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    Clinical Trial Results:
    A Phase 1/2 Combined Dose Ranging and Randomised, Open-label, Comparative Study of the Efficacy and Safety of Plerixafor in Addition to Standard Regimens for Mobilisation of Haematopoietic Stem Cells into Peripheral Blood, and Subsequent Collection by Apheresis, Versus Standard Mobilisation Regimens Alone in Paediatric Patients, Aged 1 to <18 Years, with Solid Tumours Eligible for Autologous Transplants

    Summary
    EudraCT number
    2010-019340-40
    Trial protocol
    GB   DE   IT   ES   BE   HU   CZ   NL   DK   PL   Outside EU/EEA  
    Global end of trial date
    09 May 2017

    Results information
    Results version number
    v1(current)
    This version publication date
    24 Nov 2017
    First version publication date
    24 Nov 2017
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    MOZ15609-DFI12860
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01288573
    WHO universal trial number (UTN)
    -
    Other trial identifiers
    Study name: MOZAIC
    Sponsors
    Sponsor organisation name
    Genzyme Corporation
    Sponsor organisation address
    500 Kendall Street , Cambridge, MA, United States, 02142
    Public contact
    Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.com
    Scientific contact
    Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    EMEA-000174-PIP01-07
    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?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    06 Jun 2017
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    09 May 2017
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study is to confirm the appropriate dose and efficacy, and to characterise the safety, pharmacokinetics and pharmacodynamics of plerixafor across age and size in paediatric cancer subjects when given in addition to standard mobilisation of hematopoietic stem cells (HSCs) into peripheral blood.
    Protection of trial subjects
    The study was conducted by investigators experienced in the treatment of paediatric patients. The parent(s) or guardian(s) as well as the children were fully informed of all pertinent aspects of the clinical trial as well as the possibility to discontinue at any time. In addition to the consent form for the parent(s)/guardian(s), an assent form in child-appropriate language was provided and explained to the child. Repeated invasive procedures were minimized. The number of blood samples as well as the amount of blood drawn were adjusted according to age and weight. A topical anaesthesia may have been used to minimize distress and discomfort.  
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    18 Feb 2011
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    Safety
    Long term follow-up duration
    2 Years
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Netherlands: 3
    Country: Number of subjects enrolled
    Poland: 2
    Country: Number of subjects enrolled
    Spain: 6
    Country: Number of subjects enrolled
    United Kingdom: 7
    Country: Number of subjects enrolled
    Belgium: 1
    Country: Number of subjects enrolled
    Czech Republic: 10
    Country: Number of subjects enrolled
    France: 2
    Country: Number of subjects enrolled
    Germany: 12
    Country: Number of subjects enrolled
    Hungary: 2
    Country: Number of subjects enrolled
    Italy: 22
    Country: Number of subjects enrolled
    Israel: 5
    Worldwide total number of subjects
    72
    EEA total number of subjects
    67
    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)
    4
    Children (2-11 years)
    52
    Adolescents (12-17 years)
    16
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    The study was conducted in 11 countries between 18 February 2011 and 09 May 2017. A total of 72 subjects were enrolled and treated in the study. The study was conducted in 2 stages. Stage 1 was the dose escalation study and stage 2 was the comparative study using the appropriate dosing regimen identified in Stage 1.

    Pre-assignment
    Screening details
    During Stage 1, 27 subjects assigned to plerixafor dose group according to their age & progress with dose escalation within that age group. During Stage 2, 45 subjects randomized in 2:1 ratio to receive either plerixafor + standard mobilization or standard mobilization alone.Standard mobilization was G-CSF ± chemotherapy per site standard practice.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Stage 1: Plerixafor 160 mcg /kg: 2-<6 years
    Arm description
    Subjects aged 2-<6 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 160 mcg /kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.
    Arm type
    Experimental

    Investigational medicinal product name
    Plerixafor
    Investigational medicinal product code
    GZ316455/ SAR316455
    Other name
    Mozobil®
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Plerixafor 160 mcg/kg was administered 9 to 11 hours prior to the initiation of apheresis.

    Investigational medicinal product name
    Non-IMP: Granulocyte Colony-Stimulating Factor (G-CSF)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    10 mcg/kg daily alone or in combination with chemotherapy as per site standard practice.

    Arm title
    Stage 1: Plerixafor 240 mcg /kg: 2-<6 years
    Arm description
    Subjects aged 2-<6 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 240 mcg /kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.
    Arm type
    Experimental

    Investigational medicinal product name
    Plerixafor
    Investigational medicinal product code
    GZ316455/ SAR316455
    Other name
    Mozobil®
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Plerixafor 240 mcg/kg was administered 9 to 11 hours prior to the initiation of apheresis.

    Investigational medicinal product name
    Non-IMP: G-CSF
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    10 mcg/kg daily alone or in combination with chemotherapy per site standard practice.

    Arm title
    Stage 1: Plerixafor 320 mcg /kg: 2-<6 years
    Arm description
    Subjects aged 2-<6 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 320 mcg /kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.
    Arm type
    Experimental

    Investigational medicinal product name
    Plerixafor
    Investigational medicinal product code
    GZ316455/ SAR316455
    Other name
    Mozobil®
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Plerixafor 320 mcg/kg was administered 9 to 11 hours prior to the initiation of apheresis.

    Investigational medicinal product name
    Non-IMP: G-CSF
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    10 mcg/kg daily alone or in combination with chemotherapy per site standard practice.

    Arm title
    Stage 1: Plerixafor 160 mcg /kg: 6-<12 years
    Arm description
    Subjects aged 6-<12 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 160 mcg /kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.
    Arm type
    Experimental

    Investigational medicinal product name
    Plerixafor
    Investigational medicinal product code
    GZ316455/ SAR316455
    Other name
    Mozobil®
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Plerixafor 160 mcg/kg was administered 9 to 11 hours prior to the initiation of apheresis.

    Investigational medicinal product name
    Non IMP: G-CSF
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    10 mcg/kg daily alone or in combination with chemotherapy per site standard practice.

    Arm title
    Stage 1: Plerixafor 240 mcg /kg: 6-<12 years
    Arm description
    Subjects aged 6-<12 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 240 mcg /kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.
    Arm type
    Experimental

    Investigational medicinal product name
    Plerixafor
    Investigational medicinal product code
    GZ316455/ SAR316455
    Other name
    Mozobil®
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Plerixafor 240 mcg/kg was administered 9 to 11 hours prior to the initiation of apheresis.

    Investigational medicinal product name
    Non-IMP: G-CSF
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    10 mcg/kg daily alone or in combination with chemotherapy per site standard practice.

    Arm title
    Stage 1: Plerixafor 320 mcg /kg: 6-<12 years
    Arm description
    Subjects aged 6-<12 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 320 mcg /kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.
    Arm type
    Experimental

    Investigational medicinal product name
    Plerixafor
    Investigational medicinal product code
    GZ316455/ SAR316455
    Other name
    Mozobil®
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Plerixafor 320 mcg/kg was administered 9 to 11 hours prior to the initiation of apheresis.

