Phase II Trial Using Aldesleukin (IL-2) Following a Lymphodepleting Chemotherapy and Reinfusion of Autologous Lymphocytes Depleted of T Regulatory Lymphocytes in Metastatic Melanoma
- Determine tumor regression in patients with metastatic melanoma treated with
nonmyeloablative lymphodepleting chemotherapy comprising cyclophosphamide and
fludarabine followed by autologous CD25-positive-T-regulatory-cell-depleted lymphocyte
reinfusion and high-dose interleukin-2.
- Determine the rate of repopulation of CD25-positive T-regulatory cells in patients
treated with this regimen.
- Determine the toxicity of this regimen in these patients.
- Apheresis and CD25-positive T-regulatory cell depletion: Patients undergo 1-2 aphereses
to collect peripheral blood mononuclear cells (PBMC). CD25-positive T-regulatory cells
are depleted from the collected PBMC in vitro.
- Nonmyeloablative lymphodepleting chemotherapy: Patients receive cyclophosphamide IV
over 1 hour on days -8 and -7 and fludarabine IV over 15-30 minutes on days -6 to -2.
- Autologous CD25-positive-T-regulatory-cell-depleted lymphocyte reinfusion: Patients
receive autologous lymphocytes IV over 20-30 minutes on day 0.
- Filgrastim (G-CSF) and high-dose interleukin-2 (IL-2) therapy: Patients receive G-CSF
subcutaneously (SC) daily beginning on day 0 and continuing until blood counts recover.
Patients also receive high-dose IL-2 IV over 15 minutes 3 times daily on days 0-4 and
14-18. Patients are reevaluated 4-6 weeks after completion of high-dose IL-2 therapy.
Patients achieving stable disease or a partial response may receive additional
high-dose IL-2 as above for up to 2 retreatment courses in the absence of disease
progression or unacceptable toxicity. Retreatment begins at least 6 weeks after
autologous lymphocyte reinfusion.
After completion of study treatment, patients are followed at 4-6 weeks and then every 1-2
PROJECTED ACCRUAL: A total of 16-29 patients will be accrued for this study within 1-1.5
Masking: Open Label, Primary Purpose: Treatment
Steven A. Rosenberg, MD, PhD
NCI - Surgery Branch
United States: Food and Drug Administration
|Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support||Bethesda, Maryland 20892-1182|
|NCI - Surgery Branch||Bethesda, Maryland 20892-1201|