Ipilimumab or High-Dose Interferon Alfa-2b in Treating Patients With High-Risk Stage III or Stage IV Melanoma That Has Been Removed by Surgery

DISEASE CHARACTERISTICS:

• Diagnosis of melanoma of a cutaneous origin or unknown primary

  • No ocular melanoma or melanoma of mucosal origin

• Stage IIIB, IIIC, or IV (M1a or M1b) disease (including recurrent disease)

  • Patients with stage IV melanoma must have normal LDH and distant skin, subcutaneous, lymph node, or lung metastases
  • No other visceral metastases allowed
• Patients with unknown primary melanoma (Tx) who present with cutaneous, subcutaneous, nodal, and/or lung metastases that are completely surgically resected with free margins are allowed

• Disease that has been completely resected with negative margins on resected specimens within the past 12 weeks

  • Disease-free status documented by a complete physical examination and imaging studies within 4 weeks prior to randomization

    • Imaging studies must include a total body PET-CT scan (with or without brain) and brain MRI or CT (if MRI is contraindicated) (if PET-CT cannot be done, CT scan of neck, chest, abdomen, and pelvis should be done)
  • Patients rendered free of disease by non-surgical means not allowed

• Patients with clinically positive lymph nodes for melanoma involvement or those with positive lymph nodes identified through lymphoscintigraphic and/or dye lymphographic techniques in the groin, axilla, or neck should have additional lymphadenectomy in those sites

  • The complete lymph node dissection procedure would be considered as the last surgery in counting the 84 days unless a subsequent surgical procedure(s) was clinically required to ensure the disease-free status

• Patients with disease recurrence after adequate surgical excision of the original primary cutaneous/unknown primary melanoma are allowed even if they don't fit the strict staging criteria, but only as follows:

  • Recurrence in a regional lymph node basin after a prior complete lymph node dissection

    • Relapsed disease must be completely surgically resected with free margins
  • Recurrence in the form of in-transit or satellite metastases or distant skin/subcutaneous, nodal, or lung metastases that are completely surgically resected with free margins

  • Recurrence in a regional lymph node basin

    • Relapsed disease must be completely surgically resected with free margins

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1
• WBC ≥ 3,000/μL
• ANC ≥ 1,500/μL
• Platelet count ≥ 100,000/μL
• Hemoglobin ≥ 10 g/dL
• Serum creatinine ≤ 1.8 mg/dL
• AST and ALT ≤ 2.5 times upper limit of normal (ULN)
• Serum bilirubin < 2 times ULN (< 3 mg/dL in case of Gilbert syndrome)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use adequate method of contraception throughout the study and for 26 weeks after the last dose of high-dose recombinant interferon alfa-2b (HDI)
• No active infection requiring concurrent treatment with parenteral antibiotics

• None of the following:

  • Other significant medical, surgical, or psychiatric conditions
  • Requirement for any medication or treatment that, in the opinion of the investigator, may interfere with compliance, make the administration of high-dose ipilimumab, low-dose ipilimumab, or HDI hazardous, or obscure the interpretation of adverse events, such as a condition associated with frequent diarrhea

• No documented history of inflammatory bowel disease, including ulcerative colitis and Crohn disease, or diverticulitis

  • History of diverticulosis allowed

• No autoimmune disorders or conditions of immunosuppression that require current ongoing treatment with systemic corticosteroids (or other systemic immunosuppressants), including oral steroids or continuous use of topical steroid creams or ointments or ophthalmologic steroids

  • History of occasional (but not continuous) use of steroid inhalers allowed

• None of the following:

  • History of symptomatic autoimmune disease

    • Rheumatoid arthritis
    • Systemic progressive sclerosis (scleroderma)
    • Systemic lupus erythematosus
    • Sjögren syndrome
    • Autoimmune vasculitis (e.g., Wegener granulomatosis)
  • Motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre syndrome and myasthenia gravis)
  • Other CNS autoimmune disease (e.g., poliomyelitis, multiple sclerosis)
  • Autoimmune hypothyroid disease or type 1 diabetes allowed provided replacement therapy is administered
• Not incarcerated or compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness
• No other current malignancies except any prior in situ cancer, lobular carcinoma of the breast in situ, cervical cancer in situ, atypical melanocytic hyperplasia or melanoma in situ, multiple primary melanomas, basal or squamous skin cancer, or other malignancies for which the patient has been disease free for > 5 years

• No active or chronic infection with HIV, hepatitis B virus (HBV), or hepatitis C virus (HCV)

  • Patients must have negative serology/testing for HIV, HBV, and HCV within the past 4 weeks

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior adjuvant treatment (chemotherapy, biotherapy, or limb perfusion) after resection
• At least 21 days since prior radiotherapy, including after surgical resection
• No prior or concurrent anti-CTLA4 monoclonal antibodies, CTLA-4 inhibitor or agonist, CD137 agonist, or prior interferon-α
• At least 4 weeks since prior aldesleukin (IL-2), anti-tumor vaccine, or chemotherapy given before randomization
• No infectious disease vaccination (e.g., standard influenza, H1N1 influenza, pneumococcal, meningococcal, or tetanus toxoid) within the past 4 weeks

• No concurrent systemic corticosteroids (or other systemic immunosuppressants), including oral steroids (i.e., prednisone, dexamethasone), continuous use of topical steroid creams or ointments, or ophthalmologic steroids

  • Occasional but not continuous use of steroid inhalers allowed
  • Systemic corticosteroids (or other systemic immunosuppressants), including oral steroids (i.e., prednisone, dexamethasone), continuous use of topical steroid creams or ointments, or ophthalmologic steroids within the past 2 weeks allowed provided, in judgment of the treating physician investigator, that the patient is not likely to require resumption of treatment with these classes of drugs during the study
  • Replacement doses of steroids for patients with adrenal insufficiency allowed
• No concurrent chemotherapy or radiotherapy
• No other concurrent anticancer or investigational agent