Vaccine Therapy With or Without Interleukin-12 Followed by Daclizumab in Treating Patients With Metastatic Melanoma

Inclusion Criteria:

• Patients must have histologically confirmed melanoma with evidence of metastatic disease 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 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
• HLA-A2 positive by flow cytometry or standard HLA typing

• Must agree to undergo biopsy of accessible tumor before and after therapy, when feasible

  • If a biopsy cannot be done, then a prior pathologic specimen from the patient must show tumor cells that are positive for HMB45 and MelanA
  • The tumor must express at least 2 antigens in the vaccine for the patient to be eligible

• No untreated brain metastases

  • 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 are eligible
• Life expectancy ≥ 12 weeks
• ECOG performance status (PS) 0-1 (Karnofsky PS 80-100%)
• WBC ≥ 3,000/mm³
• ANC ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 9 g/dL
• Creatinine ≤ 1.5 times upper limit of normal (ULN)
• Total bilirubin ≤ 1.5 times ULN
• AST and ALT ≤ 2 times ULN
• LDH < 1.25 times ULN
• 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
• Negative pregnancy test
• Not pregnant or nursing
• No history of allergic reactions attributed to compounds of similar chemical or biologic composition of recombinant interleukin-12 (IL-12) or other agents used in the study
• No 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

• No patients with intrinsic immunosuppression, including seropositivity for HIV antibody

  • Patients should be tested for HIV infection

• No 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

• No 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 positive can be eligible provided they are PCR-negative

• No active or history of autoimmune disease including, but not limited to, rheumatoid arthritis (RF-positive with current or recent flare), inflammatory bowel disease, systemic lupus erythematosus (clinical evidence with ANA 1:80 or greater), ankylosing spondylitis, scleroderma, multiple sclerosis, autoimmune hemolytic anemia, or immune thrombocytopenic purpura

  • Seropositivity alone will not be considered active autoimmunity
  • Patients with immune-mediated hypothyroidism and/or vitiligo are allowed
• No active gastrointestinal bleeding or uncontrolled peptic ulcer disease
• Any number of prior therapies allowed
• At least 4 weeks since prior chemotherapy or radiotherapy (6 weeks for carmustine or mitomycin C) and recovered
• No prior vaccine containing any of the melanoma antigen peptides or prior daclizumab
• No other concurrent investigational agents
• No concurrent systemic corticosteroids (except physiologic replacement doses), or other immunosuppressive drugs (e.g., cyclosporin A)