Prostate Cancer
Conditions
Brief summary
This is an open label, Phase 2 trial of immunotherapy with sipuleucel-T as neoadjuvant treatment in men with localized prostate cancer.
Detailed description
This is a single center, open label, Phase 2 study. Subjects will be treated with 3 infusions of sipuleucel-T prior to a scheduled radical prostatectomy (RP) surgery. To assess the immune response following treatment with sipuleucel-T, tissue from the prostatectomy specimen will be compared with tissue from the core biopsy specimen obtained prior to treatment with sipuleucel T. Following RP, subjects will be randomized to receive either a booster infusion of sipuleucel T or no further treatment with sipuleucel-T (i.e., booster: no booster).
Interventions
BIOLOGICALSipuleucel-T with Booster
Sipuleucel-T is an autologous active cellular immunotherapy product designed to stimulate an immune response against prostate cancer. Sipuleucel-T consists of autologous peripheral blood mononuclear cells (PBMCs), including antigen presenting cells (APCs), that have been activated in vitro with a recombinant fusion protein.
BIOLOGICALSipuleucel-T without Booster
Sipuleucel-T is an autologous active cellular immunotherapy product designed to stimulate an immune response against prostate cancer. Sipuleucel-T consists of autologous peripheral blood mononuclear cells (PBMCs), including antigen presenting cells (APCs), that have been activated in vitro with a recombinant fusion protein.
Sponsors
University of California, San Francisco
Dendreon
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adenocarcinoma of the prostate. * Subject is scheduled for RP as the initial therapy for localized prostate cancer. * Subject is ≥ 18 years of age. * Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Subject has adequate hematologic, renal, and liver function.
Exclusion criteria
* Subject has any evidence of metastasis. * Subject received hormones, including luteinizing hormone-releasing hormone agonists, antiandrogens, or 5 α-reductase inhibitors at any time prior to study screening. * Subject has received prior radiation therapy or chemotherapy for prostate cancer. * Subject has received systemic steroid therapy within 14 days. * Subject has a history of stage III or greater cancer, excluding prostate cancer. * Subjects with a history of basal or squamous cell skin cancers are allowed, provided that the subject was adequately treated and is disease-free at the time of study screening. * Subjects with a history of stage I or II cancer must have been adequately treated and been disease-free for ≥ 3 years prior to study screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in the Number of Infiltrating CD3+ T Cells Within the Prostate Tissue Between the Biopsy and the Post-RP Tissue Specimens in Each Subject | Pre-treatment biopsy (baseline) and post-RP (12 weeks post-treatment) | CD3+ T cell infiltration within prostate tissue was quantified using immunohistochemistry (IHC) staining techniques. Cells were enumerated per unit area (cells/μm2). For post-RP tissue specimens, three areas of interest were identified: Benign tissue, tumor tissue, and tumor interface tissue. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in the Number of Infiltrating CD8+ T Cells Within the Prostate Tissue Between the Biopsy and the Post-RP Tissue Specimens in Each Subject | Pre-treatment biopsy (baseline) and post-RP (12 weeks following sipuleucel-T) | CD8+ T cell infiltration within prostate tissue was quantified using immunohistochemistry (IHC) staining techniques. Cells were enumerated per unit area (cells/μm2). For post-RP tissue specimens, three areas of interest were identified: Benign tissue, tumor tissue, and tumor interface tissue. |