    Investigational medicinal product name
    Non-IMP: G-CSF
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    10 mcg/kg daily alone or in combination with chemotherapy per site standard practice.

    Arm title
    Stage 1: Plerixafor 160 mcg /kg: 12-<18 years
    Arm description
    Subjects aged 12-<18 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 160 mcg /kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.
    Arm type
    Experimental

    Investigational medicinal product name
    Plerixafor
    Investigational medicinal product code
    GZ316455/ SAR316455
    Other name
    Mozobil®
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Plerixafor 160 mcg/kg was administered 9 to 11 hours prior to the initiation of apheresis.

    Investigational medicinal product name
    Non IMP: G-CSF
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    10 mcg/kg daily alone or in combination with chemotherapy per site standard practice.

    Arm title
    Stage 1: Plerixafor 240 mcg/kg: 12-<18 years
    Arm description
    Subjects aged 12-<18 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 240 mcg /kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.
    Arm type
    Experimental

    Investigational medicinal product name
    Plerixafor
    Investigational medicinal product code
    GZ316455/ SAR316455
    Other name
    Mozobil®
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Plerixafor 240 mcg/kg was administered 9 to 11 hours prior to the initiation of apheresis.

    Investigational medicinal product name
    Non-IMP: G-CSF
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    10 mcg/kg daily alone or in combination with chemotherapy per site standard practice.

    Arm title
    Stage 1: Plerixafor 320 mcg/kg: 12-<18 years
    Arm description
    Subjects aged 12-<18 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 320 mcg /kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.
    Arm type
    Experimental

    Investigational medicinal product name
    Plerixafor
    Investigational medicinal product code
    GZ316455/ SAR316455
    Other name
    Mozobil®
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Plerixafor 320 mcg/kg was administered 9 to 11 hours prior to the initiation of apheresis.

    Investigational medicinal product name
    Non-IMP: G-CSF
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    10 mcg/kg daily alone or in combination with chemotherapy per site standard practice.

    Arm title
    Stage 2: Standard Mobilization Regimen - G-CSF
    Arm description
    Subjects started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Treatment G-CSF (alone or in combination with chemotherapy) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.
    Arm type
    Experimental

    Investigational medicinal product name
    Non IMP: G-CSF
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    10 mcg/kg daily alone or in combination with chemotherapy per site standard practice.

    Arm title
    Stage 2: Plerixafor + Standard Mobilization Regimen -G-CSF
    Arm description
    Subjects started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 240 mcg/kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.
    Arm type
    Experimental

    Investigational medicinal product name
    Plerixafor
    Investigational medicinal product code
    GZ316455/ SAR316455
    Other name
    Mozobil®
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Plerixafor 240 mcg/kg was administered 8 to 12 hours prior to the initiation of apheresis.

    Investigational medicinal product name
    Non-IMP: G-CSF
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    10 mcg/kg daily alone or in combination with chemotherapy per site standard practice.

    Number of subjects in period 1
    Stage 1: Plerixafor 160 mcg /kg: 2-<6 years Stage 1: Plerixafor 240 mcg /kg: 2-<6 years Stage 1: Plerixafor 320 mcg /kg: 2-<6 years Stage 1: Plerixafor 160 mcg /kg: 6-<12 years Stage 1: Plerixafor 240 mcg /kg: 6-<12 years Stage 1: Plerixafor 320 mcg /kg: 6-<12 years Stage 1: Plerixafor 160 mcg /kg: 12-<18 years Stage 1: Plerixafor 240 mcg/kg: 12-<18 years Stage 1: Plerixafor 320 mcg/kg: 12-<18 years Stage 2: Standard Mobilization Regimen - G-CSF Stage 2: Plerixafor + Standard Mobilization Regimen -G-CSF
    Started
    3
    3
    3
    3
    3
    3
    3
    3
    3
    15
    30
    Completed
    2
    2
    3
    2
    3
    0
    2
    2
    1
    10
    25
    Not completed
    1
    1
    0
    1
    0
    3
    1
    1
    2
    5
    5
         Progressive disease
             -
             -
             -
             -
             -
             1
             -
             -
             -
             1
             -
         Death
             -
             -
             -
             1
             -
             1
             -
             1
             1
             3
             3
         Other than specified
             1
             -
             -
             -
             -
             -
             1
             -
             1
             -
             1
         Consent withdrawn by subject
             -
             -
             -
             -
             -
             -
             -
             -
             -
             1
             1
         Lost to follow-up
             -
             1
             -
             -
             -
             1
             -
             -
             -
             -
             -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Stage 1: Plerixafor 160 mcg /kg: 2-<6 years
    Reporting group description
    Subjects aged 2-<6 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 160 mcg /kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

    Reporting group title
    Stage 1: Plerixafor 240 mcg /kg: 2-<6 years
    Reporting group description
    Subjects aged 2-<6 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 240 mcg /kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

    Reporting group title
    Stage 1: Plerixafor 320 mcg /kg: 2-<6 years
    Reporting group description
    Subjects aged 2-<6 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 320 mcg /kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

    Reporting group title
    Stage 1: Plerixafor 160 mcg /kg: 6-<12 years
    Reporting group description
    Subjects aged 6-<12 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 160 mcg /kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

    Reporting group title
    Stage 1: Plerixafor 240 mcg /kg: 6-<12 years
    Reporting group description
    Subjects aged 6-<12 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 240 mcg /kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

    Reporting group title
    Stage 1: Plerixafor 320 mcg /kg: 6-<12 years
    Reporting group description
    Subjects aged 6-<12 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 320 mcg /kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

    Reporting group title
    Stage 1: Plerixafor 160 mcg /kg: 12-<18 years
    Reporting group description
    Subjects aged 12-<18 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 160 mcg /kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

    Reporting group title
    Stage 1: Plerixafor 240 mcg/kg: 12-<18 years
    Reporting group description
    Subjects aged 12-<18 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 240 mcg /kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

    Reporting group title
    Stage 1: Plerixafor 320 mcg/kg: 12-<18 years
    Reporting group description
    Subjects aged 12-<18 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 320 mcg /kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

    Reporting group title
    Stage 2: Standard Mobilization Regimen - G-CSF
    Reporting group description
    Subjects started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Treatment G-CSF (alone or in combination with chemotherapy) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

    Reporting group title
    Stage 2: Plerixafor + Standard Mobilization Regimen -G-CSF
    Reporting group description
    Subjects started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 240 mcg/kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

