Peptide Vaccination for Patients at High Risk for Recurrent Melanoma

Human leukocyte antigens (HLA-A)*0201 positive patients at high risk for recurrence of melanoma, or completely resected metastatic melanoma will receive immunization with peptides representing human leukocyte antigen (HLA)-restricted T cell epitopes of the melanoma antigen recognized by T-cells (MART-1) or glycoprotein 100 (gp100) melanoma antigens emulsified in Montanide ISA-51 or Montanide trademark(TM) ISA 51 vegetable grade (VG). Patients will be randomized to receive one of three different melanoma antigen recognized by T-cells (MART-1) peptides or to receive a combination of a melanoma antigen recognized by T-cells (MART-1) peptide plus a glycoprotein 100 (gp100) peptide. This study is designed to evaluate the immunologic effects of the different peptide immunizations.

• INCLUSION CRITERIA:

Human leukocyte antigens (HLA-A)*0201 patients, age greater than or equal to 16 years, with lesions greater than or equal to 1.5 mm in thickness, or greater than or equal to 1 positive lymph node, or ulcerated lesions, or local recurrence, or completely resected metastatic melanoma, within 6 months of surgical resection will be considered. Patients must be clinically disease free at the time of protocol entry as documented by radiologic studies within 6 weeks of patient entry.

Serum creatinine of 2.0 mg/dl or less.

Total bilirubin 1.6 mg/dl or less, except for patients with Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dl.

White blood cell (WBC) 3000/mm^3 or greater.

Platelet count 90,000 mm^3 or greater.

Serum aspartate aminotransferase (AST)/alanine aminotransferase (ALT) less than three times normal.

Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Patients of both genders must be willing to practice effective birth control during this trial because the potential for teratogenic effects are unknown.

Patients may have had prior adjuvant treatment with immunotherapy, including interferon, or may have had treatment for metastatic disease and are now no evidence of disease (NED), including chemotherapy or biotherapy, as long as 3 weeks have elapsed since prior systemic therapy.

Exclusion criteria

Patients will be excluded:

• who have ocular or mucosal melanoma.
• who are undergoing or have undergone in the past 3 weeks any systemic therapy except surgery for their cancer, and must have recovered from any adverse effects of treatment prior to entry, other than those that do not have clinical implications, e.g. vitiligo, alopecia.
• have active systemic infections, autoimmune disease or any known immunodeficiency disease.
• who require systemic steroid therapy.
• who are pregnant or breastfeeding.
• who are known to be positive for hepatitis B surface antigen (B(s)AG) or human immunodeficiency virus (HIV) antibody.
• who have any form of active primary or secondary immunodeficiency or who have not recovered immune competence after chemotherapy or radiation therapy.
• who have previously been immunized with melanoma antigen recognized by T-cells (MART)-1.
• who have known hypersensitivity to any of the agents used in this study.

ELIGIBILITY FOR ADMINISTRATION OF Interleukin-2 (IL-2):

Patients who develop progressive disease while receiving peptide alone must meet the following criteria to be eligible to receive Interleukin-2 (IL-2):

• Patients must have measurable metastatic melanoma.
• Patients may not have active major medical illnesses such as cardiac ischemia, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease.
• Patients with recent prolonged history of cigarette smoking or symptoms of respiratory dysfunction must have a normal pulmonary function test as evidenced by a forced expiratory volume 1 (FEV 1) greater than 60% predicted.
• Patients with electrocardiogam (EKG) abnormalities, symptoms of cardiac ischemia or arrhythmias or age greater than 50 years will have a normal stress cardiac test (stress thallium, stress multi-gated acquisition scan (MUGA), dobutamine echocardiogram or other stress test).
• Patients must be willing to sign a durable power of attorney (DPA).
• Serum creatinine of 2.0 mg/dl or less.
• Total bilirubin 2.0 mg/dl or less, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dl.
• White blood cell (WBC) 3000/mm^3 or greater.
• Platelet count 90,000 mm^3 or greater.