Cell Therapy for Metastatic Melanoma Using CD8 Enriched Tumor Infiltrating Lymphocytes

Summary

Background: \- One experimental treatment for certain types of cancer is cell therapy, which involves collecting lymphocytes (white blood cells) from a tumor, growing them in the laboratory in large numbers, and then modifying the cells with a gene (interleukin-12 (IL-12)) that stimulates the immune system to attack and destroy the cancer cells. Because this treatment is experimental, researchers are interested in determining the side effects and overall effectiveness of cell therapy using white blood cells modified with IL-12 as a treatment for aggressive cancer. Objectives: \- To determine the safety and effectiveness of cell therapy using IL-12 modified tumor white blood cells to treat metastatic melanoma. Eligibility: \- Individuals greater than or equal to 18 years of age and less than or equal to age 66 who have been diagnosed with metastatic melanoma. Design: * Participants will be screened with a medical history, physical examination, blood and urine tests, and imaging studies. * Cells for treatment will be collected during tumor biopsy or surgery. * Prior to the start of cell therapy, participants will have imaging procedures, heart and lung function tests, and blood and urine tests, as well as leukapheresis to collect additional white blood cells. * For 5 days before the cell infusion, participants will be admitted for inpatient chemotherapy with cyclophosphamide and fludarabine to suppress the immune system in preparation for the cell therapy. * Participants will receive the modified white blood cells as an infusion 1 to 4 days after the last dose of chemotherapy. The day after the infusion, participants will receive filgrastim to stimulate blood cell growth. * Participants will remain as inpatients for at least 5 to 10 days to recover from the treatment, and will be followed regularly after the treatment to study side effects and general effectiveness. * Participants who initially respond to treatment but have a relapse may have one additional treatment using the same procedure.

Timeline

Start

2010-10

Primary completion

2015-03

Completion

2015-03

Outcome

Outcome not reported

Stopped: “Unexpected toxicities, likely due to TIL/IL-12 \& low % of durable responses.”

Publications

• Background Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics, 2007. CA Cancer J Clin. 2007 Jan-Feb;57(1):43-66. doi: 10.3322/canjclin.57.1.43.
• Background Atkins MB, Lotze MT, Dutcher JP, Fisher RI, Weiss G, Margolin K, Abrams J, Sznol M, Parkinson D, Hawkins M, Paradise C, Kunkel L, Rosenberg SA. High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. J Clin Oncol. 1999 Jul;17(7):2105-16. doi: 10.1200/JCO.1999.17.7.2105.
• Background Gogas HJ, Kirkwood JM, Sondak VK. Chemotherapy for metastatic melanoma: time for a change? Cancer. 2007 Feb 1;109(3):455-64. doi: 10.1002/cncr.22427.
• Results Zhang L, Morgan RA, Beane JD, Zheng Z, Dudley ME, Kassim SH, Nahvi AV, Ngo LT, Sherry RM, Phan GQ, Hughes MS, Kammula US, Feldman SA, Toomey MA, Kerkar SP, Restifo NP, Yang JC, Rosenberg SA. Tumor-infiltrating lymphocytes genetically engineered with an inducible gene encoding interleukin-12 for the immunotherapy of metastatic melanoma. Clin Cancer Res. 2015 May 15;21(10):2278-88. doi: 10.1158/1078-0432.CCR-14-2085. Epub 2015 Feb 18.
• Kerkar SP, Goldszmid RS, Muranski P, Chinnasamy D, Yu Z, Reger RN, Leonardi AJ, Morgan RA, Wang E, Marincola FM, Trinchieri G, Rosenberg SA, Restifo NP. IL-12 triggers a programmatic change in dysfunctional myeloid-derived cells within mouse tumors. J Clin Invest. 2011 Dec;121(12):4746-57. doi: 10.1172/JCI58814. Epub 2011 Nov 7.

Drugs

Indications