The primary objective of this study is to evaluate the safety and feasibility of administering an allogeneic GM-CSF-secreting lethally irradiated whole melanoma cell vaccine ("melanoma GVAX"), alone or in combination with low dose cyclophosphamide (CPM), for the adjuvant treatment of patients with surgically resected stage IIB-IV melanoma. Secondarily, the investigators will assess in vitro correlates of anti-melanoma immunization by melanoma GVAX, including serological and cellular immune responses in patients treated with either the vaccine alone or the vaccine given with low dose CPM.

Inclusion Criteria:

• Any patient age ≥18 years with melanoma of cutaneous or mucosal origin, and with clinicopathologic stage IIB, IIC, III or IV that has been completely resected
• Patients must be able to provide informed consent.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Life expectancy of at least 6 months.
• Adequate hematologic function.
• Adequate renal function
• Adequate hepatic function
• Patients of both genders must agree to practice effective birth control during the study period and for at least 4 weeks after the last treatment.

Exclusion Criteria:

• Patients whose primary site of melanoma is ocular.
• Are undergoing or have undergone in the past 4 weeks any systemic treatment for melanoma.
• Are undergoing or have undergone in the past 2 weeks any surgery or focal radiation therapy.
• Have active systemic infections, coagulation disorders (including therapeutic anticoagulation), or other major medical or psychiatric illnesses.
• Are known to be positive for hepatitis B surface antigen, anti-Hepatitis C Virus or anti-Human Immunodeficiency Virus (HIV) antibody (because of possible immune effects of these conditions).
• Documented history of autoimmune disease, for example, systemic lupus erythematosus, sarcoidosis, rheumatoid arthritis, glomerulonephritis, or vasculitis.
• Any form of primary or secondary immunodeficiency. This would include hereditary disorders such as ataxia-telangiectasia or Wiskott-Aldrich syndrome, or acquired immune deficiencies such as following bone marrow transplantation.
• Requirement for systemic steroid therapy or immunosuppressive therapy.
• Have received any type of cancer immunotherapy, including but not limited to interleukin-2, interferon alfa or melanoma vaccines.
• Have been diagnosed with another invasive cancer within the past 3 years.
• Radiographic evidence of melanoma recurrence.
• Pregnant or lactating women.
• Known or suspected hypersensitivity to GM-CSF, pentastarch, hetastarch, corn, Dimethyl sulfoxide, fetal bovine serum or trypsin (porcine origin).