High-dose IL-2 treatment for metastatic melanoma has been approved by the FDA in 1998. Studies of GM-CSF plus IL-2 have not addressed the approved dose and schedule. This protocol will study the combination of HD-IL2 and GM-CSF given the potential synergistic interactions discussed above.

The primary objectives of this phase II multicenter trial are to:

Determine the 1 and 2-year survival of patients treated according to protocol. Assess the safety and toxicity of this regimen in this patient population.

The secondary objectives are to:

Determine the freedom from progression (FFP). Measure the response rate (RR). Obtain immunological data from the use of this regimen in vivo (as separate project: Moffitt?).

The proposed study is a multicenter phase II trial of HD-IL-2 in combination with GM-CSF. GM-CSF will be started 7 days before day 1 of HD-IL-2 and will be continued for 4 weeks to day 28, encompassing two cycles of HD-IL2. The first 9 patients will be closely monitored for unexpected toxicity.

Inclusion Criteria:

• Histologically confirmed diagnosis of melanoma with measurable disease

• Patients with stage IV or unresectable advanced melanoma

• Age at least 16 years.

• ECOG performance status of 0-1

• Life expectancy > 3 months

• Adequate major organ function to tolerate therapy, as defined by:

  • Total bilirubin 2.0 mg/dL.
  • Creatinine 1.8 mg/dL.
  • WBC 3,000/mm3.
  • Platelet count 100,000/mm3.

• Patients 50 years of age with one or more cardiac risk factors must demonstrate normal exercise stress test, stress thallium test, or comparable cardiac ischemia evaluation

• Left ventricular ejection fraction > 40%

• Women of childbearing age must agree to use barrier method birth control and demonstrate a negative pregnancy test prior to initiation of protocol therapy. Periodic negative urine pregnancy tests will also be required.

• Patients must give written informed consent

Exclusion Criteria:

• No prior HD- IL-2 for stage IV/unresectable advanced disease. Prior low dose IL-2 is allowed.
• No more than 2 prior chemotherapy regimens are allowed.
• No active CNS metastases. Treated CNS metastases without recurrence or progression for > 8 weeks are allowed.
• No concurrent use of systemic corticosteroids
• Pregnant and/or lactating are excluded
• No concurrent antineoplastic treatments, including chemotherapy, biologic response modifiers, radiation, vaccines, or other experimental therapies.
• No treatment for melanoma within the previous 4 weeks.