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    Clinical Trial Results:
    Randomized Phase III Study of Intensive Chemotherapy with or without Dasatinib (Sprycel™) in Adult Patients with Newly Diagnosed Core-Binding Factor Acute Myeloid Leukemia (CBF-AML) AMLSG 21-13

    Summary
    EudraCT number
    		 2013-003117-18
    Trial protocol
    		 DE   AT  
    Global end of trial date
    19 Feb 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    21 Feb 2025
    First version publication date
    21 Feb 2025
    Other versions
    Summary report(s)
    		 AMLSG 21-13_Final report

    Trial information

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    Trial identification
    Sponsor protocol code
    AMLSG21-13
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02013648
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Universitätsklinikum Ulm
    Sponsor organisation address
    Albert-Einstein-Allee 29, Ulm, Germany, 89081
    Public contact
    AMLSG Studienzentrale, Universitätsklinikum Ulm, +49 731500 45715, aml.sekretariat@uniklinik-ulm.de
    Scientific contact
    AMLSG Studienzentrale, Universitätsklinikum Ulm, +49 731500 45715, aml.sekretariat@uniklinik-ulm.de
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    07 Nov 2024
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    19 Feb 2024
    Global end of trial reached?
    Yes
    Global end of trial date
    19 Feb 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Primary Efficacy Objective • To assess event-free survival (EFS) after intensive induction (daunorubicin and cytarabine) and consolidation (high-dose cytarabine) chemotherapy with or without dasatinib in patients with CBF-AML Secondary Objectives • To assess the interaction between type of CBF-AML [t(8;21) 3versus inv(16)] and randomization accordingly on all survival endpoints • To assess cumulative incidence of relapse (CIR) and death (CID) • To assess relapse-free (RFS) and overall survival (OS) • To assess outcome according to KIT mutational status • To assess pharmacodynamic inhibition of KIT • To assess toxicity
    Protection of trial subjects
    In this study, safety was assessed by evaluating the following: reported adverse events, clinical laboratory test results, vital signs measurements, ECG findings, chest X-ray, echo scan, physical examination findings, monitoring of concomitant therapy. For each safety parameter, all findings (whether normal or abnormal) were recorded in the eCRF.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    29 Aug 2014
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Austria: 30
    Country: Number of subjects enrolled
    Germany: 174
    Worldwide total number of subjects
    204
    EEA total number of subjects
    204
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    176
    From 65 to 84 years
    28
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 First patient in: 29.08.2014 Last patient last visit: 19.02.2024 Recruitment was not interrupted during the study.

    Pre-assignment
    Screening details
    		 Molecular genetic analysis (central AMLSG reference lab) of blood and bone marrow was performed at baseline within 48 hours to make an enrollment possible.

    Pre-assignment period milestones
    Number of subjects started
    		 204
    Number of subjects completed
    		 202

    Pre-assignment subject non-completion reasons
    Reason: Number of subjects
    		 Consent withdrawn by subject: 2
    Period 1
    Period 1 title
    Overall trial period (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Arm A: Standard
    Arm description
    		 -
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Cytarabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    In the first induction cycle, cytarabine was administered by continuous intravenous infusion in a dose of 200 mg/m2 from day 1 to day 7. In the (optional) second induction cycle, cytarabine was administered by intravenous infusion in a dose of 200mg/m2 from day 1 to day 5. In all consolidation cycles, cytarabine was administered by intravenous infusion in a dose of 3 g/m2 twice a day on days 1, 2 and 3. For patients > 60 years of age, dose of cytarabine was reduced to 1 g/m2.

    Investigational medicinal product name
    Daunorubicin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    In the first induction cycle, daunorubicin was administered by in a dose of 60 mg/m2 on days 1, 2 and 3. In an optional second induction cycle, daunorubicin was administered in a dose of 50 mg/m2 on days 1,2 and 3.

    Arm title
    		 Arm B: Dasatinib
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    Cytarabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    In the first induction cycle, cytarabine was administered by continuous intravenous infusion in a dose of 200 mg/m2 from day 1 to day 7. In the (optional) second induction cycle, cytarabine was administered by intravenous infusion in a dose of 200mg/m2 from day 1 to day 5. In all consolidation cycles, cytarabine was administered by intravenous infusion in a dose of 3 g/m2 twice a day on days 1, 2 and 3. For patients > 60 years of age, dose of cytarabine was reduced to 1 g/m2.

    Investigational medicinal product name
    Daunorubicin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    In the first induction cycle, daunorubicin was administered by in a dose of 60 mg/m2 on days 1, 2 and 3. In an optional second induction cycle, daunorubicin was administered in a dose of 50 mg/m2 on days 1,2 and 3.

    Investigational medicinal product name
    Dasatinib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Dasatinib was administered in a dose of 100 mg daily on days 8 to 21 in the first induction cycle and on days 6 to 21 in the second induction cycle. In the consolidation cycles, 100 mg dasatinib was administered on days 4 to 28. After consolidation therapy, patients received one year of dasatinib maintenance therapy (100 mg per day).

    Number of subjects in period 1 [1]
    		Arm A: Standard Arm B: Dasatinib
    Started
    102
    100
    Completed
    74
    27
    Not completed
    28
    73
         Adverse event, serious fatal
    5
    5
         Consent withdrawn by subject
    9
    15
         Adverse event, non-fatal
    4
    27
         Other reasons
    5
    10
         Lack of efficacy
    4
    15
         Protocol deviation
    1
    1
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: N=204 patients were enrolled overall into the trial. Two patients were excluded due to violation of inclusion/exclusion criteria (invalid informed consent) and therefore were not included into the Intention-to-treat population which represents the baseline population.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Arm A: Standard
    Reporting group description
    		 -

    Reporting group title
    Arm B: Dasatinib
    Reporting group description
    		 -

