A Randomized Phase II Study of Multipeptide Vaccination With or Without IL-12, Then Combined With Regulatory T Cell Depletion Using Daclizumab in Patients With Metastatic Melanoma
I. To determine whether admixture of recombinant interleukin-12 (IL-12) with vaccine
emulsion will increase the frequency of vaccine-induced CD8+ T cells in the blood.
II. To determine whether administration of daclizumab will deplete CD4+CD25+ regulatory T
cells from the peripheral and potentiate specific immune responses induced by vaccination.
III. To determine whether vaccination with or without daclizumab will be safe in this
I. To determine whether vaccination with or without daclizumab will have clinical activity
in patients with advanced melanoma.
II. To determine whether clinical response may be associated with particular gene expression
profiles in the tumor microenvironment.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive multipeptide vaccination comprising recombinant MAGE-3.1 antigen,
MART-1 antigen, gp100 antigen, and NA17-A2 peptide emulsified with Montanide ISA-51
intradermically (ID) or subcutaneously (SC) on days 1, 22, and 50.
ARM II: Patients receive vaccination as in arm I with an admixture of recombinant
interleukin-12 (IL-12) on days 1, 22, and 50.
In both arms, patients are evaluated for immune response. Patients with partial response or
stable disease may be immunized for up to a maximum of 1 year. Patients with complete
response may be treated with 1 additional course of 3 vaccinations.
EXPANDED COHORT: Additional patients are accrued to the arm with higher immune response and
receive daclizumab IV over 15 minutes on day -7. Patients then receive vaccination as in arm
I or arm II on days 1, 22, and 50 in the absence of disease progression or unacceptable
Peripheral blood mononuclear cells are collected at baseline and periodically during study
for correlative studies.
After completion of study therapy, patients are followed up every 3 months.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Frequency of vaccine-induced CD8+ T cells assessed by ELISPOT
Baseline and every 9 weeks (after every 3 vaccinations)
University of Chicago Comprehensive Cancer Center
United States: Food and Drug Administration
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