| Change in Antigen PA2024-specific T Cell Immunity in Peripheral Blood | Baseline (screening visit) and up to 12-weeks post-RP visit (24 weeks following sipuleucel-T) | Antigen PA2024-specific T cell immune response is measured using interferon gamma (IFN-γ) enzyme-linked immunospot (ELISPOT) assays. This analysis was performed as previously described in Fong L et al. (J Immunol. 2001;167(12):7150-7156.). The unit of analysis is the number of IFN-γ ELISPOT counts per 300,000 peripheral blood mononuclear cells. |
| Change in Antigen PAP-specific T Cell Immunity in Peripheral Blood | Baseline (screening visit) and up to 12-weeks post-RP visit (24 months post sipuleucel-T) | Antigen PAP-specific T cell immune response is measured using interferon gamma (IFN-γ) enzyme-linked immunospot (ELISPOT) assays. PAP = Prostatic Acid Phosphatase. |
| Change in the Number of Infiltrating CD4+ T Cells Within the Prostate Tissue Between the Biopsy and the Post-RP Tissue Specimens in Each Subject | Pre-treatment biopsy (baseline) and post-RP (12 weeks post-treatment) | CD4+ T cell infiltration within prostate tissue was quantified using immunohistochemistry (IHC) staining techniques. Cells were enumerated per unit area (cells/μm2). For post-RP tissue specimens, three areas of interest were identified: Benign tissue, tumor tissue, and tumor interface tissue. |
| Effect of a Post-RP Booster Infusion of Sipuleucel-T Over Time of Antigen PAP-Specific T Cell Immunity in the Peripheral Blood. | 12 Weeks Post-RP (Pre-booster) and up to 72 Weeks post-RP | The number of PAP-specific T cells was enumerated by interferon gamma (IFN-γ) enzyme-linked immunospot (ELISPOT) assays (memory T cells). PAP = Prostatic Acid Phosphatase. |
| Comparison of Booster Effect in Antigen PA2024-Specific T Cell Immunity Over Time Between the Two Randomized Groups | 12 Weeks Post-RP (Pre-booster) and up to 72 Weeks post-RP | The number of Antigen PA2024-specific T cells was enumerated by interferon gamma (IFN-γ) enzyme-linked immunospot (ELISPOT) assays (memory T cells). The two groups were compared in the statistical model are: Randomized to Booster and Randomized to No Booster. |
| Comparison of Booster Effect in Antigen PAP-Specific T Cell Immunity Over Time Between the Two Randomized Groups | 12 Weeks Post-RP (Pre-booster) and up to 72 Weeks post-RP | The number of Antigen PAP-specific T cells was enumerated by interferon gamma (IFN-γ) enzyme-linked immunospot (ELISPOT) assays (memory T cells). The two groups were compared in the statistical model are: Randomized to Booster and Randomized to No Booster. PAP = Prostatic Acid Phosphatase. |
| Effect of a Post-RP Booster Infusion of Sipuleucel-T Over Time of Antigen PA2024-Specific T Cell Immunity in the Peripheral Blood. | 12 Weeks Post-RP (Pre-booster) and up to 72 Weeks post-RP | The number of PA2024-specific T cells was enumerated by interferon gamma (IFN-γ) enzyme-linked immunospot (ELISPOT) assays (memory T cells). |
Countries
United States
Participant flow
Recruitment details
The study was conducted across 6 sites in the US. Screening and enrollment occurred from Sept 2008 - Dec 2012. 42 subjects were registered. 41 subjects received at least 1 sipuleucel-T infusion prior to radical prostatectomr (RP),18 subjects were randomized to the booster group,15 were randomized to the no booster group; and 8 were not randomized.