    Reporting group values
    		 Arm A: Standard Arm B: Dasatinib Total
    Number of subjects
    		 102 100 202
    Age categorical
    Units: Subjects
        18-60 years
    		 82 78 160
        >60 years
    		 20 22 42
    Age continuous
    Units: years
        median (full range (min-max))
    		 48.9 (18.3 to 75.7) 49.7 (18.2 to 77.0) -
    Gender categorical
    Units: Subjects
        Female
    		 51 56 107
        Male
    		 51 44 95
    CBF Type
    Units: Subjects
        inv(16)
    		 53 55 108
        t(8;21)
    		 49 45 94
    Type of AML
    Units: Subjects
        deNovo AML
    		 95 84 179
        secondary AML
    		 1 3 4
        therapy-related AML
    		 5 12 17
        Not recorded
    		 1 1 2
    KIT mutation status
    Units: Subjects
        Mutation
    		 32 26 58
        Wildtype
    		 70 74 144
    FLT3-ITD mutation status
    Units: Subjects
        Positive
    		 4 1 5
        Negative
    		 98 99 197
    FLT3-TKD mutation status
    Units: Subjects
        Positive
    		 10 11 21
        Negative
    		 92 89 181
    ECOG Performance Status
    Units: Subjects
        ECOG 0
    		 50 61 111
        ECOG 1
    		 40 33 73
        ECOG 2
    		 7 5 12
        Not recorded
    		 5 1 6
    White blood cell count (diagnosis)
    Units: Giga/l
        median (full range (min-max))
    		 12.5 (0.5 to 177) 9.72 (0.31 to 205) -
    Hemoglobin
    Units: g/dl
        median (full range (min-max))
    		 8.8 (3.6 to 14.0) 9.1 (4.2 to 15.4) -
    Platelet count
    Units: Giga/l
        median (full range (min-max))
    		 36 (5 to 247) 40 (6 to 230) -
    LDH
    Units: U/l
        median (full range (min-max))
    		 503 (133 to 2610) 416 (5 to 2940) -
    Bone marrow blasts
    Units: Percentage
        median (full range (min-max))
    		 53 (5 to 95) 60 (5 to 100) -
    Peripheral blood blasts
    Units: Percentage
        median (full range (min-max))
    		 33 (0 to 82) 31.5 (0 to 90) -
    Height
    Units: cm
        median (full range (min-max))
    		 171 (152 to 203) 173 (152 to 193) -
    Weigth
    Units: kg
        median (full range (min-max))
    		 82 (47 to 138) 77 (50 to 147) -

    End points

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    End points reporting groups
    Reporting group title
    Arm A: Standard
    Reporting group description
    		 -

    Reporting group title
    Arm B: Dasatinib
    Reporting group description
    		 -

    Subject analysis set title
    ITT population
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    All randomized patients with a valid informed consent. Not included in ITT were patients who withdraw informed consent before start of treatment. Patients in this population were analysed according to the treatment arm assigned at randomization.

    Subject analysis set title
    Safety population
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Safety population included all patients of the ITT population who received at least one dose or part of a dose of one of the study medications (Daunorubicin, Idarubicin, Cytarabine, Dasatinib) during the treatment phase.

    Primary: Event-free Survival

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    End point title
    		 Event-free Survival
    End point description
    The primary endpoint of the study was event-free survival; an event was defined as one of the following: • Refractory disease, defined as failure to achieve at least a PR after the first induction cycle and CR or CRi after an optional second induction cycle • Death by any cause • Hematologic Relapse • Molecular persistence • Molecular relapse.
    End point type
    Primary
    End point timeframe
    after 48 months
    End point values
    		 Arm A: Standard Arm B: Dasatinib ITT population
    Number of subjects analysed
    102
    100
    202
    Units: %
        number (confidence interval 95%)
    41 (32 to 52)
    44 (35 to 56)
    42 (36 to 50)
    Attachments
    		 Event-free survival_overall
    Event-free survival_ according treatment
    EFS_according KIT mutation status
    Statistical analysis title
    		 Primary analysis Event-free survival (univariate)
    Statistical analysis description
    The EFS is formally compared between treatment arms using the stratified logrank test with strata of patient age at registration (≤ 60 years vs >60 years) and CBF-AML type (t(8;21) vs inv(16)).
    Comparison groups
    Arm B: Dasatinib v Arm A: Standard
    Number of subjects included in analysis
    202
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.66
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.92
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.63
         upper limit
    		 1.33
    Statistical analysis title
    		 Event-free survival (multivariate)
    Comparison groups
    Arm A: Standard v Arm B: Dasatinib
    Number of subjects included in analysis
    202
    Analysis specification
    Pre-specified
    Analysis type
    		 other [1]
    P-value
    		 = 0.995 [2]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.67
         upper limit
    		 1.48
    Notes
    [1] - Multivariable analysis adjusted for the following potential prognostic covariates: • Age, Sex • Eastern Cooperative Oncology Group (ECOG) status (0-1 vs. 2+) • WBC (log-10 transformed) • KIT mutation status • FLT3 mutation status • AML Type (de novo vs.secondary/therapy-related) • CBF type (inv(16) vs. t(8;21)) • Minimal residual disease status (MRD at low level/negative vs. positive as time-dependent covariate)
    [2] - No significant treatment effect, but negative prognostic effects for higher white blood cell count (HR for log10 increase 2.01; p<.001), KIT status (HR 1.96; p=0.002) and in trend for MRD positivity (HR 1.66; p=0.052).
    Statistical analysis title
    		 Subgroup analysis: KIT mutation
    Comparison groups
    Arm A: Standard v Arm B: Dasatinib
    Number of subjects included in analysis
    202
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.77
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.91
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.47
         upper limit
    		 1.73
    Statistical analysis title
    		 Subgroup analysis: KIT wildtype
    Comparison groups
    Arm B: Dasatinib v Arm A: Standard
    Number of subjects included in analysis
    202
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.99
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.63
         upper limit
    		 1.59
    Statistical analysis title
    		 Analysis of interaction effect on EFS
    Comparison groups
    Arm B: Dasatinib v Arm A: Standard
    Number of subjects included in analysis
    202
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [3]
    P-value
    		 = 0.322
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.68
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.31
         upper limit
    		 1.47
    Notes
    [3] - Interaction effect between treatment arm and CBF-AML type

    Secondary: Overall survival (OS)

