• To evaluate the kinetics of enhanced thymic activity measured by TREC analysis and flow cytometric analysis following sex hormone ablation by Leuprolide in melanoma patients. [ Time Frame: 3 Years ] [ Designated as safety issue: No ]
• To assess whether there are significant differences in overall quality of life (QOL) between patients receiving Leuprolide to those not receiving leuprolide. [ Time Frame: 3 Years ] [ Designated as safety issue: No ]

Primary Objective:

1. To compare the tumor-specific immune responses to melanoma-specific peptide vaccines, gp100 and MAGE-3 in the presence or absence of a luteinizing hormone-releasing hormone (LHRH) agonist-Leuprolide, in patients with stage IIb and III melanoma, uveal melanoma or stage IV melanoma that the metastatic lesion(s) has been surgically removed.

Secondary Objectives:

1. To evaluate the kinetics of enhanced thymic activity measured by TREC analysis and flow cytometric analysis following sex hormone ablation by Leuprolide in melanoma patients.
2. To assess whether there are significant differences in overall quality of life (QOL) between patients receiving Leuprolide to those not receiving leuprolide.

This study uses vaccines named gp100 or MAGE-3 to immunize patients with melanoma. The type of melanoma they will be used for contains a protein that is also found in the vaccines. These vaccines are designed to stimulate immune cells, also called T cells, to recognize and kill melanoma cells. Leuprolide will be studied to determine whether it will (is designed to) improve your response to the vaccine.

Before treatment starts, you will have what are called " screening tests". These tests will help doctors to decide if it is safe and appropriate for you to take part in the study. You will have a complete medical history and physical exam. Blood (about 4 tablespoons) will be collected for routine tests. You will be tested for HIV. This treatment requires that a person's ability to fight off infection to be normal; therefore anyone who has HIV cannot participate in this study, since they would not have a normal ability to fight infection. You will be asked to sign a separate HIV consent at the time of your HIV test. CT scans of the chest, abdomen, and pelvis will be performed. You will also have an MRI/CT of the brain, and an electrocardiogram (ECG-a test to measure the electrical activity of the heart) performed. Women who are able to have children must have a negative blood or urine pregnancy test.

If you are eligible for this treatment, you will be assigned to one of the two groups that either receive one vaccine or two different vaccines, depending on your tissue type (either gp100 vaccine alone or gp100 and MAGE-3 vaccines). A small amount of the vaccine(s) will be injected under your skin to test your body's immune response to the vaccines. The size of the skin reaction will be measured at 48-72 hours. This skin test will be done before you receive any vaccine, at 6 months, and at 12 months, if possible.The participant and/or participant's family will be given detailed verbal and written instructions on how to measure any reaction to the skin tests. A data sheet and ruler (cm/mm) will be given to the participant.

You will then be randomly assigned (as in the toss of a coin) to one of 2 treatment groups. Participants in one group will receive leuprolide with the vaccine(s). Participants in the other group will not receive leuprolide. Which group you are assigned to will depend partially on your age.

If you are assigned to receive leuprolide injection, you will also have a bone mineral density test to check on the strength of your bones.

Before the treatment starts, you will be asked to answer a questionnaire about your quality of life and sexual functioning. Then at 3 months and 12 months of treatment, you will be asked again to answer the same questionnaire. It should take about 20 minutes each time to finish the questionnaire.

The vaccines will be injected in the skin every 3 weeks for a total of 48 weeks. Those patients in Group I will receive 32 injections of peptide, whereas those patients in Group II will receive 64 injections of peptide over a 48 week period. If you are assigned to receive leuprolide, then leuprolide will be injected in the muscle at the beginning of the study and at 12 weeks, for a total of 2 additional injections. Both the vaccine and leuprolide injections will be given each time at the melanoma outpatient clinic at M. D. Anderson.

Blood (about 4 teaspoons) will be taken at 6 weeks, 12 weeks, then every 12 weeks up to 48 weeks, or at any time if your tumor starts to grow back. Researchers will use this blood to find out how well your immune cells are working to fight your tumor cells.