Participants by arm
| Arm | Count |
|---|---|
| Sipuleucel-T With Booster Subjects received 3 infusions of sipuleucel-T 12 weeks prior to RP, and then an additional booster infusion 13 weeks following RP. | 18 |
| Sipuleucel-T Without Booster Subjects received 3 infusions of sipuleucel-T 12 weeks prior to RP, with no further sipuleucel-T treatment. | 16 |
| Sipuleucel-T Without Randomization to Booster Subjects received 3 infusions of sipuleucel-T 12 weeks prior to RP, and declined participation in the post-RP booster phase(received no further sipuleucel-T treatment). | 8 |
| Total | 42 |
Baseline characteristics
| Characteristic | Sipuleucel-T Without Booster | Sipuleucel-T Without Randomization to Booster | Sipuleucel-T With Booster | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 3 Participants | 4 Participants | 11 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 5 Participants | 14 Participants | 31 Participants |
| Age, Continuous | 61.4 years STANDARD_DEVIATION 5.3 | 62.1 years STANDARD_DEVIATION 5.7 | 60.5 years STANDARD_DEVIATION 5.6 | 61.1 years STANDARD_DEVIATION 5.4 |
| Region of Enrollment United States | 16 participants | 8 participants | 18 participants | 42 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 16 Participants | 8 Participants | 18 Participants | 42 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 18 / 18 | 14 / 16 | 8 / 8 |
| serious Total, serious adverse events | 1 / 18 | 4 / 16 | 1 / 8 |
Outcome results
Primary
Change in the Number of Infiltrating CD3+ T Cells Within the Prostate Tissue Between the Biopsy and the Post-RP Tissue Specimens in Each Subject
CD3+ T cell infiltration within prostate tissue was quantified using immunohistochemistry (IHC) staining techniques. Cells were enumerated per unit area (cells/μm2). For post-RP tissue specimens, three areas of interest were identified: Benign tissue, tumor tissue, and tumor interface tissue.
Time frame: Pre-treatment biopsy (baseline) and post-RP (12 weeks post-treatment)
Population: All subjects who received at least 1 infusion of sipuleucel-T and underwent subsequent RP.~Results are not presented by arm because all assessments were performed prior to randomization to booster.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Biopsy Benign Tissue | Change in the Number of Infiltrating CD3+ T Cells Within the Prostate Tissue Between the Biopsy and the Post-RP Tissue Specimens in Each Subject | 2.33 cells/μm2 | Standard Error 0.34 |
| Post-RP Benign Tissue | Change in the Number of Infiltrating CD3+ T Cells Within the Prostate Tissue Between the Biopsy and the Post-RP Tissue Specimens in Each Subject | 2.03 cells/μm2 | Standard Error 0.19 |
| Post-RP Tumor Tissue | Change in the Number of Infiltrating CD3+ T Cells Within the Prostate Tissue Between the Biopsy and the Post-RP Tissue Specimens in Each Subject | 1.98 cells/μm2 | Standard Error 0.18 |
| Post-RP Tumor Interface | Change in the Number of Infiltrating CD3+ T Cells Within the Prostate Tissue Between the Biopsy and the Post-RP Tissue Specimens in Each Subject | 6.39 cells/μm2 | Standard Error 0.61 |
Comparison: A 2-fold increase in CD3+ T cell counts from biopsy to post-RP was considered a positive response. The number of infiltrating CD3+ T cells/μm2 was coded as binary with each subject categorized as having at least a 2-fold increase from baseline or not. One sample Chi-square test for a binary response, with a null hypothesis of 15% was implemented. The tests were done using post-treatment post-RP benign tissue, tumor tissue, and tumor interface compared to the biopsy benign tissue.p-value: 195% CI: [1.7, 30.7]Chi-squared
Comparison: A 2-fold increase in CD3+ T cell counts from biopsy to post-RP was considered a positive response. The number of infiltrating CD3+ T cells/μm2 was coded as binary with each subject categorized as having at least a 2-fold increase from baseline or not. One sample Chi-square test for a binary response, with a null hypothesis of 15% was implemented. The tests were done using post-treatment post-RP benign tissue, tumor tissue, and tumor interface compared to the biopsy benign tissue.p-value: 195% CI: [3.5, 34.3]Chi-squared
Comparison: A 2-fold increase in CD3+ T cell counts from biopsy to post-RP was considered a positive response. The number of infiltrating CD3+ T cells/μm2 was coded as binary with each subject categorized as having at least a 2-fold increase from baseline or not. One sample Chi-square test for a binary response, with a null hypothesis of 15% was implemented. The tests were done using post-treatment post-RP benign tissue, tumor tissue, and tumor interface compared to the biopsy benign tissue.p-value: <0.00195% CI: [52.3, 88.3]Chi-squared
Secondary
Change in Antigen PA2024-specific T Cell Immunity in Peripheral Blood
Antigen PA2024-specific T cell immune response is measured using interferon gamma (IFN-γ) enzyme-linked immunospot (ELISPOT) assays. This analysis was performed as previously described in Fong L et al. (J Immunol. 2001;167(12):7150-7156.). The unit of analysis is the number of IFN-γ ELISPOT counts per 300,000 peripheral blood mononuclear cells.
