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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

Phase 1
18 Years
Open (Enrolling)
Prostate Cancer

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Trial Information

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

Efficacy Endpoints:

- 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
treatment arms:

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.

Inclusion Criteria:

- Patients with histologically proven prostate cancer and tumors limited to the
prostate (including seminal vesicle involvement, provided all visible disease was
surgically removed) that have completed local therapy and have an elevated PSA after
surgery or rising PSA after radiation therapy, as defined below.

- Age > 18 years.

- Histologically confirmed diagnosis of prostate cancer.

- Previous treatment with definitive surgery or radiation therapy or both.

- No evidence of metastatic disease on physical exam, CT/MRI/CXR (see section 7.1 for
radiologic imaging), and bone scan within 4 weeks prior to randomization.

- Prior neoadjuvant/adjuvant hormonal or chemotherapy is allowed if it was last used >
12 months prior to enrollment.

- No therapy modulating testosterone levels (such as leuteinizing-hormone
releasing-hormone agonists/antagonists and antiandrogens) is permitted within 12
months prior to enrollment. Agents such as 5α-reductase inhibitors, ketoconazole,
megestrol acetate, systemic steroids (replacement doses of steroids are allowed),
PC-SPES, Saw Palmetto are not permitted at any time during the period that the PSA
values are being collected.

- Hormone-sensitive prostate cancer as evident by a serum total testosterone level >
150 ng/dL or >6 nmol/L at the time of enrollment within 4 weeks prior to

- No other signs of clinical recurrence or dissemination of prostate cancer as defined
by normal CT-scan or MRI of the pelvis without local recurrence, and bone scan
negative for metastases, and chest X-ray negative for metastases. Prostascint scans
will not be used to assess disease prior to study entry.

- No concomitant therapy with steroids (replacement doses of steroids are allowed.

- All patients must have evidence of biochemical progression as determined by a
reference PSA value followed by 1 confirmatory rising PSA value, higher than the
previous value, obtained at least 2 weeks apart. All of these PSA values must be
obtained at the same reference lab, and all must be done within 6 months prior to

- The most recent of the PSA values must be > 2.0 ng/ml. This measurement must be
obtained within 1 month prior to enrollment.

- The PSA doubling time (PSA-DT) must be less than 12 months.

- ECOG performance status 0 or 1.

- Patients must have normal organ and marrow function as defined below:

- Absolute neutrophil count >1,500/ul

- Platelets >100,000/ul

- Total bilirubin 1.5 x upper limit of normal (ULN)

- SGOT (AST) and SGPT (ALT) < 2.5 x institutional ULN

- Creatinine 1.5 x ULN

- The effects of dendritic cell vaccines on the developing human fetus are unknown. For
this reason men must agree to use adequate contraception (hormonal or barrier method
of birth control) prior to study entry and for the duration of study participation.

Exclusion Criteria:

- Patients must not be receiving other investigational agents or concurrent anticancer

- No uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.

- Patients must not have active eczema, atopic dermatitis, or other exfoliative skin
conditions (e.g., burns, impetigo, varicella zoster, severe acne, contact dermatitis,
psoriasis, herpes or other open rashes or wounds).

- Presence of an active acute or chronic infection, including urinary tract infection,
HIV or viral hepatitis HIV patients are excluded based on immunosuppression which may
render them unable to respond to the vaccine; patients with chronic hepatitis are
excluded because of concern that hepatitis could be exacerbated by the injections. If
clinically indicate HIV/viral hepatitis testing will be performed to confirm status.

- Patients with a history of auto-immune disease such as, but not restricted to,
inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis,
scleroderma, or multiple sclerosis. Patients receiving replacement thyroid hormone
would be eligible.

- No concurrent use of systemic steroids, except for local (topical, nasal, or inhaled)
steroid use (replacement doses of steroids allowed).

- Subjects with concurrent additional malignancy (with exception of non-melanoma skin
cancers and superficial bladder cancer or malignancy within last 3 years).

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

The primary feasibility objective is the ability to successfully generate and administer the alpha-DC1 vaccine.

Outcome Time Frame:

ongoing throughout trial

Safety Issue:


Principal Investigator

Appleman J Leonard, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Pittsburgh


United States: Food and Drug Administration

Study ID:




Start Date:

September 2009

Completion Date:

September 2013

Related Keywords:

  • Prostate Cancer
  • Prostate
  • Androgen Ablation
  • PSA Progression
  • Prostatic Neoplasms



University of Pittsburgh Cancer Institute Pittsburgh, Pennsylvania  15213