Injection Of AJCC Stage IIB, IIC, III And IV Melanoma Patients With A Multi-Epitope Peptide Vaccine Using GM-CSF DNA As An Adjuvant: A Pilot Trial To Assess Safety And Immunity
This is a pilot trial to investigate the use of GM-CSF DNA as an adjuvant for peptide
vaccination in patients with metastatic melanoma. The objective of this study is to
determine the safety and adjuvant effect of vaccination with the gene coding for human
GM-CSF with a multi-epitope melanoma peptide vaccine (tyrosinase and gp100 peptides) in
patients with AJCC stage IIB, IIC, III and IV melanoma who are HLA-A2+. We will assess
whether use of GM-CSF DNA is safe and generates an immune response to peptides derived from
antigens on melanoma cells.
In the Dose Ranging part of the study, cohorts of 3 patients will be treated at increasing
dose levels of GM-CSF DNA delivered subcutaneously (100, 400, or 800 ug), followed by
administration of both peptides subcutaneously to the same site on day 5 or day 6. Patients
will be treated monthly for three immunizations. Pharmacokinetic studies will be performed
during the first cycle. Patients' peripheral blood mononuclear cells will be collected in
order to measure the T cell responses induced by the vaccines. Toxicity will be assessed
during this part of the study, although we do not expect to achieve a dose limiting toxicity
(DLT). The dose for the second part of the study will be the maximum tolerated dose.
The second part of the study will assess the immunological efficacy of the vaccine. Nine
patients will receive GM-CSF DNA delivered subcutaneously at one site, followed by
administration of both peptides to the same site on day 5 or day 6, every month for three
immunizations. A total of at least 18 patients is planned for both phases of the study.
Patients' peripheral blood mononuclear cells will be collected in order to measure the T
cell responses induced by the vaccines. Specifically, Elispot assays for CD8+ T cells
responses against the peptides will be assessed, and will be the primary method to determine
the generation of a specific immune response to the peptide antigens.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To establish the safety and a recommended dose of subcutaneous human GM-CSF DNA given in conjunction with a multi-epitope peptide vaccine in patients with AJCC stage IIB, IIC, III and IV melanoma who are HLA-A2+.
Up to 15 years post treatment,
Miguel-Angel Perales, MD
Memorial Sloan-Kettering Cancer Center
United States: Food and Drug Administration
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