Peptide Vaccination for Patients at High Risk for Recurrent Melanoma
Condition: Melanoma
MeSH terms: Melanoma
Intervention: Glycoprotein 100 (GP100): 209-217 (210M); Interleukin-2 (IL-2); Montanide ISA 51; Melanoma antigen recognized by T-cells (MART)-1: 27-35; 27-35 (27L): melanoma antigen recognized by T-cells (MART)-1; melanoma antigen recognized by T-cells (MART)-1: 26-35(27L)
Intervention description: 720,000 IU/kg as an intravenous bolus over a 15 minute period every 8 hours and continuing for up to 4 days (a maximum of 12 doses).
Intervention MeSH terms: polysaccharide-K; Interleukin-2; Monatide (IMS 3015)
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 138.0
Sex: All
Minimum age: 7 Years
Healthy volunteers: No
Keywords: Adjuvant Therapy; MART-1 Peptides; GP100 Peptide; Immunologic Response; Melanoma

Summary:

      This study will examine the effectiveness and side effects of an experimental vaccine to
      prevent recurrence of melanoma. The likelihood of melanoma returning is higher in patients
      who have melanoma lesions deep in the skin, in patients who have had positive lymph nodes,
      and in patients who have had surgery for metastatic disease (cancer that has spread beyond
      the primary site). Melanoma tumors produce proteins called glycoprotein 100 (gp100) and
      melanoma-associated antigen recognized by T cells 1 (MART-1). Vaccination with specific
      pieces of these proteins (peptides) may boost the immune system's fight against the cancer.
      The vaccine injections are mixed with an oil-based substance called Montanide ISA-51, which
      is intended to increase the immune response to the peptide.

      Patients 16 years of age and older whose melanoma has been surgically removed and who are
      currently free of disease may be eligible for this study. Candidates will be screened with a
      physical examination and blood and urine tests. An electrocardiogram (EKG), x-rays and other
      imaging studies will be done if recent results are not available. Some candidates may require
      heart tests, such as a cardiac stress test or echocardiogram, or lung function tests. In
      addition, all candidates will be tested for human leukocyte antigen (HLA) tissue type;
      patients must be type human leukocyte antigens (HLA-A)*0201, the type on which this vaccine
      is based.

      Participants will be randomly assigned to receive one of four different vaccines to determine
      which peptides offer the best immunity. Each treatment course consists of two injections of
      the vaccines every 3 weeks for four times. The injections are given under the skin of the
      thigh. After every other treatment course (every 6 months), patients will undergo a series of
      x-rays and scans to look for tumor. The immunizations may continue for up to 12 months as
      long as the melanoma does not return. The injections are given at the National Institutes of
      Health (NIH) Clinical Center. Patients are monitored for 1 hour after each injection and have
      blood tests and a physical examination to look for treatment side effects.

      Patients will be followed with blood tests every 12 weeks to monitor body functions. They
      will also undergo leukapheresis-a procedure to collect white blood cells-before starting
      treatment and about 3 to 4 weeks after the fourth vaccine to evaluate how the vaccines affect
      the action of the immune system cells. For this procedure, blood is drawn through a needle in
      the arm, similar to donating blood. The blood goes through a machine that separates out the
      lymphocytes (white blood cells), and the rest of the blood is returned through a needle in
      the other arm. Some patients may undergo a biopsy-surgical removal of a small piece of tissue
      under local anesthetic-of normal skin and tumor or lymph node tissue to examine the effects
      of the vaccines on the tumor immune cells.

      Patients whose disease returns during the first course of vaccine therapy will have surgery
      to remove the tumor and will continue to receive the vaccine treatment. Patients whose tumor
      returns after completing one course of therapy may receive a substance called interleukin-2
      (IL-2), which can boost immune function against the tumor. interleukin-2 (IL-2) is given
      intravenously (through a small tube placed in a vein) every 8 hours for 4 days. This regimen
      is repeated after 10 to 14 days. Those who respond to interleukin-2 (IL-2) will have a third
      course of treatment after 2 months. Patients whose disease recurs after treatment will be
      taken off the study and will be referred back to their referring physician or to another
      study, if an appropriate one is available.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

        Human leukocyte antigens (HLA-A)*0201 patients, age greater than or equal to 16 years, with
        lesions greater than or equal to 1.5 mm in thickness, or greater than or equal to 1
        positive lymph node, or ulcerated lesions, or local recurrence, or completely resected
        metastatic melanoma, within 6 months of surgical resection will be considered. Patients
        must be clinically disease free at the time of protocol entry as documented by radiologic
        studies within 6 weeks of patient entry.

        Serum creatinine of 2.0 mg/dl or less.

        Total bilirubin 1.6 mg/dl or less, except for patients with Gilbert's Syndrome who must
        have a total bilirubin less than 3.0 mg/dl.

        White blood cell (WBC) 3000/mm^3 or greater.

        Platelet count 90,000 mm^3 or greater.

        Serum aspartate aminotransferase (AST)/alanine aminotransferase (ALT) less than three times
        normal.

        Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

        Patients of both genders must be willing to practice effective birth control during this
        trial because the potential for teratogenic effects are unknown.

        Patients may have had prior adjuvant treatment with immunotherapy, including interferon, or
        may have had treatment for metastatic disease and are now no evidence of disease (NED),
        including chemotherapy or biotherapy, as long as 3 weeks have elapsed since prior systemic
        therapy.

        EXCLUSION CRITERIA:

        Patients will be excluded:

          1. who have ocular or mucosal melanoma.

          2. who are undergoing or have undergone in the past 3 weeks any systemic therapy except
             surgery for their cancer, and must have recovered from any adverse effects of
             treatment prior to entry, other than those that do not have clinical implications,
             e.g. vitiligo, alopecia.

          3. have active systemic infections, autoimmune disease or any known immunodeficiency
             disease.

          4. who require systemic steroid therapy.

          5. who are pregnant or breastfeeding.

          6. who are known to be positive for hepatitis B surface antigen (B(s)AG) or human
             immunodeficiency virus (HIV) antibody.

          7. who have any form of active primary or secondary immunodeficiency or who have not
             recovered immune competence after chemotherapy or radiation therapy.

          8. who have previously been immunized with melanoma antigen recognized by T-cells
             (MART)-1.

          9. who have known hypersensitivity to any of the agents used in this study.

        ELIGIBILITY FOR ADMINISTRATION OF Interleukin-2 (IL-2):

        Patients who develop progressive disease while receiving peptide alone must meet the
        following criteria to be eligible to receive Interleukin-2 (IL-2):

          1. Patients must have measurable metastatic melanoma.

          2. Patients may not have active major medical illnesses such as cardiac ischemia,
             myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary
             disease.

          3. Patients with recent prolonged history of cigarette smoking or symptoms of respiratory
             dysfunction must have a normal pulmonary function test as evidenced by a forced
             expiratory volume 1 (FEV 1) greater than 60% predicted.

          4. Patients with electrocardiogam (EKG) abnormalities, symptoms of cardiac ischemia or
             arrhythmias or age greater than 50 years will have a normal stress cardiac test
             (stress thallium, stress multi-gated acquisition scan (MUGA), dobutamine
             echocardiogram or other stress test).

          5. Patients must be willing to sign a durable power of attorney (DPA).

          6. Serum creatinine of 2.0 mg/dl or less.

          7. Total bilirubin 2.0 mg/dl or less, except in patients with Gilbert's Syndrome who must
             have a total bilirubin less than 3.0 mg/dl.

          8. White blood cell (WBC) 3000/mm^3 or greater.

          9. Platelet count 90,000 mm^3 or greater.