At around 24 weeks and 48 weeks into treatment, your will have CT scans of the chest, abdomen and pelvis to check on the status of your disease. At around 24 weeks, if you are receiving leuprolide and had an abnormal bone mineral density test before the treatment, you will also have the second bone mineral density test to check on the strength of your bones.

You may be taken off study if your disease gets worse or intolerable side effects occur. If you are taken off study, you will be asked to have repeat scans and a physical exam, including blood (about 4 tablespoons) for routine tests.

Following the first 48 week treatment period, you will be evaluated every 3 months for one year, every 4 months for one year, every 6 months for one year, and then once a year from then on if clinically feasible.

You will have an MRI/CT of the brain, chest, abdomen and pelvis to check on the status of your disease. If your disease gets worse or intolerable side effects occur, you will be taken off study.

Blood (about 4 tablespoons) will be drawn for routine lab tests. An additional 4 tablespoons of blood will be drawn at each follow-up visit to determine how long the t-cell counts remain high.

This is an investigational study. Gp100 and MAGE-3 vaccines are experimental and authorized for research use only. Leuprolide is approved in treating prostate cancer patients and other gynecological diseases, but is not approved for treatment of melanoma. Up to 100 patients will take part in this study. All will be enrolled at M. D. Anderson.

• Drug: Leuprolide
• Biological: GP100: 209-217(210M) Peptide
• Biological: MAGE-3 Peptide

• Experimental: Group IA: HLA-A*0201 positive/HLA-DP4 negative treated with gp100 + Leuprolide
• Experimental: Group IB: HLA-A*0201 positive/HLA-DP4 negative treated with gp100 - No Leuprolide
• Experimental: Group IIA: HLA-A*0201positive/HLA-DP4 positive treated with gp100 + MAGE-3 + Leuprolide
• Experimental: Group IIB: HLA-A*0201positive/HLA-DP4 positive treated with gp100 + MAGE-3 - No Leuprolide

Inclusion Criteria:

1. HLA-A *0201 positive
2. Patients >/= 18 years old with histologically documented diagnosis of stage IIb-IV melanomas and are clinically rendered free of disease after surgery
3. Uveal melanoma patients following definitive treatment of radiation therapy and/or enucleation.
4. Karnofsky Performance Scale >/= 60%.
5. WBC >/= 3000/mm^3.
6. Platelet count >/= 90,000mm^3.
7. Serum creatinine </= 2.0mg/dl.
8. Serum ALT </= 3 X upper limit of normal(ULN))
9. Total bilirubin equal or less than 2X upper limit of normal (ULN)), except for patient with Gilbert's syndrome who must have a total bilirubin less than 3.0mg/dl.
10. Seronegative for HIV antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune competence and thus be less responsive to the experimental treatment and more susceptible to its toxicities.)
11. Negative pregnancy test by serum or urine b-HCG test for women who have menstruation in the past 12 months and without sterilization surgery.
12. Unless surgically sterile by bilateral tubal-ligation or vasectomy of partner(s), the subject agrees to continue to use a barrier method of contraception throughout the study such as: condom, or diaphragm, or sponge plus spermicide. Abstinence is an acceptable form of birth control.

Exclusion Criteria:

1. Prior systemic therapy (including immunomodulate agents), radiation or surgery requiring general anesthesia for melanoma within 28 days of starting study treatment.
2. Autoimmune diseases.
3. Concurrent systemic or inhaled steroid therapy.
4. Any form of active primary or secondary immunodeficiency.
5. History of immunization with gp100 or MAGE-3.
6. Prior malignancy except for the following: adequately treated basal cell or squamous cell skin cancer, in-situ cervical cancer, surgically treated Stage I or II cancer from which the patient is currently in complete remission (at least for 5 years), or any other cancer from which the patient has been disease-free for 5 years.
7. Received a LHRH agonist within the past 5 years.
8. Use of oral contraceptive, hormone replacement therapy or androgen preparations.
9. Hypersensitivity to gonadotropin-releasing hormone analogues.
10. Active systemic infections requiring intravenous antibiotics.
11. Lactating women or women planning lactation during the study.