A Phase II Study to Evaluate Safety and Efficacy of Combined Treatment With Ipilimumab and Intratumoral Interleukin-2

Inclusion Criteria: * Willing and able to give written informed consent; * Histological diagnosis of malignant melanoma; * Stage IV melanoma; * At least one injectable lesions \> 5 mm (longest diameter) or at least 5 injectable lesions \< 5 mm. * Measurable disease. Note: lesions, which are designated for direct IL -2 injections, must not be considered in the evaluation of measurability; * Men and women, at least 18 years of age; * Patient must have demonstrated 1 of the following in response to at least 1 cycle of 1 or more systemic regimens: 1. relapse following an objective response (PR/CR); 2. failed to demonstrate an objective response (PR/CR); or 3. inability to tolerate treatment due to unacceptable toxicity * At least 4 weeks since treatment (chemotherapy, biochemotherapy, surgery, radiation, immunotherapy, etc.) for melanoma and recovered from any clinically significant toxicity experienced during treatment; * Life expectancy ≥3 months; * ECOG performance status of 0 or 1; * Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours before the start of ipilimumab; * No known active or chronic infection with HIV, Hepatitis B, or Hepatitis C * Required values for initial laboratory tests: * Men of fathering potential must be using an adequate method of contraception to avoid conception throughout the study and for up to 26 weeks after the last dose of investigational product in such a manner that the risk of pregnancy is minimized Exclusion Criteria: * Any other prior malignancy from which the patient has been disease-free for less than 5 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix; * Ocular melanoma; mucosal melanoma * Either untreated or symptomatic central nervous system (CNS) metastases (patients with brain metastases who are identified at screening may be rescreened after the lesion(s) have been appropriately treated); * Autoimmune disease: Patients with a history of inflammatory bowel disease are excluded from this study, as are patients with a history of symptomatic autoimmune 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). Patients with vitiligo may be included. * 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 AEs, such as a condition associated with frequent diarrhea. * Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to 1 month before or after any dose of ipilimumab). * A history of prior systemic treatment with ipilimumab, CD137 agonist, CTLA 4 inhibitor, CTLA-4 agonist or IL-2 in stage IV melanoma. * Concomitant or less than 4 weeks off therapy with any of the following: interferon; other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other investigation therapies; chronic use of systemic corticosteroids. * Women of childbearing potential (WOCBP), defined in Section 5.3, who: 1. are unwilling or unable to use an acceptable method of contraception to avoid pregnancy for their entire study period and for at least 26 weeks after cessation of study drug, or 2. have a positive pregnancy test at baseline, or 3. are pregnant or breastfeeding. * Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious) illness.