Pomalidomide for Kaposi Sarcoma in People With or Without HIV

* INCLUSION CRITERIA: * Age greater than or equal to 18 Years. * Any human immunodeficiency virus (HIV) status. * Kaposi sarcoma pathologically confirmed by Department of Pathology, Clinical Center, National Institutes of Health. * At least five measurable Kaposi sarcoma (KS) lesions with no previous local radiation, surgical or intralesional cytotoxic therapy that would prevent response assessment for that lesion. * Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to 2 * Life expectancy greater than or equal to 6 months * For patients with HIV-associated KS: * Must be receiving, and adherent to, a highly active antiretroviral therapy (HAART) regimen consistent with current clinical guidelines. * Must have been receiving HAART for at least one month. * Must have achieved an HIV viral load (VL) \<10,000 copies/mL. * The following hematological parameters: * Hemoglobin greater than or equal to 10 g/dL * Platelets greater than or equal to 75,000 cells/mm(3) * Absolute neutrophil count (ANC) greater than or equal to 1000 cells/mm(3) * The following biochemical parameters: * Estimated or measured creatinine clearance greater than or equal to 45mL/minute * Serum alanine aminotransferase (ALT) less than or equal to 2.5 times upper limit of normal * Serum aspartate aminotransferase (AST) less than or equal to 2.5 times upper limit of normal * Bilirubin less than or equal to 1.5 times upper limit of normal unless the patient is receiving protease inhibitor therapy (e.g., indinavir, ritonavir, nelfinavir, or atazanavir) known to be associated with increased bilirubin, in which case total bilirubin less than or equal to 7.5 mg/dL with direct fraction less than or equal to 0.7 mg/dL. * Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 14 days prior to and again within 24 hours before starting pomalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking pomalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a vasectomy. All subjects must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure. Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods, and also * All study participants must agree to be registered into the mandatory POMALYST Risk Evaluation and Mitigation Strategy (REMS) program and be willing and able to comply with the requirements of the POMALYST REMS program. * Females of reproductive potential must be willing to adhere to the scheduled pregnancy testing as required in the POMALYST REMS program. * Able to take aspirin 81mg daily or if intolerant of aspirin, able to take a substitute thromboprophylaxis such as low molecular weight heparin at a thromboprophylactic dose (such as enoxaparin 0.5mg/kg once daily). * Willing and able to give informed consent. * For subjects with HIV-associated entered after a tolerable dose has been determined, KS lesions must be either: * Increasing despite HAART and HIV suppression below the limit of detection (48 copies/mL) in the two months prior to screening or * Stable despite HAART for at least three months. Stable disease must be symptomatic (examples of symptomatic disease include disease associated with pain, edema, psychological distress and/or social withdrawal). This is to gain preliminary information about pomalidomide activity without confounding due to HAART initiation. EXCLUSION CRITERIA: * Symptomatic pulmonary KS. * Symptomatic visceral KS (except for non-ulcerating disease restricted to the oral cavity). * Specific KS therapy, including cytotoxic chemotherapy but not including HAART, within the past 4 weeks (6 weeks if the therapy was bevacizumab). * Use of other anticancer treatments or agents within the past 4 weeks (6 weeks if the therapy was a monoclonal antibody). * History of malignant tumors other than KS, unless: * In complete remission for greater than or equal to 1 year from the time response was first documented or * Completely resected basal cell carcinoma or * In situ squamous cell carcinoma of the cervix or anus. * History of infection meeting any of the following criteria: * Any infection that would be scored as grade 4 by Common Terminology Criteria for Adverse Events (CTCAE) that occurred within six weeks of study screening. * Any infection that would be scored as grade 3 by CTCAE that occurred within two weeks of study screening. * History of fungal and mycobacterial infections, unless at least six weeks has passed since the completion of induction antimicrobial therapy. Patients may be receiving consolidation therapy for infections of these types. * Any abnormality that would be scored as a greater than or equal to grade 3 toxicity by CTCAE, except: * Obesity is not considered an abnormality for the purposes of eligibility assessment unless in the opinion of the Principal Investigator or Lead Associate Investigator its clinical consequences in a particular subject places the subject at unacceptable risk if they were to participate in the study or confounds the ability to interpret data from the study. * Lymphopenia * Asymptomatic hyperuricemia, hypophosphatemia, or creatine kinase (CK) Elevations * Direct manifestations of KS * Direct manifestations of HIV infection, except for neurologic or cardiac manifestations * Direct manifestations of HIV therapy, except for neurologic or cardiac manifestations. * History of venous or arterial thromboembolism, unless: * Line-related thrombosis without embolus occurring greater than or equal to 1 year prior to screening. Complications resulting from atherosclerotic coronary artery disease, peripheral vascular disease, or cerebrovascular disease (including infarction) are not considered exclusion criteria unless in the opinion of the Principal Investigator or Lead Associate Investigator their clinical consequences in a particular subject places the subject at unacceptable risk if they were to participate in the study or confounds the ability to interpret data from the study * Known drug-related, inherited, or acquired procoagulant disorder including prothrombin gene mutation 20210, antithrombin III deficiency, protein C deficiency, protein S deficiency and antiphospholipid syndrome but not including heterozygosity for the Factor V Leiden mutation or the presence of a lupus anticoagulant in the absence of other criteria for the antiphospholipid syndrome. * Pregnancy. * Breast feeding (if lactating, must agree not to breast feed while taking pomalidomide). * Prior therapy with pomalidomide. * Known hypersensitivity to thalidomide, lenalidomide or pomalidomide. including prior development of erythema nodosum if characterized by a desquamating rash while taking thalidomide, lenalidomide or pomalidomide. * Any condition, including the presence of laboratory abnormalities, which in the opinion of the Principal Investigator or Lead Associate Investigator places the subject at unacceptable risk if they were to participate in the study or confounds the ability to interpret data from the study.