Clinical Trial Results:
Preparation and application of autologous immunohybridoma cells for the treatment of prostate cancer
|
Summary
|
|
EudraCT number |
2012-005498-29 |
Trial protocol |
SI |
Global end of trial date |
08 Nov 2016
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
06 May 2020
|
First version publication date |
06 May 2020
|
Other versions |
|
Summary report(s) |
Results summary |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
2.28
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
Celica Biomedical
|
||
Sponsor organisation address |
Tehnološki park 24, Ljubljana, Slovenia, 1000
|
||
Public contact |
Clinical trial information desk
, Celica Biomedical, 386 (0)1544 36 04, office@celicabiomedical.com
|
||
Scientific contact |
Clinical trial information desk, Celica Biomedical, 386 (0)1544 36 04, robert.zorec@celica.si
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
08 May 2017
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
08 Nov 2016
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
08 Nov 2016
|
||
Was the trial ended prematurely? |
No
|
||
|
General information about the trial
|
|||
Main objective of the trial |
Main objectives of the trial were to assess safety, feasibility, tolerability and non-toxicity of the treatment with autologous dendritic-tumor hybridoma cells and the effect on the quality of live of the patients with castration resistant prostate cancer.
|
||
Protection of trial subjects |
Prostate biopsy samples were taken under local anesthesia (10 mL of 2% xylocaine periprostatic injection, plus intrarectal application of 10 mL of 2% xylocaine jelly; both AstraZeneca, UK), using
transrectal ultrasonography (B-K Medical, UltraView 800, USA), a biopsy gun with 18G needles (Magnum reusable biopsy gun; Bard Biopsy Systems, USA). The removal of prostate tumor tissue did not cause pain or other side effects or inconvenience to the patients. All patients received per oral ciprofloxacin prophylaxis (2 × 500 mg daily for 5 days) and were advised not to perform major physical activity for a few days.
|
||
Background therapy |
continuous androgen-deprivation therapy standard supportive therapy for prevention of skeleton-related events (ie, denosumab, once monthly) | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
03 Feb 2014
|
||
Long term follow-up planned |
Yes
|
||
Long term follow-up rationale |
Safety, Efficacy, Ethical reason, Scientific research | ||
Long term follow-up duration |
27 Months | ||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Slovenia: 22
|
||
Worldwide total number of subjects |
22
|
||
EEA total number of subjects |
22
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
0
|
||
From 65 to 84 years |
22
|
||
85 years and over |
0
|
||
|
|||||||||||||||||||
|
Recruitment
|
|||||||||||||||||||
Recruitment details |
Dates of recruitment period: from February 2014 to January 2016 Territories: Slovenia | ||||||||||||||||||
|
Pre-assignment
|
|||||||||||||||||||
Screening details |
Histologically proven prostate cancer; Progressive disease; No signs of previous therapy toxicity; During the trial, patients should not receive chemotherapy treatment in parallel; Patients should be without corticosteroid; Not receiving any previous immunotherapy; Hormonal therapy permitted to maintain castration levels of testosterone. | ||||||||||||||||||
|
Pre-assignment period milestones
|
|||||||||||||||||||
Number of subjects started |
22 | ||||||||||||||||||
Number of subjects completed |
22 | ||||||||||||||||||
|
Period 1
|
|||||||||||||||||||
Period 1 title |
baseline period
|
||||||||||||||||||
Is this the baseline period? |
Yes | ||||||||||||||||||
Allocation method |
Randomised - controlled
|
||||||||||||||||||
Blinding used |
Double blind | ||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Carer, Assessor | ||||||||||||||||||
|
Arms
|
|||||||||||||||||||
Are arms mutually exclusive |
Yes
|
||||||||||||||||||
|
Arm title
|
aHyC | ||||||||||||||||||
Arm description |
Received autologous hybridoma cell (aHyC) vaccine - first. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
autologous hybridoma cell vaccine
|
||||||||||||||||||
Investigational medicinal product code |
aHyC
|
||||||||||||||||||
Other name |
|||||||||||||||||||
Pharmaceutical forms |
Injection
|
||||||||||||||||||
Routes of administration |
Subcutaneous use
|
||||||||||||||||||
Dosage and administration details |
Each patient received four injections of aHyC vaccine at 3-week intervals. The number of cells in each vaccine varied with each patient, however, in all cases, these were the maximal numbers of autologous cells that could be obtained from the prostate tissue samples and leukocyte concentrates (median cell number per vaccine: 7.7 × 10'6).
|
||||||||||||||||||
|
Arm title
|
control | ||||||||||||||||||
Arm description |
Received vaccine vehicle (placebo) - first. | ||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||
Investigational medicinal product name |
vaccine vehicle
|
||||||||||||||||||
Investigational medicinal product code |
placebo
|
||||||||||||||||||
Other name |
|||||||||||||||||||
Pharmaceutical forms |
Injection
|
||||||||||||||||||
Routes of administration |
Subcutaneous use
|
||||||||||||||||||
Dosage and administration details |
Each patient received four injections of vaccine vehicle at 3-week intervals.
