A Dose Ranging Trial of MART-1/gp100/Tyrosinase/NY-ESO-1 Peptide-Pulsed Dendritic Cells Matured Using Cytokines With Autologous Lymphocyte Infusion With or Without Escalating Doses of Fludarabine for Patients With Chemotherapy-naive Metastatic Melanoma
This is a dose ranging study of intranodal administration of autologous dendritic cells (DC)
pulsed with tumor antigen class I peptides derived from MART-1 (26-35) (27L), gp100 (209-217
(210M), gp100 280-288 (288V), NY-ESO-1 157-165 (165V) and tyrosinase 207-215 as well as
class II MART-1 (51-73), NY-ESO-1 (119-143), MAGE-3 (243-258) and tyrosinase (450-462)
peptides preceded by Autologous Lymphocyte Infusion (ALI) and one of two doses of
Fludarabine. The nine or ten amino acid peptides representing HLA-A2 restricted T cell
epitopes of MART-1, gp100, NY-ESO-1 and tyrosinase will be pulsed onto autologous dendritic
cells produced by incubation of peripheral blood mononuclear cells obtained by apheresis
with interleukin-4 (IL-4) and GM-CSF and pulsed with four helper peptides then matured with
a cytokine cocktail including TNF-a, IL-6, IL-1b and PGE2. Melanoma antigen peptide-pulsed
dendritic cells will be administered at a total dose of 10 million cells each for four
intranodal injections to patients with chemotherapy-naïve metastatic melanoma.
DC matured with a cytokine cocktail and pulsed with class I and II peptides will be injected
intranodally, weekly for two doses, then every two weeks for two doses, for a total of four
injections to each cohort.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Overall Survival (OS)
Overall Survival is defined as the time from first day of treatment to time of death due to any cause. If a patient is still alive, survival time is censored at the time of last follow-up.
3 years, 6 months
Jeffrey S. Weber, M.D., Ph.D.
H. Lee Moffitt Cancer Center and Research Institute
United States: Institutional Review Board
|H. Lee Moffitt Cancer Center and Research Institute||Tampa, Florida 33612|