A Phase II Study Using a Peptide Vaccine With or Without Aldesleukin Following a Lymphodepleting Chemotherapy and Reinfusion of Autologous Lymphocytes Depleted of T Regulatory Lymphocytes in Metastatic Melanoma
I. Determine the ability of gp100 and MART-1 peptide vaccines with or without a high-dose
interleukin-2 (IL-2), when administered after a nonmyeloablative, lymphodepleting
preparative regimen and reinfusion of autologous CD25+ T-regulatory-depleted lymphocytes, to
mediate tumor regression in patients with metastatic melanoma.
I. Determine the generation of antitumor lymphocytes and the rate of repopulation of CD25+
T-regulatory cells in patients treated with this regimen.
II. Determine the toxicity of this treatment regimen.
OUTLINE: This is a randomized study. Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients undergo apheresis and in-vitro depletion of T-regulatory cells. Patients
then receive a nonmyeloablative, lymphocyte-depleting preparative regimen comprising
cyclophosphamide IV over 1 hour on days -8 and -7 and fludarabine IV over 15-30 minutes on
days -6 to -2 followed by autologous T-regulatory-depleted lymphocytes IV over 20-30 minutes
on day 0. Patients receive vaccination with gp100:209-217 (210M) and MART-1:27-35 peptides
emulsified in Montanide ISA-51 subcutaneously (SC) on days 0-3, 20-23, 41-44, and 62-65.
Patients also receive filgrastim (G-CSF) SC beginning on day 1 and continuing until blood
ARM II: Patients receive treatment as in arm I. Patients also receive high-dose IL-2 IV over
15 minutes every 8 hours on days 0-4, beginning after the lymphocyte infusion. IL-2
treatment repeats every 3 weeks for up to 4 courses in the absence of disease progression or
After completion of study treatment, patients are followed every 1-3 months.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Objective clinical response (CR or PR)
Up to 2 years
National Cancer Institute Surgery Branch
United States: Food and Drug Administration
|National Cancer Institute Surgery Branch||Bethesda, Maryland 20892-1201|