MART-1:26-35 (27L) peptide vaccine(NCI)

Background:
Melanoma antigen recognized by T cells (MART-1) is a gene that is present in melanoma cells.
This study tests an experimental treatment that uses the patient's own lymphocytes (type of white blood cell), which are specially selected and genetically modified with a gene called anti-MART-1 transduced cells (F5) to target and destroy their tumor. Some of the cells are given as an infusion and others are given as a vaccine.
The anti-MART-1 F5 cells are currently being studied in other patients in combination with chemotherapy and IL-2 (aldesleukin) therapy.
Objectives:
-To determine if the anti-MART-1 F5 treatment can improve the immune system's ability to shrink tumors and to prevent melanoma from recurring.
Eligibility:
Patients 18 years of age and older whose melanoma has been removed and are currently disease-free, but who are at risk for recurrence.
Patients who do not have ocular or mucosal melanoma.
Patients with tissue type human leukocyte antigens (HLA-A)*0201).
Design:
Workup: Patients have scans, x-rays, laboratory tests, other tests as needed and leukapheresis, a procedure for collecting white cells to modify in the laboratory and later reinfuse into the patient.
Patients are assigned to one of four study groups:
Group 1 receives anti-MART-1 F5 cells by 30-minute infusion through a vein on day 0.
Group 2 receives anti-MART-1 F5 cells on day 0 followed by injections of MART-1 vaccine, which contains MART-1 and an oil-based liquid called Montanide ISA-51 VG. The vaccine is repeated on day 30.
Group 3 receives anti-MART-1 F5 cells on day 0 followed by injections of low-dose IL-2 for 5 days (days 0-4).
Group 4 receives anti-MART-1 F5 cells on day 0 followed by MART-1 vaccine and low-dose IL-2 for 5 days. The vaccine is repeated on day 30.
Recovery: Patients are monitored closely and given medicines to prevent or treat any side effects of therapy.
Leukapheresis: Patients undergo leukapheresis at 1 and 3 months after therapy to collect cells to examine the effects of the treatment on the immune system.
Follow-up: Patients return to National Institutes of Health (NIH) 35 days after completing treatment and then at 3 months and every 6 months thereafter for evaluation with a physical examination, review of side effects, laboratory tests and scans. They have blood tests at 3, 6 and 12 months after treatment and then once a year after that. A biopsy may be requested after treatment ends to examine the effects of treatment on the immune system. All patients return to NIH for a physical examination once a year for 5 years and then complete a follow-up questionnaire for another 10 years.

This experiment will test the safety and effectiveness of a treatment for melanoma in which certain lymphocytes (a type of white blood cell) are taken from the patient, grown in the laboratory, and returned after the patient's immune system has been weakened with immune-suppressing drugs. Some patients will also receive interleukin-2 (IL-2), a drug that may enhance the activity of the re-infused lymphocytes.
Patients with metastatic melanoma (melanoma whose tumor has spread) who have been treated unsuccessfully with gp100 vaccination may participate in this study. They will undergo apheresis or a tumor biopsy, or both, to collect lymphocytes. In apheresis, whole blood is drawn through a needle in the arm. A machine separates the blood components and removes the white cells. The rest of the blood is returned to the donor through a needle in the other arm. A biopsy is a surgical procedure to remove a small piece of tumor tissue.
Several weeks before the lymphocytes are collected, patients will receive injections of growth colony stimulating factor (G-CSF) every day for five days. This drug stimulates white cell production, permitting as many cells as possible to be obtained during collection. The lymphocytes will then be grown in larger numbers in the laboratory.
Seven days before the cells are re-infused, the patient is admitted to the hospital and a catheter (small tube) is placed in a large vein in the chest or neck. Two drugs, cyclophosphamide and fludarabine, are given through the tube. These drugs suppress the immune system so that it will not interfere with the work of the reinfused lymphocytes. The lymphocytes are then injected through the catheter over a 30-minute period. After the infusion, patients who receive IL-2 will be given the drug in a high dose over a 15-minute period every eight hours for up to five days. Patients whose condition does not permit high-dose IL-2, such as those with a heart condition or lung problem, may receive a low-dose regimen, with the drug given as a shot under the skin of the thigh or abdomen for five days followed by a 2-day break, continuing for a total of six weeks. These patients receive a higher dose the first week and then half that dose the next five weeks.
Blood and tissue samples will be taken before and during the study to evaluate the size of the tumor and assess treatment. If, 3-5 weeks after therapy is completed, the patient's tumor has stabilized or shrunk, the entire treatment, except for chemotherapy, may be repeated two more times.