Ipilimumab and Isolated Chemotherapeutic Limb Perfusion with Melphalan and Dactinomycin in Treating Patients with Stage IIIB-IV Melanoma of the Extremity That Cannot Be Removed by Surgery

Inclusion Criteria

• Willing and able to give informed consent
• Histologic diagnosis of melanoma with in transit metastasis stage IIIB, IIIC, or IV
• White blood cell count (WBC) >= 2,000/uL
• Absolute neutrophil count (ANC) >= 1,000/uL
• Platelets >= 50 x 10^3/uL
• Hemoglobin >= 8 g/dL
• Creatinine =< 3.0 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN
• Bilirubin =< 3.0 x ULN (except patients with Gilbert's syndrome, who must have a total bilirubin less than 3.0 mg/dL)
• No active or chronic infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C
• Karnofsky performance status >= 60
• Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 8 weeks after the last dose of investigational product, in such a manner that the risk of pregnancy is minimized; WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not post-menopausal; post-menopause is defined as: * Amenorrhea >= 12 consecutive months without another cause, or * For women with irregular menstrual periods and taking hormone replacement therapy (HRT), a documented serum follicle stimulating hormone (FSH) level >= 35 mIU/mL
• Women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing abstinence or where their partner is sterile (e.g., vasectomy) should be considered to be of childbearing potential
• WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 72 hours before the start of ipilimumab

Exclusion Criteria

• Any other malignancy that requires active treatment
• Autoimmune disease: patients with a history of inflammatory bowel disease are excluded from this study, as are patients with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [e.g., Wegener's granulomatosis]); motor neuropathy considered of autoimmune origin (e.g. Guillain-Barre syndrome)
• Any underlying medical or psychiatric condition, which in the opinion of the investigator will make the administration of ipilimumab hazardous or obscure the interpretation of adverse events (AEs), such as a condition associated with frequent diarrhea
• Patients with underlying heart conditions who are deemed ineligible for surgery by cardiology consult
• Any history of prior treatment with ipilimumab or prior CD137 agonist or cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) inhibitor or agonist
• Concomitant therapy with any of the following: aldesleukin (IL-2), interferon, or other non-study immunotherapy regimens; immunosuppressive agents; other investigation therapies; or chronic use of systemic corticosteroids
• Women of childbearing potential (WOCBP) who: * Are unwilling or unable to use an acceptable method of contraception to avoid pregnancy for their entire study period and for at least 8 weeks after cessation of study drug, or * Have a positive pregnancy test at baseline, or * Are pregnant or breastfeeding
• Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness
• Persons of reproductive potential must agree to use an adequate method of contraception throughout treatment and for at least 8 weeks after ipilimumab is stopped
• Sexually active WOCBP must use an effective method of birth control during the course of study, in a manner such that risk of failure is minimized; before study enrollment, WOCBP must be advised of the importance of avoiding pregnancy during study participation and the potential risk factors for an unintentional pregnancy; all WOCBP MUST have a negative pregnancy test before first receiving ipilimumab; if the pregnancy test is positive, the patient must not receive ipilimumab and must not be enrolled in the study
• Patients in this study may not use vaccines for the treatment of cancer or prevention of disease unless indicated as a component of the protocol regimen (including those for common medical conditions) for up to one month pre and post dosing with ipilimumab
• Patients may not use any of the following therapies during the study: * Any non-study anti-cancer agent (investigational or non-investigational) * Any other investigational agents * Any other (non-CA184024 related) CTLA-4 inhibitors or agonists * CD137 agonists * Immunosuppressive agents * Chronic systemic corticosteroids * Any non-oncology vaccine therapies used for the prevention of infectious diseases (for up to 30 days prior to or after any dose of study drug)