Phase II trial to study the effectiveness of combining interleukin-12 and interferon alfa in treating patients who have metastatic malignant melanoma. Interleukin-12 may kill tumor cells by stopping blood flow to the tumor and by stimulating a person's white blood cells to kill cancer cells. Interferon alfa may interfere with the growth of the cancer cells. Combining interleukin-12 and interferon alfa may kill more tumor cells.

PRIMARY OBJECTIVES:

I. To estimate the clinical response rates in patients with metastatic malignant melanoma treated with rhIL-12 and interferon alfa-2b.

II. To estimate the progression-free survival in patients with metastatic malignant melanoma treated with rhIL-12 and interferon alfa-2b.

SECONDARY OBJECTIVES:

I. To measure serum levels of interferon-gamma. II. To measure levels of JAK-STAT signaling intermediates in patient PBMCs and tumor samples.

III. To analyze interferon-alpha-induced STAT signaling in patient PBMCs. IV. To determine the expression of IFN-regulated genes in patient PBMCs and tumor tissues.

V. To determine the pattern of gene expression induced by treatment with IL-12 and interferon-alpha using DNA microarray techniques in patient PBMCs.

OUTLINE: This is a multicenter study.

Patients receive interleukin-12 IV over 5-15 seconds on day 1 and interferon alfa subcutaneously on days 2-6. Treatment repeats every 2 weeks in the absence of unacceptable toxicity. Patients are reassessed after 6 courses. Patients with a complete response receive 2 additional courses. Patients with a partial response or stable disease continue treatment in the absence of disease progression.

Patients are followed every 3 months for 1 year and then every 6 months for 1 year.

Inclusion Criteria:

• Histological or cytological diagnosis of cutaneous melanoma and clinical evidence of distant, metastatic, non-resectable regional lymphatic, or extensive in transit recurrent disease

• Patients must have measurable disease; measurable disease is defined as the presence of at least one measurable lesion; if the measurable disease is restricted to a solitary lesion, its neoplastic nature should be confirmed by cytology/histology; measurable lesions are defined as lesions that can be accurately measured in at least one dimension with the longest diameter >= 20 mm using conventional techniques or >= 10 mm with spiral CT scan

  • Lesions that are considered intrinsically non-measurable include the following:

    • Bone lesions;
    • Leptomeningeal disease;
    • Ascites;
    • Pleural/pericardial effusion;
    • Inflammatory breast disease;
    • Lymphangitis cutis/pulmonis;
    • Abdominal masses that are not confirmed and followed by imaging techniques;
    • Lytic lesions;
    • Lesions that are situated in a previously irradiated area

• No history of peripheral neuropathy, brain metastases or other central nervous system disease

• No history of/active autoimmune disease, hemolytic anemia or concurrent requirement for corticosteroids, including topical or inhaled

• No hepatitis BSAg, known HIV disease or other major active illness; patients with risk factors for HIV should be tested; patients with these illnesses are more likely to experience significant side effects from the study treatment

• No history of severe peptic ulcer disease or gastrointestinal bleeding unless there is objective evidence that the condition is inactive or resolved

• No uncontrolled or severe cardiovascular disease, diabetes, pulmonary disease, or infection

• No chemotherapy, radiotherapy, or anti-hormonal therapy within three weeks prior to the initiation of therapy on this study

• No prior therapy with IL-12

• No prior therapy with IFN-alpha for metastatic disease (e.g., biochemotherapy); prior adjuvant therapy with IFN-a is acceptable as long as the patient remained disease-free for 12 months or longer following the last IFN-a treatment

• No prior cytokine therapy for metastatic disease (e.g., high-dose IL-2)

• No more than one prior chemotherapy regimen

• CTC (ECOG) performance status 0-1

• Non-pregnant, non-nursing; treatment under this protocol would expose an unborn child to significant risks; women and men of reproductive potential should agree to use an effective means of birth control; women of child-bearing age will undergo pregnancy testing

• ANC >= 1500/μL

• Platelets >= 100,000/μL

• Hemoglobin > 9 g/dL (may be post transfusion or may receive EPO)

• U-HCG or Serum HCG Negative (if patient of child-bearing potential)