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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

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

androgen ablation (AA)

DC1 vaccine

Leonard J Appleman, MD, PhD

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.).

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.

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

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 percentage of patients for which the alpha-DC1 vaccine was generated and for which 4 vaccine injections were administered (1 injection every 4 weeks).

The percentage of patients who experienced vaccine related toxicity.

The mean difference between time to relapse on androgen ablation plus alpha DC-1 vaccine vs androgen ablation

University of Pittsburgh

Roswell Park Cancer Institute

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

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

DC1 vaccine: 3-5 x 10e6 cells total

Cohort A

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

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

DC1 vaccine: 3-5 x 10e6 cells total

Cohort B

Total

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

Despite numerous attempts to obtain required data from the previous IND holder where the data is housed, including attempts to contact study PI and team, no responses were obtained and no data were available for this some Outcome Measures.

Senior Administrator, Compliance - Clinical Research Services

Percentage of Patients to Successfully Generate and Administer the Alpha-DC1 Vaccine

Tolerability and Toxicity of the Alpha-DC1 Vaccine

Despite numerous attempts to obtain required data from the previous IND holder where the data is housed, including attempts to contact study PI and team, no responses were obtained and no data are available for this Outcome Measure.

The Effect of the DC1 Vaccine on Time to PSA Progression Compared to AA Alone

The IND holder where the data is housed has stated that the data for this outcome was not collected.

Change in PSA Velocity Prior to and Following the Proposed Treatment.

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)

Evaluate the Vaccination-induced Changes of Th1/Th2 Profiles of the Responses to PAP and PSMA

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

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

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Dendritic Cell (DC)-Based Vaccines Loaded With Allogeneic Prostate Cell Lines in Combination With Androgen Ablation in Patients With Prostate Cancer	NCT00970203	Cancer of Prost... Cancer of the P... Neoplasms, Pros... Neoplasms, Pros... Prostate Cancer Prostate Neopla... Prostatic Cance...	androgen ablati... DC1 vaccine	18 Years -	Roswell Park Cancer Institute
Dendritic Cell (DC)-Based Vaccines Loaded With Allogeneic Prostate Cell Lines in Combination With Androgen Ablation in Patients With Prostate Cancer	NCT00970203	Cancer of Prost... Cancer of the P... Neoplasms, Pros... Neoplasms, Pros... Prostate Cancer Prostate Neopla... Prostatic Cance...	androgen ablati... DC1 vaccine	18 Years -	Roswell Park Cancer Institute

Spots Global Cancer Trial Database for androgen ablation (aa)