A Vaccine (CDX-1401) With or Without a Biologic Drug (CDX-301) for the Treatment of Patients With Stage IIB-IV Melanoma
Condition: Cutaneous Melanoma; Melanoma; Melanoma of Unknown Primary; Mucosal Melanoma; Ocular Melanoma; Stage IIB Cutaneous Melanoma AJCC v6 and v7; Stage IIC Cutaneous Melanoma AJCC v6 and v7; Stage III Cutaneous Melanoma AJCC v7; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7
MeSH terms: Melanoma; Skin Neoplasms
Intervention: DEC-205/NY-ESO-1 Fusion Protein CDX-1401; Poly ICLC; Recombinant Flt3 Ligand
Intervention description: Given SC or ID; Given SC; Given SC
Intervention MeSH terms: Poly I-C; Carboxymethylcellulose Sodium; Poly ICLC; Flt3 ligand protein
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 60.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies the effect of a vaccine called CDX-1401 given with or without a
      biologic drug called CDX-301 in treating patients with stage IIB-IV melanoma. The cancer
      vaccine CDX-1401 attaches to a protein that is made in tumor cells. The vaccine helps the
      body recognize the tumor to fight the cancer. The biologic drug CDX-301 may help the body
      make more of the tumor fighting cells, known as dendritic cells. Another biologic drug,
      poly-ICLC, may stimulate the immune system and help these dendritic cells mature so that they
      can recognize the tumor. Giving CDX-301 may make the immune response to a combination of
      CDX-1401 and poly-ICLC better.
    

Eligibility criteria:

        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 < 18 years of age, children are excluded from
                  this study, but will be eligible for future pediatric trials.

          -  Eastern Cooperative Oncology Group (ECOG) performance score of 0-1

          -  Life expectancy of at least 6 months

          -  Leukocytes >= 3,000/mcL

          -  Absolute neutrophil count >= 1,000/mcL

          -  Platelets >= 75,000/mcL

          -  Hemoglobin > 9 g/dL

          -  Total bilirubin < 1.5 x institutional upper limit of normal (bilirubin < 3 x
             institutional upper limit of normal for Gilbert's syndrome)

          -  Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT])
             =< 2.5 x institutional upper limit of normal

          -  Creatinine < 1.5 x institutional upper limit of normal OR creatinine clearance >= 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 < 0.125 mg/kg/day (absolute maximum of 10
                  mg/day) as replacement therapy is permitted

               -  Inhaled or topical corticosteroids are permitted

          -  Patients who are receiving any other investigational agents

          -  Current or history of systemic autoimmune disease requiring systemic therapy.

               -  NOTE: The following will not be exclusionary:

                    -  The presence of laboratory evidence of autoimmune disease (e.g., positive
                       antinuclear antibody [ANA] titer) without associated symptoms

                    -  Clinical evidence of vitiligo

                    -  Other forms of depigmenting illness

          -  Cardiovascular disease that meets one of the following: congestive heart failure (New
             York Heart Association Class III or IV), active angina pectoris, or recent myocardial
             infarction (within the last 6 months)

          -  Cirrhosis or chronic hepatitis C virus positivity or chronic hepatitis B infection

               -  NOTE: A positive hepatitis B serology indicative of previous immunization (i.e.,
                  hepatitis B virus surface antibody [HBsAb]-positive and hepatitis B virus core
                  antibody [HBcAb]-negative), or a fully resolved acute hepatitis B virus infection
                  is not an exclusion criterion

          -  Known history of immunodeficiency disorder other than HIV-positive status

          -  Extensive active brain disease including symptomatic brain metastases or presence of
             leptomeningeal disease

               -  NOTE: Patients with brain metastasis, after definitive therapy with surgery or
                  stereotactic radiation and stable off steroids for >= 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 or poly-ICLC

          -  Prior organ allograft or allogeneic transplantation, if the transplanted tissue is
             still in place

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements

          -  Medical or psychiatric illness that would, in the opinion of the investigator,
             preclude participation in the study or the ability of patients to provide informed
             consent for themselves

          -  History of pulmonary disease such as emphysema or chronic obstructive pulmonary
             disease (COPD) (forced expiratory volume in 1 second [FEV1] < 60% of predicted for
             height and age). Pulmonary function tests (PFTs) are required in patients with
             prolonged smoking history or symptoms of respiratory dysfunction

          -  Vaccinations other than those given as part of this research study (with the exception
             of influenza vaccine) are prohibited throughout the duration of study participation.

               -  NOTE: Influenza vaccination (inactivated) is permitted during the flu season. The
                  preferred time is 7 to 14 days after CDX-1401 administration