TCRMulticenter Phase I/IIa Study Using T-cell Receptor Gene Therapy in Metastatic Melanoma

Fecha de inicio: 1 de marzo de 2012

Inclusion Criteria: * Patients must be ≥ 18 years of age. * Patients must have inoperable stage IIIc or stage IV melanoma (AJCC), including ocular or mucosal melanoma, progressing after standard of care therapy, if available. * Patients must be HLA-A\*0201 positive. * The primary tumor and/or metastasis have to be positive for MART-1 (\>10% of tumor cells). * Patients with measurable disease (RECIST 1.1) * Patients must have a clinical performance status of ECOG 0 or 1. * Patients of both genders must be willing to practice a highly effective method of birth control during treatment and for four months after receiving the preparative regimen. * Patients must be able to understand and sign the Informed Consent document. Specific lab values Exclusion Criteria: * Life expectancy of less than three months. * Requirement for systemic steroid therapy. * Patients who have a history of CNS metastases. * Patients with malignant pleural effusion or ascites. * Any immunosuppressive chemotherapy or systemic steroid therapy within the last 3 weeks. * Patients who have: history of coronary revascularization, documented LVEF of less than 45%, clinically significant atrial and/or ventricular arrhythmias including but not limited to atrial fibrillation, ventricular tachycardia, 2° or 3° heart block, documented FEV1 less than or equal to 60% predicted for patients with a history of cigarette smoking (greater than 20 pack/year within the past 2 years) and with symptoms of respiratory distress * All patients' toxicities due to prior non-systemic treatment must have recovered to a grade 1 or less. Patients may have undergone minor surgical procedures or focal palliative radiotherapy (to non-target lesions) within the past 4 weeks, as long as all toxicities have recovered to grade 1 or less. * Women who are pregnant or breastfeeding, because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant. A negative pregnancy test before inclusion in the trial is required for all women of child bearing potential. * Any active systemic infections, coagulation disorders or other active major medical illnesses, such as active autoimmune disease requiring anti-TNF treatment.