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    End point title
    		 Overall survival (OS)
    End point description
    Overall survival (OS), defined as the time from the date of randomization to the date of death due to any cause. For patients who were still alive and patients who were lost to follow up, OS was censored at the date they were last known to be alive (latest at the end of study).
    End point type
    Secondary
    End point timeframe
    48 months
    End point values
    		 Arm A: Standard Arm B: Dasatinib ITT population
    Number of subjects analysed
    102
    100
    202
    Units: %
        number (confidence interval 95%)
    76 (68 to 85)
    78 (70 to 87)
    77 (71 to 83)
    Attachments
    		 Overall survival_overall
    Overall survival_according treatment
    Overall survival_KIT status
    Statistical analysis title
    		 Overall survival (univariate)
    Comparison groups
    Arm B: Dasatinib v Arm A: Standard
    Number of subjects included in analysis
    202
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.79
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.93
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.53
         upper limit
    		 1.63
    Statistical analysis title
    		 Overall survival (multivariate)
    Comparison groups
    Arm A: Standard v Arm B: Dasatinib
    Number of subjects included in analysis
    202
    Analysis specification
    Pre-specified
    Analysis type
    		 other [4]
    P-value
    		 = 0.887
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.96
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.51
         upper limit
    		 1.79
    Notes
    [4] - Multivariable analysis models were adjusted for the following potential prognostic covariates: • Age, Sex • Eastern Cooperative Oncology Group (ECOG) status (0-1 vs. 2+) • WBC (log-10 transformed) • KIT mutation status • FLT3 mutation status • AML Type (de novo vs.secondary/therapy-related) • CBF type (inv(16) vs. t(8;21)) • Minimal residual disease status (MRD at low level/negative vs. positive as time-dependent covariate)
    Statistical analysis title
    		 Subgroup analysis: KIT mutation
    Comparison groups
    Arm A: Standard v Arm B: Dasatinib
    Number of subjects included in analysis
    202
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.39
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.64
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.24
         upper limit
    		 1.75
    Statistical analysis title
    		 Subgroup analysis: KIT wildtype
    Comparison groups
    Arm B: Dasatinib v Arm A: Standard
    Number of subjects included in analysis
    202
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.77
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.55
         upper limit
    		 2.27
    Statistical analysis title
    		 Interaction analysis OS
    Statistical analysis description
    Interaction effect between treatment arm and CBF-AML type
    Comparison groups
    Arm B: Dasatinib v Arm A: Standard
    Number of subjects included in analysis
    202
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.383
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.59
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.18
         upper limit
    		 1.97

    Secondary: Relapse-free survival (RFS)

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    End point title
    		 Relapse-free survival (RFS)
    End point description
    Relapse-free survival (RFS) was defined as the time from first CR/CRi until hematologic/ molecular relapse or molecular persistence or death, whichever comes first.
    End point type
    Secondary
    End point timeframe
    48 months
    End point values
    		 Arm A: Standard Arm B: Dasatinib ITT population
    Number of subjects analysed
    98
    91
    189
    Units: %
        number (confidence interval 95%)
    42 (33 to 54)
    49 (39 to 61)
    45 (39 to 53)
    Attachments
    		 Relapse-free survival _overall
    Relapse-free survival_according treatment
    RFS_according KIT mutation status
    Statistical analysis title
    		 Relapse-free survival (univariate)
    Comparison groups
    Arm B: Dasatinib v Arm A: Standard
    Number of subjects included in analysis
    189
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.31
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.82
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.55
         upper limit
    		 1.21
    Statistical analysis title
    		 Relapse-free survival (multivariate)
    Comparison groups
    Arm B: Dasatinib v Arm A: Standard
    Number of subjects included in analysis
    189
    Analysis specification
    Pre-specified
    Analysis type
    		 other [5]
    P-value
    		 = 0.494 [6]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.86
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.57
         upper limit
    		 1.32
    Notes
    [5] - Multivariable analysis models were adjusted for the following potential prog- nostic covariates: • Age, Sex • Eastern Cooperative Oncology Group (ECOG) status (0-1 vs. 2+) • WBC (log-10 transformed) • KIT mutation status • FLT3 mutation status • AML Type (de novo vs.secondary/therapy-related) • CBF type (inv(16) vs. t(8;21)) • Minimal residual disease status (MRD at low level/negative vs. positive as time-dependent covariate)
    [6] - No signifcant treatment effect, but negative effect on EFS for higher white blood cell count (HR for log10 increase 2.21; p<.001), KIT status (HR 2.15; p<.001) and presence of CBF-AML type t(8;21) (HR 1.58; p=0.048).
    Statistical analysis title
    		 Interaction analysis RFS
    Comparison groups
    Arm A: Standard v Arm B: Dasatinib
    Number of subjects included in analysis
    189
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.264
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.62
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.27
         upper limit
    		 1.44
    Statistical analysis title
    		 Subgroup analysis: KIT mutation
    Comparison groups
    Arm A: Standard v Arm B: Dasatinib
    Number of subjects included in analysis
    189
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.59
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.83
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.42
         upper limit
    		 1.63
    Statistical analysis title
    		 Subgroup analysis: KIT wildtype
    Comparison groups
    Arm A: Standard v Arm B: Dasatinib
    Number of subjects included in analysis
    189
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.64
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.89
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.42
         upper limit
    		 1.63

    Secondary: Cumulative incidence of relapse (CIR)

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    End point title
    		 Cumulative incidence of relapse (CIR)
    End point description
    The analyses of CIR and CID are restricted to patients in the ITT population who achieved CR/CRi. CIR and CID are analysed using a competing risks model for time to relapse (TTR) and non- relapse mortality (NRM). TTR is defined as the time from first CR/CRi to until hematologic/ molecular relapse or molecular persistence. Deaths in remission are considered as a competing event. NRM is defined as the time from achievement of a remission (CR/CRi) to death without prior re- lapse or molecular persistence. Relapse or molecular persistence after achieving CR/CRi are considered as a competing event. Patients who are not known to have relapsed, being molecularly persistent or died are censored at the date of last clinical response assessment for both endpoints.
    End point type
    Secondary
    End point timeframe
    48 months
    End point values
    		 Arm A: Standard Arm B: Dasatinib ITT population
    Number of subjects analysed
    98
    91
    189
    Units: %
        number (confidence interval 95%)
    52 (42 to 62)
    47 (36 to 57)
    50 (42 to 57)
    Attachments
    		 CIR_CID_overall
    CIR_CID_according treatment
    Statistical analysis title
    		 Cumulative incidence of relapse (univariate)
    Comparison groups
    Arm B: Dasatinib v Arm A: Standard
    Number of subjects included in analysis
    189
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.37
    Method
    		 Gray's test
    Confidence interval