|
||||||||||||||||||
|
|||||||||||||||||||
|
Period 2
|
|||||||||||||||||||
Period 2 title |
cross-over
|
||||||||||||||||||
Is this the baseline period? |
No | ||||||||||||||||||
Allocation method |
Randomised - controlled
|
||||||||||||||||||
Blinding used |
Double blind | ||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Carer, Assessor | ||||||||||||||||||
|
Arms
|
|||||||||||||||||||
Are arms mutually exclusive |
Yes
|
||||||||||||||||||
|
Arm title
|
aHyC | ||||||||||||||||||
Arm description |
Received vaccine vehicle (placebo). | ||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||
Investigational medicinal product name |
vaccine vehicle
|
||||||||||||||||||
Investigational medicinal product code |
placebo
|
||||||||||||||||||
Other name |
|||||||||||||||||||
Pharmaceutical forms |
Injection
|
||||||||||||||||||
Routes of administration |
Subcutaneous use
|
||||||||||||||||||
Dosage and administration details |
Each patient received four injections of vaccine vehicle at 3-week intervals.
|
||||||||||||||||||
|
Arm title
|
control | ||||||||||||||||||
Arm description |
Received autologous hybridoma cell (aHyC) vaccine. | ||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||
Investigational medicinal product name |
autologous hybridoma cell vaccine
|
||||||||||||||||||
Investigational medicinal product code |
aHyC
|
||||||||||||||||||
Other name |
|||||||||||||||||||
Pharmaceutical forms |
Injection
|
||||||||||||||||||
Routes of administration |
Subcutaneous use
|
||||||||||||||||||
Dosage and administration details |
Each patient received four injections of aHyC vaccine at 3-week intervals. The number of cells in each vaccine varied with each patient, however, in all cases, these were the maximal numbers of autologous cells that could be obtained from the prostate tissue samples and leukocyte concentrates (median cell number per vaccine: 7.7 × 10'6).
|
||||||||||||||||||
|
|||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
aHyC
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Received autologous hybridoma cell (aHyC) vaccine - first. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
control
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Received vaccine vehicle (placebo) - first. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
aHyC
|
||
Reporting group description |
Received autologous hybridoma cell (aHyC) vaccine - first. | ||
Reporting group title |
control
|
||
Reporting group description |
Received vaccine vehicle (placebo) - first. | ||
Reporting group title |
aHyC
|
||
Reporting group description |
Received vaccine vehicle (placebo). | ||
Reporting group title |
control
|
||
Reporting group description |
Received autologous hybridoma cell (aHyC) vaccine. | ||
|
||||||||||||||||
End point title |
Safety | |||||||||||||||
End point description |
Adverse events (AEs) were monitored during medical examinations.
|
|||||||||||||||
End point type |
Primary
|
|||||||||||||||
End point timeframe |
Time-frame to observe adverse effects: from the first application in the first period until the start of the second period (cross-over) - to compare both arms.
|
|||||||||||||||
|
||||||||||||||||
Statistical analysis title |
z-test of proportions | |||||||||||||||
Comparison groups |
aHyC v control
|
|||||||||||||||
Number of subjects included in analysis |
20
|
|||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||
Analysis type |
equivalence | |||||||||||||||
P-value |
≤ 0.05 | |||||||||||||||
Method |
z-test of proportions | |||||||||||||||
Confidence interval |
||||||||||||||||
|
||||||||||||||||
End point title |
Quality of life (QL) | |||||||||||||||
End point description |
||||||||||||||||
End point type |
Primary
|
|||||||||||||||
End point timeframe |
For the comparison of QL the evaluation period was set up to 4 months after the first application of aHyC vaccine or placebo. A t-test was used to compare QL between aHyC and placebo arm.
|
|||||||||||||||
|
||||||||||||||||
Statistical analysis title |
t-test | |||||||||||||||
Statistical analysis description |
The mean quality of life score was calculated for up to 4 months after receiving first aHyC or placebo, for each patient who completed the questionnaire. From these data, the mean score in QL for aHyC and placebo arm was calculated, and the difference was tested with a 2-tailed t-test.
|
|||||||||||||||
Comparison groups |
aHyC v control
|
|||||||||||||||
Number of subjects included in analysis |
17
|
|||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||
Analysis type |
equivalence | |||||||||||||||
P-value |
≤ 0.05 | |||||||||||||||
Method |
t-test, 2-sided | |||||||||||||||
Parameter type |
Mean difference (final values) | |||||||||||||||
Confidence interval |
||||||||||||||||
level |
95% | |||||||||||||||
sides |
2-sided
|
|||||||||||||||
lower limit |
- | |||||||||||||||
upper limit |
- | |||||||||||||||
Variability estimate |
Standard error of the mean
|
|||||||||||||||
|
|||||||||||||
End point title |
C-reactive protein | ||||||||||||
End point description |
|||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Values at the begging of the cross-over period are given for each arm. Baseline values for each arm were also different, but can not be inserted in this forms.
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Serum PSA | ||||||||||||
End point description |
|||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Values at the begging of the cross-over period are given for each arm. Baseline values for each arm were also different, but can not be inserted in this forms.
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Regulatory natural killer (NK) cells | ||||||||||||
End point description |
For each patient a percent of change in NK population was calculated.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From the beginning of baseline period until the beginning of cross-over period.
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Overall survival | ||||||||||||
End point description |
In both arms median Overall survival was not reached at the time off cut-off date. Instead, median observation periods are given, from the diagnosis of CRPC until the cut-off date or death. However, an additional parameter was analyzed to evaluate efficacy: time-to-next-treatment (TTNT), which was significantly prolonged in aHyC patients (see also attached document: Results summary).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From CRPC diagnosis until the cut-off date (Jan 31, 2019) or death.
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
The observation period was set from the first application until 6 months after the last application in cross-over period (aHyC or placebo).
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
17
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
All patients
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
The reporting group consists of all patients who participated in the trial, whether or not they received the aHyC vaccine (N = 20). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
