ray A, Wang D, Mbisa G, et al. Kaposi sarcoma (KS)- associated herpesvirus microRNA sequence analysis and KS risk in a European AIDS-KS case control study. J Infect Dis. 2010;202(7):1126-35. 150. Engels EA, Biggar RJ, Marshall VA, Walters MA, Gamache CJ, Whitby D, et al.  
Detection and quantification of Kaposi's sarcoma-associated herpesvirus to predict AIDSassociated Kaposi's sarcoma. Aids. 2003;17(12):1847-51.  
151. Engels EA, Whitby D, Goebel PB, Stossel A, Waters D, Pintus A, et al. Identifying human herpesvirus 8 infection: performance characteristics of serologic assays. J Acquir Immune Defic Syndr. 2000;23(4):346-54. 152. Palmer S, Wiegand AP, Maldarelli F, Bazmi H, Mican JM, Polis M, et al. New real-time reverse transcriptase-initiated PCR assay with single-copy sensitivity for human immunodeficiency virus type 1 RNA in plasma. J Clin Microbiol. 2003;41(10):4531-6. 153. Viala-Danten M, Dubois D, Gilet H, Martin S, Peeters K, Cella D. Psychometric evaluation of the functional assessment of HIV Infection (FAHI) questionnaire and its usefulness in clinical trials. Qual Life Res. 2010;19(8):1215-27.  
154. de Sanjose S, Mbisa G, Perez-Alvarez S, Benavente Y, Sukvirach S, Hieu NT, et al.  
Geographic variation in the prevalence of Kaposi sarcoma-associated herpesvirus and risk factors for transmission. J Infect Dis. 2009;199(10):1449-56. 155. Engels EA, Atkinson JO, Graubard BI, McQuillan GM, Gamache C, Mbisa G, et al. Risk factors for human herpesvirus 8 infection among adults in the United States and evidence for sexual transmission. J Infect Dis. 2007;196(2):199-207. 156. Mbulaiteye SM, Atkinson JO, Whitby D, Wohl DA, Gallant JE, Royal S, et al. Risk factors for human herpesvirus 8 seropositivity in the AIDS Cancer Cohort Study. J Clin Virol. 2006;35(4):442-9. 157. Grulich AE, Cunningham P, Munier ML, Prestage G, Amin J, Ringland C, et al. Sexual behaviour and human herpesvirus 8 infection in homosexual men in Australia. Sex Health. 2005;2(1):13-8.
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16 appendices 16.1 appendix 1

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 lifethreatening human birth defects. If Pomalidomide is taken during pregnancy, it may cause birth defects or death to an unborn baby.
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criteria for females of childbearing

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 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.
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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.
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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.
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before starting study drug female

FCBP must have two negative pregnancy tests (sensitivity of at least 25 mIU/mL) prior to starting study drug. The first pregnancy test must be performed within 10-14 days prior to the start of study drug and the second pregnancy test must be performed within 24 hours prior to the start of study drug. The patient may not receive study drug until the study doctor has verified that the results of these pregnancy tests are negative. Male Patients: Must practice complete abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 28 days following study drug discontinuation, even if he has undergone a successful vasectomy.
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during study participation and for

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.
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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.
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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.  
16.2 APPENDIX 2: POMALIDOMIDE EDUCATION AND COUNSELING GUIDANCE D**OCUMENT**
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
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- 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.
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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) - 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.
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female not of childbearing potential

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: 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

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.
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what is the most important

