Epithelial Ovarian Cancer
Conditions
Keywords
Cvac
Brief summary
The purpose of this study is to determine the safety and efficacy of an investigational therapeutic agent (Cvac) in ovarian cancer patients in first or second remission and to determine its ability to prevent cancer from returning. Study objectives Primary objectives: * To confirm the safety of administering Cvac in this population. * To determine the effects of Cvac on progression-free survival (PFS). Secondary objectives: * To determine overall survival (OS) for ovarian cancer patients who receive Cvac after achieving remission in the first or second-line setting. * Evaluation of host immunologic response to Cvac administration.
Detailed description
An initial cohort of 7 patients were treated with Cvac in an open-label phase to confirm the safety and consistency of manufacturing between Cvac drug product manufactured in the United States (US) and Australia. After the manufacturing characteristics of Cvac were confirmed to be consistent and each patient in the initial cohort had completed 1 injection cycle of Cvac with no serious or treatment-related Grade 3 or 4 adverse events (AEs), 56 patients were enrolled and randomized (1:1) to either Cvac or observational standard of care (OSC).
Interventions
BIOLOGICALCvac
Cvac consists of autologous dendritic cells (DCs) incubated with the antigen, mannosylated fusion protein (M-FP), to target the DCs to the specific mucin 1 antigen.
Sponsors
Prima BioMed Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Female subjects ≥ 18 years old with histologically confirmed Stage III or IV epithelial ovarian, primary peritoneal or fallopian tube cancer who have previously undergone surgical cytoreduction and received first or second line conventional chemotherapy and are currently in complete remission (based on clinical and radiologic studies). * Cancer antigen (CA)-125 ≤ upper limit of normal with a prior history of an elevated CA-125. * Able and willing to undergo mononuclear cell collection. * Not more than 12 weeks between enrollment and the last dose of chemotherapy that resulted in complete remission. * No prior surgery to the peritoneum or pleural space within 28 days of enrollment, excluding removal of catheters used for chemotherapy administration. * No prior treatment with an investigational product within 30 days of enrollment. * Baseline electrocardiogram within normal limits or any abnormalities deemed not indicative of cardiac disease for which intervention is required. * Serum creatinine ≤ 2 mg/dL. * Serum aspartate aminotransferase or serum alanine aminotransferase ≤ 2.5x the upper limit of normal or serum total bilirubin ≤ 1.5x the upper limit of normal. * White blood cell count ≥ 3.0 K/µL; absolute neutrophil count ≥ 1.5K/µL; hemoglobin ≥ 9.0 g/dL, and platelets ≥ 100,000/mm\^3. (These complete blood count results are required for enrollment. It should be noted that complete blood count results, including monocyte count ≥ 0.2 × 10\^9/L, will be needed prior to leukapheresis to determine if sufficient dendritic cells can be obtained for Cvac™ manufacture.) * Life expectancy of at least 12 months. * Eastern Cooperative Oncology Group Performance Status of 0-1. * All toxicities from prior therapies, excluding alopecia, must have resolved to Common Terminology Criteria for Adverse Events Grade ≤ 1. * Must be non-pregnant and, if of childbearing potential, must use adequate birth control (hormonal or barrier method of birth control or abstinence) for the duration of the study and for 3 months after study completion. * Able to provide written informed consent.
