Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   38942   clinical trials with a EudraCT protocol, of which   6397   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Phase II Trial of Sequential treatment with Cytoreductive therapy and Reduced Intensity Conditioning Allogeneic Stem Cell Transplantation for Relapsed/ Refractory Acute Myeloid Leukemia, High Risk Myelodysplasia, or other High Risk Myeloid Malignancies

    Summary
    EudraCT number
    2007-000806-64
    Trial protocol
    GB  
    Global end of trial date
    09 Dec 2014

    Results information
    Results version number
    v1(current)
    This version publication date
    08 Sep 2017
    First version publication date
    08 Sep 2017
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    BLT004973
    Additional study identifiers
    ISRCTN number
    ISRCTN32336114
    US NCT number
    -
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Barts Health NHS Trust
    Sponsor organisation address
    JRMO, 5 Walden Street, London, United Kingdom, E1 2EF
    Public contact
    CECM Trials Team, Queen Mary University of London, 0044 02078828197, bci-cecmmonitoring@qmul.ac.uk
    Scientific contact
    CECM Trials Team, Queen Mary University of London, 0044 02078828197, bci-cecmmonitoring@qmul.ac.uk
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    09 Dec 2015
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    09 Dec 2014
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    To determine whether it is safer and more effective, in treating high risk Myeloid Malignancies, to immediately follow chemotherapy with Allogeneic Haemopoietic Stem Cell Transplantation than to treat in two distinct phases, with a break to determine remission status.
    Protection of trial subjects
    Side effects were closely monitored during and after the study. The patient information sheet included details on expected adverse events for patients and clinicians to look out for and also detailed that unexpected events may occur. The independent data monitoring committee for the trial was in place throughout to closely assess the side effects of the interventiohn on a regular basis to make sure there were no excess risks to patients. Monitoring was performed throughout the study to provide real-time review of source data to allow for early detection of signals.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    02 Jul 2007
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United Kingdom: 54
    Worldwide total number of subjects
    54
    EEA total number of subjects
    54
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    53
    From 65 to 84 years
    1
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    Between 24.7.07 and 9.12.14, 54 patients with refractory or relapsed Acute Myeloid Leukaemia, High Risk Myelodysplasia or other high risk Myeloid Malignancy were recruited within the United Kingdom.

    Pre-assignment
    Screening details
    Inclusion criteria included patients with histologically documented AML (any WHO type), MDS or other high risk myeloid malignancy, with primary induction failure, or at relapse where the patient was not a candidate for a myeloablative transplant.

    Period 1
    Period 1 title
    Overall Trial (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Non-randomised - controlled
    Blinding used
    Not blinded

    Arms
    Arm title
    Study Intervention
    Arm description
    Sequential treatment with cytoreductive therapy and reduced inetnsity conditioning allogeneic stem cell transplantation
    Arm type
    Experimental

    Investigational medicinal product name
    Cytarabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Low Dose Cytarabine(10mg/m2 sc bd for 14 days to be repeated at 28 day intervals if necessary) can be administered at the Investigator’s discretion for disease control in patients with rapidly progressive disease when conditioning has to be delayed (e.g awaiting unrelated donor clearance). D-15: Cytarabine 1.5g/m2 (1 dose-pm) IV D-14: Cytarabine 1.5g/m2 BD IV D-13: Cytarabine 1.5g/m2 BD IV D-12: Cytarabine 1.5g/m2 BD IV D-11: Cytarabine 1.5g/m2 BD IV D-10: Cytarabine 1.5g/m2 BD IV D-9: Cytarabine 1.5g/m2 (1 dose-am) IV

    Investigational medicinal product name
    Daunorubicin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    D-15: Daunorubicin 45mg/m2 OD IV D-14: Daunorubicin 45mg/m2 OD IV D-13: Daunorubicin 45mg/m2 OD IV

