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

NCT ID: NCT00970203

Last Updated: 2020-11-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-09-30
• Study Completion Date: 2019-10-05

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.).

Detailed Description

Dendritic cells or "DCs" are special white blood cells that stimulate the immune system. This study is being done to test the feasibility, safety and efficacy of a specific type of dendritic cell when injected under the skin of patients with prostate cancer. The researchers conducting this study will evaluate the time to prostate specific antigen (PSA) progression and will also be performing tests to see how the immune system is responding to the injections.

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.

Primary Objectives

• Feasibility objective: the ability to successfully generate and administer the alpha-DC1 vaccine.
• Safety objective: assess the tolerability and toxicity of the alpha-DC1 vaccine.
• Efficacy objective: evaluate the effect of the alpha-DC1 vaccine on time to PSA progression compared to AA alone. PSA progression is defined as a rise in the PSA value to e 1.0 ng/mL.

Secondary Objectives

• To determine the change in PSA velocity prior to and following the proposed treatment.
• To 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).
• To evaluate the vaccination-induced changes of Th1/Th2 profiles of the responses to PAP and PSMA.
• To 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.
• To 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.

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 patients.

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 1, 4, 8, and 12.

Conditions

Cancer of Prostate; Cancer of the Prostate; Neoplasms, Prostate; Neoplasms, Prostatic; Prostate Cancer; Prostate Neoplasms; Prostatic Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

androgen ablation (AA)

Intervention Type: BIOLOGICAL

Lupron 22.5 mg or Zoladex 10.8 mg

DC1 vaccine

Intervention Type: BIOLOGICAL

3-5 x 10e6 cells total

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

Group Type: EXPERIMENTAL

androgen ablation (AA)

Intervention Type: BIOLOGICAL

Lupron 22.5 mg or Zoladex 10.8 mg

DC1 vaccine

Intervention Type: BIOLOGICAL

3-5 x 10e6 cells total

Interventions

androgen ablation (AA)

Lupron 22.5 mg or Zoladex 10.8 mg

Intervention Type: BIOLOGICAL

DC1 vaccine

3-5 x 10e6 cells total

Intervention Type: BIOLOGICAL

Other Intervention Names

alpha dendritic cell 1 vaccine

Eligibility Criteria

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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

University of Pittsburgh

OTHER

Sponsor Role: collaborator

Roswell Park Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Leonard J Appleman, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

University of Pittsburgh Cancer institute

Pittsburgh, Pennsylvania, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

06-070

Identifier Type: -

Identifier Source: org_study_id