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RATIONALE: Drugs used in chemotherapy, such as fludarabine and cyclophosphamide, work in different ways to stop tumor cells from dividing so they stop growing or die. Treated white blood cells, vaccines, and aldesleukin may make the body build an immune response to kill tumor cells.
PURPOSE: This phase II trial is studying how well giving fludarabine and cyclophosphamide together with white blood cell infusion, vaccine therapy, and aldesleukin works in treating patients with recurrent or refractory metastatic melanoma.
- Determine complete clinical tumor regression in patients with recurrent or refractory metastatic melanoma treated with lymphocyte-depleting nonmyeloablative preparative chemotherapy comprising fludarabine and cyclophosphamide followed by autologous lymphocyte infusion, recombinant fowlpox virus encoding gp100 peptide, and aldesleukin.
- Determine the survival of patients treated with this regimen.
- Determine the safety of this regimen in these patients.
OUTLINE: Patients are stratified according to the availability of suitable reactive cells (peripheral blood lymphocytes [PBL] vs tumor-infiltrating lymphocytes [TIL]).
- Autologous lymphocyte activation and expansion: Autologous PBL or TIL are activated in vitro with gp100:209-217 (210M) antigen (gp100) and expanded.
- Lymphocyte-depleting nonmyeloablative preparative regimen: Patients receive cyclophosphamide IV over 1 hour on days -7 and -6 and fludarabine IV over 15-30 minutes on days -5 to -1.
- Autologous lymphocyte infusion: Autologous PBL or TIL are reinfused over 20-30 minutes on day 0*. Patients also receive filgrastim (G-CSF) subcutaneously (SC) once daily beginning on day 1 or 2 and continuing until blood counts recover.
- Fowlpox vaccine administration: Patients receive recombinant fowlpox virus encoding gp100 peptide IV over 1-2 minutes on days 2 and 28 (if treated with high-dose aldesleukin [IL-2], as below) OR days 2 and 43 (if treated with low-dose IL-2, as below).
- IL-2 therapy: Patients receive high-dose IL-2 IV over 15 minutes every 8 hours on days 0*-4 (beginning within 24 hours after lymphocyte infusion) and 28-32 OR low-dose IL-2 SC on days 0*-4 (beginning within 24 hours after lymphocyte infusion), 7-11, 14-18, 21-25, 28-32, 35-39, 50-54, 57-61, 64-68, 71-75, 78-82, and 85-89.
NOTE: *Day 0 is 1-4 days after the last dose of fludarabine.
Patients are evaluated between days 72-86 (if treated with high-dose IL-2) OR days 98-123 (if treated with low-dose IL-2). Patients with stable disease or a minor, mixed, or partial response may receive up to 2 retreatment courses as above. Patients with progressive disease after IV lymphocyte infusion may be retreated with intra-arterial lymphocytes along with all other agents outlined above.
After completion of study treatment, patients are followed at 2-4 weeks (if treated with high-dose IL-2) OR at 3 weeks (if treated with low-dose IL-2) and then annually thereafter.
PROJECTED ACCRUAL: A total of 68 will be accrued for this study.
Masking: Open Label, Primary Purpose: Treatment
aldesleukin, filgrastim, fowlpox virus vaccine vector, gp100 antigen, therapeutic autologous lymphocytes, therapeutic tumor infiltrating lymphocytes, cyclophosphamide, fludarabine phosphate
NCI - Surgery Branch
National Cancer Institute (NCI)
Published on BioPortfolio: 2014-08-27T03:54:19-0400
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