    Investigational medicinal product name
    Cyclophosphamide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    D-3: Cyclophosphamide 1 g/m2 IV in 500ml N/saline D-2: Cyclophosphamide 1 g/m2 IV in 500ml N/saline

    Investigational medicinal product name
    Fludarabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    D-6: Fludarabine 25 mg/m2 i.v. OD D-5: Fludarabine 25 mg/m2 i.v. OD D-4: Fludarabine 25 mg/m2 i.v OD D-3: Fludarabine 25 mg/m2 IV D-2: Fludarabine 25 mg/m2 IV

    Investigational medicinal product name
    Methotrexate
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    D+1 Methotrexate 5mg/m2 IV OD D+3 Methotrexate 5mg/m2 IV OD D+6 Methotrexate 5mg/m2 IV OD

    Number of subjects in period 1
    Study Intervention
    Started
    54
    Completed
    49
    Not completed
    5
         Did not have surgery
    5

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Overall Trial
    Reporting group description
    -

    Reporting group values
    Overall Trial Total
    Number of subjects
    54 54
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    53 53
        From 65-84 years
    1 1
        85 years and over
    0 0
    Age continuous
    Units: years
        median (full range (min-max))
    53 (23 to 68) -
    Gender categorical
    Units: Subjects
        Female
    18 18
        Male
    36 36
    Disease type
    Units: Subjects
        Relapsed/refractory AML
    39 39
        MDS
    9 9
        High-risk myeloid malignancy
    6 6
    Prior Transplant
    Units: Subjects
        No
    44 44
        ASCT
    9 9
        ABMT
    1 1
    Donor Sex
    Units: Subjects
        Did not complete transplant
    5 5
        Male
    32 32
        Female
    17 17
    Donor-recipient sex-matching
    Units: Subjects
        Donor (M) - Recipient (F)
    8 8
        Donor (M) - Recipient (M)
    24 24
        Donor (F) - Recipient (F)
    7 7
        Donor (F) - Recipient (M)
    10 10
        Did not receive transplant
    5 5
    CMV status
    Units: Subjects
        Both negative
    13 13
        Other combinations
    36 36
        Did not receive transplant
    5 5
    Type of donor
    Units: Subjects
        Matched sibling donor
    23 23
        Matched unrelated donor
    26 26
        Did not receive transplant
    5 5
    Dx - RIC-Allo
    Units: months
        median (full range (min-max))
    15 (15 to 21) -

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    Study Intervention
    Reporting group description
    Sequential treatment with cytoreductive therapy and reduced inetnsity conditioning allogeneic stem cell transplantation

    Primary: Overall Survival (OS) at 1 and 2 years

    Close Top of page
    End point title
    Overall Survival (OS) at 1 and 2 years [1]
    End point description
    Median OS for AML=11.64 months, median OS for MDS (not reached but lower limit of 95%CI is 3.96) >3.96 months, median OS for high-risk malignancy=3.6 months; p=0.25. Median OS for over 60=4.1 months, median OS for under 60=1 year 3.24 months; p=0.34.
    End point type
    Primary
    End point timeframe
    Overall Survival (OS) at 1 and 2 years
    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 study and hence statistical analysis is not needed except the survival rate .
    End point values
    Study Intervention
    Number of subjects analysed
    54
    Units: %
    number (confidence interval 95%)
        1 year OS - Overall
    49 (34 to 62)
        1 year OS - Relapsed/refractory AML patients
    48 (31 to 63)
        1 year OS - MDS patients
    65 (25 to 87)
        1 year OS - high-risk myeloid malignancy patients
    33 (5 to 68)
        1 year OS - Under 60 years of age patients
    50 (34 to 65)
        1 year OS - 60 years of age and over patients
    40 (12 to 67)
        2 years OS - Overall
    39 (26 to 53)
        2 years OS - Relapsed/refractory AML patients
    39 (23 to 55)
        2 years OS - MDS patients
    65 (25 to 87)
        2 years OS - high-risk myeloid malignancy patients
    17 (1 to 52)
        2 years OS - Under 60 years of age patients
    41 (26 to 57)
        2 years OS - 60 years of age and over patients
    30 (7 to 58)
    Attachments
    Untitled (Filename: Overall survival for patients that underwent RIC-AlloHSCT.jpg)
    Untitled (Filename: Overall survival for patients that underwent RIC-AlloHSCT for high-risk myeloid malignancy, MDS and relapsed refractory AML.jpg)
    Untitled (Filename: Overall survival for patients below the age of 60 and for patients 60 and above following RIC-AlloHSCT.jpg)
    No statistical analyses for this end point

