Clinical Trial Results:
Use of Decitabine in Myelodysplastic Syndrome (MDS) Following Azacitidine (AZA) Failure (DEC-MDS)
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Summary
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EudraCT number |
2009-017098-40 |
Trial protocol |
GB |
Global end of trial date |
14 Aug 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
20 Oct 2018
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First version publication date |
20 Oct 2018
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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 |
DEC-MDS
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01133886 | ||
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 |
Department of Haematology, King's College Hospital, +44 0203299 1183, Lorraine.Catt@kch.nhs.uk
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Scientific contact |
Department of Haematology, King's College Hospital, +44 0203299 1183, Lorraine.Catt@kch.nhs.uk
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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 |
Department of Haematology, King's College Hospital, +44 0203299 1183, lorraine.catt@nhs.net
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Scientific contact |
Department of Haematology, King's College Hospital, +44 0203299 1183, lorraine.catt@nhs.net
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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 |
14 Aug 2014
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
14 Aug 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
14 Aug 2014
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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 assess the overall response rate (CR+PR as per IWG 2006) at 6 months in MDS patients, CMML-2 patients, and AML patients with up to 30% bone marrow blasts (previously classified as RAEB-t by the FAB MDS classification), treated with low-dose decitabine who have previously failed therapy with 5-azacitidine.
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Protection of trial subjects |
Patients are free to withdraw consent for study treatment and/or consent to participate in the study at any time and without the prejudice to further treatment. Patients who withdraw from study treatment, but are willing to continue to participate in the follow-up visits should be followed according to the procedures outlined in the protocol.
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Background therapy |
None | ||
Evidence for comparator |
n/a as this is a single arm trial. | ||
Actual start date of recruitment |
15 Dec 2010
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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: 20
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Worldwide total number of subjects |
20
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EEA total number of subjects |
20
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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) |
6
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From 65 to 84 years |
11
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85 years and over |
3
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Recruitment
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Recruitment details |
Participants were recruited from 5 centers in the United Kingdom between 2010 and 2014. | ||||||||||||||
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Pre-assignment
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Screening details |
Inclusion Criteria 18 yrs or more, 3. diagnosed MOS with 5% or more marrow blasts & IPSS risk, intermediate 2 or high risk; or chronic myelomonocytic leukemia (CMML-2); or AML with 20-30% bone marrow blasts (previously defined as RAEB-t by the FAB MOS classification). Failed therapy with azacitidine. Adequate hepatic & renal function. | ||||||||||||||
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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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Full study | ||||||||||||||
Arm description |
Patients will receive decitabine as a 20mg/m2 1-hour intravenous infusion once daily on Days 1-5 of a 4-week cycle. The initial phase of the study will comprise of 6 cycles of treatment of decitabine | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
Decitabine
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Patients will receive decitabine as a 20mg/m2 1-hour intravenous infusion once daily on Days 1-5 of a 4-week cycle.
The initial phase of the study will comprise of 6 cycles of treatment of decitabine.
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Baseline characteristics reporting groups
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Reporting group title |
Overall Trial
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Reporting group description |
At the time the trial was terminated (MHRA notification 02/Sept/2014), a total of 25 patients across all sites had consented onto the study. Only 20 patients actually received 1 or more cycles of Decitabine. Only 5 patients had 6 cycles or more and no patients met primary end point (CR or PR as per IWG 2006). | |||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Full study
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Reporting group description |
Patients will receive decitabine as a 20mg/m2 1-hour intravenous infusion once daily on Days 1-5 of a 4-week cycle. The initial phase of the study will comprise of 6 cycles of treatment of decitabine | ||
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End point title |
Primary Objective [1] | ||||||
End point description |
To assess the overall response rate (CR+PR as per IWG 2006) at 6 months in MOS patients, CMML-2 patients, and AML patients with up to 30% bone marrow blasts (previously classified as RAEB-t by the FAB MOS classification), treated with low-dose decitabine who have previously failed therapy with 5-azacitidine.
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End point type |
Primary
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End point timeframe |
6 cycles of decitabine - 6months.
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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: 5 patients had 6 cycles or more and no patients met primary end point (CR or PR as per IWG 2006. Please see attached summary document for more information. |
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| Notes [2] - 5 patients had 6 cycles or more and no patients met primary end point (CR or PR as per IWG 2006. |
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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 |
Whole trial
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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: SAEs were experienced by the study patients; there were no unexpected SAEs related to trial medication nor were than any significant AEs to report. |
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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? Yes | |||
Date |
Amendment |
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14 Dec 2010 |
Secondary objective changed to look at grade 3 and 4 treatment related toxicity only.
Assessment for: Survival, Relapse,
Subsequent treatment removed from end of treatment visit.
Text added to clarify that grade 1 and 2 haematological and organ toxicities do not need to be recorded.
Information on BSA capping included.
Text changed so that decitabine will only be delayed due to myelosuppression after 3 cycles of treatment.
Text added to define women of child bearing potential.
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09 May 2011 |
hanges to the protocol are as follows:
1) Demographics will be recorded at the screening visit.
2) ECOG performance score will be assessed at the end of treatment visit.
3) A bone marrow sample will be performed and exploratory samples taken at the end (day 21+) of the 3rd and 6th cycle instead of after day 28.
4) Patients will be recommenced on a lower dose of decitabine following a dose delay of at least 14 days.
5) All concomitant medications will be recorded from day 1 until the end of treatment visit.
6) Other administrative changes
In addition, Nottingham and Cardiff added as sites.
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18 Jul 2011 |
Protocol changed to allow dose delays due to scheduling issues.
Clarification that patients are only excluded if they have received prior intensive chemotherapy or high-dose cytarabine for the treatment of MDS or AML.
Non-Substantial amendments 3 & 4 have been incorporated into documentation |
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17 Oct 2011 |
Protocol updated to protocol v6.0
Changes in patient eligibility criteria.
Changes in labelling and labelling site.
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20 Dec 2011 |
Protocol updated to protocol v7.0, the following sections have been updated with new information from IB Edition 5
• Recognised Adverse Drug Reactions section
• Cardiovascular/Pulmonary Section
• CNS Effects
• Concomitant Medication
New edition of Investigator Brochure (Edition 5, 17-Aug-11)
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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. | |||
| At the interim analysis, a review of the current subjects recruited up to that point took place, as was the rate of recruitment. Based on this primary information it was decided by the TSC to close the study. | |||