Time frame: Baseline (screening visit) and up to 12-weeks post-RP visit (24 weeks following sipuleucel-T)
Population: All subjects who received at least 1 infusion of sipuleucel-T and underwent subsequent RP.~Results are not presented by arm because all assessments were performed prior to randomization to booster.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Biopsy Benign Tissue | Change in Antigen PA2024-specific T Cell Immunity in Peripheral Blood | 4.9 numbers of spots | Standard Error 2.4 |
| Post-RP Benign Tissue | Change in Antigen PA2024-specific T Cell Immunity in Peripheral Blood | 56.6 numbers of spots | Standard Error 14.9 |
| Post-RP Tumor Tissue | Change in Antigen PA2024-specific T Cell Immunity in Peripheral Blood | 26.5 numbers of spots | Standard Error 9.1 |
| Post-RP Tumor Interface | Change in Antigen PA2024-specific T Cell Immunity in Peripheral Blood | 52.3 numbers of spots | Standard Error 17.6 |
Comparison: The change over time was evaluated by using repeated measure analysis of variance (ANOVA) methods with a mixed model approach. The ranked data were used in the statistical model.p-value: <0.001Mixed Models Analysis
Secondary
Change in Antigen PAP-specific T Cell Immunity in Peripheral Blood
Antigen PAP-specific T cell immune response is measured using interferon gamma (IFN-γ) enzyme-linked immunospot (ELISPOT) assays. PAP = Prostatic Acid Phosphatase.
Time frame: Baseline (screening visit) and up to 12-weeks post-RP visit (24 months post sipuleucel-T)
Population: All subjects who received at least 1 infusion of sipuleucel-T and underwent subsequent RP.~Results are not presented by arm because all assessments were performed prior to randomization to booster.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Biopsy Benign Tissue | Change in Antigen PAP-specific T Cell Immunity in Peripheral Blood | 2.2 numbers of spots | Standard Error 1.7 |
| Post-RP Benign Tissue | Change in Antigen PAP-specific T Cell Immunity in Peripheral Blood | 13.3 numbers of spots | Standard Error 4.9 |
| Post-RP Tumor Tissue | Change in Antigen PAP-specific T Cell Immunity in Peripheral Blood | 2.0 numbers of spots | Standard Error 1.2 |
| Post-RP Tumor Interface | Change in Antigen PAP-specific T Cell Immunity in Peripheral Blood | 12.8 numbers of spots | Standard Error 5.6 |
Comparison: Repeated measure analysis of variance (ANOVA) methods with a mixed model approach was used. The ranked data were used in the statistical model.p-value: 0.173Mixed Models Analysis
Secondary
Change in the Number of Infiltrating CD4+ T Cells Within the Prostate Tissue Between the Biopsy and the Post-RP Tissue Specimens in Each Subject
CD4+ T cell infiltration within prostate tissue was quantified using immunohistochemistry (IHC) staining techniques. Cells were enumerated per unit area (cells/μm2). For post-RP tissue specimens, three areas of interest were identified: Benign tissue, tumor tissue, and tumor interface tissue.