    Secondary: Event Free Survival (EFS) at 1 and 2 years

    Close Top of page
    End point title
    Event Free Survival (EFS) at 1 and 2 years
    End point description
    EFS is defined as the time between day 1 and relapse or death. Any patients to reach neither relapse nor death were censored at the last date of follow-up. Median EFS for AML=9.4 months, median EFS for MDS (not reached but lower limit of 95%CI is 4) >4 months, median EFS for high-risk malignancy=2.3 months; p=0.25. Median EFS for MUD=11.2 months, median EFS for MFD=8.5 months; p=0.98. Median EFS for over 60=4.1 months, median EFS for under 60=9.4 months; p=0.67.
    End point type
    Secondary
    End point timeframe
    Event Free Survival (EFS) at 1 and 2 years
    End point values
    Study Intervention
    Number of subjects analysed
    54
    Units: %
    number (confidence interval 95%)
        1 year EFS - Overall
    43 (29 to 56)
        1 year EFS - relapsed/refractory AML patients
    40 (24 to 56)
        1 year EFS - MDS patients
    65 (25 to 87)
        1 year EFS - high-risk myeloid malignancy patients
    33 (5 to 68)
        1 year EFS - matched unrelated donor patients
    37 (17 to 57)
        1 year EFS - matched family donor patients
    48 (27 to 66)
        1 year EFS - under 60 years of age patients
    43 (28 to 58)
        1 year EFS - 60 years of age and over patients
    40 (12 to 67)
        2 years EFS - Overall
    31 (18 to 44)
        2 years EFS - relapsed/refractory AML patients
    28 (14 to 43)
        2 years EFS - MDS patients
    65 (25 to 87)
        2 years EFS - high-risk myeloid malignancy patient
    17 (1 to 52)
        2 years EFS - matched unrelated donor patients
    37 (17 to 57)
        2 years EFS - matched family donor patients
    29 (12 to 48)
        2 years EFS - under 60 years of age patients
    31 (17 to 46)
        2 years EFS - 60 years of age and over patients
    30 (7 to 58)
    Attachments
    Untitled (Filename: EFS of patients that underwent RIC-alloHSCT.jpg)
    Untitled (Filename: EFS of patients that underwent RIC-alloHSCT for high-risk myeloid malignancy, MDS and relapsed refractory AML.jpg)
    Untitled (Filename: EFS of patients that underwent RIC-alloHSCT with matched family donor and matched unrelated donor.jpg)
    Untitled (Filename: EFS of patients below the age of 60 and for patients 60 and above following RIC-AlloHSCT.jpg)
    No statistical analyses for this end point

    Secondary: Engraftment and Chimerism Analysis (Full Split Chimerism at Days 30, 60, 100 and 1 year following RIC Allo-HSCT)