    Reporting group values
    Stage 1: Plerixafor 160 mcg /kg: 2-<6 years Stage 1: Plerixafor 240 mcg /kg: 2-<6 years Stage 1: Plerixafor 320 mcg /kg: 2-<6 years Stage 1: Plerixafor 160 mcg /kg: 6-<12 years Stage 1: Plerixafor 240 mcg /kg: 6-<12 years Stage 1: Plerixafor 320 mcg /kg: 6-<12 years Stage 1: Plerixafor 160 mcg /kg: 12-<18 years Stage 1: Plerixafor 240 mcg/kg: 12-<18 years Stage 1: Plerixafor 320 mcg/kg: 12-<18 years Stage 2: Standard Mobilization Regimen - G-CSF Stage 2: Plerixafor + Standard Mobilization Regimen -G-CSF Total
    Number of subjects
    3 3 3 3 3 3 3 3 3 15 30 72
    Age categorical
    Units: Subjects
        Infants and toddlers (28 days-23 months)
    0 0 0 0 0 0 0 0 0 3 1 4
        Children (2-<12 years)
    3 3 3 3 3 3 0 0 0 10 24 52
        Adolescents (12-<18 years)
    0 0 0 0 0 0 3 3 3 2 5 16
    Gender categorical
    Units: Subjects
        Female
    2 2 3 1 1 1 1 3 2 8 11 35
        Male
    1 1 0 2 2 2 2 0 1 7 19 37

    End points

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    End points reporting groups
    Reporting group title
    Stage 1: Plerixafor 160 mcg /kg: 2-<6 years
    Reporting group description
    Subjects aged 2-<6 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 160 mcg /kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

    Reporting group title
    Stage 1: Plerixafor 240 mcg /kg: 2-<6 years
    Reporting group description
    Subjects aged 2-<6 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 240 mcg /kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

    Reporting group title
    Stage 1: Plerixafor 320 mcg /kg: 2-<6 years
    Reporting group description
    Subjects aged 2-<6 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 320 mcg /kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

    Reporting group title
    Stage 1: Plerixafor 160 mcg /kg: 6-<12 years
    Reporting group description
    Subjects aged 6-<12 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 160 mcg /kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

    Reporting group title
    Stage 1: Plerixafor 240 mcg /kg: 6-<12 years
    Reporting group description
    Subjects aged 6-<12 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 240 mcg /kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

    Reporting group title
    Stage 1: Plerixafor 320 mcg /kg: 6-<12 years
    Reporting group description
    Subjects aged 6-<12 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 320 mcg /kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

    Reporting group title
    Stage 1: Plerixafor 160 mcg /kg: 12-<18 years
    Reporting group description
    Subjects aged 12-<18 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 160 mcg /kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

    Reporting group title
    Stage 1: Plerixafor 240 mcg/kg: 12-<18 years
    Reporting group description
    Subjects aged 12-<18 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 240 mcg /kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

    Reporting group title
    Stage 1: Plerixafor 320 mcg/kg: 12-<18 years
    Reporting group description
    Subjects aged 12-<18 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 320 mcg /kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

    Reporting group title
    Stage 2: Standard Mobilization Regimen - G-CSF
    Reporting group description
    Subjects started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Treatment G-CSF (alone or in combination with chemotherapy) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

    Reporting group title
    Stage 2: Plerixafor + Standard Mobilization Regimen -G-CSF
    Reporting group description
    Subjects started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 240 mcg/kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

    Primary: Stage 2: Percentage of Subjects Achieving At least a Doubling of Peripheral Blood CD34+ Count

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    End point title
    Stage 2: Percentage of Subjects Achieving At least a Doubling of Peripheral Blood CD34+ Count [1]
    End point description
    Percentage of subjects who achieved at least a doubling of peripheral blood CD34+ count (known as successful mobilisation) from the morning of the day preceding the first apheresis day to the morning prior to apheresis was reported in this endpoint. For those subjects who did not have the first apheresis as planned, peripheral CD34+ counts from the morning of the day prior to the planned apheresis day and from the morning of the planned apheresis day itself were included in the analysis. Analysis was performed on full analysis set (FAS) which is comprised of all subjects randomized in Stage 2 according to intent-to-treat (ITT) principle (subjects were analysed according to the treatment group allocated by randomization).
    End point type
    Primary
    End point timeframe
    From the morning of the day preceding the first apheresis day to the morning prior to apheresis
    Notes
    [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint is reporting results only for stage 2 in which standard mobilization alone and plerixafor + standard mobilization was administered.
    End point values
    Stage 2: Standard Mobilization Regimen - G-CSF Stage 2: Plerixafor + Standard Mobilization Regimen -G-CSF
    Number of subjects analysed
    15
    30
    Units: percentage of subjects
        number (confidence interval 95%)
    28.6 (8.4 to 58.1)
    80 (61.4 to 92.3)
    Statistical analysis title
    G-CSF alone vs. G-CSF + Plerixafor
    Statistical analysis description
    The difference of percentage of successful mobilization was relative to standard mobilization alone treatment group. The confidence interval (CI) of the difference is based on the Wald asymptotic CI with continuity correction method.
    Comparison groups
    Stage 2: Standard Mobilization Regimen - G-CSF v Stage 2: Plerixafor + Standard Mobilization Regimen -G-CSF
    Number of subjects included in analysis
    45
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0019 [2]
    Method
    Fisher exact
    Parameter type
    Difference of percentage
    Point estimate
    51.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    18.5
         upper limit
    84.3
    Notes
    [2] - Threshold level was estimated at 0.05 level.

    Secondary: Stage 2: Median Number of Days of Apheresis Required to Reach >=2 *10^6 CD34+ cells/kg

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    End point title
    Stage 2: Median Number of Days of Apheresis Required to Reach >=2 *10^6 CD34+ cells/kg [3]
    End point description
    The number of days of apheresis to reach >=2*10^6 CD34+ cells/kg was estimated using the Kaplan-Meier method. A subject was classified as having the event if the cumulative number of CD34+ cells/kg collected reached the target of ≥2*10^6 CD34+ cells/kg. Subjects not reaching target at the end of apheresis period were censored on the last apheresis day (maximum of 5 apheresis in study). Analysis was performed on FAS. Here, 99999 represents data not calculated since majority of subjects reached CD34+ cells target within 1 day.
    End point type
    Secondary
    End point timeframe
    Day 1 up to Day 5
    Notes
    [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint is reporting results only for stage 2 in which standard mobilization alone and plerixafor + standard mobilization was administered.
    End point values
    Stage 2: Standard Mobilization Regimen - G-CSF Stage 2: Plerixafor + Standard Mobilization Regimen -G-CSF
    Number of subjects analysed
    15
    30
    Units: Days
        median (full range (min-max))
    1 (-99999 to 99999)
    1 (-99999 to 99999)
    No statistical analyses for this end point