    Secondary: Cumulative incidence of death in CR/CRi (CID)

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    End point title
    		 Cumulative incidence of death in CR/CRi (CID)
    End point description
    The analyses of CIR and CID are restricted to patients in the ITT population who achieved CR/CRi. CIR and CID are analysed using a competing risks model for time to relapse (TTR) and non- relapse mortality (NRM). TTR is defined as the time from first CR/CRi to until hematologic/ molecular relapse or molecular persistence. Deaths in remission are considered as a competing event. NRM is defined as the time from achievement of a remission (CR/CRi) to death without prior re- lapse or molecular persistence. Relapse or molecular persistence after achieving CR/CRi are considered as a competing event. Patients who are not known to have relapsed, being molecularly persistent or died are censored at the date of last clinical response assessment for both endpoints.
    End point type
    Secondary
    End point timeframe
    48 months
    End point values
    		 Arm A: Standard Arm B: Dasatinib ITT population
    Number of subjects analysed
    98
    91
    189
    Units: %
        number (confidence interval 95%)
    5 (1 to 10)
    5 (0 to 9)
    5 (2 to 8)
    Attachments
    		 CIR_CID_overall
    CIR_CID_according treatment
    Statistical analysis title
    		 Cumulative incidence of death (univariate)
    Comparison groups
    Arm B: Dasatinib v Arm A: Standard
    Number of subjects included in analysis
    189
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.96
    Method
    		 Gray's test
    Confidence interval

    Secondary: Hematological recovery induction cycle 1

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    End point title
    		 Hematological recovery induction cycle 1
    End point description
    Arm A: Standard Arm B: Dasatinib N = 107 N = 93 Component Time [days] Rate 95%-CI Rate 95%-CI ANC recovery (≥0.5 G/l) 28 0.61 (0.51, 0.70) 0.57 (0.46, 0.67) ANC recovery (≥1.5 G/l) 28 0.39 (0.29, 0.48) 0.36 (0.26, 0.47) WBC recover (≥1.0 G/l) 28 0.83 (0.74, 0.89) 0.79 (0.69, 0.87) Platelet recovery (≥50 G/l) 28 0.87 (0.79, 0.92) 0.78 (0.68, 0.85) Platelet recovery (≥100 G/l)28 0.79 (0.70, 0.86) 0.68 (0.57, 0.77)
    End point type
    Secondary
    End point timeframe
    Induction cycle 1
    End point values
    		 Safety population
    Number of subjects analysed
    200
    Units: recovery rate
        number (confidence interval 95%)
    0 (0 to 0)
    Attachments
    		 Hem recovery_induction1
    No statistical analyses for this end point

    Secondary: Hematological recovery induction cycle 2

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    End point title
    		 Hematological recovery induction cycle 2
    End point description
    Arm A: Standard Arm B: Dasatinib N = 17 N = 12 Component Time [days] Rate 95%-CI Rate 95%-CI ANC recovery (≥0.5 G/l) 28 0.74 (0.45, 0.89) 0.63 (0.29, 0.84) ANC recovery (≥1.5 G/l) 28 0.49 (0.24, 0.70) 0.39 (0.12, 0.66) WBC recover (≥1.0 G/l) 28 0.88 (0.61, 0.97) 0.92 (0.54, 0.99) Platelet recovery (≥50 G/l) 28 0.88 (0.59, 0.97) 0.92 (0.54, 0.99) Platelet recovery (≥100 G/l) 28 0.79 (0.49, 0.92) 0.92 (0.54, 0.99)
    End point type
    Secondary
    End point timeframe
    Induction cycle 2
    End point values
    		 Safety population
    Number of subjects analysed
    29
    Units: rate
        number (confidence interval 95%)
    0 (0 to 0)
    Attachments
    		 Hem recovery_induction2
    No statistical analyses for this end point

    Secondary: Hematological recovery consolidation cycle 1

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    End point title
    		 Hematological recovery consolidation cycle 1
    End point description
    Arm A: Standard Arm B: Dasatinib N = 96 N = 77 Component Time [days] Rate 95%-CI Rate 95%-CI ANC recovery (≥0.5 G/l) 28 0.80 (0.70, 0.87) 0.83 (0.71, 0.90) ANC recovery (≥1.5 G/l) 28 0.66 (0.55, 0.75) 0.65 (0.52, 0.75) WBC recovery (≥1.0 G/l) 28 0.94 (0.86, 0.97) 0.97 (0.90, 0.99) Platelet recovery (≥50 G/l) 28 0.79 (0.69, 0.86) 0.89 (0.78, 0.94) Platelet recovery (≥100 G/l) 28 0.60 (0.49, 0.69) 0.75 (0.63, 0.84)
    End point type
    Secondary
    End point timeframe
    Consolidation cycle 1
    End point values
    		 Safety population
    Number of subjects analysed
    173
    Units: rate
        number (confidence interval 95%)
    0 (0 to 0)
    Attachments
    		 Hem recovery_consolidation 1
    No statistical analyses for this end point

    Secondary: Hematological recovery consolidation cycle 2

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    End point title
    		 Hematological recovery consolidation cycle 2
    End point description
    Arm A: Standard Arm B: Dasatinib N = 94 N = 71 Component Time [days] Rate 95%-CI Rate 95%-CI ANC recovery (≥0.5 G/l) 28 0.75 (0.64, 0.82) 0.78 (0.66, 0.87) ANC recovery (≥1.5 G/l) 28 0.50 (0.40, 0.60) 0.65 (0.52, 0.75) WBC recovery (≥1.0 G/l) 28 0.88 (0.79, 0.93) 0.97 (0.89, 0.99) Platelet recovery (≥50 G/l) 28 0.59 (0.48, 0.68) 0.79 (0.67, 0.87) Platelet recovery (≥100 G/l) 28 0.43 (0.32, 0.53) 0.55 (0.42, 0.66)
    End point type
    Secondary
    End point timeframe
    Consolidation cycle 2
    End point values
    		 Safety population
    Number of subjects analysed
    165
    Units: %
        number (confidence interval 95%)
    0 (0 to 0)
    Attachments
    		 Hem recovery_consolidation 2
    No statistical analyses for this end point

