T Cell Receptor Immunotherapy Targeting NY-ESO-1 for Patients With NY-ESO-1 Expressing Melanoma

Study Summary

Background: The National Cancer Institute (NCI) Surgery Branch has developed an experimental therapy for treating patients with melanoma that involves taking white blood cells from the patient, growing them in the laboratory in large numbers, genetically modifying them, and then giving the cells back to the patient. In a previous study, the NCI Surgery Branch used the anti-ESO-1 gene and a type of virus (retrovirus) to make these tumor-fighting cells (anti-ESO-1 cells). About half of the patients who received this treatment experienced shrinking of their tumors. In this study, we are using a slightly different method of producing the anti-ESO-1 cells selected for a specific cell type, which we hope, will be better in making the tumors shrink. Objectives: The purpose of this study is to see if these tumor fighting cells (genetically modified cells) that express the receptor for the ESO-1 molecule on their surface can cause melanoma tumors to shrink and to see if this treatment is safe. Eligibility: -Adults 18 and older with cancer that has the ESO-1 molecule on tumor surfaces Design: * Work up stage: Patients will be seen as an outpatient at the National Institutes of Health (NIH) clinical Center and undergo a history and physical examination, scans, x-rays, lab tests, and other tests as needed * Leukapheresis: If the patients meet all of the requirements for the study they will undergo leukapheresis to obtain white blood cells to make the anti ESO-1 cells. {Leukapheresis is a common procedure, which removes only the white blood cells from the patient.} * Treatment: Once their cells have grown, the patients will be admitted to the hospital for the conditioning chemotherapy, the anti-ESO 1 cells and aldesleukin. They will stay in the hospital for about 4 weeks for the treatment. Follow up: Patients will return to the clinic for a physical exam, review of side effects, lab tests, and scans about every 1-3 months for the first year, and then every 6 months to 1

Primary Outcome

Response was determined by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response (CR) is disappearance of all target lesions. Partial response (PR) is 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) is 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 lesion

Interventions

• DRUG Cyclophosphamide
• DRUG Fludarabine
• DRUG Aldesleukin
• BIOLOGICAL Anti-NY ESO-1 T cell receptor (TCR) cluster of differentiation 62L (CD62L)+ cells