Vaccine Therapy With or Without Interleukin-2 in Treating Patients With Metastatic Melanoma

OBJECTIVES:

• Determine whether reinfused activated cells alone or in conjunction with high or subcutaneous dose interleukin-2 may result in clinical tumor regression in patients with metastatic melanoma who had previously failed therapy on protocols involving immunization against the gp100 molecule.
• Determine the survival of infused cells with antitumor activity in these patients.

OUTLINE: This is a salvage regimen.

Patients undergo leukopheresis to obtain peripheral blood mononuclear cells or tumor biopsy to obtain tumor infiltrating lymphocytes (TIL). Cells are incubated in the presence of gp209-2M peptide and then harvested and cloned. Patients receive 30-minute IV infusions of these in vitro sensitized cells. Treatment repeats every 2 weeks for 2 courses. An additional cohort of 8 patients receives gp209-2M peptide in Montanide ISA-51 subcutaneously in 2 different sites followed 2 days later by the adoptive transfer of cloned lymphocytes. At 4 to 6 weeks after the treatment courses, patients with stable or regressing disease may be retreated.

Patients with disease progression after 2 courses may receive 2 additional courses of cell infusion followed by interleukin-2 (IL-2) on one of two schedules. One cohort of patients receives IL-2 by intravenous bolus over 15 minutes every 8 hours beginning on the day after cell infusion and continuing for up to 5 days of each treatment course. Another cohort receives IL-2 by daily subcutaneous injections on days 1-12 of each course of therapy. If after 12-16 patients have been treated with cloned cells alone initially and responses are inadequate, subsequent patients entered into this study are randomized to receive the cell infusion followed by IL-2 on one of the two described schedules.

Patients are followed at 4-6 weeks.

PROJECTED ACCRUAL: A total of 91 patients will be accrued for this study over 2 years.

DISEASE CHARACTERISTICS:

• Histologically proven metastatic melanoma that has failed therapy on protocols involving immunization against the gp100 molecule
• Measurable or evaluable metastatic disease
• Must be HLA-A201 positive by standard HLA typing

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• Greater than 3 months

Hematopoietic:

• Absolute neutrophil count greater than 1,000/mm^3
• Platelet count greater than 100,000/mm^3
• Hemoglobin greater than 8.0 g/dL

Hepatic:

• Bilirubin no greater than 2.0 mg/dL
• ALT/AST less than 4 times upper limit of normal

Renal:

• Creatinine no greater than 1.6 mg/dL

Cardiovascular:

• For patients randomized to receive interleukin-2:

• No major medical illnesses of the cardiovascular system

Pulmonary:

• For patients randomized to receive interleukin-2:

• No major medical illnesses of the pulmonary system

Other:

• HIV negative
• Hepatitis B antigen negative
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• For patients randomized to receive interleukin-2:

• No active systemic infection
• No other major medical illnesses of immune system
• No coagulation disorders

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 4 weeks since prior biologic therapy

Chemotherapy:

• At least 4 weeks since prior chemotherapy

Endocrine therapy:

• No concurrent steroid therapy

Radiotherapy:

• At least 4 weeks since prior radiotherapy

Surgery:

• Not specified

Other:

• No concurrent active treatment of brain metastases