    Secondary: Hematological recovery consolidation cycle 3

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    End point title
    		 Hematological recovery consolidation cycle 3
    End point description
    Arm A: Standard Arm B: Dasatinib N = 94 N = 64 Component Time [days] Rate 95%-CI Rate 95%-CI ANC recovery (≥0.5 G/l) 28 0.81 (0.72, 0.88) 0.84 (0.72, 0.92) ANC recovery (≥1.5 G/l) 28 0.59 (0.48, 0.68) 0.74 (0.60, 0.84) WBC recovery (≥1.0 G/l) 28 0.93 (0.86, 0.97) 0.98 (0.89, 1.00) Platelet recovery (≥50 G/l) 28 0.64 (0.53, 0.73) 0.60 (0.47, 0.71) Platelet recovery (≥100 G/l) 28 0.42 (0.31, 0.52) 0.40 (0.28, 0.52)
    End point type
    Secondary
    End point timeframe
    Consolidation cycle 3
    End point values
    		 Safety population
    Number of subjects analysed
    158
    Units: rate
        number (confidence interval 95%)
    0 (0 to 0)
    Attachments
    		 Hem recovery_consolidation 3
    No statistical analyses for this end point

    Secondary: Hematological recovery consolidation cycle 4

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    End point title
    		 Hematological recovery consolidation cycle 4
    End point description
    Arm A: Standard Arm B: Dasatinib N = 85 N = 57 Component Time [days] Rate 95%-CI Rate 95%-CI ANC recovery (≥0.5 G/l) 28 0.82 (0.71, 0.89) 0.82 (0.69, 0.90) ANC recovery (≥1.5 G/l) 28 0.56 (0.45, 0.66) 0.61 (0.47, 0.73) WBC recovery (≥1.0 G/l) 28 0.94 (0.86, 0.97) 0.91 (0.80, 0.96) Platelet recovery (≥50 G/l) 28 0.58 (0.47, 0.68) 0.62 (0.47, 0.73) Platelet recovery (≥100 G/l) 28 0.31 (0.21, 0.41) 0.49 (0.35, 0.61)
    End point type
    Secondary
    End point timeframe
    Consolidation cycle 4
    End point values
    		 Safety population
    Number of subjects analysed
    142
    Units: %
        number (confidence interval 95%)
    0 (0 to 0)
    Attachments
    		 hematologic recovery consolidation cycle 4
    No statistical analyses for this end point

    Secondary: Rate of Early / Hypoplastic Death (ED/HD)

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    End point title
    		 Rate of Early / Hypoplastic Death (ED/HD)
    End point description
    End point type
    Secondary
    End point timeframe
    Induction therapy
    End point values
    		 Arm A: Standard Arm B: Dasatinib Safety population
    Number of subjects analysed
    101
    99
    200
    Units: Rate
        number (confidence interval 95%)
    0.02 (0.005 to 0.07)
    0.03 (0.01 to 0.09)
    0.03 (0.01 to 0.06)
    No statistical analyses for this end point

    Secondary: Event-free survival (alternative definition)

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    End point title
    		 Event-free survival (alternative definition)
    End point description
    Event-free survival additionally was analyzed utilizing the following alternative definition of EFS: EFS was calculated as the time from randomization until failure to achieve CR or CRi after induction, death after achieving CR or CRi, or relapse after achieving CR or CRi, whichever comes first. Patients without CR/CRi after induction were considered as events at the date of the assessment confirming no CR/CRi (as opposed to the original definition of EFS, where patients without CR/CRi after induction were considered as having events at day 1 of randomization). Patients still in first CR/CRi and alive or lost to follow-up wer censored at the date of last response evaluation.
    End point type
    Secondary
    End point timeframe
    48 months
    End point values
    		 Arm A: Standard Arm B: Dasatinib ITT population
    Number of subjects analysed
    102
    100
    202
    Units: %
        number (confidence interval 95%)
    57 (48 to 68)
    55 (46 to 66)
    56 (50 to 64)
    Attachments
    		 EFS_alternative definition_overall
    EFS_alternative definition_acc treatment
    Statistical analysis title
    		 EFS alternative definition (univariate)
    Comparison groups
    Arm A: Standard v Arm B: Dasatinib
    Number of subjects included in analysis
    202
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.76
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.07
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.7
         upper limit
    		 1.62

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    The adverse event reporting period began upon signing of informed consent and ended 28 days after the last treatment administration or until all drug-related toxicities were resolved, or until the Investigators assessed AEs as chronic or stable.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    26.1
    Reporting groups
    Reporting group title
    Arm A: Standard
    Reporting group description
    		 -

    Reporting group title
    Arm B: Dasatinib
    Reporting group description
    		 -

