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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.
- 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.
Masking: Open Label, Primary Purpose: Treatment
denileukin diftitox, recombinant CD40-ligand, therapeutic autologous dendritic cells
Dermatologische Klinik mit Poliklinik - Universitaetsklinikum Erlangen
National Cancer Institute (NCI)
Published on BioPortfolio: 2014-08-27T03:55:26-0400
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Members of the tumor necrosis factor receptor superfamily with specificity for CD40 LIGAND. They are found on mature B-LYMPHOCYTES, some EPITHELIAL CELLS; and lymphoid DENDRITIC CELLS. Evidence suggests that CD40-dependent activation of B-cells is important for generation of memory B-cells within the germinal centers. Mutations in the CD40 antigen gene result in HYPER-IGM IMMUNODEFICIENCY SYNDROME, TYPE 3. Signaling of the receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.
A member of the tumor necrosis factor receptor superfamily with specificity for CD40 LIGAND. It is found on mature B-LYMPHOCYTES and some EPITHELIAL CELLS, lymphoid DENDRITIC CELLS. Evidence suggests that CD40-dependent activation of B-cells is important for generation of memory B-cells within the germinal centers. Mutations of the gene for CD40 antigen result in HYPER-IGM IMMUNODEFICIENCY SYNDROME, TYPE 3. Signaling of the receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.
A membrane glycoprotein and differentiation antigen expressed on the surface of T-cells that binds to CD40 ANTIGENS on B-LYMPHOCYTES and induces their proliferation. Mutation of the gene for CD40 ligand is a cause of HYPER-IGM IMMUNODEFICIENCY SYNDROME, TYPE 1.
A membrane bound member of the TNF superfamily that is expressed on activated B-LYMPHOCYTES; MACROPHAGES; and DENDRITIC CELLS. The ligand is specific for the 4-1BB RECEPTOR and may play a role in inducing the proliferation of activated peripheral blood T-LYMPHOCYTES.
An X-linked hyper-IgM immunodeficiency subtype resulting from mutation in the gene encoding CD40 LIGAND.
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