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 lifethreatening 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.  
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.  
| 16.4                                                                                              | APPENDIX 4: PERFORMANCE STATUS SCALES                                                  |                                                                        |                                                 |
|---------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------|------------------------------------------------------------------------|-------------------------------------------------|
| ECOG Performance Status                                                                           | Karnofsky Performance Status                                                           |                                                                        |                                                 |
| Grade                                                                                             | Description                                                                            | Percent                                                                | Description                                     |
| 0                                                                                                 | Normal activity. Fully active, able to carry on  all pre-disease performance without   | disease.                                                               |                                                 |
| restriction.                                                                                      | 90                                                                                     | Able to carry on normal activity; minor signs  or symptoms of disease. |                                                 |
| 100                                                                                               | Normal, no complaints, no evidence of                                                  |                                                                        |                                                 |
| 1                                                                                                 | Symptoms, but ambulatory. Restricted in  physically strenuous activity, but ambulatory | symptoms of disease.                                                   |                                                 |
| and able to carry out work of a light or  sedentary nature (e.g., light housework, office  work). | 80                                                                                     | Normal activity with effort; some signs or                             |                                                 |
| 70                                                                                                | Cares for self, unable to carry on normal  activity or to do active work.              |                                                                        |                                                 |
| 2                                                                                                 | In bed <50% of the time. Ambulatory and  capable of all self-care, but unable to carry | care for most of his/her needs.                                        |                                                 |
| out any work activities. Up and about more  than 50% of waking hours.                             | 50                                                                                     | Requires considerable assistance and frequent  medical care.           |                                                 |
| 60                                                                                                | Requires occasional assistance, but is able to                                         |                                                                        |                                                 |
| 3                                                                                                 | In bed >50% of the time. Capable of only                                               | 40                                                                     | Disabled, requires special care and assistance. |
| limited self-care, confined to bed or chair  more than 50% of waking hours.                       | 30                                                                                     | Severely disabled, hospitalization indicated.  Death not imminent.     |                                                 |
| 4                                                                                                 | 100% bedridden. Completely disabled.  Cannot carry on any self-care. Totally           | imminent.                                                              |                                                 |
| confined to bed or chair.                                                                         | 10                                                                                     | Moribund, fatal processes progressing  rapidly.                        |                                                 |
| 20                                                                                                | Very sick, hospitalization indicated. Death not                                        |                                                                        |                                                 |
| 5                                                                                                 | Dead.                                                                                  | 0                                                                      | Dead.                                           |
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16.5 a ppendix 5 hamb

| 16.5 A PPENDIX 5: HAMB KS R ESPONSE F LOWSHEET       |                                            |                                           |          |            |
|------------------------------------------------------|--------------------------------------------|-------------------------------------------|----------|------------|
| HAMB KAPOSI SARCOMA MEASUREMENT AND RESPONSE SUMMARY |                                            |                                           |          |            |
| INITIALS                                             | DATE                                       | STUDY                                     | CYCLE    | PHOTOS     |
| BASELINE TIS                                         | T:                                         | l:                                        | s:       | REASON T1: |
| KEEP IN RESEARCH RECORD ONLY                         |                                            |                                           |          |            |
| LESION                                               | DESCRIPTION                                | FLAT OR NODULAR    DIMENSIONS             | PRODUCT  |            |
| ONE                                                  |                                            |                                           |          |            |
| two                                                  |                                            |                                           |          |            |
| THREE                                                |                                            |                                           |          |            |
| FOUR                                                 |                                            |                                           |          |            |
| FIVE                                                 | TOTAL PRODUCT                              |                                           |          |            |
| OVER 50,                                             | *FOR PATIENTS WITH UNDER 50 LESIONS, WRITE |                                           |          |            |
| TOTAL LESIONS                                        | UNDER 50*.                                 | 'TOTAL BODY' FOR AREA AND USE LEFT COLUMN |          |            |
| AREA                                                 | AREA                                       |                                           |          |            |
| NUMBER FLAT                                          | NUMBER FLAT                                |                                           |          |            |
| NUMBER NODULAR                                       | NUMBER NODULAR                             |                                           |          |            |
| TOTALS                                               | ALL                                        | NODULAR                                   | FLAT     |            |
| ORAL LESIONS                                         | PRESENT                                    | NONE                                      | NO EVAL. |            |
| DESCRIPTION IF PRESENT                               |                                            |                                           |          |            |
| VISCERAL LESIONS                                     | PRESENT                                    | NONE                                      | NO EVAL. |            |
| DESCRIPTION IF PRESENT                               |                                            |                                           |          |            |
| RESPONSETHRESHOLDS FROM:                             | RESPONSE FROM BASELINE                     |                                           |          |            |
| PARTIAL RESPONSE                                     | PROGRESSIVE DISEASE                        | RESPONSE BASED ON                         |          |            |
| TOTAL                                                | TOTAL                                      | RESPONSE FROM                             |          |            |
| NODULAR                                              | NODULAR                                    | RESPONSE BASED ON                         |          |            |
| PRODUCT                                              | PRODUCT                                    | RESPONSE CONFIRMED BY                     |          |            |
| RECORDER                                             | SIGNATURE                                  |                                           |          |            |  
hamb kaposi sarcoma measurement and response summary  
  