Exclusion criteria
* Coexisting or other malignancies unless in complete remission for not less than 3 years. Does not include in situ carcinoma of the cervix or basal cell or squamous cell carcinoma of the skin for which no restrictions apply, assuming they have been adequately treated. * Ovarian germ cell, sarcoma, or mixed Mullerian tumors. * Prior cancer vaccine or cellular therapy. * Active uncontrolled infections or any organ system toxicity ≥ Grade 2 by Common Terminology Criteria for Adverse Events criteria. * Inability to provide informed consent or to comply with study-related procedures. * Concurrent systemic treatment with steroids or other immunosuppressive agents. * Diagnosed immunodeficiency and/or autoimmune disorders. * Myocardial infarction in the past 6 months and/or clinically significant heart disease. * Infection with human immunodeficient virus (HIV), hepatitis B or C virus. * Pregnant or breastfeeding. * Evidence or history of central nervous system metastases. * Full dose anticoagulation therapy administered within 7 days of leukapheresis procedure. * Hematopoietic growth factors administered within 14 days of enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | Baseline to 48 weeks after the last visit or dose of Cvac (up to 104 weeks) | Progression-free survival was defined as the time from randomization to the date of documented disease progression or death from any cause, whichever occurred earlier. Disease progression occurred when a patient met either the Gynecologic Cancer Intergroup (GCIG) cancer-antigen (CA)-125 definition or the Response Evaluation Criteria in Solid Tumors (RECIST) radiological definition of progressive disease. The GCIG CA-125 definition of disease progression was defined as a CA-125 level ≥ 2 × the upper limit of normal documented on 2 occasions at least 1 week apart. The radiological RECIST criteria of disease progression was defined as the appearance of new lesions or an overall increase ≥ 20% or at least 5 mm in existing tumors. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | Baseline to the end of the study (up to 4 years 10 months) | Overall survival was defined as the time from randomization until death from any cause. |
| Change From Baseline in Mucin 1 Antibody Levels at Weeks 20, 56, and 104 | Baseline to Week 104 | Mucin 1 antibodies were assessed in serum samples using a quantitative enzyme-linked immunosorbent assay (ELISA). Detection was achieved with electrochemiluminescence. |
| Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Baseline to Week 104 | Intracellular cytokine staining (ICS) for IL2, IL4, IL17, tumor necrosis factor (TNF), and interferon gamma (IFNg) was done in both CD4+ and CD8+ cells from serum samples collected at Weeks, 20, 56, and 104. Intracellular cytokine staining data were acquired with 8-color flow cytometry on a BD LSR II flow cytometer and a high-throughput screening microplate reader. |
Countries
Australia, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Non-randomized Cvac Participants received 6-8 intradermal injections of Cvac at 4 sites along both upper arms and both thighs. The 6-8 injections contained \
60 × 10\^6 dendritic cells. Following evaluation after the first dose, participants received additional injections as described for the randomized Cvac group below. | 7 |
| Randomized Cvac Participants received 6-8 intradermal injections of Cvac at 4 sites along both upper arms and both thighs every 4 weeks for 24 weeks (7 doses at Weeks 8, 12, 16, 20, 24, 28, and 32), and then every 8 weeks for 24 weeks (3 doses at Weeks 40, 48, and 56). The 6-8 injections contained \
60 × 10\^6 dendritic cells. | 29 |
| Observational Standard of Care Participants in this group did not receive any treatment during the study. | 27 |
| Total | 63 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 0 | 0 | 1 |
| Overall Study | Disease Progression | 5 | 20 | 18 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 |
| Overall Study | Reason Not Specified | 0 | 1 | 0 |
| Overall Study | Withdrew Consent | 0 | 1 | 2 |
Baseline characteristics
| Characteristic | Non-randomized Cvac | Randomized Cvac | Observational Standard of Care | Total |
|---|---|---|---|---|
| Age, Continuous | 52.4 Years STANDARD_DEVIATION 10.3 | 56.8 Years STANDARD_DEVIATION 8.5 | 56.2 Years STANDARD_DEVIATION 9.5 | 56.1 Years STANDARD_DEVIATION 9.1 |
| Sex: Female, Male Female | 7 Participants | 29 Participants | 27 Participants | 63 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 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 | 7 / 7 | 25 / 26 | 22 / 24 |
| serious Total, serious adverse events | 0 / 7 | 4 / 26 | 0 / 24 |
Outcome results
Primary
Progression-free Survival
Progression-free survival was defined as the time from randomization to the date of documented disease progression or death from any cause, whichever occurred earlier. Disease progression occurred when a patient met either the Gynecologic Cancer Intergroup (GCIG) cancer-antigen (CA)-125 definition or the Response Evaluation Criteria in Solid Tumors (RECIST) radiological definition of progressive disease. The GCIG CA-125 definition of disease progression was defined as a CA-125 level ≥ 2 × the upper limit of normal documented on 2 occasions at least 1 week apart. The radiological RECIST criteria of disease progression was defined as the appearance of new lesions or an overall increase ≥ 20% or at least 5 mm in existing tumors.
