Feasibility, Safety and Efficacy Evaluation of Alpha-Type 1 Dendritic Cell(DC)-Based Vaccines Loaded With Allogeneic Prostate Cell Lines in Combination With Androgen Ablation in Patients With PSA Progression After Local Therapy for Prostate Cancer
- The primary efficacy endpoint is to evaluate the effect of the alpha-DC1 vaccine on
time to PSA progression.
- PSA progression is defined as a rise in the PSA value to > 1.0ng/ml.
- The secondary efficacy objectives include:
- To determine the change in PSA velocity prior to and following the proposed treatment
- To estimate time to development of metastatic disease
- To evaluate the immunologic response to the vaccine in all patients
- To evaluate the immune response to HLA-A2.1 restricted peptides derived from PAP and
PSMA in patients who are A2.1 positive
- EPIMAX analysis will be used to define the magnitude and cytokine production profiles
of CD4+ and CD8+ T cell responses to the overlapping peptide libraries and individual
peptides covering the entire span of PAP and PSMA molecules.
This is a 2 group crossover trial in which patients are randomly assigned to one of two
A. 3 months of androgen ablation (AA) to be followed at PSA progression by 3 months of the
combination of AA and alpha-type 1 dendritic cell vaccine (DC1) B. 3 months of the
combination of AA and alpha-type 1 dendritic cell vaccine followed at PSA progression by 3
months of AA.
In this crossover trial each patient will serve as their own control. Following either
therapy the time to PSA progression, defined as the time between treatment and the first
instance of PSA increase to 1ng/ml. The endpoint is the difference between time to PSA
progression for the combination of AA + DC1 compared to AA alone. A total of 12 evaluable
patients (6 patients/arm) will be enrolled on the trial. Patients who do not complete both
courses (AA and AA+DCV) will be replaced. This schema will also help us better estimate the
time to PSA recovery following 3 months of limited androgen ablation in our cohort of
All patients in Cohort B, will commence DC1-based vaccination 2 weeks prior to treatment
with the LHRH analogue. Each patient will receive four i.d. doses of the vaccine at weeks
1, 4, 8, and 12. The LHRH analogue (Lupron 22.5 mg or Zoladex 10.8 mg), will be
administered 2 weeks after the 1st dose of the DC vaccine. Additional courses of
vaccination can be administered to any patients without evidence of disease progression,
every 3 months for up to 12 months.
Patients will undergo a thorough pre-study evaluation, and then undergo leukapheresis to
generate the DC-based vaccine. Each patient will receive 4 doses of intradermal
(i.d.)DC1-based vaccine at weeks 0/1, 4, 8, and 12.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment
The primary feasibility objective is the ability to successfully generate and administer the alpha-DC1 vaccine.
ongoing throughout trial
Appleman J Leonard, MD, PhD
University of Pittsburgh
United States: Food and Drug Administration
|University of Pittsburgh Cancer Institute||Pittsburgh, Pennsylvania 15213|