Time frame: Pre-treatment biopsy (baseline) and post-RP (12 weeks post-treatment)
Population: All subjects who received at least 1 infusion of sipuleucel-T and underwent subsequent RP.~Results are not presented by arm because all assessments were performed prior to randomization to booster
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Biopsy Benign Tissue | Change in the Number of Infiltrating CD4+ T Cells Within the Prostate Tissue Between the Biopsy and the Post-RP Tissue Specimens in Each Subject | 0.93 cells/μm2 | Standard Error 0.24 |
| Post-RP Benign Tissue | Change in the Number of Infiltrating CD4+ T Cells Within the Prostate Tissue Between the Biopsy and the Post-RP Tissue Specimens in Each Subject | 0.43 cells/μm2 | Standard Error 0.09 |
| Post-RP Tumor Tissue | Change in the Number of Infiltrating CD4+ T Cells Within the Prostate Tissue Between the Biopsy and the Post-RP Tissue Specimens in Each Subject | 0.74 cells/μm2 | Standard Error 0.13 |
| Post-RP Tumor Interface | Change in the Number of Infiltrating CD4+ T Cells Within the Prostate Tissue Between the Biopsy and the Post-RP Tissue Specimens in Each Subject | 3.83 cells/μm2 | Standard Error 0.49 |
Comparison: A 2-fold increase in CD4+ T cell counts from biopsy to post-RP was considered a positive response. The number of infiltrating CD4+ T cells/μm2 was coded as binary with each subject categorized as having at least a 2-fold increase from baseline or not. One sample Chi-square test for a binary response, with a null hypothesis of 15% was implemented. The tests were done using post-treatment post-RP benign tissue, tumor tissue, and tumor interface compared to the biopsy benign tissue.p-value: 195% CI: [4, 37.2]Chi-squared
Comparison: A 2-fold increase in CD4+ T cell counts from biopsy to post-RP was considered a positive response. The number of infiltrating CD4+ T cells/μm2 was coded as binary with each subject categorized as having at least a 2-fold increase from baseline or not. One sample Chi-square test for a binary response, with a null hypothesis of 15% was implemented. The tests were done using post-treatment post-RP benign tissue, tumor tissue, and tumor interface compared to the biopsy benign tissue.p-value: 0.01495% CI: [13.1, 51.6]Chi-squared
Comparison: A 2-fold increase in CD4+ T cell counts from biopsy to post-RP was considered a positive response. The number of infiltrating CD4+ T cells/μm2 was coded as binary with each subject categorized as having at least a 2-fold increase from baseline or not. One sample Chi-square test for a binary response, with a null hypothesis of 15% was implemented. The tests were done using post-treatment post-RP benign tissue, tumor tissue, and tumor interface compared to the biopsy benign tissue.p-value: <0.00195% CI: [62.8, 96]Chi-squared
Secondary
Change in the Number of Infiltrating CD8+ T Cells Within the Prostate Tissue Between the Biopsy and the Post-RP Tissue Specimens in Each Subject
CD8+ T cell infiltration within prostate tissue was quantified using immunohistochemistry (IHC) staining techniques. Cells were enumerated per unit area (cells/μm2). For post-RP tissue specimens, three areas of interest were identified: Benign tissue, tumor tissue, and tumor interface tissue.
