vaccine therapy with or without interleukin-2 in treating patients with metastatic melanoma that has not responded to previous treatment

Conditions: Melanoma (Skin)

Summary: rationale: vaccines may make the body build an immune response to kill tumor cells. interleukin-2 may stimulate a person's white blood cells to kill tumor cells. combining vaccine therapy with interleukin-2 may be an effective treatment for metastatic melanoma. purpose: randomized phase ii trial to compare the effectiveness of vaccine therapy plus interleukin-2 to that of vaccine therapy alone in treating patients who have metastatic melanoma that has not responded to previous treatment.

objectives: * determine the clinical responses in patients with hla-a0201-positive refractory metastatic melanoma treated with tyrosinase-related protein-2:180-188 peptide vaccine alone. * determine the clinical response rate of patients who have an immediate need to receive interleukin-2 (il-2) in addition to this vaccine. * compare the immunologic response, in terms of changes in t-cell precursors before and after treatment, in patients treated with this vaccine with or without il-2. * compare the toxicity profile of these regimens in these patients. outline: this is a randomized, open-label study. patients who need immediate interleukin-2 (il-2) receive tyrosinase-related protein-2 (trp-2):180-188 peptide vaccine emulsified with montanide isa-51 on day 1 and high-dose il-2 iv over 15 minutes once every 8 hours on days 2-5. treatment repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. patients who do not need immediate il-2 are randomized to 1 of 2 treatment arms. * arm i: patients receive trp-2:180-188 peptide vaccine emulsified with montanide isa-51 subcutaneously (sc) on day 1. treatment repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. * arm ii: patients receive trp-2:180-188 peptide vaccine emulsified with montanide isa-51 sc once weekly on weeks 1-4. treatment repeats every 7 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. patients who have a complete response (cr) receive 1 additional course after achieving cr. patients who have progressive disease while receiving vaccine alone may cross over to receive peptide vaccine with il-2 for at least 2 courses. patients are followed at 3 weeks. projected accrual: a maximum of 83 patients (19-33 who need immediate interleukin-2 (il-2); 15-25 per treatment arm who do not need immediate il-2) will be accrued for this study within 1 year.

Eligibility criteria:
disease characteristics: * diagnosis of metastatic melanoma * refractory to standard therapy * no resectable locoregional disease * hla-a0201 positive * measurable disease * previously resected brain metastases, brain metastases stable after prior radiosurgery, or brain metastases less than 1 cm and without edema allowed patient characteristics: age: * 16 and over performance status: * ecog 0-2 life expectancy: * more than 3 months hematopoietic: * wbc at least 3,000/mm\^3 * platelet count at least 90,000/mm\^3 * no coagulation disorders hepatic: * bilirubin no greater than 2.0 mg/dl (3.0 mg/dl for patients with gilbert's syndrome) * ast/alt less than 3 times normal * hepatitis b surface antigen negative renal: * creatinine no greater than 2.0 mg/dl cardiovascular: * no major medical illness of the cardiovascular system * no cardiac ischemia\* * no myocardial infarction\* * no cardiac arrhythmias\* note: \* for interleukin-2 (il-2) administration pulmonary: * no major medical illness of the respiratory system * no obstructive or restrictive pulmonary disease (for il-2 administration) immunologic: * hiv negative * no primary or secondary immunodeficiency * no known immunodeficiency disease * no autoimmune disease * no active systemic infections other: * not pregnant * negative pregnancy test * fertile patients must use effective contraception prior concurrent therapy: biologic therapy: * at least 3 weeks since prior biologic therapy for melanoma * no prior immunization to tyrosinase-related protein-2 antigen * no other concurrent biologic therapy for melanoma chemotherapy: * at least 3 weeks since prior chemotherapy for melanoma and recovered * no concurrent chemotherapy for melanoma endocrine therapy: * at least 3 weeks since prior endocrine therapy for melanoma * no concurrent systemic steroid therapy * no concurrent endocrine therapy for melanoma radiotherapy: * see disease characteristics * at least 3 weeks since prior radiotherapy for melanoma and recovered * no concurrent radiotherapy for melanoma surgery: * see disease characteristics other: * no other concurrent therapy for melanoma

Keywords: stage iv melanoma recurrent melanoma