Clinical Trial Results:
Pilot safety/tolerability study of Lenalidomide administered as monotherapy and in combination with standard chemotherapy for Acute Myeloid Leukaemia/high-risk Myelodysplastic Syndrome with structural abnormalities of chromosome 5
Summary
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EudraCT number |
2008-004891-28 |
Trial protocol |
GB |
Global end of trial date |
31 Jul 2013
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Results information
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Results version number |
v1(current) |
This version publication date |
28 Feb 2016
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First version publication date |
28 Feb 2016
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Other versions |
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Summary report(s) |
End of Trial 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 |
HM08 / 8451
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Additional study identifiers
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ISRCTN number |
ISRCTN58492795 | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Leeds Teaching Hospitals NHS Trust
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Sponsor organisation address |
34 Hyde Terrace, Leeds, United Kingdom, LS2 9LN
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Public contact |
CTRU QA department, Leeds Institute of Clinical Trials Research, 0113 34331477, medctruq@leeds.ac.uk
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Scientific contact |
CTRU QA department, Leeds Institute of Clinical Trials Research, 0113 34331477, medctruq@leeds.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 |
11 Jan 2011
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
11 Jan 2011
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Global end of trial reached? |
Yes
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Global end of trial date |
31 Jul 2013
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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 |
To assess safety, tolerability and efficacy of the combination of oral Lenalidomide administered as a single agent and simultaneously with induction chemotherapy using Cytosine Arabinoside, Daunorubicin +/- Etoposide (ADE) for patients with AML/MDS and chromosome 5 cytogenetic abnormalities.
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Protection of trial subjects |
All chemotherapy treatment involves some side effects as well as potential benefits. The side effects will be monitored closely and the dose adjusted to minimise these. It is not expected that patients will have all these side effects and it is not possible to predict which ones patients will experience or how severe or serious they may be. If a patient experiences a severe reaction, then the study treatment may be discontinued and alternative treatment will be recommended.
Currently, all drugs used to treat AML/MDS have potential side effects. The possible side effects of the drugs used in this
study are detailed in the patient information sheet.
The potential for pain, discomfort or distress is no more than is usual for other patients receiving treatment for AML/MDS.
Patients may experience side effects from their treatment and will undergo blood tests and medical assessments.
However, these are all part of standard patient management.
Patients will need to attend hospital as an inpatient during the combination chemotherapy and allogeneic transplant
stages, but this would be required even if they were not taking part in the trial.
The bone marrow tests are potentially painful. This trial only requires samples to be taken at the same timepoints as
would be required for routine clinical management.
The CTRU will comply with all aspects of Data Protection Act 1998. All information collected during the course of the trial
will be kept strictly confidential.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
20 Aug 2009
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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: 14
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Worldwide total number of subjects |
14
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EEA total number of subjects |
14
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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 |
8
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||
Pre-assignment
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Screening details |
- | ||||||
Pre-assignment period milestones
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Number of subjects started |
14 | ||||||
Number of subjects completed |
14 | ||||||
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 | ||||||
Arms
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Arm title
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Lenalidomide monotherapy | ||||||
Arm description |
Lenalidomide monotherapy followed by a combination of Lenalidomide and intensive intravenous chemotherapy | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Lenalidomide
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Investigational medicinal product code |
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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 |
Cycle 1:
Days 1 – 21 10mg Lenalidomide p.o / day.
Days 22-28 Rest 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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End points reporting groups
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Reporting group title |
Lenalidomide monotherapy
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Reporting group description |
Lenalidomide monotherapy followed by a combination of Lenalidomide and intensive intravenous chemotherapy |
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End point title |
Early death rate [1] | ||||||
End point description |
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End point type |
Primary
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End point timeframe |
≤ 30 days since start of combination chemotherapy
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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: No statistical analyses have been specified for this primary endpoint due to the trial having one treatment group and therefore no comparator. The results from this primary end point have been entered into the ‘end point values’ section within ‘end point definitions’. |
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No statistical analyses for this end point |
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End point title |
Platelet recovery and survival 42 days from last dose of the first course of the combination chemotherapy [2] | ||||||
End point description |
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End point type |
Primary
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End point timeframe |
42 days from last dose of the first course of the combination chemotherapy
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Notes [2] - 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: No statistical analyses have been specified for this primary endpoint due to the trial having one treatment group and therefore no comparator. The results from this primary end point have been entered into the ‘end point values’ section within ‘end point definitions’. |
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No statistical analyses for this end point |
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End point title |
Complete remission rate [3] | ||||||
End point description |
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End point type |
Primary
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End point timeframe |
day 21 post the last cycle of lenalidomide plus intensive chemotherapy
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Notes [3] - 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: No statistical analyses have been specified for this primary endpoint due to the trial having one treatment group and therefore no comparator. The results from this primary end point have been entered into the ‘end point values’ section within ‘end point definitions’. |
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No statistical analyses for this end point |
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End point title |
Response rates for each cycle | ||||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Cycle 1
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No statistical analyses for this end point |
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End point title |
Neutrophil and platelet recovery | ||||||
End point description |
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End point type |
Secondary
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End point timeframe |
42 days post monotherapy
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No statistical analyses for this end point |
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End point title |
Blood product usage (number of blood transfusions) | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
cycle 1
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No statistical analyses for this end point |
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End point title |
Days in hospital | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
cycle 1
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No statistical analyses for this end point |
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End point title |
Days on antibiotics | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
cycle 1
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No statistical analyses for this end point |
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End point title |
Toxicity | ||||||
End point description |
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End point type |
Secondary
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End point timeframe |
in the trial
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No statistical analyses for this end point |
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End point title |
Proportion of patients proceeding to allograft/DLI/maintenance therapy | ||||||
End point description |
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End point type |
Secondary
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End point timeframe |
in the trial
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No statistical analyses for this end point |
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End point title |
Survival | ||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
in the trial
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No statistical analyses for this end point |
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End point title |
Relapse-free survival | ||||||
End point description |
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End point type |
Secondary
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End point timeframe |
in the trial
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No statistical analyses for this end point |
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End point title |
AML transformation of MDS | ||||||
End point description |
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End point type |
Secondary
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End point timeframe |
in the trial
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No statistical analyses for this end point |
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End point title |
Haematological improvement for each cycle in patients with MDS | ||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Cycle 1
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No statistical analyses for this end point |
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End point title |
Blood product usage (number of platelet transfusions) | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
cycle 1
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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 |
ARs- time of start of protocol treatment until 30 days post cessation of trial therapy for patients receiving chemotherapy / maintenance.
SAEs and SUSARS until 30 days post last trial treatment or 100 days post transplant
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Adverse event reporting additional description |
For ARs only data relating to Neuropathy and Thromboembolic events will be collected following an allogeneic stem cell transplant/DLI and this will be collected until 100 days post transplant/DLI.
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Assessment type |
Systematic | ||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||
Dictionary version |
14
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Frequency threshold for reporting non-serious adverse events: 0% | |||
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: See attached end of trial report submitted to the MHRA on 06/05/2014 for details of adverse events. Leeds Institute of Clinical Trials Research is an academic trials unit where full MedDRA coding is not the standard. It has therefore not been possible for adverse event data to be accurately entered into the full data view within EudraCT as all mandatory categories cannot be completed. |
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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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04 Jun 2009 |
- Change in AE reporting definition
-Change in exclusion criteria following on from DMEC advise
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08 Jul 2010 |
- Study design amended to remove the monotherapy phase for patients with ≥5% blasts following on from the temporary halt of the trial. The trial was reopened with this amended design. |
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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 |