    Serious adverse events
    		 Arm A: Standard Arm B: Dasatinib
    Total subjects affected by serious adverse events
         subjects affected / exposed
    36 / 101 (35.64%)
    63 / 99 (63.64%)
         number of deaths (all causes)
    5
    5
         number of deaths resulting from adverse events
    5
    5
    Vascular disorders
    Angiopathy
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral ischaemia
         subjects affected / exposed
    1 / 101 (0.99%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgical and medical procedures
    Surgery
         subjects affected / exposed
    1 / 101 (0.99%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Diarrhoea
         subjects affected / exposed
    0 / 101 (0.00%)
    4 / 99 (4.04%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Administration site reaction
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    2 / 101 (1.98%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 1
         deaths causally related to treatment / all
    1 / 1
    1 / 1
    Pyrexia
         subjects affected / exposed
    2 / 101 (1.98%)
    9 / 99 (9.09%)
         occurrences causally related to treatment / all
    1 / 2
    5 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sudden death
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Immune system disorders
    Allergic reaction to excipient
         subjects affected / exposed
    0 / 101 (0.00%)
    3 / 99 (3.03%)
         occurrences causally related to treatment / all
    0 / 0
    4 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Vaginal haemorrhage
         subjects affected / exposed
    1 / 101 (0.99%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pulmonary oedema
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute respiratory distress syndrome
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Dyspnoea
         subjects affected / exposed
    0 / 101 (0.00%)
    2 / 99 (2.02%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epistaxis
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemothorax
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoxia
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    0 / 101 (0.00%)
    4 / 99 (4.04%)
         occurrences causally related to treatment / all
    0 / 0
    4 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    6 / 101 (5.94%)
    4 / 99 (4.04%)
         occurrences causally related to treatment / all
    3 / 6
    2 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pulmonary hemorrhage
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory disorder
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Depression
         subjects affected / exposed
    0 / 101 (0.00%)
    2 / 99 (2.02%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood bilirubin increased
         subjects affected / exposed
    0 / 101 (0.00%)
    2 / 99 (2.02%)
         occurrences causally related to treatment / all
    0 / 0
    6 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood creatine phosphokinase increased
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigation abnormal
         subjects affected / exposed
    0 / 101 (0.00%)
    3 / 99 (3.03%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutrophil count decreased
         subjects affected / exposed
    0 / 101 (0.00%)
    4 / 99 (4.04%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Platelet count decreased
         subjects affected / exposed
    3 / 101 (2.97%)
    6 / 99 (6.06%)
         occurrences causally related to treatment / all
    4 / 4
    12 / 13
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Troponin T increased
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Weight increased
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    White blood cell count decreased
         subjects affected / exposed
    1 / 101 (0.99%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    0 / 101 (0.00%)
    2 / 99 (2.02%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinus tachycardia
         subjects affected / exposed
    1 / 101 (0.99%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Ataxia
         subjects affected / exposed
    1 / 101 (0.99%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhage intracranial
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Paraesthesia
         subjects affected / exposed
    1 / 101 (0.99%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 101 (0.99%)
    2 / 99 (2.02%)
         occurrences causally related to treatment / all
    2 / 2
    5 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    5 / 101 (4.95%)
    2 / 99 (2.02%)
         occurrences causally related to treatment / all
    5 / 6
    5 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Anal fistula
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Ileus
         subjects affected / exposed
    0 / 101 (0.00%)
    3 / 99 (3.03%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal ischaemia
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Large intestinal haemorrhage
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stomatitis
         subjects affected / exposed
    1 / 101 (0.99%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hepatic failure
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Liver disorder
         subjects affected / exposed
    0 / 101 (0.00%)
    2 / 99 (2.02%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Dermatitis acneiform
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Purpura
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rash maculo-papular
         subjects affected / exposed
    0 / 101 (0.00%)
    2 / 99 (2.02%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal disorder
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    Adrenal insufficiency
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthritis
         subjects affected / exposed
    1 / 101 (0.99%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Abdominal infection
         subjects affected / exposed
    1 / 101 (0.99%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anorectal infection
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    2 / 101 (1.98%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device related infection
         subjects affected / exposed
    1 / 101 (0.99%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterocolitis infectious
         subjects affected / exposed
    1 / 101 (0.99%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    2 / 101 (1.98%)
    6 / 99 (6.06%)
         occurrences causally related to treatment / all
    4 / 4
    3 / 8
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Pleural infection
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    4 / 101 (3.96%)
    13 / 99 (13.13%)
         occurrences causally related to treatment / all
    2 / 4
    8 / 14
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Rhinitis
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    10 / 101 (9.90%)
    5 / 99 (5.05%)
         occurrences causally related to treatment / all
    6 / 11
    5 / 5
         deaths causally related to treatment / all
    1 / 3
    0 / 0
    Skin infection
         subjects affected / exposed
    2 / 101 (1.98%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Soft tissue infection
         subjects affected / exposed
    1 / 101 (0.99%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tooth infection
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 101 (0.99%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hyperglycaemia
