Vaccine Therapy in Treating Patients With Stage III or Stage IV Melanoma
RATIONALE: Vaccines made from a person's white blood cells mixed with tumor proteins may make the body build an immune response to kill tumor cells. Biological therapies such as denileukin diftitox may be able to deliver cancer-killing substances directly to melanoma cells. Combining vaccine therapy with biological therapy may kill more tumor cells.
PURPOSE: Phase I/II trial to study the effectiveness of combining vaccine therapy with denileukin diftitox in treating patients who have stage III or stage IV melanoma.
Biological: denileukin diftitox
Biological: recombinant CD40-ligand
Biological: therapeutic autologous dendritic cells
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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)|
- Safety and tolerability as assessed by clinical and laboratory evaluation at every visit [ Designated as safety issue: Yes ]
- Overall survival as assessed by clinical staging (CT scan and positron emission tomography [PET]) every 3 months [ Designated as safety issue: No ]
- Depletion of regulatory T-cells as assessed by tetramer stainings at every visit [ Designated as safety issue: No ]
- Induction of antigen-specific immune responses as assessed by elispot and tetramer staining at every visit [ Designated as safety issue: No ]
- Time to progression as assessed by clinical staging (CT scan and PET) every 3 months [ Designated as safety issue: No ]
- Objective response rate as assessed by clinical staging (CT scan and PET) every 3 months [ Designated as safety issue: No ]
|Study Start Date:||October 2002|
|Study Completion Date:||May 2012|
|Primary Completion Date:||October 2011 (Final data collection date for primary outcome measure)|
- 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 months.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00056134
|Dermatologische Klinik mit Poliklinik - Universitaetsklinikum Erlangen|
|Erlangen, Germany, D-91052|
|Study Chair:||Gerold Schuler||Dermatologische Klinik MIT Poliklinik-Universitaetsklinikum Erlangen|