    Secondary: Stage 2: Yield of CD34+ (*10^6 cells/kg ) Cells for Each Apheresis

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    End point title
    Stage 2: Yield of CD34+ (*10^6 cells/kg ) Cells for Each Apheresis [4]
    End point description
    Apheresis commenced on the morning following the day when the peripheral blood (PB) CD34+ count reached the target trigger point minimum of 7 CD34+ cells/mcl. Here, 99999 represented that data was not estimable as none of the evaluable subjects had Day 3 apheresis except for 1 subject in the plerixafor + standard mobilization arm. Analysis was performed on FAS population. Here 'n' signifies number of subjects with available data for specified category.
    End point type
    Secondary
    End point timeframe
    Days 1 up to Day 3 following apheresis
    Notes
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint is reporting results only for stage 2 in which standard mobilization alone and plerixafor + standard mobilization was administered.
    End point values
    Stage 2: Standard Mobilization Regimen - G-CSF Stage 2: Plerixafor + Standard Mobilization Regimen -G-CSF
    Number of subjects analysed
    15
    30
    Units: cells (*10^6 cells/kg)
    arithmetic mean (standard deviation)
        Day 1 (n= 14, 29)
    17.57 ± 20.79
    19.44 ± 36.7
        Day 2 (n = 2, 3)
    2.8 ± 3.3
    0.69 ± 1.07
        Day 3 (n = 0, 1)
    99999 ± 99999
    0.06 ± 99999
    No statistical analyses for this end point

    Secondary: Stage 2: Total CD34+ Cell Yield

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    End point title
    Stage 2: Total CD34+ Cell Yield [5]
    End point description
    The cumulative CD34+ cells/kg yield was calculated by summing the CD34+ yield from each apheresis. Analysis was performed on FAS population. Number of subjects analysed=number of subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Day 1 up to Day 3 following apheresis
    Notes
    [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint is reporting results only for stage 2 in which standard mobilization alone and plerixafor + standard mobilization was administered.
    End point values
    Stage 2: Standard Mobilization Regimen - G-CSF Stage 2: Plerixafor + Standard Mobilization Regimen -G-CSF
    Number of subjects analysed
    14
    29
    Units: cells (*10^6 cells/kg)
        arithmetic mean (standard deviation)
    17.61 ± 20.76
    19.44 ± 36.69
    No statistical analyses for this end point

    Secondary: Stage 2: Percentage of Subjects Proceeding to Autologous Transplant

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    End point title
    Stage 2: Percentage of Subjects Proceeding to Autologous Transplant [6]
    End point description
    The percentage of subjects proceeding to autologous transplant was calculated using the total number of subjects in the corresponding analysis set as the denominator. Analysis was performed on FAS population.
    End point type
    Secondary
    End point timeframe
    Within 6 months of last apheresis (up to maximum duration of 2.5 years)
    Notes
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint is reporting results only for stage 2 in which standard mobilization alone and plerixafor + standard mobilization was administered.
    End point values
    Stage 2: Standard Mobilization Regimen - G-CSF Stage 2: Plerixafor + Standard Mobilization Regimen -G-CSF
    Number of subjects analysed
    15
    30
    Units: percentage of subjects
        number (confidence interval 95%)
    66.7 (38.4 to 88.2)
    76.7 (57.7 to 90.1)
    No statistical analyses for this end point

    Secondary: Stage 2: Percentage of Subjects Successfully Engrafting

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    End point title
    Stage 2: Percentage of Subjects Successfully Engrafting [7]
    End point description
    Successful engrafting was when both absolute neutrophil count (ANC) & platelet were successfully engrafted. Percentage of subjects with successful engraftment was calculated using the total number of subjects in each treatment group who received transplantation as the denominator. Analysis was performed on FAS population. Number of subjects analysed= number of subjects who underwent grafting.
    End point type
    Secondary
    End point timeframe
    24 months after transplant (up to maximum duration of 2.5 years)
    Notes
    [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint is reporting results only for stage 2 in which standard mobilization alone and plerixafor + standard mobilization was administered.
    End point values
    Stage 2: Standard Mobilization Regimen - G-CSF Stage 2: Plerixafor + Standard Mobilization Regimen -G-CSF
    Number of subjects analysed
    10
    23
    Units: percentage of subjects
        number (confidence interval 95%)
    100 (69.2 to 100)
    100 (85.2 to 100)
    No statistical analyses for this end point

    Secondary: Stage 2: Percentage of Subjects with Durable Engraftment

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    End point title
    Stage 2: Percentage of Subjects with Durable Engraftment [8]
    End point description
    Durable engraftment was defined as subjects with both ANC and platelet engrafted and who remained in the engraftment status at 3, 6, 12, and 24 months post-transplant. The percentage of subjects with durable engraftment at 3, 6, 12, and 24 months post-transplant was calculated using the total number of subjects in each treatment group who received transplant as the denominator. Analysis was performed on FAS population. Number of subjects analysed=number of subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    At 3, 6, 12 and 24 months post-transplant (up to maximum duration of 2.5 years)
    Notes
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint is reporting results only for stage 2 in which standard mobilization alone and plerixafor + standard mobilization was administered.
    End point values
    Stage 2: Standard Mobilization Regimen - G-CSF Stage 2: Plerixafor + Standard Mobilization Regimen -G-CSF
    Number of subjects analysed
    10
    23
    Units: percentage of subjects
    number (confidence interval 95%)
        Month 3
    100 (69.2 to 100)
    91.3 (72 to 98.9)
        Month 6
    90 (55.5 to 99.7)
    87 (66.4 to 97.2)
        Month 12
    80 (44.4 to 97.5)
    87 (66.4 to 97.2)
        Month 24
    80 (44.4 to 97.5)
    82.6 (61.2 to 95)
    No statistical analyses for this end point

    Secondary: Stage 1 and Stage 2: Overview of Safety

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    End point title
    Stage 1 and Stage 2: Overview of Safety
    End point description
    Any untoward medical occurrence in a subject who received investigational medicinal product was considered an AE regardless of causal relationship with this treatment. Treatment-Emergent Adverse Events (TEAEs): AEs that developed/worsened/became serious during from the date of enrollment until 30 days after the last dose of subject’s study mobilization regimen/until the 1st dose of next anticancer therapy or pre-transplant myeloablative therapy, whichever occurred first. Serious AE (SAE):any untoward medical occurrence that resulted in any of following outcomes: death, life-threatening, required initial/prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect/considered as medically important event. Any TEAE included both serious & non-serious AEs. Safety set was defined as all subjects who received at least one dose of study drug.
    End point type
    Secondary
    End point timeframe
    From baseline up to the follow up visit (up to 6.2 years)
    End point values
    Stage 1: Plerixafor 160 mcg /kg: 2-<6 years Stage 1: Plerixafor 240 mcg /kg: 2-<6 years Stage 1: Plerixafor 320 mcg /kg: 2-<6 years Stage 1: Plerixafor 160 mcg /kg: 6-<12 years Stage 1: Plerixafor 240 mcg /kg: 6-<12 years Stage 1: Plerixafor 320 mcg /kg: 6-<12 years Stage 1: Plerixafor 160 mcg /kg: 12-<18 years Stage 1: Plerixafor 240 mcg/kg: 12-<18 years Stage 1: Plerixafor 320 mcg/kg: 12-<18 years Stage 2: Standard Mobilization Regimen - G-CSF Stage 2: Plerixafor + Standard Mobilization Regimen -G-CSF
    Number of subjects analysed
    3
    3
    3
    3
    3
    3
    3
    3
    3
    15
    30
    Units: percentage of subjects
    number (not applicable)
        Any TEAE
    67
    33
    33
    67
    67
    67
    100
    33
    67
    66.7
    76.7
        Any treatment-emergent SAE
    33.33
    0
    0
    66.67
    0
    33.33
    66.67
    0
    33.33
    26.7
    30
    No statistical analyses for this end point