  
| LEFT   | RIGHT   |       |       |       |       |
|--------|---------|-------|-------|-------|-------|
| LEVEL  | DIST.   | DIAM. | LEVEL | DIST. | DIAM. |
| ANKLE  | 0cm     | ANKLE | 0cm   |       |       |
| KNEE   | KNEE    |       |       |       |       |
| THIGH  | THIGH   |       |       |       |       |
| PELVIS | PELVIS  |       |       |       |       |  
16.6 APPENDIX 6: FUNCTIONAL ASSESSMENT OF QUALITY OF LIFE (V.4) ASSESSMENT TOOL
(ENGLISH V**ERSION**)
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  
| 1. PHYSICAL WELL-BEING         | Not at                                           | A little   | Some     | Quite a   | Very   |    |
|--------------------------------|--------------------------------------------------|------------|-----|-----------|--------|----|
| all                            | bit                                              | what       | bit | 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 | 0          | 1   | 2         | 3      | 4  |
| meeting the needs of my family |                                                  |            |     |           |        |    |
| 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  |  
| 2. EMOTIONAL WELL-BEING/LIVING WITH HIV Not at  all HI5 I am concerned about what the future holds for  me   |
|--------------------------------------------------------------------------------------------------------------|  
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 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  
| A little  bit   |
|-----------------|  
| Some      | Quite a   | Very   |
|------|-----------|--------|
| what | bit       | much   |  
0 1 2 3 4  
| 3. LIVING WITH KS   | Not at                                        | A little   | Some     | Quite a   | Very   |    |
|---------------------|-----------------------------------------------|------------|-----|-----------|--------|----|
| all                 | bit                                           | what       | bit | much      |        |    |
| HKS1                | Pain has interfered with my normal work or    | 0          | 1   | 2         | 3      | 4  |
| activities          |                                               |            |     |           |        |    |
| 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  |  
| 4. FUNCTIONAL AND GLOBAL WELL-BEING Not at   | A little                                           | Some      | Quite a   | Very   |    |    |
|----------------------------------------------|----------------------------------------------------|------|-----------|--------|----|----|
| all                                          | bit                                                | what | bit       | 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        | 0    | 1         | 2      | 3  | 4  |
| illness                                      |                                                    |      |           |        |    |    |
| 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  |  
| 5. SOCIAL WELL-BEING     | Not at                                                                                                                                                                        | A little   | Some     | Quite a   | Very   |    |
|--------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------|-----|-----------|--------|----|
| all                      | bit                                                                                                                                                                           | what       | bit | 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                                                                                                                                   | 0          | 1   | 2         | 3      | 4  |
| about my illness         |                                                                                                                                                                               |            |     |           |        |    |
| GS6                      | I feel close to my partner (or the person who is                                                                                                                              | 0          | 1   | 2         | 3      | 4  |
| my main support)         |                                                                                                                                                                               |            |     |           |        |    |
| 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                                                                                                                                                                        | A little   | Some     | Quite a   | Very   |    |
| all                      | bit                                                                                                                                                                           | what       | bit | 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  |
untitled h1
5. social well-being