    Close Top of page
    End point title
    Engraftment and Chimerism Analysis (Full Split Chimerism at Days 30, 60, 100 and 1 year following RIC Allo-HSCT)
    End point description
    Neutrophil Engraftment and Platelet Engraftment are calculated as time between day 1 to first of two consecutive days with a neutrophil count exceeding 500/μ and to the first day of three consecutive days with an unsupported platelet count exceeding 20 x 109 / L respectively. 37 patients experienced complete haematologic recovery after RIC-allogeneic SCT. The median time to achieve more than 0.5x109/L neutrophils in the peripheral blood was 18.5 days (range, 10–30) after transplantation; a sustained platelet count greater than 20x109/L was achieved at 14.5 days (range, 6-39), 12 patients did not reach this count by the time of death or censoring) after transplantation. Chimerism studies demonstrate that by one year median engraftment was 97%. Full split chimerism studies confirmed over 98% donor engraftment in both CD3 and CD15 at 1 year.
    End point type
    Secondary
    End point timeframe
    Time to Engraftment is categorised as Neutrophil Engraftment and Platelet Engraftment. Full Split Chimerism at Days 30, 60, 100 and 1 year following RIC Allo-HSCT.
    End point values
    Study Intervention
    Number of subjects analysed
    54
    Units: %
    median (inter-quartile range (Q1-Q3))
        Day 30: Whole Blood
    96 (50 to 98)
        Day 30: CD3
    95 (87 to 98)
        Day 30: CD15
    95 (25.5 to 98)
        Day 60: Whole Blood
    92 (35 to 98)
        Day 60: CD3
    92 (83 to 97)
        Day 60: CD15
    93.5 (11 to 98)
        Day 100: Whole Blood
    77.5 (20 to 96)
        Day 100: CD3
    94 (82 to 97)
        Day 100: CD15
    73 (13 to 98)
        1 year: Whole Blood
    97 (94 to 100)
        1 year: CD3
    98 (96 to 100)
        1 year: CD15
    99 (94 to 100)
    Attachments
    Untitled (Filename: Neutrophil engraftment following transplantation.jpg)
    Untitled (Filename: Platelet engraftment following transplantation.jpg)
    No statistical analyses for this end point

    Secondary: Incidence and Grade of Acute Graft versus Host Disease (GVHD)

    Close Top of page
    End point title
    Incidence and Grade of Acute Graft versus Host Disease (GVHD)
    End point description
    Grades were only recorded for acute GVHD where available.
    End point type
    Secondary
    End point timeframe
    GVHD in patients following RIC Allo-HSCT.
    End point values
    Study Intervention
    Number of subjects analysed
    54
    Units: Subjects
        Acute: Yes
    10
        Acute: No
    44
        Chronic: Yes
    10
        Chronic: No
    44
        Acute: Grade: N/A
    36
        Acute: Grade: 1
    4
        Acute: Grade: 2
    3
        Acute: Grade: 3
    1
        Acute: Grade: 4
    1
    No statistical analyses for this end point

    Secondary: Treatment Related Mortality (TRM) at d100, 1 and 2 years and cause of mortality

    Close Top of page
    End point title
    Treatment Related Mortality (TRM) at d100, 1 and 2 years and cause of mortality
    End point description
    Treatment Related Mortality Rate is calculated for deaths when there is no evidence of leukaemia within 100 days of treatment and then within 1 and 2 year. Median TRM rates for MFD > 8.63 months. Median TRM rates for MUD > 1 year 5.8 months. Cause of mortality was mainly categorised as AML, GVHD or infection related.
    End point type
    Secondary
    End point timeframe
    Cumulative incidence of TRM at 100 days, 1 year and 2 years.
    End point values
    Study Intervention
    Number of subjects analysed
    54
    Units: %
    number (confidence interval 95%)
        Cumulative incidence of TRM: 100 days
    16 (8 to 29)
        Cumulative incidence of TRM: 1 year
    32 (21 to 48)
        Cumulative incidence of TRM: 2 years
    36 (23 to 53)
        Cumulative incidence of TRM: MUD: 100 days
    19 (8 to 40)
        Cumulative incidence of TRM: MFD: 100 days
    14 (5 to 37)
    Attachments
    Untitled (Filename: Treatment related mortality following RIC Allo-HSCT.jpg)
    Untitled (Filename: TRM following RIC-alloHSCT with matched family donor and matched unrelated donor.jpg)
    Untitled (Filename: Cause of mortality.jpg)
    No statistical analyses for this end point

