This study will test the body's immune response to an experimental anti-cancer vaccine in fighting melanoma. The vaccine is intended to stimulate immune cells called lymphocytes to attack tumors containing gp100 and tyrosinase, two protein fractions (peptides) commonly produced by melanomas. The vaccine contains these peptides and an oil-based liquid called Montanide ISA-51, another experimental substance that is intended to boost the immune reaction to the peptides.

Patients 16 years of age and older with stage II or stage III melanoma (i.e., at least one positive lymph node), or whose tumor has been surgically removed may be eligible for this study. Patients must be clinically free of disease at the time they enter the study. (Patients who had positive lymph node(s) or surgery to remove their metastasis have a high likelihood of disease relapse.) Candidates will be screened with a physical examination, blood and urine tests, and an electrocardiogram. Patients must have the tissue type HLA-A*0201; this will be determined by a blood test.

Participants will have scans and X-rays to evaluate that they are disease free. They will then be randomly assigned to one of three treatment schedules: one group will receive the vaccine once a week for 10 weeks; a second group will receive it four times-once every 3 weeks; and the third group will receive it four times a week every 3 weeks for four times. The vaccine is given as an injection (shot) in the thigh. Treatment will continue for 10 to 12 months, and physical examinations and blood tests will be done frequently to assess side effects. Scans and x-rays will be repeated at least every 6 months to evaluate for tumor recurrence.

About 40 cc (8 teaspoons) of blood will be drawn every 12 weeks. Patients will undergo leukapheresis before starting treatment and again after the fourth vaccine in patients receiving weekly injections, and after the second and fourth vaccine in those receiving injections every 3 weeks. In this procedure, whole blood is collected through a needle placed in an arm vein. The blood circulates through a machine that separates it into its components. The lymphocytes are then removed, and the rest of the blood-red cells, platelets and plasma-is returned to the body through a second needle in the other arm. Leukapheresis is done to evaluate how the vaccine affects the action of lymphocytes.

A biopsy of normal skin and tumor or lymph node may be done to examine the effects of the vaccine on the immune cells in the tumor. Depending on the type and location of tissue, biopsies may be performed with a needle (needle biopsy), with a small sharp cookie-cutter instrument (punch biopsy), or with a small knife (excisional biopsy).

Patients whose cancer returns during or after peptide treatment may be given a treatment called interleukin-2 (IL-2), to boost the immune reaction to the tumor. IL-2 is infused through a vein over 15 minutes, and is given every 8 hours for 4 days every 3 to 4 weeks. Patients who receive IL-2 will remain in the hospital for 5-7 days for this treatment.

Condition	Treatment or Intervention	Phase
Melanoma	Drug: gp100: 209-217(210M)  Drug: Tyrosinase: 368-376(370D)  Drug: Montanide ISA 51  Drug: IL-2  Drug: Tyrosinase: 240-251 (244s)  Drug: Tyrosinase: 206-214  Drug: TRP-1 (ORF#):1-9  Drug: Gp100:17-25	Phase II

Further Study Details: 

Expected Total Enrollment:  324

HLA-A201, A1, A3, A24 or A31 positive patients at high risk for recurrence of melanoma, or completely resected metastatic melanoma will receive immunization with peptides representing HLA-restricted T cell epitopes of melanoma antigens emulsified in Incomplete Freund's Adjuvant (IFA). Patients will be randomized to receive peptides by one of three different schedules. Additionally one exploratory arm of patients who are HLA-A201 will receive the peptides emulsified together on the every 3 week times four schedule. This study is designed to compare the immunologic effects of the different schedules of peptide immunization.

Genders Eligible for Study:  Both

Criteria

INCLUSION CRITERIA:
HLA-A1, A0201, A3, A24, or A31 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.
WBC 3000/mm(3) or greater,
Platelet count 90,000 mm(3) or greater,
Serum AST/ALT less than three times normal,
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.
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.
Have active systemic infections, autoimmune disease or any known immunodeficiency disease.
Who require systemic steroid therapy.
Who are pregnant.
Who are known to be positive for hepatitis B(s)AG or 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 gp100, tyrosinase or TRP-1.
To be eligible to receive IL-2, patients may not have active major medial illnesses such as cardiac ischemia, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease.
To be eligible to receive IL-2, patients must be willing to sign a durable power or attorney (DPA).

Maryland
      National Cancer Institute (NCI), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States

Study ID Numbers:  000216; 00-C-0216
Record last reviewed:  July 1, 2004
Last Updated:  November 29, 2004
Record first received:  September 20, 2000
ClinicalTrials.gov Identifier:  NCT00006287
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08