16.7 APPENDIX 7: FUNCTIONAL ASSESSMENT OF QUALITY OF LIFE (V.4) ASSESSMENT TOOL
(SPANISH V**ERSION**)
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   | Muchísimo   |    |    |
|------------------------------------------|--------------------------------------------------|--------|---------|---|----|----|
| 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 | 0      | 1       | 2 | 3  | 4  |
| atender a las necesidades de mi familia  |                                                  |        |         |   |    |    |
| GP4                                      | Tengo dolor                                      | 0      | 1       | 2 | 3  | 4  |
| GP5                                      | Me molestan los efectos secundarios del          | 0      | 1       | 2 | 3  | 4  |
| tratamiento                              |                                                  |        |         |   |    |    |
| 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  |
| 96                                       |                                                  |        |         |   |    |    |  
| 2. ESTADO EMOCIONAL/VIVIENDO CON VIH Nada   | Un                                        | Algo   | Mucho   | Much   |    |    |
|---------------------------------------------|-------------------------------------------|--------|---------|---|----|----|
| poco                                        | 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    | 0      | 1       | 2 | 3  | 4  |
| personal                                    |                                           |        |         |   |    |    |
| HI2                                         | Me cuesta trabajo hablar de mi enfermedad | 0      | 1       | 2 | 3  | 4  |
| con otras personas                          |                                           |        |         |   |    |    |
| HI4                                         | Temo contagiar mi enfermedad a otras      | 0      | 1       | 2 | 3  | 4  |
| personas                                    |                                           |        |         |   |    |    |
| HI5                                         | Estoy preocupado(a) por lo que me pueda   | 0      | 1       | 2 | 3  | 4  |
| pasar                                       |                                           |        |         |   |    |    |
| B7                                          | Me preocupan las consecuencias del estrés | 0      | 1       | 2 | 3  | 4  |
| (la tensión) en mi enfermedad               |                                           |        |         |   |    |    |
| HI10                                        | Mi enfermedad me da vergüenza             | 0      | 1       | 2 | 3  | 4  |
untitled h1
3. viviendo con ks

| 3. VIVIENDO CON KS                       | Nada                                           | Un   | Algo   | Mucho   | Much   |    |
|------------------------------------------|------------------------------------------------|------|--------|---------|---|----|
| poco                                     | ísimo                                          |      |        |         |   |    |
| HKS1                                     | El dolor interfiere con mi trabajo normal y    | 0    | 1      | 2       | 3 | 4  |
| mis actividades                          |                                                |      |        |         |   |    |
| HKS2                                     | Estoy satisfecho con mi apariencia fisica      | 0    | 1      | 2       | 3 | 4  |
| HKS3                                     | He tenido inchazon en la cara, brazos o        | 0    | 1      | 2       | 3 | 4  |
| piernas                                  |                                                |      |        |         |   |    |
| 4. ESTADO GENERAL DE FUNCIONAMIENTO Nada | Un                                             | Algo | Mucho  | Much         |   |    |
| poco                                     | ísimo                                          |      |        |         |   |    |
| GF1                                      | Puedo trabajar (incluya trabajo en el hogar)   | 0    | 1      | 2       | 3 | 4  |
| GF2                                      | Me satisface mi trabajo (incluya trabajo en el | 0    | 1      | 2       | 3 | 4  |
| hogar)                                   |                                                |      |        |         |   |    |
| 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     | 0    | 1      | 2       | 3 | 4  |
| actual                                   |                                                |      |        |         |   |    |
| GE2                                      | Estoy satisfecho(a) de cómo estoy              | 0    | 1      | 2       | 3 | 4  |
| enfrentando mi enfermedad                | 98                                             |      |        |         |   |    |  
| Version Date: 11/19/2021 GE3 Estoy perdiendo las esperanzas en la lucha   | 0                                           | 1   | 2    | 3     | 4   |    |
|---------------------------------------------------------------------------|---------------------------------------------|-----|------|-------|-----|----|
| contra mi enfermedad                                                      |                                             |     |      |       |     |    |
| 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  | Algo | Mucho | Much     |    |
| poco                                                                      | ísimo                                       |     |      |       |     |    |
| GS1                                                                       | Me siento cercano(a) a mis amistades        | 0   | 1    | 2     | 3   | 4  |
| GS2                                                                       | Recibo apoyo emocional por parte de mi      | 0   | 1    | 2     | 3   | 4  |
| familia                                                                   |                                             |     |      |       |     |    |
| 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 | 0   | 1    | 2     | 3   | 4  |
| comunica mi familia acerca de mi  enfermedad                              |                                             |     |      |       |     |    |
| GS6                                                                       | Me siento cercano(a) a mi pareja (o a la    | 0   | 1    | 2     | 3   | 4  |
| persona que es mi principal fuente de apoyo)                              |                                             |     |      |       |     |    |
| HI3                                                                       | Tengo quien me ayude, si lo necesito        | 0   | 1    | 2     | 3   | 4  |  
| 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 | Algo | Mucho | Much    |    |
| poco                | 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  |  
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:____________________________________   |
|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|  
16.9 APPENDIX 9: CALCULATION OF CREATININE C**LEARANCE** 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)