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

Completed · Phase 2

Conditions studied: Melanoma, Skin Cancer

In brief

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.

Key facts

Study ID

NCT00509288

Run by

National Cancer Institute (NCI)

People needed

24

Starts

2007-06-01

Expected to finish

2012-07-01

Last updated by the study team

2012-12-28

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may not qualify if…

• Patients with reactive TIL (IFN-gamma release greater than 200 pg/mL) available based on overnight co-culture assay with autologous tumor or MHC-matched tumor cells.
• Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant.
• Active systemic infections, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease.
• Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
• Opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities).
• Systemic steroid therapy.
• History of severe immediate hypersensitivity reaction to any of the agents used in this study.
• History of coronary revascularization or ischemic symptoms.
• Any patient known to have an left ventricular ejection fraction (LVEF) less than or equal to 45 percent.
• Documented LVEF of less than or equal to 45 percent tested in patients with:
• Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block.
• Age greater than or equal to 60 years old.
• Documented forced expiratory volume 1 (FEV1) less than or equal to 60 percent predicted tested in patients with:
• A prolonged history of cigarette smoking (20 pk/yrs of smoking).
• Symptoms of respiratory dysfunction.

Where it is running

• National Institutes of Health Clinical Center, 9000 Rockville Pike — Bethesda, Maryland, United States

Full record on ClinicalTrials.gov

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