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 were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43871   clinical trials with a EudraCT protocol, of which   7290   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).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    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:
    Clinical phase II trial to evaluate the safety and efficacy of clofarabine and treosulfan conditioning prior to peripheral blood stem cells transplantation in paediatric and adult patients with advanced haematological malignancies

    Summary
    EudraCT number
    		 2008-006972-31
    Trial protocol
    		 IT  
    Global end of trial date
    19 Feb 2015

    Results information
    Results version number
    		 v1(current)
    This version publication date
    07 May 2021
    First version publication date
    07 May 2021
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    Clo3o
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    IRCCS Ospedale San Raffaele
    Sponsor organisation address
    Via Olgettina, 60, Milano, Italy, 20132
    Public contact
    Dept. of Haematology/Transplant Unit, IRCCS Ospedale San Raffaele, 0039 0226434289, ciceri.clinicaltrials@hsr.it
    Scientific contact
    Dept. of Haematology/Transplant Unit, IRCCS Ospedale San Raffaele, 0039 0226434289, ciceri.clinicaltrials@hsr.it
    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
    19 Feb 2015
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    19 Feb 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Safety: Evaluation of cumulative incidence non-relapse mortality (NRM); Evaluation of cumulative incidence and severity of acute and chronic graft vs. host disease (GvHD). Efficacy: Engraftment; Evaluation of progression free survival (PFS); Evaluation of overall survival (OS); Evaluation of relapse incidence (RI).
    Protection of trial subjects
    N.A.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    23 Nov 2009
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Italy: 44
    Worldwide total number of subjects
    44
    EEA total number of subjects
    44
    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)
    2
    Adults (18-64 years)
    40
    From 65 to 84 years
    2
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 From November 2009 to November 2013, we enrolled 44 patients (median age 47 yers old), 36 affected by acute myeloid leukemia, 5 by acute lymphoblastic leukemia and 3 by myelodisplastic syndrome. The study was conducted in 4 Italian Bone Marrow Transplant Centers.

    Pre-assignment
    Screening details
    		 Both pediatric and adult patients were included (age range, 13-69 years), each with an available HLA-matched related or unrelated donor. HLA compatibility among donor-recipient pairs was assessed by 10-loci molecular typing (HLAA,-B, -C, -DRB1, -DQB1), with no more than a 2-allele disparity allowed.

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

    Arms
    Arm title
    		 Clo-Treo HSCT
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    Clofarabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    40 mg/mq within 60-120minutes i.v. (from day -6 to day -2)

    Investigational medicinal product name
    Treosulfan
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    14 g/mq within 120 minutes i.v. (from day -6 to day -4)

    Number of subjects in period 1
    		Clo-Treo HSCT
    Started
    44
    Completed
    44

    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
    		 44 44
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        median (full range (min-max))
    		 47 (13 to 69) -
    Gender categorical
    Units: Subjects
        Female
    		 22 22
        Male
    		 22 22
    Disease diagnosis
    Units: Subjects
        AML
    		 36 36
        MDS
    		 3 3
        ALL
    		 5 5
    Status at transplant
    Units: Subjects
        First CR
    		 16 16
        Other CR
    		 9 9
        Active disease
    		 16 16
        Upfront
    		 3 3
    Comorbidities (HCT-CI)
    Units: Subjects
        Zero
    		 15 15
        1-2
    		 12 12
        3-4
    		 17 17
    Disease Risk Index (DRI)
    Units: Subjects
        Low
    		 1 1
        Intermediate
    		 26 26
        High
    		 13 13
        Very High
    		 4 4
    CMV serostatus (host/donor)
    Units: Subjects
        negative/negative
    		 2 2
        negative/positive
    		 2 2
        positive/negative
    		 11 11
        positive/positive
    		 29 29
    Donor-recipient HLA matching
    Units: Subjects
        MRD (10/10)
    		 22 22
        MUD (8/10)
    		 1 1
        MUD (9/10)
    		 7 7
        MUD (10/10)
    		 14 14
    Subject analysis sets

    Subject analysis set title
    MRD Transplant
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Allogenic haematopietic stem cells were derived from a sibling

    Subject analysis set title
    MUD Transplant
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Allogeneic haematopoietic stem cells were derived from a well-matched unrelated donor

    Subject analysis sets values
    		 MRD Transplant MUD Transplant
    Number of subjects
    22
    22
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        median (full range (min-max))
    43 (13 to 61)
    50 (16 to 69)
    Gender categorical
    Units: Subjects
        Female
    13
    9
        Male
    9
    13
    Disease diagnosis
    Units: Subjects
        AML
    17
    19
        MDS
    3
    0
        ALL
    2
    3
    Status at transplant
    Units: Subjects
        First CR
    8
    8
        Other CR
    4
    5
        Active disease
    7
    9
        Upfront
    3
    0
    Comorbidities (HCT-CI)
    Units: Subjects
        Zero
    10
    5
        1-2
    5
    7
        3-4
    7
    10
    Disease Risk Index (DRI)
    Units: Subjects
        Low
    1
    0
        Intermediate
    14
    12
        High
    5
    8
        Very High
    2
    2
    CMV serostatus (host/donor)
    Units: Subjects
        negative/negative
    0
    2
        negative/positive
    1
    1
        positive/negative
    3
    8
        positive/positive
    18
    11
    Donor-recipient HLA matching
    Units: Subjects
        MRD (10/10)
    22
    0
        MUD (8/10)
    0
    1
        MUD (9/10)
    0
    7
        MUD (10/10)
    0
    14

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Clo-Treo HSCT
    Reporting group description
    		 -

    Subject analysis set title
    MRD Transplant
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Allogenic haematopietic stem cells were derived from a sibling

    Subject analysis set title
    MUD Transplant
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Allogeneic haematopoietic stem cells were derived from a well-matched unrelated donor

    Primary: Cumulatve Incidence of Non Relapse Mortality (NRM)

    		 Close Top of page
    End point title
    		 Cumulatve Incidence of Non Relapse Mortality (NRM) [1]
    End point description
    NRM was defined as death without evidence of disease progression or relapse. Disease progressione or relapse was treated as competing event in the NRM analyses
    End point type
    Primary
    End point timeframe
    Evaluation of the cumulative incidence of NRM on day +100
    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 study is a non-controlled phase II study. For efficacy comparison, mainly EBMT registry data or published papers will be used. According to Simon's two-stage design method the total number of patients needed to asses an expected NRM of 20% was 45. The cumulative incidence method with competing risk was used for NRM.
    End point values
    		 Clo-Treo HSCT
    Number of subjects analysed
    44
    Units: percent
        median (confidence interval 95%)
    18 (7 to 30)
    No statistical analyses for this end point

    Secondary: Cumulative incidence and severity of acute and chronic graft vs. host disease (GvHD)

    		 Close Top of page
    End point title
    		 Cumulative incidence and severity of acute and chronic graft vs. host disease (GvHD)
    End point description
    End point type
    Secondary
    End point timeframe
    Evaluation of cumulative incidence and severity of aGvHD until day 100 and cGvHD during total follow-up.
    End point values
    Number of subjects analysed
    Units: percent
    median (confidence interval 95%)
        Grades 2-4 aGvHD
        Grades 3-4 aGvHD
        cGvHD
    No statistical analyses for this end point

    Secondary: Primary Engrafment

    		 Close Top of page
    End point title
    		 Primary Engrafment
    End point description
    End point type
    Secondary
    End point timeframe
    Neutrophil engraftment was defined as a neutrophil count >= 5 x 109/L for more than 3 consecutive days; platelet engraftment was defined as a platelet count >= 20 x 109/L for more than 3 consecutive days in the absence of transfusions.
    End point values
    Number of subjects analysed
    Units: day
    median (full range (min-max))
        Neutrophil recovery
        Platelet recovery
    No statistical analyses for this end point

    Secondary: Overall survival (OS)

    		 Close Top of page
    End point title
    		 Overall survival (OS)
    End point description
    End point type
    Secondary
    End point timeframe
    1 year
    End point values
    Number of subjects analysed
    Units: percent
    median (confidence interval 95%)
        Low-intermediate DRI
        High-very high DRI
        Overall
    No statistical analyses for this end point

    Secondary: Progression-free survival (PFS)

    		 Close Top of page
    End point title
    		 Progression-free survival (PFS)
    End point description
    End point type
    Secondary
    End point timeframe
    1 year
    End point values
    Number of subjects analysed
    Units: percent
    median (confidence interval 95%)
        Low-intermediate DRI
        High-very high DRI
        Overall
    No statistical analyses for this end point

    Secondary: Relapse incidence

    		 Close Top of page
    End point title
    		 Relapse incidence
    End point description
    End point type
    Secondary
    End point timeframe
    1 year
    End point values
    Number of subjects analysed
    Units: percent
    median (confidence interval 95%)
        Low-intermediate DRI
        High-very high DRI
        Overall
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information [1]
    Timeframe for reporting adverse events
    Between day -6 and day +28 the patient will be asked and examined by the investigator for the occurrence of AEs. This time period is assumed to be appropriate for the evaluation of adverse events directly related to the conditioning regimen.
    Adverse event reporting additional description
    - patients’ charts - laboratory reports - doctor’s letters - nurses documentation
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 CTCAE
    Dictionary version
    3.0
    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: Non-serious adverse events were not collected. Please see the publication for futher information.

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    30 Jul 2009
    Review of the study design with definition of endpoints.
    14 Nov 2011
    Inclusion criteria modification: extension to patients with high-risk hematological malignancies; possibility of using for transplantation stem cells from bone marrow and not only PBSC (as standard for pediatric patients)

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/31605823
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Sun May 05 11:08:17 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA