IPI-Biotherapy for Patients Previously Treated With Cytotoxic Drugs With Metastatic Melanoma

Study Groups: If you are found to be eligible to take part in this study, you will be assigned to a study group based on when you join this study. Up to 5 groups of 3-6 participants will be enrolled in the Phase I portion of the study, and up to 64 participants will be enrolled in Phase II. If you are enrolled in the Phase I portion, the dose of ipilimumab you receive will depend on when you joined this study. The first group of participants will receive the lowest dose level of ipilimumab. Each new group will receive a higher dose of ipilimumab than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of ipilimumab is found. If you are enrolled in the Phase II portion, you will receive ipilimumab at the highest dose that was tolerated in the Phase I portion. All participants will receive the same dose level of interferon alfa-2b and aldesleukin. Study Drug Administration: The study drugs will be given in 3 stages: induction, consolidation, and maintenance. Induction: Induction will last 12 weeks. You will receive the study drugs in up to four 3-week cycles: * You will receive ipilimumab by vein over 90 minutes on Day 1 of each cycle. * You will receive aldesleukin in the hospital by vein as a continuous infusion on Days 2-5 of each cycle. * You will receive interferon alfa-2b as an injection under your skin on Days 1-5 of each cycle. Consolidation: Consolidation will last 12 weeks. You will receive the study drugs in up to four 3-week cycles: * You will receive ipilimumab by vein over 90 minutes on Day 1 of Cycle 1. * You will receive aldesleukin in the hospital by vein as a continuous infusion on Days 2-5 of each cycle. * You will receive interferon alfa-2b as an injection under your skin on Days 1-5 of each cycle. Maintenance: Maintenance will last about 1½ years. You will receive ipilimumab by vein over 90 minutes on Day 1 of up to six 12-week cycles. Other Drugs: You will be given other drugs to help lower the risk of side effects. The study staff will tell you about these drugs, how they will be given, and the possible risks. Study Visits: Before each cycle (+/- 3 days): * You will be asked about any drugs you may be taking and any side effects you may have had. * Your performance status will be recorded. * Your vital signs will be measured. * Blood (about 1 teaspoon) will be drawn for routine tests and tests of your liver and kidney function. * If you are able to become pregnant, you will have a blood (about 1 teaspoon) or urine pregnancy test. Every week, blood (about 1 teaspoon) will be drawn for routine tests. At the end of each cycle, you will have a physical exam, including measurement of your weight. Any tumor that can be felt with the hands will be measured during the physical exam to see if it has changed size. Every 2 cycles (+/- 7 days), you will have a chest x-ray and CT or MRI scans to check the status of the disease. Anytime the doctor thinks it is needed, photos of the skin lesions will be taken. Your private areas will be covered (as much as possible), and a picture of your face will not be taken unless there are lesions on your face. Length of Study: You may continue taking the study drugs for up to 2 years. You will no longer be able to take the study drugs if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions. Your participation on the study will be over once you have completed the end-of-treatment visit and follow-up. End-of-Treatment Visit: Within 14 days after you stop the study therapy, the following tests and procedures will be performed: * You will have a physical exam, including measurement of your vital signs and weight. * Your performance status will be recorded. * You will be asked about any drugs you may be taking and any side effects you may have had. * Blood (about 2 tablespoons) will be drawn for routine tests. * If the doctor thinks it is needed, you will have a CT or MRI scan. Every 2 months for up to 3 years, you will also be contacted by phone or during a clinic visit to see how you are doing. This is an investigational study. Ipilimumab, interferon alfa-2b, and aldesleukin are FDA approved and commercially available to treat melanoma. Giving these drugs in combination is investigational. Up to 88 patients will take part in this study. All will be enrolled at MD Anderson.