Interleukin-12 and Interferon Alfa in Treating Patients With Metastatic Malignant Melanoma

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)