Immunotherapy Study for Patients With Stage IV Melanoma

Inclusion Criteria: * Histological/cytological diagnosis of melanoma. AJCC stage IV (any T, any N, M1), metastatic, progressive, refractory, melanoma. * Patients may have advanced unresectable stage IV disease, resectable stave IV disease or recently resected stage IV disease (\<10 weeks prior) with no apparent disease. * Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1. * Serum albumin ≥3.0 gm/dL. * Adequate organ function including: * A. Marrow: Hemoglobin ≥10.0 gm/dL, absolute granulocyte count (AGC) ≥1,000/mm3, platelets ≥75,000/mm3, absolute lymphocyte count ≥475/mm3. * B. Hepatic: Serum total bilirubin ≤2.5 x upper limit of normal (ULN), ALT (SGPT) and AST (SGOT) ≤2.5 x ULN. * C. Renal: Serum creatinine (sCr) ≤ 1.5 x upper limit of normal. * Prior therapy for melanoma that may include surgery, radiation therapy, immunotherapy including interleukins and interferon, and/or ≤2 different regiments of systemic chemotherapy, targeted therapy, or other experimental systemic therapies. Prior treatment with immune checkpoint inhibitors is not allowed. * Patients must be ≥4 weeks since major surgery, radiotherapy, chemotherapy (6 weeks if they were treated with nitrosureas) or biotherapy/targeted therapies. * Patients must have the ability to understand the study, its risks, side effects, potential benefits and be able to give written informed consent to participate. Patients may not be consented by a durable power of attorney (DPA). * Male and female subjects of child producing potential must agree to use contraception or avoidance of pregnancy measures while enrolled on study and receiving the experimental drug, and for one month after the last immunization. Exclusion Criteria: * Age \<18-years-old. * Active CNS metastases or carcinomatous meningitis. Patients with CNS lesions that have been treated and who have no evidence of progression in the brain on CT/MRI for ≥1 month are eligible. Pregnant or nursing women due to the unknown effects of immunization on the developing fetus or newborn infant. * Other malignancy within five years, except the following may be eligible: * patients curatively treated for localized squamous or basal cell carcinoma of the skin or for carcinoma in situ of the uterine cervix (CIN) or breast, * patients with a history of malignant tumor who have been disease free for at least five years and are not currently being treated. * History of an allogeneic solid organ transplant or bone marrow transplant, or current active immunosuppressive therapy such as cyclosporine, tacrolimus, etc. * Subjects taking systemic (parentally or orally) corticosteroid therapy for any reason, including replacement therapy for hypoadrenalism, are not eligible. Topical steroids are acceptable as are intranasal steroids. * Active infection or antibiotics within 48 hours prior to study enrollment, including unexplained fever (temp \> 38.1°C), if deemed clinically significant by the treating physician. * Evidence of active autoimmune disease (e.g., systemic lupus erythematosis, rheumatoid arthritis, with the exception of vitiligo. Patients with a remote history of asthma or mild asthma are eligible. * Other serious medical conditions that may be expected to limit life expectancy to less than 2 years (e.g., liver cirrhosis). * Any condition, psychiatric or otherwise, that would preclude informed consent, consistent follow-up or compliance with any aspect of the study (e.g., untreated schizophrenia or other significant cognitive impairment, etc). * Patients having previously undergone splenectomy. * Patients with known hepatitis or unstable liver disease, and/or positive serologies for Hepatitis B or C and HIV. * Patients with sickle-cell anemia or thalassemia major. * Subjects who received prior treatment with immune checkpoint inhibition, consisting of ipilimumab, tremelimumab, nivolumab, pembrolizumab or other antibody to CTLA4 or PD-1.