Phase II Study of Metastatic Melanoma With Lymphodepleting Conditioning and Infusion of Anti-MART-1 F5 TCR-Gene-Engineered Lymphocytes

Summary

Background: * Human peripheral blood lymphocytes have been engineered to express a T-cell receptor (TCR) that recognizes a blood type,HLA-A 0201 (human leukocyte antigen) derived from the gp100 protein. A retroviral vector was constructed that can deliver the T-cell receptor (TCR) to cells. * Patients' cells will be converted into cells able to recognize and fight melanoma tumors. Objectives: * To determine whether TCR-engineered lymphocytes can be put in cells removed from patients' tumors or blood and then reinfused, with the purpose of shrinking tumors. * To evaluate safety and effectiveness of the treatment. Eligibility: * Patients 18 years of age or older with metastatic cancer melanoma (cancer that has spread beyond the original site). * Patient's leukocyte antigen type is HLA-A 0201. Design: -Patients undergo the following procedures: * Leukapheresis (on two occasions). This is a method of collecting large numbers of white blood cells. The cells obtained in the first leukapheresis procedure are grown in the laboratory, and the anti-MART-1 protein is inserted into the cells using an inactivated (harmless) virus in a process called retroviral transduction. Cells collected in the second leukapheresis procedure are used to evaluate the effectiveness of the study treatment. * Chemotherapy. Patients are given chemotherapy through a vein (intravenously, IV) over 1 hour for 2 days to suppress the immune system so that the patient's immune cells do not interfere with the treatment. * Treatment with anti-melanoma antigen recognized by T-cells (MART)-1. Patients receive an intravenous (IV) infusion of the treated cells containing anti-MART-1 protein, followed by infusions of a drug called IL-2 (aldesleukin), which helps boost the effectiveness of the treated white cells. * Patients are given support medications to prevent complications such as infections. * Patients may undergo a tumor biopsy (removal of a small piece of tumor tissue). * Patients are evaluated with laboratory tests and imaging tests, such as CT (computed tomography) scans, 4 to 6 weeks after treatment and then once a month for 3 to 4 months to determine the response to treatment. * Patients have blood tests at 3, 6, and 12 months and then annually for 5 years.

Timeline

Start

2007-06

Primary completion

2011-07

Completion

2012-07

Publications

• Background Kawakami Y, Eliyahu S, Delgado CH, Robbins PF, Rivoltini L, Topalian SL, Miki T, Rosenberg SA. Cloning of the gene coding for a shared human melanoma antigen recognized by autologous T cells infiltrating into tumor. Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3515-9. doi: 10.1073/pnas.91.9.3515.
• Background Kawakami Y, Eliyahu S, Sakaguchi K, Robbins PF, Rivoltini L, Yannelli JR, Appella E, Rosenberg SA. Identification of the immunodominant peptides of the MART-1 human melanoma antigen recognized by the majority of HLA-A2-restricted tumor infiltrating lymphocytes. J Exp Med. 1994 Jul 1;180(1):347-52. doi: 10.1084/jem.180.1.347.
• Background Kawakami Y, Eliyahu S, Delgado CH, Robbins PF, Sakaguchi K, Appella E, Yannelli JR, Adema GJ, Miki T, Rosenberg SA. Identification of a human melanoma antigen recognized by tumor-infiltrating lymphocytes associated with in vivo tumor rejection. Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6458-62. doi: 10.1073/pnas.91.14.6458.
• Abate-Daga D, Hanada K, Davis JL, Yang JC, Rosenberg SA, Morgan RA. Expression profiling of TCR-engineered T cells demonstrates overexpression of multiple inhibitory receptors in persisting lymphocytes. Blood. 2013 Aug 22;122(8):1399-410. doi: 10.1182/blood-2013-04-495531. Epub 2013 Jul 16.

Drugs

Indications