    Secondary: Stage 2: Percentage of Subjects Who Had Hospitalization

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    End point title
    Stage 2: Percentage of Subjects Who Had Hospitalization [9]
    End point description
    Analysis was performed on safety set for stage 2 which included all randomized subjects who received at least one study dose (either plerixafor or standard mobilization) in Stage 2. Subjects from Stage 2 were to be analysed for safety according to the treatment they actually received.
    End point type
    Secondary
    End point timeframe
    From randomisation in stage 2 until the end of study (up to maximum duration of 2.5 years)
    Notes
    [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint is reporting results only for stage 2 in which standard mobilization alone and plerixafor + standard mobilization was administered.
    End point values
    Stage 2: Standard Mobilization Regimen - G-CSF Stage 2: Plerixafor + Standard Mobilization Regimen -G-CSF
    Number of subjects analysed
    15
    30
    Units: percentage of subjects
        number (not applicable)
    86.7
    90
    No statistical analyses for this end point

    Secondary: Stage 2: Percentage of Subjects With Tumor Cell Mobilisation Positive in Peripheral Blood

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    End point title
    Stage 2: Percentage of Subjects With Tumor Cell Mobilisation Positive in Peripheral Blood [10]
    End point description
    Tumour cell mobilisation was evaluated by assessment of blood samples for the presence of tumour cells in peripheral blood. Blood samples were collected on the morning of the day preceding the first apheresis day and in the morning prior to G-CSF administration on the first apheresis day itself, as well as in apheresis product after first, second and third apheresis prior to cryopreservation in subjects with neuroblastoma, Ewing’s sarcoma and alveolar rhabdomyosarcoma. Analysis was performed on safety set for stage-2. Here 'n' signifies number of subjects with available data for specified categories for each arm respectively.
    End point type
    Secondary
    End point timeframe
    On morning at Day prior to first planned apheresis, morning of first planned apheresis day, first apheresis, second apheresis, third apheresis additional apheresis days (maximum of 5 apheresis) (up to maximum duration of 2.5 years)
    Notes
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint is reporting results only for stage 2 in which standard mobilization alone and plerixafor + standard mobilization was administered.
    End point values
    Stage 2: Standard Mobilization Regimen - G-CSF Stage 2: Plerixafor + Standard Mobilization Regimen -G-CSF
    Number of subjects analysed
    15
    30
    Units: percentage of subjects
    number (not applicable)
        on morning prior to 1st apheresis(n=9, 20)
    11.1
    0
        on morning of 1st apheresis (n=9, 21)
    0
    0
        at 1st apheresis (n=10, 20)
    10
    5
        at 2nd apheresis (n=2, 2)
    100
    0
        at 3rd apheresis (n= 0, 1)
    0
    0
    No statistical analyses for this end point

    Secondary: Stage 2: Post-Transplant Relapse Rate

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    End point title
    Stage 2: Post-Transplant Relapse Rate [11]
    End point description
    Relapse rate was defined as the percentage of subjects with relapse at 3, 6, 12, and 24 months post-transplant. It was summarized using Kaplan-Meier methods for subjects who received transplant. Time to relapse for subjects who received transplant was defined as the time interval from the date of transplant to the date of first recorded recurrent or progressive disease. Subjects with no recurrent or progressive disease recorded were censored at their last visit. The start date was the date of transplant. Analysis was performed on safety set for stage 2. Number of subjects analysed=subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    At month 3, 6, 12, and 24 after transplant (up to a maximum duration of 2.5 years)
    Notes
    [11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint is reporting results only for stage 2 in which standard mobilization alone and plerixafor + standard mobilization was administered.
    End point values
    Stage 2: Standard Mobilization Regimen - G-CSF Stage 2: Plerixafor + Standard Mobilization Regimen -G-CSF
    Number of subjects analysed
    10
    23
    Units: Percentage of subjects
    number (confidence interval 95%)
        Month 3 post-transplant
    0.1 (0.015 to 0.527)
    0.087 (0.022 to 0.305)
        Month 6 post-transplant
    0.1 (0.015 to 0.527)
    0.087 (0.022 to 0.305)
        Month 12 post-transplant
    0.1 (0.015 to 0.527)
    0.13 (0.044 to 0.352)
        Month 24 post-transplant
    0.55 (0.266 to 0.873)
    0.304 (0.158 to 0.534)
    No statistical analyses for this end point

    Secondary: Stage 2: Post-Apheresis Relapse Rate

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    End point title
    Stage 2: Post-Apheresis Relapse Rate [12]
    End point description
    Relapse rate was defined as the percentage of subjects with relapse at 3, 6, 12, and 24 months post-apheresis. It was summarized using Kaplan-Meier methods for subjects who had apheresis. Time to relapse for subjects who received transplant or not was defined as time interval from the date of last apheresis to the date of the recorded recurrent or progressive disease. Subjects with no recurrent or progressive disease was censored at the last visit. The start date was the date of last apheresis. Analysis was performed on safety set for stage 2. 99999 represents data not calculated as very low number of subject had event (relapse).
    End point type
    Secondary
    End point timeframe
    At month 3, 6, 12, and 24 after apheresis (up to maximum duration of 2.5 years)
    Notes
    [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint is reporting results only for stage 2 in which standard mobilization alone and plerixafor + standard mobilization was administered.
    End point values
    Stage 2: Standard Mobilization Regimen - G-CSF Stage 2: Plerixafor + Standard Mobilization Regimen -G-CSF
    Number of subjects analysed
    15
    30
    Units: percentage of subjects
    number (confidence interval 95%)
        Month 3 post-apheresis
    0.071 (0.01 to 0.409)
    0 (-99999 to 99999)
        Month 6 post-apheresis
    0.071 (0.01 to 0.409)
    0.036 (0.005 to 0.228)
        Month 12 post-apheresis
    0.071 (0.01 to 0.409)
    0.071 (0.018 to 0.257)
        Month 24 post-apheresis
    0.357 (0.167 to 0.657)
    0.253 (0.129 to 0.459)
    No statistical analyses for this end point

    Secondary: Stage 2: Percentage of Subjects With Secondary Malignancies

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    End point title
    Stage 2: Percentage of Subjects With Secondary Malignancies [13]
    End point description
    The occurrence of secondary malignancies during the 24 months after the last planned transplant performed in the 6-month period after last study apheresis (or 24 months after last dose of study mobilisation treatment for subjects who did not undergo transplant within 6 months after last study apheresis) was recorded for all subjects. Analysis was performed on safety set for stage 2. Here, 99999 represents data not calculated as no subject in both arms had any secondary malignancy.
    End point type
    Secondary
    End point timeframe
    Up to 24 months post transplant period (up to a maximum duration of 2.5 years)
    Notes
    [13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint is reporting results only for stage 2 in which standard mobilization alone and plerixafor + standard mobilization was administered.
    End point values
    Stage 2: Standard Mobilization Regimen - G-CSF Stage 2: Plerixafor + Standard Mobilization Regimen -G-CSF
    Number of subjects analysed
    15
    30
    Units: percentage of subjects
        number (not applicable)
    99999
    99999
    No statistical analyses for this end point

    Secondary: Stage 2: Percentage of Subjects with Primary Graft Failure

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    End point title
    Stage 2: Percentage of Subjects with Primary Graft Failure [14]
    End point description
    Primary graft failure was defined by the criteria below in the absence of evidence of other causes such as progressive cancer, renal failure, chronic bleeding, severe infection, drug induced cytopaenias, or development of new haematological problems (nutritional or otherwise). Primary neutrophil graft failure was defined as the failure to achieve a sustained ANC of >=0.5*10^9/L (defined by 3 consecutive laboratory values on 3 different days) or >=1.0*10^9/L for 1 day within 30 days post-transplant. Primary platelet graft failure was defined as the failure to achieve a sustained platelet count >=20*10^9/L (defined by at least 3 consecutive platelet laboratory values obtained over at least 7 days without transfusion) within 100 days post-transplant. Analysis was performed on safety set for stage 2. Number of subjects analysed=subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Up to 100 days post-transplant or until disease recurrence or progression whichever occurred first (up to a maximum duration of 2.5 years)
    Notes
    [14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint is reporting results only for stage 2 in which standard mobilization alone and plerixafor + standard mobilization was administered.
    End point values
    Stage 2: Standard Mobilization Regimen - G-CSF Stage 2: Plerixafor + Standard Mobilization Regimen -G-CSF
    Number of subjects analysed
    10
    23
    Units: percentage of subjects
    number (not applicable)
        Primary neutrophil graft failure
    0
    0
        Primary platelet graft failure
    0
    4.3
    No statistical analyses for this end point

    Secondary: Stage 2: Percentage of Subjects With Secondary Graft Failure

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    End point title
    Stage 2: Percentage of Subjects With Secondary Graft Failure [15]
    End point description
    Secondary graft failure was defined as confirmation of one of the following in the absence of evidence of other causes such as recurrence or progression of cancer, renal failure, chronic bleeding, severe infection, drug-induced cytopaenias, or development of new haematological problems (nutritional or otherwise). Neutrophils: after achieving neutrophil engraftment, there is a subsequent decrease in ANC such that the ANC falls to <0.5*10^9/L for at least 7 days regardless of growth factor support. Platelets: after achieving primary platelet engraftment, there was a subsequent decrease in platelet counts below 10*10^9/L for 7 days (defined by at least 2 consecutive platelet laboratory values obtained over at least 7 days) or required sustained platelet transfusion support. Analysis was performed on safety set for stage 2. Number of subjects analysed=subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Up to 24 months post-transplant or until disease recurrence or progression whichever occurred first (up to a maximum duration of 2.5 years)
    Notes
    [15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint is reporting results only for stage 2 in which standard mobilization alone and plerixafor + standard mobilization was administered.
    End point values
    Stage 2: Standard Mobilization Regimen - G-CSF Stage 2: Plerixafor + Standard Mobilization Regimen -G-CSF
    Number of subjects analysed
    10
    23
    Units: percentage of subjects
    number (not applicable)
        Secondary neutrophil graft failure
    0
    0
        Secondary platelet graft failure
    0
    4.3
    No statistical analyses for this end point

    Secondary: Stage 2: Median Time to Secondary Graft Failure

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    End point title
    Stage 2: Median Time to Secondary Graft Failure [16]
    End point description
    Median time to secondary graft failure was defined as the time interval from the date of successful engraftment to the date of documented secondary graft failure for those subjects who had achieved successful engraftment. Subjects without graft failure at the end of the follow-up period were to be censored at the last visit. Analysis was performed using Kaplan-Meier method. Analysis was performed on safety set for stage 2. Here, 99999 represents data not calculated as no subjects had event (secondary graft failure).
    End point type
    Secondary
    End point timeframe
    From date of engraftment till the graft failure (up to a maximum duration of 2.5 years)
    Notes
    [16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint is reporting results only for stage 2 in which standard mobilization alone and plerixafor + standard mobilization was administered.
    End point values
    Stage 2: Standard Mobilization Regimen - G-CSF Stage 2: Plerixafor + Standard Mobilization Regimen -G-CSF
    Number of subjects analysed
    15
    30
    Units: months
        number (confidence interval 95%)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    No statistical analyses for this end point

    Secondary: Stage 2: Overall Survival at Month 3, 6, 12 and 24 Post- Transplant

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    End point title
    Stage 2: Overall Survival at Month 3, 6, 12 and 24 Post- Transplant [17]
    End point description
    Overall survival for subjects who received transplant(s) was defined as the time interval from the date of transplantation to the date of death. Subjects alive at the end of the follow-up period were to be censored at the last follow-up visit with known alive status. Kaplan-Meier method was used to estimate the confidence intervals (CIs), using a log transformation. Percentage of subjects with OS were estimated. Analysis was performed on safety set for stage 2. Number of subjects analysed=subjects evaluable for this endpoint. Here, 99999 represents data (95% CI) not calculated as very low number of subjects had event.
    End point type
    Secondary
    End point timeframe
    At 3, 6, 12 and 24 Months Post Transplant (up to a maximum duration of 2.5 years)
    Notes
    [17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint is reporting results only for stage 2 in which standard mobilization alone and plerixafor + standard mobilization was administered.
    End point values
    Stage 2: Standard Mobilization Regimen - G-CSF Stage 2: Plerixafor + Standard Mobilization Regimen -G-CSF
    Number of subjects analysed
    10
    23
    Units: percentage of subjects
    number (confidence interval 95%)
        Month 3
    1 (-99999 to 99999)
    0.957 (0.729 to 0.994)
        Month 6
    0.9 (0.473 to 0.985)
    0.957 (0.729 to 0.994)
        Month 12
    0.9 (0.473 to 0.985)
    0.957 (0.729 to 0.994)
        Month 24
    0.675 (0.291 to 0.882)
    0.87 (0.648 to 0.956)
    No statistical analyses for this end point

    Secondary: Stage 2: Overall Survival Rate for Subjects at 3, 6, 12 and 24 Months Post Apheresis

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    End point title
    Stage 2: Overall Survival Rate for Subjects at 3, 6, 12 and 24 Months Post Apheresis [18]
    End point description
    Overall survival for all subjects was calculated as the time interval from the date of last apheresis to the date of death. Subjects alive at the end of the follow-up period were to be censored at the last follow-up visit with known alive status. Kaplan-Meier method was used to estimate the CIs, using a log transformation Percentage of subjects with OS were estimated. Analysis was performed on safety set for stage 2. Here, 99999 represents data (95% CI) not calculated as very low number of subjects had event.
    End point type
    Secondary
    End point timeframe
    At 3, 6, 12 and 24 Months Post Apheresis (up to a maximum duration of 2.5 years)
    Notes
    [18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint is reporting results only for stage 2 in which standard mobilization alone and plerixafor + standard mobilization was administered.
    End point values
    Stage 2: Standard Mobilization Regimen - G-CSF Stage 2: Plerixafor + Standard Mobilization Regimen -G-CSF
    Number of subjects analysed
    15
    30
    Units: percentage of subjects
    number (confidence interval 95%)
        Month 3
    1 (-99999 to 99999)
    1 (-99999 to 99999)
        Month 6
    1 (-99999 to 99999)
    1 (-99999 to 99999)
        Month 12
    0.929 (0.591 to 0.99)
    0.964 (0.772 to 0.995)
        Month 24
    0.766 (0.433 to 0.919)
    0.893 (0.704 to 0.964)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (up to post-transplant follow up visit of 2 years) regardless of seriousness or relationship to investigational product.
    Adverse event reporting additional description
    Reported AEs are TEAEs that is AEs that developed/worsened during the on treatment period (from the date of randomization until 30 days after the last dose of subject’s study mobilization regimen, or until the first dose of their next anticancer therapy or pre-transplant myeloablative therapy or 2-year follow-up period).
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    20.0
    Reporting groups
    Reporting group title
    Stage 1: Plerixafor 160 mcg /kg: 2-<6 years
    Reporting group description
    Subjects aged 2-<6 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 160 mcg /kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

    Reporting group title
    Stage 1: Plerixafor 240 mcg /kg: 2-<6 years
    Reporting group description
    Subjects aged 2-<6 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 240 mcg /kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

    Reporting group title
    Stage 1: Plerixafor 320 mcg /kg: 2-<6 years
    Reporting group description
    Subjects aged 2-<6 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 320 mcg /kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

    Reporting group title
    Stage 1: Plerixafor 160 mcg /kg: 6-<12 years
    Reporting group description
    Subjects aged 6-<12 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 160 mcg /kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

    Reporting group title
    Stage 1: Plerixafor 240 mcg /kg: 6-<12 years
    Reporting group description
    Subjects aged 6-<12 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 240 mcg /kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

    Reporting group title
    Stage 1: Plerixafor 320 mcg /kg: 6-<12 years
    Reporting group description
    Subjects aged 6-<12 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 320 mcg/kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

    Reporting group title
    Stage 1: Plerixafor 160 mcg /kg: 12-<18 years
    Reporting group description
    Subjects aged 12-<18 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 160 mcg/kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

    Reporting group title
    Stage 1: Plerixafor 240 mcg/kg: 12-<18 years
    Reporting group description
    Subjects aged 12-<18 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 240 mcg/kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

    Reporting group title
    Stage 1: Plerixafor 320 mcg/kg: 12-<18 years
    Reporting group description
    Subjects aged 12-<18 years started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 320 mcg/kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

    Reporting group title
    Stage 2: Standard Mobilization Regimen- G-CSF
    Reporting group description
    Subjects started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Treatment G-CSF (alone or in combination with chemotherapy) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

    Reporting group title
    Stage 2: Plerixafor + Standard Mobilization Regimen -G-CSF
    Reporting group description
    Subjects started with standard mobilization with G-CSF 10 mcg/kg/day in the morning, alone or in combination with chemotherapy. Once a “trigger point” of 7 CD34+ cells/mcL in peripheral blood was reached treatment with plerixafor was initiated. Plerixafor 240 mcg/kg was administered in the evening and the daily dose of G-CSF (as part of the standard mobilization regimen) the following morning approximately 1 hour before each apheresis. Treatment (plerixafor and G-CSF) was continued until a minimum of 2*10^6 CD34+ cells/kg were collected or for up to a maximum of 5 aphereses.