         subjects affected / exposed
    1 / 101 (0.99%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tumour lysis syndrome
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Arm A: Standard Arm B: Dasatinib
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    100 / 101 (99.01%)
    99 / 99 (100.00%)
    Vascular disorders
    Embolism
         subjects affected / exposed
    6 / 101 (5.94%)
    3 / 99 (3.03%)
         occurrences all number
    8
    9
    Haematoma
         subjects affected / exposed
    13 / 101 (12.87%)
    6 / 99 (6.06%)
         occurrences all number
    22
    12
    Hypertension
         subjects affected / exposed
    12 / 101 (11.88%)
    18 / 99 (18.18%)
         occurrences all number
    24
    51
    Hypotension
         subjects affected / exposed
    19 / 101 (18.81%)
    21 / 99 (21.21%)
         occurrences all number
    24
    28
    General disorders and administration site conditions
    Administration site reaction
         subjects affected / exposed
    7 / 101 (6.93%)
    10 / 99 (10.10%)
         occurrences all number
    16
    15
    Chills
         subjects affected / exposed
    13 / 101 (12.87%)
    12 / 99 (12.12%)
         occurrences all number
    15
    26
    Fatigue
         subjects affected / exposed
    29 / 101 (28.71%)
    35 / 99 (35.35%)
         occurrences all number
    54
    100
    General disorder
         subjects affected / exposed
    7 / 101 (6.93%)
    9 / 99 (9.09%)
         occurrences all number
    15
    13
    Influenza like illness
         subjects affected / exposed
    1 / 101 (0.99%)
    6 / 99 (6.06%)
         occurrences all number
    1
    9
    Injection site reaction
         subjects affected / exposed
    15 / 101 (14.85%)
    8 / 99 (8.08%)
         occurrences all number
    31
    12
    Pain
         subjects affected / exposed
    51 / 101 (50.50%)
    43 / 99 (43.43%)
         occurrences all number
    122
    87
    Pyrexia
         subjects affected / exposed
    67 / 101 (66.34%)
    64 / 99 (64.65%)
         occurrences all number
    171
    201
    Immune system disorders
    Allergic reaction to excipient
         subjects affected / exposed
    17 / 101 (16.83%)
    15 / 99 (15.15%)
         occurrences all number
    30
    17
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    23 / 101 (22.77%)
    27 / 99 (27.27%)
         occurrences all number
    39
    44
    Dyspnoea
         subjects affected / exposed
    16 / 101 (15.84%)
    20 / 99 (20.20%)
         occurrences all number
    22
    33
    Epistaxis
         subjects affected / exposed
    24 / 101 (23.76%)
    18 / 99 (18.18%)
         occurrences all number
    37
    24
    Oropharyngeal pain
         subjects affected / exposed
    15 / 101 (14.85%)
    11 / 99 (11.11%)
         occurrences all number
    25
    14
    Pleural effusion
         subjects affected / exposed
    2 / 101 (1.98%)
    16 / 99 (16.16%)
         occurrences all number
    2
    23
    Pneumonitis
         subjects affected / exposed
    7 / 101 (6.93%)
    8 / 99 (8.08%)
         occurrences all number
    10
    9
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    10 / 101 (9.90%)
    12 / 99 (12.12%)
         occurrences all number
    12
    15
    Depression
         subjects affected / exposed
    7 / 101 (6.93%)
    11 / 99 (11.11%)
         occurrences all number
    10
    31
    Insomnia
         subjects affected / exposed
    31 / 101 (30.69%)
    29 / 99 (29.29%)
         occurrences all number
    81
    70
    Restlessness
         subjects affected / exposed
    4 / 101 (3.96%)
    7 / 99 (7.07%)
         occurrences all number
    7
    8
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    12 / 101 (11.88%)
    14 / 99 (14.14%)
         occurrences all number
    39
    52
    Aspartate aminotransferase increased
         subjects affected / exposed
    8 / 101 (7.92%)
    12 / 99 (12.12%)
         occurrences all number
    22
    26
    Blood alkaline phosphatase increased
         subjects affected / exposed
    6 / 101 (5.94%)
    8 / 99 (8.08%)
         occurrences all number
    16
    10
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    8 / 101 (7.92%)
    9 / 99 (9.09%)
         occurrences all number
    25
    23
    C-reactive protein increased
         subjects affected / exposed
    20 / 101 (19.80%)
    21 / 99 (21.21%)
         occurrences all number
    50
    60
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    13 / 101 (12.87%)
    10 / 99 (10.10%)
         occurrences all number
    35
    28
    Investigation abnormal
         subjects affected / exposed
    11 / 101 (10.89%)
    15 / 99 (15.15%)
         occurrences all number
    16
    27
    Neutrophil count decreased
         subjects affected / exposed
    68 / 101 (67.33%)
    71 / 99 (71.72%)
         occurrences all number
    226
    263
    Platelet count decreased
         subjects affected / exposed
    95 / 101 (94.06%)
    92 / 99 (92.93%)
         occurrences all number
    477
    452
    Prothrombin time prolonged
         subjects affected / exposed
    6 / 101 (5.94%)
    3 / 99 (3.03%)
         occurrences all number
    10
    5
    Vitamin D decreased
         subjects affected / exposed
    7 / 101 (6.93%)
    1 / 99 (1.01%)
         occurrences all number
    18
    2
    Weight decreased
         subjects affected / exposed
    5 / 101 (4.95%)
    6 / 99 (6.06%)
         occurrences all number
    6
    6
    Weight increased
         subjects affected / exposed
    22 / 101 (21.78%)
    21 / 99 (21.21%)
         occurrences all number
    43
    36
    White blood cell count decreased
         subjects affected / exposed
    93 / 101 (92.08%)
    84 / 99 (84.85%)
         occurrences all number
    438
    378
    Hypocalcaemia
         subjects affected / exposed
    10 / 101 (9.90%)
    14 / 99 (14.14%)
         occurrences all number
    11
    19
    Hypokalaemia
         subjects affected / exposed
    51 / 101 (50.50%)
    53 / 99 (53.54%)
         occurrences all number
    113
    107
    Injury, poisoning and procedural complications
    Infusion related reaction
         subjects affected / exposed
    6 / 101 (5.94%)
    6 / 99 (6.06%)
         occurrences all number
    7
    8
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    1 / 101 (0.99%)
    7 / 99 (7.07%)
         occurrences all number
    1
    10
    Cardiac disorder
         subjects affected / exposed
    6 / 101 (5.94%)
    4 / 99 (4.04%)
         occurrences all number
    9
    4
    Sinus tachycardia
         subjects affected / exposed
    95 / 101 (94.06%)
    10 / 99 (10.10%)
         occurrences all number
    15
    17
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    10 / 101 (9.90%)
    12 / 99 (12.12%)
         occurrences all number
    15
    13
    Headache
         subjects affected / exposed
    38 / 101 (37.62%)
    35 / 99 (35.35%)
         occurrences all number
    117
    95
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    95 / 101 (94.06%)
    91 / 99 (91.92%)
         occurrences all number
    457
    490
    Febrile neutropenia
         subjects affected / exposed
    49 / 101 (48.51%)
    49 / 99 (49.49%)
         occurrences all number
    99
    127
    Haematological disorders
         subjects affected / exposed
    6 / 101 (5.94%)
    2 / 99 (2.02%)
         occurrences all number
    6
    2
    Leukocytosis
