Phase II Study of Short-Term Cultured Anti-Tumor Autologous Lymphocytes After Lymphocyte-Depleting Chemotherapy in Metastatic Melanoma

Study Summary

Background: * Most therapeutic therapies for metastatic melanoma have focused on the ability of T-cell lymphocytes to kill cells of tumors. * An adaptive cell transfer therapy has been pioneered, in which cells are grown for a short time in the laboratory. The way they are grown may have a better effect in a patient's body than do other cells that are cultured for a longer time. Objectives: * To determine whether tumor-infiltrating lymphocytes (TIL) 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 human leukocyte antigens (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 TIL cells (called young TIL cells) are 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 young TIL cells. Patients receive an IV infusion of the treated cells, followed by infusions the drug aldesleukin-2 (IL-2), 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 test

Primary Outcome

Clinical response is defined as complete response (CR)- a disappearance of all target lesions, partial response (PR) - at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD. Progression (PD)- at least a 20% increase in the sum of the LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Stable disease (SD) - neither sufficient shrinkage to

Interventions

• DRUG Cyclophosphamide
• DRUG Fludarabine phosphate
• RADIATION Total body irradiation
• BIOLOGICAL therapeutic autologous lymphocytes
• BIOLOGICAL aldesleukin