Cyclophosphamide and Fludarabine Followed by Cellular Adoptive Immunotherapy and Vaccine Therapy in Patients With Metastatic Melanoma
Condition: Melanoma (Skin)
MeSH terms: Melanoma
Study type: Interventional
Phase: Phase 1

Summary: 
      RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide and fludarabine, may be used
      to prepare the body for other treatments, such as cellular adoptive immunotherapy. Biological
      therapies, such as cellular adoptive immunotherapy, may stimulate the immune system in
      different ways and stop tumor cells from growing. Vaccines may help the body build an
      effective immune response to kill tumor cells. Giving cyclophosphamide together with
      fludarabine followed by biological therapy may be an effective treatment for metastatic
      melanoma.

      PURPOSE: This phase I trial is studying the side effects of giving cyclophosphamide together
      with fludarabine followed by cellular adoptive immunotherapy, and vaccine therapy in treating
      patients with metastatic melanoma.
    

Detailed description: 
      OBJECTIVES:

        -  Determine the magnitude and duration of the expansion of antigen-specific T-cells
           present in post-vaccination peripheral blood mononuclear cells and reinfused after
           immunosuppression in patients with metastatic melanoma.

        -  Characterize the T-cell subsets (phenotype, function, T-cell receptor repertoire) in
           these patients.

        -  Determine the tumor response in patients treated with this regimen.

        -  Determine the toxicity of this regimen in these patients.

      OUTLINE: This is an open-label dose-finding study. Patients undergo leukapheresis to collect
      whole peripheral blood mononuclear cells (PBMC). Patients are then assigned to 1 of 3
      treatment groups.

        -  Group 1 (closed to accrual as of 5/8/2007): Patients receive cyclophosphamide IV on days
           -7 and -6 and fludarabine IV on days -5 to -3. Patients undergo autologous PBMC infusion
           on day 0. Patients also receive vaccination comprising Melan-A vaccine emulsified in
           incomplete Freund's adjuvant (IFA) subcutaneously (SC) once every 3 weeks beginning on
           day 0.

        -  Group 2 (closed to accrual as of 8/15/2007): Patients receive cyclophosphamide IV at a
           higher dose than in group 1 on days -7 and -6 and fludarabine IV on days -5 to -3.
           Patients also receive an autologous PBMC infusion and Melan-A vaccine emulsified in IFA
           as in group 1.

        -  Group 3: Patients receive cyclophosphamide IV at 30 mg/kg on days -7 and -6. Patients
           also receive fludarabine 30 mg/m2 IV on days -5 to -3, autologous PBMC infusion on day
           0,and Melan-A vaccine emulsified in IFA and IMP321. The first 3 patients receive 25
           micrograms of IMP321, in the absence of severe 3 or 4 toxicity, the dose will be
           escalated to IMP321 250 micrograms.

      PROJECTED ACCRUAL: A total of 9 patients will be accrued for this study.
    

Intervention name(s): Melan-A VLP vaccine, IMP321 adjuvant; adoptive immunotherapy; therapeutic autologous lymphocytes; cyclophosphamide; fludarabine phosphate
Intervention type(s): Biological; Biological; Biological; Drug; Drug
Intervention MeSH terms: Cyclophosphamide; Fludarabine; Fludarabine phosphate
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: stage IV melanoma; recurrent melanoma