Vaccine Therapy and GM-CSF With or Without Low-Dose Aldesleukin in Treating Patients With Stage II, Stage III, or Stage IV Melanoma
Condition: Melanoma (Skin)
MeSH terms: Melanoma
Study type: Interventional
Phase: Phase 1

Summary: 
      RATIONALE: Vaccines made from peptides may help the body build an effective immune response
      to kill tumor cells. Colony-stimulating factors, such as GM-CSF, may increase the number of
      immune cells found in bone marrow or peripheral blood. Aldesleukin may stimulate the white
      blood cells to kill tumor cells. Giving vaccine and different doses of GM-CSF mixed in
      incomplete Freund's adjuvant, with or without aldesleukin, may kill more tumor cells.

      PURPOSE: This phase I trial is studying the side effects and how well giving vaccine therapy
      together with GM-CSF, with or without low-dose aldesleukin, works in treating patients with
      stage II, stage III, or stage IV melanoma.
    

Detailed description: 
      OBJECTIVES:

        -  Determine the safety and toxicity profile of peptide vaccine comprising MART-1 antigen,
           gp100 antigen, and survivin antigen in combination with sargramostim (GM-CSF) emulsified
           in incomplete Freund's adjuvant (IFA) with or without low-dose aldesleukin in patients
           with stage II-IV melanoma.

        -  Determine the immunologic effects of two different doses of GM-CSF coemulsified with
           melanoma peptides in IFA in these patients.

        -  Determine the immunological effects of low-dose aldesleukin therapy administered after
           peptide immunization in these patients.

        -  Collect preliminary data on the impact of the vaccine on clinical outcomes in these
           patients.

      OUTLINE: This is a pilot study. Patients are stratified according to disease stage (II vs III
      or IV). Patients are sequentially enrolled into 1 of 4 different dose schedules.

        -  Dose schedule 1: Patients receive gp100 antigen, MART-1 antigen, survivin antigen, and
           sargramostim (GM-CSF) emulsified in incomplete Freund's adjuvant (peptide vaccine)
           subcutaneously (SC) on day 1. Treatment repeats every 21 days for 4 courses in the
           absence of disease progression or unacceptable toxicity.

        -  Dose schedule 2: Patients receive peptide vaccine as in group 1. Patients also receive
           low-dose aldesleukin SC twice daily on days 7-20. Treatment repeats every 21 days for 4
           courses in the absence of disease progression or unacceptable toxicity.

        -  Dose schedule 3: Patients receive peptide vaccine as in group 1 except with a higher
           dose of GM-CSF. Treatment repeats every 21 days for 4 courses in the absence of disease
           progression or unacceptable toxicity.

        -  Dose schedule 4: Patients receive peptide vaccine as in group 1 except with a higher
           dose of GM-CSF. Patients also receive low-dose aldesleukin SC twice daily on days 7-20.
           Treatment repeats every 21 days for 4 courses in the absence of disease progression or
           unacceptable toxicity.

      Cohorts of 5 patients receive treatment at subsequent dose schedule until the maximum
      tolerated dose schedule (MTDS) is determined. The MTDS is defined as the dose schedule
      preceding that at which 2 of 5 patients experience dose-limiting toxicity within the first
      course.

      After completion of study therapy, patients are followed every 3 months for up to 2 years.

      PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.
    

Intervention name(s): MART-1 antigen; IL-2; gp100 antigen; GM-CSF; MART-1a peptide
Intervention type(s): Biological; Biological; Biological; Biological; Biological
Intervention description(s): 1000 mcg; Day 1 of a 21 day cycle x 4; 0.5x10^6/m^2; 1000 mcg; Day 1 of a 21 day cycle x 4; 300mcg; 1000 mcg; Day 1 of a 21 day cycle x 4
Other intervention name(s): Interleukin-2, Proleukin®, aldesleukin; Leukine-Liquid, sargramostatin
Intervention MeSH terms: Aldesleukin; Interleukin-2
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: stage II melanoma; stage III melanoma; stage IV melanoma; recurrent melanoma