Time frame: Baseline to 48 weeks after the last visit or dose of Cvac (up to 104 weeks)
Population: Intent-to-treat population: All randomized participants. Efficacy data were not collected on the initial cohort of 7 non-randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Randomized Cvac | Progression-free Survival | 12.89 Months |
| Observational Standard of Care | Progression-free Survival | 8.64 Months |
Secondary
Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104
Intracellular cytokine staining (ICS) for IL2, IL4, IL17, tumor necrosis factor (TNF), and interferon gamma (IFNg) was done in both CD4+ and CD8+ cells from serum samples collected at Weeks, 20, 56, and 104. Intracellular cytokine staining data were acquired with 8-color flow cytometry on a BD LSR II flow cytometer and a high-throughput screening microplate reader.
Time frame: Baseline to Week 104
Population: Intent-to-treat population: All randomized participants. Efficacy data were not collected on the initial cohort of 7 non-randomized participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Randomized Cvac | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 104: IFNg in CD4+ cells (n's=3, 1) | -1.3833 Arbitrary units | Standard Deviation 0.3474 |
| Randomized Cvac | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 20: IL4 in CD4+ cells (n's=21, 14) | -0.0702 Arbitrary units | Standard Deviation 0.3781 |
| Randomized Cvac | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 20: IL2 in CD8+ cells (n's=21, 14) | -0.3724 Arbitrary units | Standard Deviation 0.3808 |
| Randomized Cvac | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 20: IL17 in CD8+ cells (n's=21, 14) | -0.8268 Arbitrary units | Standard Deviation 1.6737 |
| Randomized Cvac | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 56: IL4 in CD4+ cells (n's=2, 2) | -0.3824 Arbitrary units | Standard Deviation 0.1417 |
| Randomized Cvac | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 56: IL17 in CD4+ cells (n's=2, 2) | -0.9413 Arbitrary units | Standard Deviation 0.6249 |
| Randomized Cvac | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 56: IL4 in CD8+ cells (n's=2, 2) | 0.0622 Arbitrary units | Standard Deviation 0.095 |
| Randomized Cvac | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 104: IL4 in CD4+ cells (n's=3, 1) | -0.3328 Arbitrary units | Standard Deviation 0.1972 |
| Randomized Cvac | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 104: IL17 in CD4+ cells (n's=3, 1) | -1.1783 Arbitrary units | Standard Deviation 0.597 |
| Randomized Cvac | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 104: TNF in CD4+ cells (n's=3, 1) | -6.4140 Arbitrary units | Standard Deviation 2.3691 |
| Randomized Cvac | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 104: IL2 in CD8+ cells (n's=3, 1) | -1.1586 Arbitrary units | Standard Deviation 0.3643 |
| Randomized Cvac | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 104: TNF in CD8+ cells (n's=3, 1) | -5.1697 Arbitrary units | Standard Deviation 2.6055 |
| Randomized Cvac | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 104: IFNg in CD8+ cells (n's=3, 1) | -5.1340 Arbitrary units | Standard Deviation 3.0755 |
| Randomized Cvac | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 20: IL2 in CD4+ cells (n's=21, 14) | -1.4022 Arbitrary units | Standard Deviation 0.973 |
| Randomized Cvac | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 20: IL17 in CD4+ cells (n's=21, 14) | -1.0544 Arbitrary units | Standard Deviation 1.1481 |
| Randomized Cvac | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 20: TNF in CD4+ cells (n's=21, 14) | -2.7106 Arbitrary units | Standard Deviation 2.1428 |
| Randomized Cvac | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 20: IFNg in CD4+ cells (n's=21, 14) | -1.3576 Arbitrary units | Standard Deviation 1.5922 |
| Randomized Cvac | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 20: IL4 in CD8+ cells (n's=21, 14) | -0.1495 Arbitrary units | Standard Deviation 0.1218 |
| Randomized Cvac | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 20: TNF in CD8+ cells (n's=21, 14) | -2.0802 Arbitrary units | Standard Deviation 2.0004 |
| Randomized Cvac | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 20: IFNg in CD8+ cells (n's=21, 14) | -2.8385 Arbitrary units | Standard Deviation 2.5259 |
| Randomized Cvac | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 56: IL2 in CD4+ cells (n's=2, 2) | -1.6798 Arbitrary units | Standard Deviation 2.1394 |
| Randomized Cvac | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 56: TNF in CD4+ cells (n's=2, 2) | -5.9500 Arbitrary units | Standard Deviation 3.3064 |
| Randomized Cvac | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 56: IFNg in CD4+ cells (n's=2, 2) | -1.2676 Arbitrary units | Standard Deviation 0.4039 |
| Randomized Cvac | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 56: IL2 in CD8+ cells (n's=2, 2) | -0.9438 Arbitrary units | Standard Deviation 0.0057 |
| Randomized Cvac | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 56: IL17 in CD8+ cells (n's=2, 2) | -0.0396 Arbitrary units | Standard Deviation 0.0136 |
| Randomized Cvac | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 56: TNF in CD8+ cells (n's=2, 2) | -5.8027 Arbitrary units | Standard Deviation 3.2811 |
| Randomized Cvac | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 56: IFNg in CD8+ cells (n's=2, 2) | -5.9300 Arbitrary units | Standard Deviation 3.7024 |
| Randomized Cvac | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 104: IL2 in CD4+ cells (n's=3, 1) | -2.3179 Arbitrary units | Standard Deviation 1.8772 |
| Randomized Cvac | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 104: IL4 in CD8+ cells (n's=3, 1) | -0.1241 Arbitrary units | Standard Deviation 0.0688 |
| Randomized Cvac | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 104: IL17 in CD8+ cells (n's=3, 1) | -0.2485 Arbitrary units | Standard Deviation 0.3395 |
| Observational Standard of Care | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 20: IFNg in CD4+ cells (n's=21, 14) | -1.0243 Arbitrary units | Standard Deviation 1.2047 |
| Observational Standard of Care | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 20: IL2 in CD8+ cells (n's=21, 14) | -0.4562 Arbitrary units | Standard Deviation 0.5527 |
| Observational Standard of Care | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 56: IL4 in CD8+ cells (n's=2, 2) | -0.0622 Arbitrary units | Standard Deviation 0.095 |
| Observational Standard of Care | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 20: IL4 in CD8+ cells (n's=21, 14) | -0.5607 Arbitrary units | Standard Deviation 1.4552 |
| Observational Standard of Care | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 20: IL17 in CD8+ cells (n's=21, 14) | -0.1232 Arbitrary units | Standard Deviation 0.1367 |
| Observational Standard of Care | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 104: IL2 in CD8+ cells (n's=3, 1) | -0.1277 Arbitrary units | — |
| Observational Standard of Care | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 56: IL4 in CD4+ cells (n's=2, 2) | -0.3824 Arbitrary units | Standard Deviation 0.1417 |
| Observational Standard of Care | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 20: TNF in CD8+ cells (n's=21, 14) | -1.9156 Arbitrary units | Standard Deviation 2.1254 |
| Observational Standard of Care | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 56: IL17 in CD8+ cells (n's=2, 2) | -0.0396 Arbitrary units | Standard Deviation 0.0136 |
| Observational Standard of Care | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 20: IFNg in CD8+ cells (n's=21, 14) | -2.3178 Arbitrary units | Standard Deviation 2.1022 |
| Observational Standard of Care | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 104: IL4 in CD4+ cells (n's=3, 1) | -0.2912 Arbitrary units | — |
| Observational Standard of Care | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 104: IL2 in CD4+ cells (n's=3, 1) | -1.4545 Arbitrary units | — |
| Observational Standard of Care | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 104: IL17 in CD4+ cells (n's=3, 1) | -1.0044 Arbitrary units | — |
| Observational Standard of Care | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 56: IL2 in CD4+ cells (n's=2, 2) | -1.6798 Arbitrary units | Standard Deviation 2.1394 |
| Observational Standard of Care | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 20: IL2 in CD4+ cells (n's=21, 14) | -1.1842 Arbitrary units | Standard Deviation 1.0945 |
| Observational Standard of Care | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 104: IFNg in CD4+ cells (n's=3, 1) | -1.5452 Arbitrary units | — |
| Observational Standard of Care | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 56: IL17 in CD4+ cells (n's=2, 2) | -0.9413 Arbitrary units | Standard Deviation 0.6249 |
| Observational Standard of Care | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 104: IL4 in CD8+ cells (n's=3, 1) | -0.1282 Arbitrary units | — |
| Observational Standard of Care | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 104: IL17 in CD8+ cells (n's=3, 1) | -0.4682 Arbitrary units | — |
| Observational Standard of Care | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 56: TNF in CD8+ cells (n's=2, 2) | -5.8027 Arbitrary units | Standard Deviation 3.2811 |
| Observational Standard of Care | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 104: TNF in CD8+ cells (n's=3, 1) | -1.6795 Arbitrary units | — |
| Observational Standard of Care | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 56: TNF in CD4+ cells (n's=2, 2) | -5.9500 Arbitrary units | Standard Deviation 3.3064 |
| Observational Standard of Care | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 104: IFNg in CD8+ cells (n's=3, 1) | -2.3506 Arbitrary units | — |
| Observational Standard of Care | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 104: TNF in CD4+ cells (n's=3, 1) | -2.9642 Arbitrary units | — |
| Observational Standard of Care | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 20: IL4 in CD4+ cells (n's=21, 14) | -0.1651 Arbitrary units | Standard Deviation 0.2876 |
| Observational Standard of Care | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 56: IFNg in CD4+ cells (n's=2, 2) | -1.2676 Arbitrary units | Standard Deviation 0.4039 |
| Observational Standard of Care | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 20: IL17 in CD4+ cells (n's=21, 14) | -0.3960 Arbitrary units | Standard Deviation 0.4052 |
| Observational Standard of Care | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 56: IFNg in CD8+ cells (n's=2, 2) | -5.9300 Arbitrary units | Standard Deviation 3.7024 |
| Observational Standard of Care | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 20: TNF in CD4+ cells (n's=21, 14) | -1.8939 Arbitrary units | Standard Deviation 1.7481 |
| Observational Standard of Care | Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Week 56: IL2 in CD8+ cells (n's=2, 2) | -0.9438 Arbitrary units | Standard Deviation 0.0057 |
Secondary
Change From Baseline in Mucin 1 Antibody Levels at Weeks 20, 56, and 104
Mucin 1 antibodies were assessed in serum samples using a quantitative enzyme-linked immunosorbent assay (ELISA). Detection was achieved with electrochemiluminescence.
Time frame: Baseline to Week 104
Population: Intent-to-treat population: All randomized participants. Efficacy data were not collected on the initial cohort of 7 non-randomized participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Randomized Cvac | Change From Baseline in Mucin 1 Antibody Levels at Weeks 20, 56, and 104 | Week 104 (n's=10, 10) | -203.0 Arbitrary units | Standard Deviation 4413.4 |
| Randomized Cvac | Change From Baseline in Mucin 1 Antibody Levels at Weeks 20, 56, and 104 | Week 20 (n's=21, 13) | 957.2 Arbitrary units | Standard Deviation 9127.3 |
| Randomized Cvac | Change From Baseline in Mucin 1 Antibody Levels at Weeks 20, 56, and 104 | Week 56 (n's=8, 6) | -1113.9 Arbitrary units | Standard Deviation 12033.3 |
| Observational Standard of Care | Change From Baseline in Mucin 1 Antibody Levels at Weeks 20, 56, and 104 | Week 56 (n's=8, 6) | -19063.1 Arbitrary units | Standard Deviation 41323.7 |
| Observational Standard of Care | Change From Baseline in Mucin 1 Antibody Levels at Weeks 20, 56, and 104 | Week 20 (n's=21, 13) | -2854.8 Arbitrary units | Standard Deviation 9411.8 |
| Observational Standard of Care | Change From Baseline in Mucin 1 Antibody Levels at Weeks 20, 56, and 104 | Week 104 (n's=10, 10) | -1956.7 Arbitrary units | Standard Deviation 5711.1 |
Secondary
Overall Survival
Overall survival was defined as the time from randomization until death from any cause.
Time frame: Baseline to the end of the study (up to 4 years 10 months)
Population: Intent-to-treat population: All randomized participants. Efficacy data were not collected on the initial cohort of 7 non-randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Randomized Cvac | Overall Survival | NA Months |
| Observational Standard of Care | Overall Survival | NA Months |