Clinical Trial Results:
Preclinical phase 0 micro dose study to evaluate the effekt of R-CHOP chemotherapy on cellular gene-expression.
- Establisment of a preclinical model for in vivo evaluation of molecular biological efects.
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Summary
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EudraCT number |
2011-002677-30 |
Trial protocol |
DK |
Global end of trial date |
11 May 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
18 Dec 2019
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First version publication date |
18 Dec 2019
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
KFE2011.04
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
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WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Department of Haematology, Aalborg Hospital
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Sponsor organisation address |
Sdr. Skovvej 15, Aalborg, Denmark, 9000
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Public contact |
Hæmatologisk Forskningsafsnit, Professor Tarec C. El-Galaly, MD, DMSc, Department of Haematology, Aalborg Hospital, 45 97663869, lit@rn.dk
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Scientific contact |
Hæmatologisk Forskningsafsnit, Professor Tarec C. El-Galaly, MD, DMSc, Department of Haematology, Aalborg Hospital, 45 97663869, lit@rn.dk
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
18 Sep 2019
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
11 May 2016
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Global end of trial reached? |
Yes
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Global end of trial date |
11 May 2016
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
To establish a clinical method for phase 0 studies with the combination chemotherapy R-CHOP as focal-point.
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Protection of trial subjects |
Data are pseudo-anonymized in downstream handling.
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Background therapy |
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Evidence for comparator |
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Actual start date of recruitment |
01 Jul 2014
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Denmark: 9
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Worldwide total number of subjects |
9
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EEA total number of subjects |
9
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
5
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From 65 to 84 years |
4
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85 years and over |
0
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Recruitment
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Recruitment details |
The study treatment constitutes 1% of the planned standard R-CHOP treatment and will be given two hours prior to standard treatment. Blood samples are taken at baseline, 15, 30, 60 and 120 minutes for microarray analysis. Subjects are included with informed consent. | |||||||||
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Pre-assignment
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Screening details |
Planned treatment with R-CHOP for a hematologic disease in accordance with current guidelines at Aalborg Hospital. | |||||||||
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Period 1
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Period 1 title |
Overall period
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | |||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Rituximab | |||||||||
Arm description |
Rituximab 0,1 mg administered and blood samples drawn at 0, 30, 60, 90, 120 minutes | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
MabThera (rituximab)
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Investigational medicinal product code |
SUB12570MIG
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Other name |
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
0,1 mg
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Arm title
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Doxorubicin | |||||||||
Arm description |
Doxorubicin 0,1 mg administered and blood samples drawn after 0, 30, 30, 90, 120 minutes. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Adriamycin
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Investigational medicinal product code |
SUB06391MIG
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Other name |
Doxorubicin
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Pharmaceutical forms |
Powder for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
0,1 mg
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Baseline characteristics reporting groups
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Reporting group title |
Overall period
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Reporting group description |
All subjects | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
All subjects
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Subject analysis set type |
Full analysis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
All subjects
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End points reporting groups
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Reporting group title |
Rituximab
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Reporting group description |
Rituximab 0,1 mg administered and blood samples drawn at 0, 30, 60, 90, 120 minutes | ||
Reporting group title |
Doxorubicin
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Reporting group description |
Doxorubicin 0,1 mg administered and blood samples drawn after 0, 30, 30, 90, 120 minutes. | ||
Subject analysis set title |
All subjects
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
All subjects
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End point title |
Establish a clinical method for a phase 0 trial with R-CHOP as a focal point [1] | ||||||||||||
End point description |
10 subjects were included in the study and 1 was subsequently excluded.
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End point type |
Primary
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End point timeframe |
4 November 2014 - 11 May 2016
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: We have successfully included and analyzed data from 9 subjects illustrating that our setup supports the primary endpoint. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
To identify a genetic profile of genes that are up- or downregulated during R-CHOP treatment, and through these data identify specifik pathways for each drug individually and for the entire combinaiton therapy. | |||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Before 31 December 2016.
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Statistical analysis title |
Linear models | |||||||||
Statistical analysis description |
Global GEP.
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Comparison groups |
Doxorubicin v Rituximab
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Number of subjects included in analysis |
9
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Analysis specification |
Pre-specified
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Analysis type |
other [2] | |||||||||
P-value |
< 0.05 | |||||||||
Method |
ANOVA | |||||||||
Parameter type |
Differentially expressed genes | |||||||||
Confidence interval |
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95% | |||||||||
sides |
2-sided
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lower limit |
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upper limit |
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| Notes [2] - The analysis on the significant genes included unsupervised clustering and it was assessed whether clustering based on time or patient occurred. Detection of patterns across time by inspecting the PCA trajectories over time of all the significant genes, in both 2 and 3-dimensions were conducted. Finally, detection of change in patterns of gene expression over time by applying self-organizing maps (SOMS) was pursued. By unsupervised clustering, data did not cluster by patients nor time. |
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Adverse events information
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Timeframe for reporting adverse events |
2 hours
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Adverse event reporting additional description |
Facial heat flush and chills to Rituximab.
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
CTCAE | |||||||||||||||||||||||||||||||||
Dictionary version |
3.0
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Reporting groups
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Reporting group title |
Rituximab
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Reporting group description |
Subjects included in the Rituximab arm. | |||||||||||||||||||||||||||||||||
Reporting group title |
Doxorubicin
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Reporting group description |
Subjects in the Doxorubicin arm. | |||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | ||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||||||
Interruptions (globally) |
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| Were there any global interruptions to the trial? Yes | |||||||
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Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||||||
| None reported | |||||||
