Clinical Trial Results:
A phase 2 study of the monocyte-targeted histone deacetylase inhibitor tefinostat (CHR-2845) in chronic myelomonocytic leukaemia (CMML)
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Summary
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EudraCT number |
2015-002281-23 |
Trial protocol |
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Global end of trial date |
31 May 2019
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Results information
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Results version number |
v1(current) |
This version publication date |
17 Dec 2021
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First version publication date |
17 Dec 2021
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Other versions |
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Summary report(s) |
MONOCLE final report |
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 |
Spon1345-14
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Additional study identifiers
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ISRCTN number |
ISRCTN17394489 | ||
US NCT number |
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WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Cardiff university
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Sponsor organisation address |
30-36 Newport Road, Cardiff, United Kingdom, CF24 0DE
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Public contact |
Centre for trials research, Cardiff University, Centre for trials research, Cardiff University, +44 02920687620, ctr@cardiff.ac.uk
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Scientific contact |
Centre for trials research, Cardiff University, Cardiff University, +44 02920687620, ctr@cardiff.ac.uk
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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 |
01 Nov 2021
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
08 May 2018
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Global end of trial reached? |
Yes
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Global end of trial date |
31 May 2019
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
1. Is tefinostat (CHR-2845) safe and tolerable for patients with CMML?
2. Is tefinostat clinically effective in CMML? (primary efficacy endpoint will be overall clinical response rate according to the International Consortium MDS/MPN Response Criteria).
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Protection of trial subjects |
All subjects remained under the care of a hematological consultant.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Jun 2016
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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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 |
United Kingdom: 21
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Worldwide total number of subjects |
21
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EEA total number of subjects |
0
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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) |
2
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From 65 to 84 years |
18
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85 years and over |
1
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Recruitment
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Recruitment details |
Recruitment began in January 2017. 21 patients were enrolled into the study, 2 were excluded (one was ineligible and one was recruited in error after recruitment freeze), 19 received at least 1 dose of tefinostat, 1 was excluded from toxicity analysis, 13 were discontinued and then 6 were included in efficacy analysis. | ||||||||||||||||||
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Pre-assignment
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Screening details |
The following screening assessments should be performed prior to registration and within 28 days of commencing the first cycle of tefinostat therapy (days -28 to 0): Medical history and demographics, physical examination, ECG, pregnancy test and contraception, hematology, biochemistry, urinalysis, quality of life. | ||||||||||||||||||
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Period 1
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Period 1 title |
Overall trial (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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Arm title
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Tefinostat | ||||||||||||||||||
Arm description |
A phase 2 study of the monocyte-targeted histone deacetylase inhibitor tefinostat (CHR-2845) in chronic myelomonocytic leukaemia (CMML). | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Tefinostat
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Investigational medicinal product code |
CHR-2845
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Tefinostat will be administered orally on a continuous basis, starting at a once daily dose of 360mg. The dose of tefinostat may be escalated or de-escalated for reasons of tolerability and clinical efficacy.
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| Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: One patient enrolled in the trial was ineligible and therefore was not included in the baseline period. |
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Baseline characteristics reporting groups
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Reporting group title |
Overall trial
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Efficacy
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
All patients who completed 6 cycles of tefinostat will be included in the efficacy analysis evaluated at the end of cycle 6.
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Subject analysis set title |
Safety
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Subject analysis set type |
Safety analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Patients who died or withdrew before the end of cycle 2 but not for toxicity reasons, will be excluded from analysis for assessment of the toxicity outcome.
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End points reporting groups
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Reporting group title |
Tefinostat
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Reporting group description |
A phase 2 study of the monocyte-targeted histone deacetylase inhibitor tefinostat (CHR-2845) in chronic myelomonocytic leukaemia (CMML). | ||
Subject analysis set title |
Efficacy
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
All patients who completed 6 cycles of tefinostat will be included in the efficacy analysis evaluated at the end of cycle 6.
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Subject analysis set title |
Safety
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Patients who died or withdrew before the end of cycle 2 but not for toxicity reasons, will be excluded from analysis for assessment of the toxicity outcome.
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End point title |
Safety | |||||||||||||||
End point description |
Safety and tolerability of tefinostat defined as the proportion of patients experiencing CTC grade 3-4 non-haematological toxicity or death thought to be at least possibly related to tefinostat during the first two cycles of treatment
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End point type |
Primary
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End point timeframe |
During the first two cycles of treatment.
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Statistical analysis title |
Safety | |||||||||||||||
Statistical analysis description |
It is felt that if more than 40% of patients suffer unacceptable toxicity then the treatment should be rejected, and if fewer than 20% suffer some toxicity then the toxicity profile is considered acceptable.
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Comparison groups |
Tefinostat v Safety
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Number of subjects included in analysis |
36
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Analysis specification |
Pre-specified
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Analysis type |
other [1] | |||||||||||||||
Method |
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Parameter type |
Proportion (95% CI) | |||||||||||||||
Point estimate |
5.6
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Confidence interval |
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95% | |||||||||||||||
sides |
2-sided
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lower limit |
0.1 | |||||||||||||||
upper limit |
27.3 | |||||||||||||||
| Notes [1] - Calculated proportion and 95% confidence interval |
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End point title |
Efficacy | |||||||||||||||
End point description |
Overall clinical response rate (according to International Consortium MDS/MPN Response Criteria)
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End point type |
Primary
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End point timeframe |
Assessed at the end of cycle 6
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Statistical analysis title |
Efficacy | |||||||||||||||
Statistical analysis description |
The primary clinical efficacy objective of the study is to determine overall response rate after 6 cycles of tefinostat. It is felt that if the overall response rate is below 10% the treatment should be rejected, and if above 30% the treatment is sufficiently promising to warrant further evaluation in a phase III trial.
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Comparison groups |
Tefinostat v Efficacy
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Number of subjects included in analysis |
12
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Analysis specification |
Pre-specified
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Analysis type |
other [2] | |||||||||||||||
Method |
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Parameter type |
Proportion (95% CI) | |||||||||||||||
Point estimate |
5.3
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Confidence interval |
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level |
95% | |||||||||||||||
sides |
2-sided
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lower limit |
0.1 | |||||||||||||||
upper limit |
26 | |||||||||||||||
| Notes [2] - Note: Only 6 patients were evaluable for efficacy at the end of cycle 6. The 13 patients who withdrew previously achieved no clinical benefit and are included in the denominator. Thus the proportion is 1/19. |
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Adverse events information
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Timeframe for reporting adverse events |
Information about adverse events will be collected and recorded for all patients from the time of start of protocol treatment until 30 days after the last dose of tefinostat therapy.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
20
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Reporting groups
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Reporting group title |
All patients receiving at least one dose of tefinostat
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Reporting group description |
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Date |
Amendment |
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25 Jul 2017 |
Update of protocol to version 3.0 - Addition of Urinalysis to the schedule of study assessments |
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26 Jan 2018 |
Update of protocol, PIS 1 and PIS 2. Major changes as a result of an updated IB. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
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 | |||