    Serious adverse events
    Stage 1: Plerixafor 160 mcg /kg: 2-<6 years Stage 1: Plerixafor 240 mcg /kg: 2-<6 years Stage 1: Plerixafor 320 mcg /kg: 2-<6 years Stage 1: Plerixafor 160 mcg /kg: 6-<12 years Stage 1: Plerixafor 240 mcg /kg: 6-<12 years Stage 1: Plerixafor 320 mcg /kg: 6-<12 years Stage 1: Plerixafor 160 mcg /kg: 12-<18 years Stage 1: Plerixafor 240 mcg/kg: 12-<18 years Stage 1: Plerixafor 320 mcg/kg: 12-<18 years Stage 2: Standard Mobilization Regimen- G-CSF Stage 2: Plerixafor + Standard Mobilization Regimen -G-CSF
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 3 (66.67%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    2 / 3 (66.67%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    9 / 30 (30.00%)
    4 / 15 (26.67%)
         number of deaths (all causes)
    0
    0
    0
    1
    0
    1
    0
    1
    1
    3
    3
         number of deaths resulting from adverse events
    Injury, poisoning and procedural complications
    Blood Stem Cell Harvest Failure
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 30 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Surgical and medical procedures
    Bone Marrow Harvest
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 30 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pulmonary Embolism
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 30 (0.00%)
    1 / 15 (6.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Bone Marrow Failure
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 30 (3.33%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Febrile Neutropenia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 3 (66.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    3 / 30 (10.00%)
    2 / 15 (13.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Leukopenia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 30 (0.00%)
    1 / 15 (6.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 30 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 30 (6.67%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Hydrocephalus
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 30 (3.33%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 30 (6.67%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 30 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal Inflammation
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 30 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Stomatitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 30 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 30 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 30 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Abdominal Infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 30 (0.00%)
    1 / 15 (6.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enterobacter Bacteraemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 30 (0.00%)
    1 / 15 (6.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    Stage 1: Plerixafor 160 mcg /kg: 2-<6 years Stage 1: Plerixafor 240 mcg /kg: 2-<6 years Stage 1: Plerixafor 320 mcg /kg: 2-<6 years Stage 1: Plerixafor 160 mcg /kg: 6-<12 years Stage 1: Plerixafor 240 mcg /kg: 6-<12 years Stage 1: Plerixafor 320 mcg /kg: 6-<12 years Stage 1: Plerixafor 160 mcg /kg: 12-<18 years Stage 1: Plerixafor 240 mcg/kg: 12-<18 years Stage 1: Plerixafor 320 mcg/kg: 12-<18 years Stage 2: Standard Mobilization Regimen- G-CSF Stage 2: Plerixafor + Standard Mobilization Regimen -G-CSF
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    2 / 3 (66.67%)
    1 / 3 (33.33%)
    2 / 3 (66.67%)
    3 / 3 (100.00%)
    2 / 3 (66.67%)
    2 / 3 (66.67%)
    3 / 3 (100.00%)
    1 / 3 (33.33%)
    1 / 3 (33.33%)
    20 / 30 (66.67%)
    10 / 15 (66.67%)
    Vascular disorders
    Hyperaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 30 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Hypertension
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 30 (3.33%)
    0 / 15 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Hypotension
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 30 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Immune system disorders
    Drug Hypersensitivity
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 30 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    General disorders and administration site conditions
    Catheter Site Pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 30 (3.33%)
    0 / 15 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Chest Pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 30 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Extravasation
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 30 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Fatigue
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 30 (0.00%)
    3 / 15 (20.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    4
    Injection Site Reaction
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 30 (6.67%)
    0 / 15 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    2
    0
    Malaise
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 30 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Mucosal Inflammation
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 30 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Pyrexia
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 30 (3.33%)
    1 / 15 (6.67%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    1
    0
    0
    1
    1
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 30 (3.33%)
    0 / 15 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Injury, poisoning and procedural complications
    Allergic Transfusion Reaction
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 30 (3.33%)
    0 / 15 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Back Injury
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 30 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Brain Contusion
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 30 (3.33%)
    0 / 15 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Infusion Related Reaction
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 30 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Procedural Pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 30 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Thermal Burn
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 30 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Investigations
    Alanine Aminotransferase Increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 30 (6.67%)
    2 / 15 (13.33%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    2
    2
    Antithrombin Iii Decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 30 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Aspartate Aminotransferase Increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 30 (6.67%)
    1 / 15 (6.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    2
    1
    Blood Bicarbonate Increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 30 (3.33%)
    0 / 15 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Echocardiogram Abnormal
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 30 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Platelet Count Decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    6 / 30 (20.00%)
    2 / 15 (13.33%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    6
    2
    Weight Decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 30 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Cardiac disorders
    Tachycardia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 30 (3.33%)
    0 / 15 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 30 (6.67%)
    1 / 15 (6.67%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    2
    1
    Increased Viscosity Of Upper Respiratory Secretion
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 30 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Rhinorrhoea
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 30 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    9 / 30 (30.00%)
    3 / 15 (20.00%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    0
    0
    1
    9
    3
    Febrile Neutropenia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 30 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Hypofibrinogenaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 30 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Leukopenia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 30 (3.33%)
    0 / 15 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Neutropenia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 30 (3.33%)
    1 / 15 (6.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    1
    Thrombocytopenia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 30 (3.33%)
    1 / 15 (6.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    3
    1
    Nervous system disorders
    Headache
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    2 / 30 (6.67%)
    0 / 15 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    0
    3
    2
    0
    Intracranial Venous Sinus Thrombosis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 30 (3.33%)
    0 / 15 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Seizure
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 30 (3.33%)
    0 / 15 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Eye disorders
    Optic Atrophy
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 30 (3.33%)
    0 / 15 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Pupils Unequal
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 30 (3.33%)
    0 / 15 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Vision Blurred
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 30 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Ear and labyrinth disorders
    Deafness
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 30 (3.33%)
    0 / 15 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Gastrointestinal disorders
    Abdominal Distension
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 30 (3.33%)
    0 / 15 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Abdominal Pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    3 / 30 (10.00%)
    0 / 15 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    3
    0
    Abdominal Pain Upper
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 30 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    1
    Constipation
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 30 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    Dental Caries
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 30 (3.33%)
    1 / 15 (6.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    1
    Diarrhoea
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 3 (66.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    3 / 30 (10.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    3
    0
    0
    4
    1
    Dyspepsia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 30 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Lip Dry
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 30 (3.33%)
    0 / 15 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Nausea
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    1 / 3 (33.33%)
    2 / 30 (6.67%)
    3 / 15 (20.00%)
         occurrences all number
    0
    0
    0
    1
    1
    0
    0
    1
    1
    3
    4
    Proctalgia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 30 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Stomatitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 30 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    1
    Vomiting
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    1 / 3 (33.33%)
    1 / 3 (33.33%)
    2 / 3 (66.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    3 / 30 (10.00%)
    2 / 15 (13.33%)
         occurrences all number
    0
    0
    0
    1
    1
    1
    2
    0
    0
    3
    3
    Renal and urinary disorders
    Dysuria
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 30 (3.33%)
    0 / 15 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 30 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Rash Papular
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 30 (3.33%)
    0 / 15 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Urticaria
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 30 (3.33%)
    0 / 15 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Musculoskeletal and connective tissue disorders
    Back Pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 30 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Pain In Extremity
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 30 (3.33%)
    0 / 15 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    1
    0
    Endocrine disorders
    Cushingoid
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 30 (3.33%)
    0 / 15 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Metabolism and nutrition disorders
    Decreased Appetite
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 30 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Hyperglycaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 30 (3.33%)
    1 / 15 (6.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    1
    Hypoalbuminaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    3 / 30 (10.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    3
    1
    Hypocalcaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 30 (6.67%)
    1 / 15 (6.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    2
    1
    Hypokalaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 30 (3.33%)
    2 / 15 (13.33%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    2
    2
    Hypomagnesaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 30 (3.33%)
    0 / 15 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Hyponatraemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 30 (3.33%)
    0 / 15 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Hypophosphataemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 30 (3.33%)
    1 / 15 (6.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    1
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 30 (3.33%)
    0 / 15 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Conjunctivitis Viral
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 30 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Device Related Infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 30 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Enterobacter Infection
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 30 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Escherichia Urinary Tract Infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 30 (3.33%)
    0 / 15 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Febrile Infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 30 (3.33%)
    0 / 15 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Otitis Media
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 30 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Rhinitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    3 / 30 (10.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    3
    1
    Staphylococcal Infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 30 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Viral Upper Respiratory Tract Infection
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 30 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    04 Nov 2013
    Following amendments were made: - Dose from phase I (stage 1 of the study) was incorporated for phase II use (stage 2). - Sub-grouping for stratification was changed based on information from stage 1 population recruited: Ewing’s and other STS; Lymphoma; Neuroblastoma; Other malignancies including brain tumours. - The age range for the study was modified to 1 to <18 years to allow potential inclusion of 1 to 2 year olds if feasible (no minimal number of 1-2 y old subjects required), as requested by the Paediatrics Development Committee of the EMA (PIP). - Modifications arising from discussions with the DMC and the Investigators following Stage 1 were incorporated, such as: • Timing of G CSF administration • Limited PK sampling timing • Selected Lab Value minimums for ANC and platelets. - Administrative details were updated from original Genzyme protocol to Sanofi standards and procedures (study management transferred to Sanofi).

    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
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