Time frame: Pre-treatment biopsy (baseline) and post-RP (12 weeks following sipuleucel-T)
Population: All subjects who received at least 1 infusion of sipuleucel-T and underwent subsequent RP.~Results are not presented by arm because all assessments were performed prior to randomization to booster
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Biopsy Benign Tissue | Change in the Number of Infiltrating CD8+ T Cells Within the Prostate Tissue Between the Biopsy and the Post-RP Tissue Specimens in Each Subject | 0.65 cells/μm2 | Standard Error 0.08 |
| Post-RP Benign Tissue | Change in the Number of Infiltrating CD8+ T Cells Within the Prostate Tissue Between the Biopsy and the Post-RP Tissue Specimens in Each Subject | 0.94 cells/μm2 | Standard Error 0.14 |
| Post-RP Tumor Tissue | Change in the Number of Infiltrating CD8+ T Cells Within the Prostate Tissue Between the Biopsy and the Post-RP Tissue Specimens in Each Subject | 0.88 cells/μm2 | Standard Error 0.12 |
| Post-RP Tumor Interface | Change in the Number of Infiltrating CD8+ T Cells Within the Prostate Tissue Between the Biopsy and the Post-RP Tissue Specimens in Each Subject | 2.87 cells/μm2 | Standard Error 0.25 |
Comparison: A 2-fold increase in CD8+ T cell counts from biopsy to post-RP was considered a positive response. The number of infiltrating CD8+ T cells/μm2 was coded as binary with each subject categorized as having at least a 2-fold increase from baseline or not. One sample Chi-square test for a binary response, with a null hypothesis of 15% was implemented. The tests were done using post-treatment post-RP benign tissue, tumor tissue, and tumor interface compared to the biopsy benign tissue.p-value: 0.00295% CI: [16.3, 53.9]Chi-squared
Comparison: A 2-fold increase in CD8+ T cell counts from biopsy to post-RP was considered a positive response. The number of infiltrating CD8+ T cells/μm2 was coded as binary with each subject categorized as having at least a 2-fold increase from baseline or not. One sample Chi-square test for a binary response, with a null hypothesis of 15% was implemented. The tests were done using post-treatment post-RP benign tissue, tumor tissue, and tumor interface compared to the biopsy benign tissue.p-value: 0.03695% CI: [11.7, 47.7]Chi-squared
Comparison: A 2-fold increase in CD8+ T cell counts from biopsy to post-RP was considered a positive response. The number of infiltrating CD8+ T cells/μm2 was coded as binary with each subject categorized as having at least a 2-fold increase from baseline or not. One sample Chi-square test for a binary response, with a null hypothesis of 15% was implemented. The tests were done using post-treatment post-RP benign tissue, tumor tissue, and tumor interface compared to the biopsy benign tissue.p-value: <0.00195% CI: [69.3, 98.3]Chi-squared
Secondary
Comparison of Booster Effect in Antigen PA2024-Specific T Cell Immunity Over Time Between the Two Randomized Groups
The number of Antigen PA2024-specific T cells was enumerated by interferon gamma (IFN-γ) enzyme-linked immunospot (ELISPOT) assays (memory T cells). The two groups were compared in the statistical model are: Randomized to Booster and Randomized to No Booster.
Time frame: 12 Weeks Post-RP (Pre-booster) and up to 72 Weeks post-RP
Population: Subjects received at least 1 infusion of sipuleucel-T, were randomized to receive either a booster infusion or no further treatment following RP, and had blood samples suitable for ELISPOT analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Biopsy Benign Tissue | Comparison of Booster Effect in Antigen PA2024-Specific T Cell Immunity Over Time Between the Two Randomized Groups | 35.6 number of spots | Standard Error 14.9 |
| Post-RP Benign Tissue | Comparison of Booster Effect in Antigen PA2024-Specific T Cell Immunity Over Time Between the Two Randomized Groups | 81.7 number of spots | Standard Error 44.4 |
| Post-RP Tumor Tissue | Comparison of Booster Effect in Antigen PA2024-Specific T Cell Immunity Over Time Between the Two Randomized Groups | 25.6 number of spots | Standard Error 9.7 |
| Post-RP Tumor Interface | Comparison of Booster Effect in Antigen PA2024-Specific T Cell Immunity Over Time Between the Two Randomized Groups | 22.3 number of spots | Standard Error 9.2 |
| Booster: 48 Weeks Post-RP | Comparison of Booster Effect in Antigen PA2024-Specific T Cell Immunity Over Time Between the Two Randomized Groups | 23.5 number of spots | Standard Error 13.1 |
| No Booster: 48 Weeks Post-RP | Comparison of Booster Effect in Antigen PA2024-Specific T Cell Immunity Over Time Between the Two Randomized Groups | 19.5 number of spots | Standard Error 9.3 |
| Booster: 72 Weeks Post-RP | Comparison of Booster Effect in Antigen PA2024-Specific T Cell Immunity Over Time Between the Two Randomized Groups | 18.0 number of spots | Standard Error 5 |
| No Booster: 72 Weeks Post-RP | Comparison of Booster Effect in Antigen PA2024-Specific T Cell Immunity Over Time Between the Two Randomized Groups | 12.6 number of spots | Standard Error 3.7 |
Comparison: The change over time was evaluated by using repeated measure analysis of variance (ANOVA) methods with a mixed model approach. The ranked data were used in the statistical model.p-value: 0.95Mixed Models Analysis
Secondary
Comparison of Booster Effect in Antigen PAP-Specific T Cell Immunity Over Time Between the Two Randomized Groups
The number of Antigen PAP-specific T cells was enumerated by interferon gamma (IFN-γ) enzyme-linked immunospot (ELISPOT) assays (memory T cells). The two groups were compared in the statistical model are: Randomized to Booster and Randomized to No Booster. PAP = Prostatic Acid Phosphatase.
Time frame: 12 Weeks Post-RP (Pre-booster) and up to 72 Weeks post-RP
Population: Subjects received at least 1 infusion of sipuleucel-T, were randomized to receive either a booster infusion or no further treatment following RP, and had blood samples suitable for ELISPOT analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Biopsy Benign Tissue | Comparison of Booster Effect in Antigen PAP-Specific T Cell Immunity Over Time Between the Two Randomized Groups | 9.2 numbers of spots | Standard Error 5.4 |
| Post-RP Benign Tissue | Comparison of Booster Effect in Antigen PAP-Specific T Cell Immunity Over Time Between the Two Randomized Groups | 20.2 numbers of spots | Standard Error 13.9 |
| Post-RP Tumor Tissue | Comparison of Booster Effect in Antigen PAP-Specific T Cell Immunity Over Time Between the Two Randomized Groups | 0.3 numbers of spots | Standard Error 0.9 |
| Post-RP Tumor Interface | Comparison of Booster Effect in Antigen PAP-Specific T Cell Immunity Over Time Between the Two Randomized Groups | 4.8 numbers of spots | Standard Error 1.6 |
| Booster: 48 Weeks Post-RP | Comparison of Booster Effect in Antigen PAP-Specific T Cell Immunity Over Time Between the Two Randomized Groups | 6.2 numbers of spots | Standard Error 4.8 |
| No Booster: 48 Weeks Post-RP | Comparison of Booster Effect in Antigen PAP-Specific T Cell Immunity Over Time Between the Two Randomized Groups | 2.7 numbers of spots | Standard Error 1.7 |
| Booster: 72 Weeks Post-RP | Comparison of Booster Effect in Antigen PAP-Specific T Cell Immunity Over Time Between the Two Randomized Groups | 0.4 numbers of spots | Standard Error 1 |
| No Booster: 72 Weeks Post-RP | Comparison of Booster Effect in Antigen PAP-Specific T Cell Immunity Over Time Between the Two Randomized Groups | 1.9 numbers of spots | Standard Error 1.7 |
Comparison: The change over time was evaluated by using repeated measure analysis of variance (ANOVA) methods with a mixed model approach. The ranked data were used in the statistical model.p-value: 0.048Mixed Models Analysis
Secondary
Effect of a Post-RP Booster Infusion of Sipuleucel-T Over Time of Antigen PA2024-Specific T Cell Immunity in the Peripheral Blood.
The number of PA2024-specific T cells was enumerated by interferon gamma (IFN-γ) enzyme-linked immunospot (ELISPOT) assays (memory T cells).
Time frame: 12 Weeks Post-RP (Pre-booster) and up to 72 Weeks post-RP
Population: Subjects received at least 1 infusion of sipuleucel-T, were randomized to receive a booster, and had blood samples suitable for ELISPOT analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Biopsy Benign Tissue | Effect of a Post-RP Booster Infusion of Sipuleucel-T Over Time of Antigen PA2024-Specific T Cell Immunity in the Peripheral Blood. | 35.6 numbers of spots | Standard Error 14.9 |
| Post-RP Benign Tissue | Effect of a Post-RP Booster Infusion of Sipuleucel-T Over Time of Antigen PA2024-Specific T Cell Immunity in the Peripheral Blood. | 25.6 numbers of spots | Standard Error 9.7 |
| Post-RP Tumor Tissue | Effect of a Post-RP Booster Infusion of Sipuleucel-T Over Time of Antigen PA2024-Specific T Cell Immunity in the Peripheral Blood. | 23.5 numbers of spots | Standard Error 13.1 |
| Post-RP Tumor Interface | Effect of a Post-RP Booster Infusion of Sipuleucel-T Over Time of Antigen PA2024-Specific T Cell Immunity in the Peripheral Blood. | 18.0 numbers of spots | Standard Error 5 |
Comparison: The change over time was evaluated by using repeated measure analysis of variance (ANOVA) methods with a mixed model approach to allow for a varying number of follow-up measurements. The ranked data were used in the statistical model.p-value: 0.667Mixed Models Analysis
Comparison: The change over time was evaluated by using repeated measure analysis of variance (ANOVA) methods with a mixed model approach to allow for a varying number of follow-up measurements. The ranked data were used in the statistical model.p-value: 0.191Mixed Models Analysis
Comparison: The change over time was evaluated by using repeated measure analysis of variance (ANOVA) methods with a mixed model approach to allow for a varying number of follow-up measurements. The ranked data were used in the statistical model.p-value: 0.699Mixed Models Analysis
Secondary
Effect of a Post-RP Booster Infusion of Sipuleucel-T Over Time of Antigen PAP-Specific T Cell Immunity in the Peripheral Blood.
The number of PAP-specific T cells was enumerated by interferon gamma (IFN-γ) enzyme-linked immunospot (ELISPOT) assays (memory T cells). PAP = Prostatic Acid Phosphatase.
Time frame: 12 Weeks Post-RP (Pre-booster) and up to 72 Weeks post-RP
Population: Subjects received at least 1 infusion of sipuleucel-T, were randomized to receive a booster, and had blood samples suitable for ELISPOT analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Biopsy Benign Tissue | Effect of a Post-RP Booster Infusion of Sipuleucel-T Over Time of Antigen PAP-Specific T Cell Immunity in the Peripheral Blood. | 9.2 number of spots | Standard Error 5.4 |
| Post-RP Benign Tissue | Effect of a Post-RP Booster Infusion of Sipuleucel-T Over Time of Antigen PAP-Specific T Cell Immunity in the Peripheral Blood. | 0.3 number of spots | Standard Error 0.9 |
| Post-RP Tumor Tissue | Effect of a Post-RP Booster Infusion of Sipuleucel-T Over Time of Antigen PAP-Specific T Cell Immunity in the Peripheral Blood. | 6.2 number of spots | Standard Error 4.8 |
| Post-RP Tumor Interface | Effect of a Post-RP Booster Infusion of Sipuleucel-T Over Time of Antigen PAP-Specific T Cell Immunity in the Peripheral Blood. | 0.4 number of spots | Standard Error 1 |
Comparison: The change over time was evaluated by using repeated measure analysis of variance (ANOVA) methods with a mixed model approach to allow for a varying number of follow-up measurements. The ranked data were used in the statistical model.p-value: 0.086Mixed Models Analysis
Comparison: The change over time was evaluated by using repeated measure analysis of variance (ANOVA) methods with a mixed model approach to allow for a varying number of follow-up measurements. The ranked data were used in the statistical model.p-value: 0.432Mixed Models Analysis
Comparison: The change over time was evaluated by using repeated measure analysis of variance (ANOVA) methods with a mixed model approach to allow for a varying number of follow-up measurements. The ranked data were used in the statistical model.p-value: 0.249Mixed Models Analysis