Don't get left behind! The modernized is coming. Check it out now.
Say goodbye to!
The new site is coming soon - go to the modernized
Working… Menu

Dendritic Cell (DC)-Based Vaccines Loaded With Allogeneic Prostate Cell Lines in Combination With Androgen Ablation in Patients With Prostate Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00970203
Recruitment Status : Completed
First Posted : September 2, 2009
Results First Posted : May 7, 2020
Last Update Posted : November 3, 2020
University of Pittsburgh
Information provided by (Responsible Party):
Roswell Park Cancer Institute

Brief Summary:
This study will evaluate the feasibility, safety, and efficacy of intradermal vaccination of prostate cancer patients with alpha-type-1-polarized dendritic cells (DC1) loaded with apoptotic allogeneic tumor (LNCap). The study will target men with recurrent prostate cancer, who failed local therapy, have no measurable metastasis, but have a rising PSA with a doubling time of less than 10 months. The selection of this study group enables us to evaluate time to PSA progression, a highly relevant, clinical primary endpoint of efficacy in this two arm study. In order to facilitate infiltration of vaccination-induced T cells into tumor site(s) and to reduce tumor-specific tolerance, subjects will receive the vaccine in combination with limited androgen ablation (AA) with a LHRH analogue for 3 months. Subjects will be randomly assigned to one of two cohorts. In cohort A subjects will be first treated with limited AA alone for 3 months, and at the time of PSA relapse (PSA ≥ 1 ng/dL) will receive the DC vaccine in conjunction with AA. In cohort B, the sequence of treatment will be reversed. Efficacy will be estimated as the within-subject difference in time to PSA relapse following the combination treatment as compared to the AA alone, thus, each subject will serve as his own control. All subjects will commence the DC1-based vaccination 2 weeks prior to treatment with the LHRH analogue. Each subject will receive 1 intradermal (i.d.) dose of the vaccine at weeks 1, 5, 9, and 13 for a total of 4 doses. Additional courses of vaccination may be administered to subjects without evidence of disease progression every 3 months (±1 month) for up to 12 months depending on the number of doses originally produced and available after the 4 intended protocol doses. All doses of the vaccine will be administered intradermally (i.d.).

Condition or disease Intervention/treatment Phase
Cancer of Prostate Cancer of the Prostate Neoplasms, Prostate Neoplasms, Prostatic Prostate Cancer Prostate Neoplasms Prostatic Cancer Biological: androgen ablation (AA) Biological: DC1 vaccine Phase 2

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 13 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : September 2009
Actual Primary Completion Date : October 5, 2018
Actual Study Completion Date : October 5, 2019

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Cohort A

3 months of androgen ablation followed at PSA progression by 3 months of the combination of androgen ablation + DC1 vaccine

AA: Lupron 22.5 mg or Zoladex 10.8 mg DC vaccine: intradermal (id) vaccine of 3-5 x 10e6 cells

Biological: androgen ablation (AA)
Lupron 22.5 mg or Zoladex 10.8 mg

Biological: DC1 vaccine
3-5 x 10e6 cells total
Other Name: alpha dendritic cell 1 vaccine

Experimental: Cohort B

3 months of the combination of androgen ablation + DC1 vaccine followed at PSA progression by 3 months of androgen ablation

AA: Lupron 22.5 mg or Zoladex 10.8 mg DC vaccine: intradermal (id) vaccine of 3-5 x 10e6 cells

Biological: androgen ablation (AA)
Lupron 22.5 mg or Zoladex 10.8 mg

Biological: DC1 vaccine
3-5 x 10e6 cells total
Other Name: alpha dendritic cell 1 vaccine

Primary Outcome Measures :
  1. Percentage of Patients to Successfully Generate and Administer the Alpha-DC1 Vaccine [ Time Frame: 16 weeks ]
    The percentage of patients for which the alpha-DC1 vaccine was generated and for which 4 vaccine injections were administered (1 injection every 4 weeks).

  2. Tolerability and Toxicity of the Alpha-DC1 Vaccine [ Time Frame: 16 weeks ]
    The percentage of patients who experienced vaccine related toxicity.

  3. The Effect of the DC1 Vaccine on Time to PSA Progression Compared to AA Alone [ Time Frame: Approximately 18 months ]
    The mean difference between time to relapse on androgen ablation plus alpha DC-1 vaccine vs androgen ablation

Secondary Outcome Measures :
  1. Change in PSA Velocity Prior to and Following the Proposed Treatment. [ Time Frame: Approximately 18 months ]
  2. Evaluate (in All Subjects) the Vaccination-induced DTH Responses to LNCap, the Cell Line Vaccine, and to Compare This With Vaccination-induced Responses to Tumor-untreated Antigen (KLH) [ Time Frame: Approximately 17 weeks ]
  3. Evaluate the Vaccination-induced Changes of Th1/Th2 Profiles of the Responses to PAP and PSMA [ Time Frame: Approximately 18 to 24 months ]
  4. Evaluate the CTL Responses in Blood to the Whole LNCap Cells (in All Subjects) and (in All Subjects Who Are HLA-A2 Positive) the CTL Responses to HLA-A2.1 Restricted Peptides Derived From PAP and PSMA [ Time Frame: Approximately 18 to 24 months ]
  5. Comprehensively Evaluate the CD4+ and CD8+ T Cell Responses (Fine Specificity and Th1/Th2/Treg Cytokine Profile) to the Previously-identified and Novel Immunogenic Epitopes of PAP and PSMA, Using the EPIMAX System [ Time Frame: Approximately 18 to 24 months ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

Eligibility Criteria

  • Patients with histologically proven prostate cancer and tumors limited to the prostate (including seminal vesicle involvement, provided all visible disease was surgically removed) who have completed local therapy and have an elevated PSA after surgery or rising PSA after radiation therapy, as defined below.
  • Age 18 years or older
  • 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, androgen deprivation therapy, or chemotherapy is allowed if it was last used > 12 months prior to first vaccination.
  • No therapy modulating testosterone levels (such as leuteinizing-hormone releasing-hormone agonists/antagonists and antiandrogens) is permitted within 12 months prior to first vaccination. Agents such as 5α-reductase inhibitors, ketoconazole, megestrol acetate, systemic steroids (replacement doses of steroids are allowed), PC-SPES, and 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 randomization.
  • 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 enrollment.
  • 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/µL
    • Platelets > 100,000/µL
    • 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 therapy.
  • 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. Adrenal replacement doses of corticosteroids are allowed.
  • Subjects with concurrent additional malignancy (with exception of non-melanoma skin cancers and superficial bladder cancer or malignancy within last 3 years).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00970203

Layout table for location information
United States, Pennsylvania
University of Pittsburgh Cancer institute
Pittsburgh, Pennsylvania, United States, 15232
Sponsors and Collaborators
Roswell Park Cancer Institute
University of Pittsburgh
Layout table for investigator information
Principal Investigator: Leonard J Appleman, MD, PhD University of Pittsburgh
  Study Documents (Full-Text)

Documents provided by Roswell Park Cancer Institute:
Layout table for additonal information
Responsible Party: Roswell Park Cancer Institute Identifier: NCT00970203    
Other Study ID Numbers: 06-070
First Posted: September 2, 2009    Key Record Dates
Results First Posted: May 7, 2020
Last Update Posted: November 3, 2020
Last Verified: October 2020
Keywords provided by Roswell Park Cancer Institute:
Androgen Ablation
PSA Progression
Additional relevant MeSH terms:
Layout table for MeSH terms
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Genital Diseases
Urogenital Diseases
Prostatic Diseases
Male Urogenital Diseases
Immunologic Factors
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists