Vaccination of HLA-A1 and/or -A2+ Stage III or IV Melanoma Patients With Tumor Peptide-Loaded Autologous Dendritic Cells With Prior Depletion of CD25-Positive Cells Using Denileukin Difitox (ONTAK)
- Compare the efficacy of vaccination with autologous dendritic cells pulsed with tumor
and influenza antigen peptides with or without ex vivo CD40-ligand and denileukin
diftitox, in terms of tumor-specific T-cell response, in patients with HLA-A1- and/or
HLA-A2.1-positive stage III or IV melanoma.
- Determine the safety and tolerability of these vaccinations in these patients.
- Determine tumor response in patients treated with these vaccinations.
- Phase I (Administration of denileukin diftitox and vaccinations #1 to #4): Patients
undergo leukapheresis for collection of peripheral blood mononuclear cells (PMBC). PBMC
are processed for the generation of dendritic cells (DC) to be used for vaccinations.
DC are pulsed with HLA-A1- and HLA-A2.1-restricted peptides derived from
melanoma-associated tumor antigens. DC are pulsed with or without ex vivo treatment
with CD40-ligand. Patients receive denileukin diftitox IV for 3 consecutive days before
the first vaccination. Patients receive 4 pulsed DC vaccinations subcutaneously (SC) on
days 1, 14, 42, and 70 in the absence of disease progression or unacceptable toxicity.
Patients who show a tumor response (at least stable disease) may receive vaccination #5 and
further booster vaccinations.
- Phase II: DC are generated and pulsed as in phase I. Patients receive up to 6
additional booster pulsed DC vaccinations SC on days 126, 184, 268, 356, 520, and 692
in the absence of disease progession or unacceptable toxicity.
Patients are followed for 10 years.
PROJECTED ACCRUAL: A total of 8-30 patients will be accrued for this study within 6-12
Masking: Open Label, Primary Purpose: Treatment
Safety and tolerability as assessed by clinical and laboratory evaluation at every visit
Dermatologische Klinik MIT Poliklinik-Universitaetsklinikum Erlangen
United States: Federal Government