RATIONALE: 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. Biological therapies, such as cellular adoptive immunotherapy, may stimulate the immune system in different ways and stop tumor cells from growing. Aldesleukin may stimulate white blood cells to kill tumor cells. Giving cyclophosphamide together with cellular adoptive immunotherapy and aldesleukin may be an effective treatment for metastatic melanoma.
PURPOSE: This phase I trial is studying the side effects of cyclophosphamide, cellular adoptive immunotherapy, and aldesleukin in treating patients with metastatic melanoma.
Primary Outcome Measures:
- Safety [ Designated as safety issue: Yes ]
- Duration of in vivo persistence of adoptively transferred CD8+ cytotoxic T-lymphocyte clones [ Designated as safety issue: Yes ]
Secondary Outcome Measures:
- Response [ Designated as safety issue: No ]
| Estimated Enrollment: |
12 |
| Study Start Date: |
November 2006 |
| Estimated Primary Completion Date: |
April 2009 (Final data collection date for primary outcome measure) |
OBJECTIVES:
Primary
- Assess the safety and toxicity of cyclophosphamide, adoptive immunotherapy comprising autologous CD8+ antigen-specific cytotoxic T-lymphocyte (CTL) clones, and aldesleukin in patients with metastatic melanoma.
- Assess the duration of in vivo persistence of adoptively transferred CD8+ CTL clones.
Secondary
- Evaluate the antitumor effect of this regimen in these patients.
OUTLINE: This is a nonrandomized study. Patients undergo leukapheresis or blood draws for collection of peripheral blood mononuclear cells for the generation of antigen-specific cytotoxic T-lymphocyte (CTL) clones. Patients are assigned to 1 of 2 treatment cohorts.
- Cohort I: Patients receive cyclophosphamide IV on days -3 and -2 and autologous CD8+ CTL clones IV over 30-60 minutes on day 0. Patients also receive high-dose aldesleukin subcutaneously (SC) 3 times a day on days 0-5 in the absence of disease progression or unacceptable toxicity.
- Cohort II: Patients receive cyclophosphamide and autologous CD8+ CTL clones as in cohort I. Patients receive low-dose aldesleukin SC twice daily on days 0-14 in the absence of disease progression or unacceptable toxicity.
After the completion of study treatment, patients are followed periodically for at least 1 year.
PROJECTED ACCRUAL: A total of 12 patients will be accrued for this study.