Vemurafenib and White Blood Cell Therapy for Advanced Melanoma

Background: Adoptive cell therapy (ACT) with tumor infiltrating lymphocytes (TIL) can mediate the regression of bulky metastatic melanoma when administered to the autologous patient along with high-dose aldesleukin (IL-2) following a non-myeloablative lymphodepleting chemotherapy preparative regimen. Vemurafenib (VEM) administration has been shown to mediate objective responses in 50-60 percent of patients with metastatic melanoma bearing a BRAF mutation though many of these responses are transient. There are several reasons to suggest that the combination of ACT with VEM will synergize in the destruction of melanoma including 1) rapid tumor destruction by VEM may provide a vaccine-like stimulus to the transferred TIL; 2) VEM has been shown to upregulate the expression of melanoma antigens; 3)VEM may make residual melanoma cells more sensitive to immune damage. Objectives: The primary objective is to determine the safety of the administration of vemurafenib in conjunction with ACT consisting of autologous TIL infused along with high dose aldesleukin following a non-myeloablative lymphodepleting preparative regimen. The secondary objectives are: * To gain preliminary information concerning the ability of the combination therapy to mediate clinical tumor regression in patients with metastatic melanoma. * To study the immunologic impact of VEM administration on the lymphoid infiltrate in melanoma deposits. Eligibility: Patients greater than or equal to 18 years old with pathologically confirmed diagnosis of metastatic melanoma that expresses the VtoE BRAF mutation and VtoK BRAF mutation. Patients with measurable disease, absolute neutrophil count greater than 1000/mm(3) and platelet count greater than 100,000/mm(3). No serious comorbid conditions such as active systemic infections, coagulation disorders, or other active major medical illnesses of the cardiovascular, respiratory or immune systems. Design: Patients will undergo biopsy or resection to obtain tumor for generation of autologous TIL cultures. When cryopreserved TIL are available patients will begin the administration of VEM 960 mg (day 1) twice daily until disease progression or patients are taken off protocol. On day -7, patients will begin a non-myeloablative lymphocyte depleting preparative regimen of cyclophosphamide (60 mg/kg/day IV) on days -7 and -6 and fludarabine (25 mg/m2/day IV) on days -5 through -1. On day 0, patients will receive between 1x109 to 2x1011 young TIL and then begin high dose aldesleukin (720,000 IU/kg IV every 8 hours for up to 15 doses). Clinical and immunologic responses will be evaluated about 4-6 weeks after the last dose of aldesleukin. This pilot trial will accrue 25 patients.