Vaccine Therapy With or Without Recombinant Interleukin-12 Followed by Daclizumab in Treating Patients With Metastatic Melanoma
Condition: Recurrent Melanoma; Stage IV Skin Melanoma
MeSH terms: Melanoma
Intervention: NA17.A2 Peptide Vaccine; Recombinant MAGE-3.1 Antigen; Recombinant Interleukin-12; MART-1 Antigen; Laboratory Biomarker Analysis
Intervention description: Given SC or ID; Given SC or ID; Given SC or ID; Given SC or ID; Correlative studies
Intervention MeSH terms: Interleukin-12
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial is studying how well giving vaccine therapy together with or
      without recombinant interleukin-12 followed by daclizumab works in treating patients with
      melanoma that has spread to other places in the body. Vaccines made from peptides or antigens
      may help the body build an effective immune response to kill tumor cells. Recombinant
      interleukin-12 may kill tumor cells by stopping blood flow to the tumor and by stimulating
      white blood cells to kill melanoma cells. Monoclonal antibodies, such as daclizumab, may
      decrease the number of regulatory T cells (T cells that suppress the activation of the
      immmune system) and may lead to a better immune response against melanoma. It is not yet
      known whether vaccine therapy is more effective with interleukin-12 and daclizumab in
      treating melanoma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically confirmed melanoma with evidence of metastatic
             disease either by radiologic or physical examination

               -  In-transit metastases are allowed

               -  Biopsy should be performed to reconfirm the diagnosis in cases of doubt

          -  Patients must have measurable disease

               -  For computed tomography (CT) imaging, this is defined as at least one lesion that
                  can be accurately measured in at least one dimension (longest diameter to be
                  recorded) as ≥ 20 mm by conventional techniques or as ≥ 10 mm by spiral CT scan

               -  For cutaneous lesions, these must be measurable with a ruler and documented
                  photographically with a ruler in place

          -  There are no limits on the number of prior therapies; patients must not have received
             a vaccine containing any of the melanoma antigen peptides, nor previously received
             daclizumab; at least 4 weeks must have passed since prior chemotherapy or radiation
             therapy (6 weeks for BCNU [carmustine] or mitomycin C)

          -  Life expectancy greater than or equal to 12 weeks

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (Karnofsky ≥ 80%)

          -  Leukocytes ≥ 3,000/mcL

          -  Absolute neutrophil count (ANC) ≥ 1,500/mcL

          -  Hemoglobin ≥ 9 g/dL

          -  Platelets ≥ 100,000/mcL

          -  Creatinine ≤ 1.5 x upper limit of normal (ULN)

          -  Total bilirubin ≤ 1.5 x ULN

          -  Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]) ≤
             2 x institutional ULN

          -  Lactate dehydrogenase (LDH) < 1.25 x ULN

          -  Human leukocyte antigen (HLA) typing: patient must express HLA-A2, either by flow
             cytometry or by standard HLA typing

          -  Patient must agree to undergo biopsy of accessible tumor before and after therapy,
             when feasible, to study tumor cell properties and characteristics of immune cells; if
             a biopsy cannot be done, then a prior pathologic specimen from the patient must show
             tumor cells that are positive for melanosome specific antigen (HMB45) and MLANA
             (MelanA); the tumor must express at least 2 antigens in the vaccine for the patient to
             be eligible

          -  Women of child-bearing potential and men must agree to use adequate contraception
             (hormonal, barrier method of birth control, or abstinence) prior to study entry, for
             the duration of treatment, and for 2 months after completion of treatment; a pregnancy
             test must be done and be negative for women of child-bearing potential; should a woman
             become pregnant or suspect she is pregnant while participating in this study, she
             should inform her treating physician immediately

          -  Ability to understand and the willingness to sign a written informed consent document

        Exclusion Criteria:

          -  Patients who have had chemotherapy, biological or radiotherapy within 4 weeks (6 weeks
             for nitrosoureas or mitomycin C) prior to entering the study or those who have not
             recovered from adverse events due to agents administered more than 4 weeks earlier

          -  Patients may not be receiving any other investigational agents

          -  Presence of untreated brain metastases; all patients must undergo brain imaging as
             part of the pre-study evaluation; only patients with no brain metastases, or with
             brain lesions successfully treated by stereotactic radiation or surgical removal
             without progression at 28-day follow-up and off corticosteroids for 4 weeks, will be
             eligible

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition IL-12 or other agents used in the study

          -  Concurrent systemic corticosteroids (except physiologic replacement doses) or other
             immunosuppressive drugs (eg. cyclosporin A)

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, significant
             cardiac arrhythmia, or psychiatric illness/social situations that would limit
             compliance with study requirements

          -  Pregnant women are excluded from this study; breastfeeding should be discontinued if
             the mother is treated with IL-12; women of child-bearing age must be tested for
             urinary or serum beta-human chorionic gonadotropin (HCG)

          -  Patients with intrinsic immunosuppression, including seropositivity for human
             immunodeficiency virus (HIV) antibody; patients should be tested for HIV; HIV-positive
             patients are ineligible

          -  Psychiatric illness that may make compliance to the clinical protocol unmanageable or
             may compromise the ability of the patient to give informed consent; patients with
             clinical evidence of dementia should have a competent designee participate in decision
             making

          -  Serious concurrent infection, including active tuberculosis, hepatitis B, or hepatitis
             C; patients should be tested for hepatitis B surface antigen and hepatitis C antibody;
             patients who are hepatitis C antibody (Ab) positive can be eligible if they are
             polymerase chain reaction (PCR)-negative

          -  Active or history of autoimmune disease including but not limited to: rheumatoid
             arthritis (rheumatoid factor [RF]-positive with current or recent flare), inflammatory
             bowel disease, systemic lupus erythematosis (clinical evidence with antinuclear
             antibody [ANA] 1:80 or greater), ankylosing spondylitis, scleroderma, multiple
             sclerosis, autoimmune hemolytic anemia, and immune thrombocytopenic purpura;
             seropositivity alone will not be considered active autoimmunity; patients with
             immune-mediated hypothyrodisim and/or vitiligo are allowed

          -  Active gastrointestinal bleeding or uncontrolled peptic ulcer disease