Anti-MART-1 F5 Lymphocytes to Treat High-Risk Melanoma Patients

Summary

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.

Timeline

Start

2008-06

Primary completion

2012-11

Completion

2012-11

Publications

• Background Schwartz RH. T cell clonal anergy. Curr Opin Immunol. 1997 Jun;9(3):351-7. doi: 10.1016/s0952-7915(97)80081-7.
• Background Rosenberg SA, Yang JC, Restifo NP. Cancer immunotherapy: moving beyond current vaccines. Nat Med. 2004 Sep;10(9):909-15. doi: 10.1038/nm1100.
• Background Dudley ME, Wunderlich JR, Robbins PF, Yang JC, Hwu P, Schwartzentruber DJ, Topalian SL, Sherry R, Restifo NP, Hubicki AM, Robinson MR, Raffeld M, Duray P, Seipp CA, Rogers-Freezer L, Morton KE, Mavroukakis SA, White DE, Rosenberg SA. Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science. 2002 Oct 25;298(5594):850-4. doi: 10.1126/science.1076514. Epub 2002 Sep 19.

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