    Secondary: Opportunistic Infections

    Close Top of page
    End point title
    Opportunistic Infections
    End point description
    End point type
    Secondary
    End point timeframe
    Incidence of opportunistic infections.
    End point values
    Study Intervention
    Number of subjects analysed
    54
    Units: Subjects
        Patients who gained an opportunistic infection
    9
        Patients unaffected
    45
    No statistical analyses for this end point

    Secondary: Duration of Hospitalisation

    Close Top of page
    End point title
    Duration of Hospitalisation
    End point description
    End point type
    Secondary
    End point timeframe
    Median hospital stay.
    End point values
    Study Intervention
    Number of subjects analysed
    54
    Units: Days
    median (inter-quartile range (Q1-Q3))
        Median hospital stay
    36 (34 to 41)
    No statistical analyses for this end point

    Adverse events

    Close Top of page
    Adverse events information [1]
    Timeframe for reporting adverse events
    All serious adverse events recorded during the study are recorded. Non-serious adverse events are not recorded in this trial
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    CTCAE
    Dictionary version
    4
    Reporting groups
    Reporting group title
    Overall trial
    Reporting group description
    -

    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: No Non-serious adverse events are recorded in this trial.
    Serious adverse events
    Overall trial
    Total subjects affected by serious adverse events
         subjects affected / exposed
    17 / 49 (34.69%)
         number of deaths (all causes)
    30
         number of deaths resulting from adverse events
    0
    Vascular disorders
    Bilateral Subdurals
         subjects affected / exposed
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pneumonia
         subjects affected / exposed
    3 / 49 (6.12%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 3
    Blood and lymphatic system disorders
    Refractory AML
         subjects affected / exposed
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    General disorders and administration site conditions
    Graft versus host disease
         subjects affected / exposed
    5 / 49 (10.20%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 5
    Infections and infestations
    E. Coli septicaemia
         subjects affected / exposed
    2 / 49 (4.08%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 2
    Cardiac Failure / Sepsis
         subjects affected / exposed
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Neutropenic infection
         subjects affected / exposed
    5 / 49 (10.20%)
         occurrences causally related to treatment / all
    1 / 5
         deaths causally related to treatment / all
    1 / 5
    Infection, multi-organ failure
         subjects affected / exposed
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Meningioma
         subjects affected / exposed
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Overall trial
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    0 / 49 (0.00%)

    More information

    Close Top of page

    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    08 Oct 2008
    Alterations to chemotherapy schedule and supportive medications to ensure consistency with site standard practice. Redefined early closing rule of 'unacceptble toxicity'. Expanded AE reporting requirements.
    09 Jul 2011
    Implementation of temporary halt while DSMB reviewed data to confirm if stopping rule had been met.
    20 Sep 2011
    Re-open to recruitment following confirmation from DSMB. Exclusion criteria amended to prevent entry of patients >60 years. Introduction of regular DSMB monit9oring. Re-classifcation of MENSA, cyclosporine, and allogeneic blood stem cells as non-IMPs.
    15 May 2012
    Change of sponsor from Barts and the London NHS Trust to Barts Health NHS Trust following institutional mergers.

    Interruptions (globally)

    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    09 Jul 2011
    The study was halted to recruitment as it had potentially reached its stopping rule (see section 11.2 of the protocol –‘The mortality rate will be monitored by calculating 95% Confidence Intervals for survival at 100 days. If the CIs show that there is a significant probability that the survival rate is less than 75% at day 100, then the study will be stopped.’). The DSMB met and confirmed that although the stopping rule had not been met, patients over 60 years should be excluded from entry to the trial going forwards.
    07 Sep 2011

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    A sample of 93 patients was aimed to establish a 95% CI of 0.1 but only 54 patients were accrued for the trial, with 49 undergoing transplant.
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2021 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA