Vaccine Therapy With or Without Cyclophosphamide in Treating Patients Who Have Undergone Surgery for Stage II, Stage III, or Stage IV Melanoma
Condition: Melanoma (Skin)
MeSH terms: Melanoma
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      RATIONALE: Vaccines made from peptides may help the body build an effective immune response
      to kill tumor cells. Drugs used in chemotherapy, such as cyclophosphamide, work in different
      ways to stop the growth of tumor cells, either by killing the cells or by stopping them from
      dividing. Cyclophosphamide may also stimulate the immune system in different ways and stop
      tumor cells from growing. Giving vaccine therapy together with cyclophosphamide after surgery
      may cause a stronger immune response to kill any remaining tumor cells. It may also prevent
      or delay the recurrence of melanoma.

      PURPOSE: This randomized phase I/II trial is studying the side effects of vaccine therapy
      when given with or without cyclophosphamide and to see how well they work in treating
      patients who have undergone surgery for stage II, stage III, or stage IV melanoma.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  Determine the safety of adjuvant vaccine therapy comprising multi-epitope melanoma
           peptides (MP) and multi-epitope melanoma helper peptides (MHP) emulsified in Montanide
           ISA-51 in patients with resected stage IIB-IV melanoma.

        -  Determine the safety of administering cyclophosphamide before vaccination in these
           patients.

        -  Compare the magnitude of immune response against vaccination comprising MP in
           combination with either MHP or tetanus toxoid helper peptide (TET) emulsified in
           Montanide ISA-51 with vs without cyclophosphamide in these patients.

      Secondary

        -  Compare the response rate and persistence of immune responses in patients treated with
           these regimens.

        -  Compare the magnitude of immune response against vaccination comprising TET or MHP with
           vs without cyclophosphamide in these patients.

        -  Compare the response rate and persistence of immune response against vaccination
           comprising TET or MHP with vs without cyclophosphamide in these patients.

        -  Determine the delayed-type hypersensitivity response to the peptide components of these
           vaccines in these patients.

        -  Compare, preliminarily, disease-free survival of patients treated with these regimens.

      OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified
      according to HLA-type (HLA-A1 positive vs HLA-A2 positive, HLA-A1 negative, or -A3 negative
      vs HLA-A3 positive, or -A1 negative) and participating center (University of Virginia [UVA]
      vs non-UVA). Patients are randomized to 1 of 4 treatment arms.

        -  Arm I: Patients receive vaccine comprising multi-epitope melanoma peptides (MP) and
           tetanus toxoid helper peptide emulsified in Montanide ISA-51 intradermally (ID) and
           subcutaneously (SC) on days 1, 8, 15, 29, 36, 43, 85, 183, 274, and 365.

        -  Arm II: Patients receive cyclophosphamide IV over 30-60 minutes on day -4. Patients then
           receive vaccine as in arm I.

        -  Arm III: Patients receive vaccine comprising MP and multi-epitope melanoma helper
           peptides emulsified in Montanide ISA-51 ID and SC on days 1, 8, 15, 29, 36, 43, 85, 183,
           274, and 365.

        -  Arm IV: Patients receive cyclophosphamide as in arm II. Patients then receive vaccine as
           in arm III.

      Treatment in all arms continues in the absence of disease progression or unacceptable
      toxicity.

      After completion of study treatment, patients are followed every 6 months for 2 years and
      then annually thereafter.

      PROJECTED ACCRUAL: A total of 173 patients will be accrued for this study within 2 years.
    

Intervention name(s): incomplete Freund's adjuvant; melanoma helper peptide vaccine; multi-epitope melanoma peptide vaccine; tetanus toxoid helper peptide; cyclophosphamide
Intervention type(s): Biological; Biological; Biological; Biological; Drug
Intervention description(s): Given intradermally and subcutaneously; Given intradermally and subcutaneously; Given intradermally and subcutaneously; Given intradermally and subcutaneously; Given IV
Intervention MeSH terms: Cyclophosphamide; Vaccines; Freund's Adjuvant
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: stage II melanoma; stage III melanoma; stage IV melanoma