LMB-2 Immunotoxin and Vaccine Therapy in Treating Patients With Metastatic Melanoma That Cannot Be Removed By Surgery

OBJECTIVES:

Primary

• Determine objective clinical response in patients with progressive, unresectable metastatic melanoma treated with recombinant LMB-2 immunotoxin and peptide vaccination comprising gp100:209-217 (210M) antigen, MART-1:27-35 antigen, and Montanide ISA-51.

Secondary

• Determine changes in levels of CD4+, CD25+ regulatory T cells in peripheral blood before and after treatment in patients treated with this regimen.
• Determine the ability of recombinant immunotoxin LMB-2 to augment peptide vaccination in these patients.
• Determine the toxicity profile of this regimen in these patients.

OUTLINE: Patients receive LMB-2 immunotoxin IV over 30 minutes twice on days 1-3. Patients then receive peptide vaccinations comprising gp100:209-217 (210M) antigen emulsified in Montanide ISA-51 subcutaneously (SC), and MART-1:27-35 vaccine emulsified in Montanide ISA-51 SC on days 4, 5, 6, and 24-27 (course 1). After week 8, patients achieving tumor response may receive 1 additional course in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically in the absence of disease progression.

PROJECTED ACCRUAL: A total of 26 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Diagnosis of metastatic melanoma

• Unresectable disease
• Progressive disease while receiving standard therapy (e.g., interleukin-2 or dacarbazine)
• HLA-A0201 positive
• Measurable disease
• The following are not allowed:

• Resectable local/regional disease
• Patients whose serum neutralizes LMB-2 in tissue culture, due either to antitoxin or antimouse-immunoglobulin G antibodies (> 75% of the activity of 1 ug/mL of LMB-2)
• Received LMB-2 on another trial

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Life expectancy more than 3 months
• WBC ≥ 3,000/mm^3
• Absolute lymphocyte count > 500/mm^3
• Platelet count ≥ 90,000/mm^3
• Bilirubin ≤ 2.0 mg/dL (≤ 3.0 mg/dL for patients with Gilbert's syndrome)
• AST and ALT ≤ 2.5 times normal
• Albumin ≥ 3.0 g/dL
• No hepatitis B surface antigen or hepatitis C positivity
• Creatinine ≤ 1.4 mg/dL
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No ongoing or active infection
• Ejection fraction ≥ 45% by echocardiogram or thallium stress test (for patients > 50 years of age OR who have a history of cardiovascular disease)
• LVEF ≥ 45%
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia
• No psychiatric illness or social situation that would preclude study compliance
• No other uncontrolled illness
• No known HIV positivity
• No autoimmune disease
• No immunodeficiency
• No other malignancies
• Must be willing to undergo leukapheresis

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• More than 12 weeks since prior monoclonal antibody therapy
• More than 3 weeks since prior and no concurrent systemic therapy for cancer
• No concurrent chronic anticoagulant therapy
• No concurrent systemic steroid therapy