Clinical Trial Results:
CMML201: A phase 2 study of azacitidine in chronic myelomonocytic leukaemia (CMML)
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Summary
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EudraCT number |
2008-006349-23 |
Trial protocol |
GB |
Global end of trial date |
21 Nov 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
29 Mar 2020
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First version publication date |
29 Mar 2020
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Other versions |
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Summary report(s) |
CMML201 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 |
HM08/8540
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Additional study identifiers
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ISRCTN number |
ISRCTN21428905 | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
University of Leeds
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Sponsor organisation address |
34 Hyde Terrace , Leeds , United Kingdom, LS2 9JT
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Public contact |
Quality Assurance Department , Leeds Institute of Clinical Trials Research
University of Leeds
LS2 9JT, medctruq@leeds.ac.uk
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Scientific contact |
Quality Assurance Department , Leeds Institute of Clinical Trials Research
University of Leeds
LS2 9JT , 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 |
21 May 2012
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
21 May 2012
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Global end of trial reached? |
Yes
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Global end of trial date |
21 Nov 2014
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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 the safety, tolerability and efficacy of azacitidine in patients with CMML.
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Protection of trial subjects |
Eligibility criteria were designed with patient safety as a primary concern and therefore none is unfairly excluded from or
included in the trial.
Consent:
Informed consent will be taken by an authorised clinically trained member of staff who will ensure that the person will
understand the purpose and nature of the study and what it involves, the benefits, risks and burdens and the alternative
treatments to the study. They will also ensure the patient is able to retain the information long enough to make an effective
decision with free choice. Patients will be allowed a minimum of 24 hours to decide if they would like to take part.
Risks, burdens and benefits:
The possible side effects of azacitidine are detailed in the patient information sheet. The side effects will be monitored
closely and the dose adjusted to minimise these. If a patient experiences a severe reaction, then the study treatment may be discontinued and alternative treatment will be recommended. The trial is a 2 stage design to ensure regular safety checks are carried out during the study by the DMEC. The DMEC will review any treatment related deaths on a continuous basis.
Confidentiality:
All information collected during the course of the trial will be kept strictly confidential. Information will be held securely on
paper and electronically at the Clinical Trials Research Unit (CTRU). The CTRU will comply with all aspects of the 1998
Data Protection Act.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
27 Jan 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: 30
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Worldwide total number of subjects |
30
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EEA total number of subjects |
30
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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) |
7
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From 65 to 84 years |
22
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85 years and over |
1
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Recruitment
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Recruitment details |
- | ||||||||||||||||||||
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Pre-assignment
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Screening details |
N=74 patients assessed for eligibility. N=42 were excluded. Of these N=26 did not meet the inclusion criteria, N=9 declined to particpate and N=7 were for another reason. | ||||||||||||||||||||
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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 | ||||||||||||||||||||
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Arms
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Arm title
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Azacitidine | ||||||||||||||||||||
Arm description |
Azacitidine 75mg/m2/sc days 1-5 & 8-9 Patients to receive a minimum of 6x28 - day cycles | ||||||||||||||||||||
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 |
Injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
The dose of azacitidine administered must be based on body surface area (BSA) and is to be calculated based
on actual body weight using a standard nomogram.
The dose should be calculated on Day 1 of each cycle; the dose should remain the same throughout a treatment
cycle but should be recalculated at the start of the next cycle. If a patient’s body weight changes by more than
10% compared with baseline body weight, or compared with a previous body weight that required a dose
adjustment, then the patient’s dose should be recalculated.
Azacitidine for subcutaneous injection (sc) should be asceptically reconstituted in 4ml of sterile water for injection
under conditions approved by the hospital pharmacy. The dilutent will contain 25mg/ml (100mg/4ml). Doses
greater than 4ml should be divided equally and injected in two separate sites.
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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 |
Azacitidine
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Reporting group description |
Azacitidine 75mg/m2/sc days 1-5 & 8-9 Patients to receive a minimum of 6x28 - day cycles | ||
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End point title |
Safety and tolerability [1] | ||||||
End point description |
Safety and tolerability are as defined by frequency of:
a) azacitidine-related death
b) any grade 3/4 non haematological adverse reaction. Adverse reaction is defined as adverse event judged by either the
Principal Investigator or the Chief Investigator (or his delegate) as having a reasonable suspected causal relationship to azacitidine .Haematological is defined as relating to haemoglobin, leukocytes (total white blood cells), lymphocytes, neutrophils/granulocytes (ANC/AGC) and platelets, non-haematological is defined as other adverse reactions.
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End point type |
Primary
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End point timeframe |
From Registration
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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: This is a single arm trial and hence there is no comparative statistical anlaysis and merely an estimate of the proportion of the primary endpoints with a 95% confidence interval. |
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End point title |
Overall response rate [2] | ||||||
End point description |
Overall response rate is defined as the sum of clinical remission, good response and minor response
determined according to Wattel et al (16) at day 28 of the sixth or last cycle of azacitidine (whichever is
the earliest)
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End point type |
Primary
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End point timeframe |
From first treatment to day 28 of the sixth or last cycle of azacitidine
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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: This is a single arm trial and hence there is no comparative statistical anlaysis and merely an estimate of the proportion of the primary endpoints with a 95% confidence interval. |
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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 |
AEs, ARs, SAEs collected for all patients from the time of start of protocol treatment until 30 days after the last dose of treatment with azacitidine. SARs and SUSARs reported until end of trial
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Assessment type |
Systematic | ||
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Dictionary used for adverse event reporting
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Dictionary name |
body system coding | ||
Dictionary version |
1
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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: It is not our standard practive to code adverse events according to the full MEDRA system. |
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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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15 Sep 2009 |
Requirement for a buccal swab at registration added to the protocol
Clarification that recruitment will be continuous between the two stages and response rates at day 28 of Cycle 3 will be used as early indicator of response. |
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30 Sep 2009 |
Carton and vial label added to the trial specific Azacitidine prior to dispatch. This differed from the label text submitted and approved as part of the Clinical Trial Authorisation. |
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17 Dec 2009 |
Celgene (supplier of the pre-labelled trial specific azacitidine) informed the CTRU of a typographical error in the labels which required regulatory approval before the product can be QP released. |
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06 Apr 2010 |
Update to the Azacitidine Investigator Brochure v6 05/09/2008 by Addendum 1, 27th August 2009, and Addendum 2, 17 September 2009. The addendums did not alter the safety profile for the study. |
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01 Nov 2010 |
Change for Principal Investigator at an existing Site. |
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03 Dec 2010 |
Clarification of haematological toxicity in the protocol. |
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02 Feb 2012 |
Amendments made to the protocol include:
Clarification of how long patients will be followed up for.
Removal of the requirement for a bone marrow aspirate to be taken every 6 months. |
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08 Jul 2013 |
The requirement for central collection of serum, bone marrow and buccal swab samples as analysis was removed.
End of Trial Definition updated. Reporting time for SARs and SUSARs amended from 30 days post treatment to end of trial. |
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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 | |||
