Clinical Trial Results:
Pilot study of 5 Azacitidine in the treatment of MDS/AML with high risk (chromosome 7 and/or complex cytogenetic abnormality)
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Summary
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EudraCT number |
2005-003732-22 |
Trial protocol |
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Global end of trial date |
01 Dec 2013
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Results information
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Results version number |
v1(current) |
This version publication date |
27 Jul 2019
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First version publication date |
27 Jul 2019
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Other versions |
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Summary report(s) |
FINAL STUDY 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 |
M7-1, Version 1, 03/08/05
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00915785 | ||
WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
King's College London
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Sponsor organisation address |
The Strand, London, United Kingdom, WC2R 2LS
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Public contact |
Professor Ghulam Mufti, King's College London, 44 020 3299 3080, ghulam.mufti@kcl.ac.uk
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Scientific contact |
Professor Ghulam Mufti, King's College London, 44 020 3299 3080, ghulam.mufti@kcl.ac.uk
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Sponsor organisation name |
King's College Hospital
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Sponsor organisation address |
Denmark Hill, London, United Kingdom, SE59RS
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Public contact |
Professor Ghulam Mufti, King's College Hospital, 44 203 299 3080, ghulam.mufti@kcl.ac.uk
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Scientific contact |
Professor Ghulam Mufti, King's College Hospital, 44 203 299 3080, ghulam.mufti@kcl.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 Dec 2013
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
01 Dec 2013
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Global end of trial reached? |
Yes
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Global end of trial date |
01 Dec 2013
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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 |
Assess complete/cytogenetic remission in patients with chromosome 7 abnormalities .
All participants will be followed up every 3 months until death due to disease progression.
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Protection of trial subjects |
Any patient who experiences a nonhematological adverse event with NCI CTC toxicity Grade 3 or 4 that is an escalation from his or her status at Baseline (prior to the first dose) will have azacitidine temporarily discontinued until the toxicity grade returns to the Baseline value. Azacitidine should be permanently discontinued if the nonhematological toxicity persists for more than 21 days, despite the temporary interruption of study drug, or if the toxicity is life threatening.
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Background therapy |
n/a | ||
Evidence for comparator |
n/a | ||
Actual start date of recruitment |
31 May 2006
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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 |
United Kingdom: 43
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Worldwide total number of subjects |
43
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EEA total number of subjects |
43
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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) |
9
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From 65 to 84 years |
34
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85 years and over |
0
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Recruitment
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Recruitment details |
This was an open-label, single centre pilot study to investigate azacitidine as first-line therapy in patients with MDS/AML with chromosome 7 abnormalities. Participants were recruited from one centre within the UK from 2006 until 2013 | ||||||||||||
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Pre-assignment
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Screening details |
Screening/baseline procedures to be performed prior to the first day of treatment. | ||||||||||||
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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 |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||||
Blinding implementation details |
Open label trial
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Arms
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Arm title
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Full study | ||||||||||||
Arm description |
Participants receive azacitidine (75 mg/m2/day SC for 7 days every 28 days). Patients will continue to receive Azacitidine until i) bone marrow disease progression or ii) relapse following documented erythroid haematologic improvement (CR, PR) or iii) unless there is unacceptable non-haematological toxicity | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
azacitidine
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder for suspension for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Participants receive azacitidine (75 mg/m2/day SC for 7 days every 28 days). Patients will continue to receive Azacitidine until i) bone marrow disease progression or ii) relapse following documented erythroid haematologic improvement (CR, PR) or iii) unless there is unacceptable non-haematological toxicity
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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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End points reporting groups
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Reporting group title |
Full study
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Reporting group description |
Participants receive azacitidine (75 mg/m2/day SC for 7 days every 28 days). Patients will continue to receive Azacitidine until i) bone marrow disease progression or ii) relapse following documented erythroid haematologic improvement (CR, PR) or iii) unless there is unacceptable non-haematological toxicity | ||
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End point title |
Primary Endpoint [1] | ||||||
End point description |
To assess the rate of haematological and cytogenetic response in patients with MDS/AML with a chromosome 7 abnormality either alone or as part of a complex clone.
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End point type |
Primary
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End point timeframe |
Duration of participation in trial
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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: Please see attached Final Study report for results data. |
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| No statistical analyses for this end point | |||||||
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End point title |
Secondary Endpoint | ||||||
End point description |
• Time to Relapse after complete remission (CR) or partial remission (PR), or Disease Progression (per IWG criteria), censored at death;
• Duration of response and duration of improvement;
• Time to AML transformation or death from any cause;
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End point type |
Secondary
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End point timeframe |
Duration of participation in trial.
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| No statistical analyses for this end point | |||||||
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Adverse events information [1]
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Timeframe for reporting adverse events |
30 days +/-2 days after the administration of the last dose of study drug
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Adverse event reporting additional description |
Adverse Events that do not require Reporting:-
Progression of disease or relapse during the course of treatment.
Hospital admissions for the treatment of progressive or relapsed disease.
Death due to disease or disease progression
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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 |
17.1
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Reporting groups
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Reporting group title |
Whole Trial
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Reporting group description |
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| Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: Adverse Events that do not require Reporting:- Progression of disease or relapse during the course of treatment. Hospital admissions for the treatment of progressive or relapsed disease. Death due to disease or disease progression |
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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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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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03 Sep 2010 |
The main changes are as follow:
1) The sample size has been changed from 40 to 50 patients. This is to enable 40 efficacy evaluable patients to be analysed.
2) The investigational medicinal product, Azacitidine, will now be supplied beyond the 6 cycles study phase until patients show bone marrow disease progression, pr progression/relapse following documented erythroid haematologic improvement (CR,PR) or unless there is unacceptable toxicity. In addition, follow up procedures have been added to include an end of study visit and three-monthly follow up after the discontinuation of study treatment.
3) Celgene Europe Limited (Celgene Corporation acquired Pharmion) gained marketing authorisation in 2008 for Vidaza (trade name for Azacitidine), however clinical trial supply will continue to be provided for this trial. The formulation for the clinical trial supply is the same as the commercial supply, but with different packaging and labelling. The SmPC is submitted for information. Handling of the trial medication has been added to the protocol.
4) The label has been updated by Celgene and submitted for approval.
5) King’s College Hospital NHS Foundation Trust and King’s College London will co-sponsor the study.
6) Secondary objective for the study has been removed.
7) Laboratory parameters and time points when the assessments are completed have been updated. The inclusion criteria on laboratory parameters have been updated.
8) Pharmacovigilance reporting section is significantly updated to include reporting of pregnancies and reporting to Joint Clinical Trials Office acting on behalf of the trial sponsors.
9) Further sections have been added to specify the following aspects of trial conduct: direct access to source data and documents, EC and Regulatory approvals, Quality assurance, data handling, publication policy and financial aspects.
10) The importer information is updated on the CTA as Cardinal Health Clinical Supply Services was acquired by Catalent Phar |
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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. | |||
| This trial is an open label intention to treat trial and as such is not statistically powered. | |||
