A Vaccine (CDX-1401) With or Without a Biologic Drug (CDX-301) for the Treatment of Patients With Stage IIB-IV Melanoma

Inclusion Criteria

• Patients with fully resected stage IIb through IV melanoma, with melanoma validated by histology or cytology, who have NOT received prior therapy.
• Patients may have had primary cutaneous, mucosal, or ocular melanoma or metastasis from an unknown primary site.
• Tissue should be submitted for evaluation of NY-ESO-1 expression and T-cell infiltrates. However, availability of tissue and/or positivity for NY-ESO-1 is not mandatory.
• Prior radiation, chemotherapy or biologics NOT allowed
• Not currently receiving any anticancer therapy
• Age >= 18 years
• Because no dosing or adverse event (AE) data are currently available on the use of CDX-1401 or CDX-301 in patients = 3,000/mcL
• Absolute neutrophil count >= 1,000/mcL
• Platelets >= 75,000/mcL
• Hemoglobin > 9 g/dL
• Total bilirubin = 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
• The first six patients enrolled in the Flt3L arm of the study cannot be human immunodeficiency virus (HIV)-positive. After the evaluation of safety in the first 6 patients, HIV-positive patients with adequate immune function as evidenced by stable CD4 counts >= 350/mm^3 are allowed to participate if the following criteria are met:
• maintained on stable antiretroviral therapy with no significant drug interactions, and
• no recent history of acquired immunodeficiency syndrome (AIDS) indicator conditions (> 2 years from enrolling in trial), and
• physician providing patient's care for HIV must also approve of patient entering the study
• Females of childbearing potential must have a negative pregnancy test within 7 days before the initiation of protocol therapy.
• The effects of CDX-1401 or CDX-301 on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) before study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception before the study, for the duration of study participation, and 4 months after completion of CDX-1401 or CDX-301 administration.
• NOTE: Subjects are considered not of child-bearing potential if they are surgically sterile, they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy, or they are postmenopausal. Menopause is the age associated with complete cessation of menstrual cycles, menses, and implies the loss of reproductive potential. By a practical definition, it assumes menopause after 1 year without menses with an appropriate clinical profile at the appropriate age.
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• Patients who have had cytotoxic chemotherapy, radiotherapy, interferon (IFN), or ipilimumab before entering the study
• Immunosuppressive therapy within 30 days prior to initiation of protocol therapy
• Steroid therapy, or steroid therapy with more than 7 consecutive days of steroids within the prior 4 weeks
• The use of prednisone or equivalent = 4 weeks, are eligible
• Other invasive cancers that are clinically active
• Pregnancy or nursing or unwilling to take adequate birth control during therapy
• NOTE: Pregnant women are excluded from this study because CDX-1401 or CDX-301 and poly-ICLC have an unknown potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with CDX-1401 or CDX-301, breastfeeding should be discontinued if the mother is treated with CDX-1401 or CDX-301 and poly-ICLC
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to CDX-1401 or CDX-301