         subjects affected / exposed
    4 / 101 (3.96%)
    9 / 99 (9.09%)
         occurrences all number
    5
    12
    Thrombocytosis
         subjects affected / exposed
    6 / 101 (5.94%)
    3 / 99 (3.03%)
         occurrences all number
    7
    4
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    3 / 101 (2.97%)
    6 / 99 (6.06%)
         occurrences all number
    5
    10
    Eye disorders
    Dry eye
         subjects affected / exposed
    9 / 101 (8.91%)
    2 / 99 (2.02%)
         occurrences all number
    19
    3
    Eye disorder
         subjects affected / exposed
    6 / 101 (5.94%)
    11 / 99 (11.11%)
         occurrences all number
    7
    14
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    23 / 101 (22.77%)
    27 / 99 (27.27%)
         occurrences all number
    30
    44
    Abdominal pain upper
         subjects affected / exposed
    16 / 101 (15.84%)
    18 / 99 (18.18%)
         occurrences all number
    28
    26
    Anal hemorrhage
         subjects affected / exposed
    1 / 101 (0.99%)
    6 / 99 (6.06%)
         occurrences all number
    1
    7
    Colitis
         subjects affected / exposed
    2 / 101 (1.98%)
    10 / 99 (10.10%)
         occurrences all number
    2
    13
    Constipation
         subjects affected / exposed
    29 / 101 (28.71%)
    40 / 99 (40.40%)
         occurrences all number
    63
    74
    Diarrhoea
         subjects affected / exposed
    48 / 101 (47.52%)
    68 / 99 (68.69%)
         occurrences all number
    72
    130
    Dysphagia
         subjects affected / exposed
    7 / 101 (6.93%)
    2 / 99 (2.02%)
         occurrences all number
    7
    3
    Flatulence
         subjects affected / exposed
    7 / 101 (6.93%)
    11 / 99 (11.11%)
         occurrences all number
    7
    24
    Gastrointestinal disorder
         subjects affected / exposed
    10 / 101 (9.90%)
    8 / 99 (8.08%)
         occurrences all number
    17
    10
    Gastrointestinal pain
         subjects affected / exposed
    8 / 101 (7.92%)
    8 / 99 (8.08%)
         occurrences all number
    11
    8
    Haemorrhoids
         subjects affected / exposed
    6 / 101 (5.94%)
    7 / 99 (7.07%)
         occurrences all number
    10
    12
    Nausea
         subjects affected / exposed
    64 / 101 (63.37%)
    71 / 99 (71.72%)
         occurrences all number
    182
    193
    Stomatitis
         subjects affected / exposed
    33 / 101 (32.67%)
    34 / 99 (34.34%)
         occurrences all number
    43
    50
    Toothache
         subjects affected / exposed
    6 / 101 (5.94%)
    7 / 99 (7.07%)
         occurrences all number
    8
    9
    Vomiting
         subjects affected / exposed
    21 / 101 (20.79%)
    33 / 99 (33.33%)
         occurrences all number
    48
    61
    Skin and subcutaneous tissue disorders
    Dermatitis acneiform
         subjects affected / exposed
    15 / 101 (14.85%)
    8 / 99 (8.08%)
         occurrences all number
    20
    10
    Dry skin
         subjects affected / exposed
    8 / 101 (7.92%)
    9 / 99 (9.09%)
         occurrences all number
    11
    9
    Petechiae
         subjects affected / exposed
    18 / 101 (17.82%)
    11 / 99 (11.11%)
         occurrences all number
    28
    12
    Pruritus
         subjects affected / exposed
    15 / 101 (14.85%)
    11 / 99 (11.11%)
         occurrences all number
    17
    23
    Rash
         subjects affected / exposed
    5 / 101 (4.95%)
    14 / 99 (14.14%)
         occurrences all number
    7
    24
    Rash maculo-papular
         subjects affected / exposed
    17 / 101 (16.83%)
    19 / 99 (19.19%)
         occurrences all number
    25
    35
    Skin disorder
         subjects affected / exposed
    14 / 101 (13.86%)
    16 / 99 (16.16%)
         occurrences all number
    21
    30
    Renal and urinary disorders
    Fluid retention
         subjects affected / exposed
    34 / 101 (33.66%)
    41 / 99 (41.41%)
         occurrences all number
    69
    78
    Renal disorder
         subjects affected / exposed
    7 / 101 (6.93%)
    4 / 99 (4.04%)
         occurrences all number
    9
    4
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    21 / 101 (20.79%)
    11 / 99 (11.11%)
         occurrences all number
    26
    20
    Bone pain
         subjects affected / exposed
    8 / 101 (7.92%)
    9 / 99 (9.09%)
         occurrences all number
    13
    13
    Musculoskeletal disorder
         subjects affected / exposed
    6 / 101 (5.94%)
    6 / 99 (6.06%)
         occurrences all number
    7
    10
    Myalgia
         subjects affected / exposed
    4 / 101 (3.96%)
    8 / 99 (8.08%)
         occurrences all number
    4
    12
    Pain in extremity
         subjects affected / exposed
    18 / 101 (17.82%)
    17 / 99 (17.17%)
         occurrences all number
    26
    32
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    3 / 101 (2.97%)
    10 / 99 (10.10%)
         occurrences all number
    4
    21
    Device related infection
         subjects affected / exposed
    19 / 101 (18.81%)
    12 / 99 (12.12%)
         occurrences all number
    22
    16
    Enterocolitis infectious
         subjects affected / exposed
    5 / 101 (4.95%)
    9 / 99 (9.09%)
         occurrences all number
    6
    12
    Infection
         subjects affected / exposed
    44 / 101 (43.56%)
    44 / 99 (44.44%)
         occurrences all number
    82
    93
    Lip infection
         subjects affected / exposed
    7 / 101 (6.93%)
    8 / 99 (8.08%)
         occurrences all number
    9
    14
    Mucosal infection
         subjects affected / exposed
    6 / 101 (5.94%)
    8 / 99 (8.08%)
         occurrences all number
    8
    13
    Pneumonia
         subjects affected / exposed
    19 / 101 (18.81%)
    31 / 99 (31.31%)
         occurrences all number
    22
    44
    Rash pustular
         subjects affected / exposed
    5 / 101 (4.95%)
    9 / 99 (9.09%)
         occurrences all number
    5
    23
    Sepsis
         subjects affected / exposed
    9 / 101 (8.91%)
    14 / 99 (14.14%)
         occurrences all number
    10
    18
    Skin infection
         subjects affected / exposed
    11 / 101 (10.89%)
    12 / 99 (12.12%)
         occurrences all number
    17
    21
    Urinary tract infection
         subjects affected / exposed
    10 / 101 (9.90%)
    15 / 99 (15.15%)
         occurrences all number
    15
    21
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    15 / 101 (14.85%)
    17 / 99 (17.17%)
         occurrences all number
    24
    33
    Hyperuricaemia
         subjects affected / exposed
    17 / 101 (16.83%)
    13 / 99 (13.13%)
         occurrences all number
    29
    23
    Hypoalbuminaemia
         subjects affected / exposed
    6 / 101 (5.94%)
    14 / 99 (14.14%)
         occurrences all number
    7
    21
    Hypomagnesaemia
         subjects affected / exposed
    9 / 101 (8.91%)
    3 / 99 (3.03%)
         occurrences all number
    10
    3
    Hypophosphataemia
         subjects affected / exposed
    5 / 101 (4.95%)
    6 / 99 (6.06%)
         occurrences all number
    5
    7

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    23 Jun 2015
    Amendment No. 1 (dated 23 June 2015) to the protocol was issued after 17 patients were enrolled. The following major procedural changes (not all-inclusive) were made to the protocol: • Add medications restricted during the treatment with dasatinib • Add supportive care medications • Include some minor administrative-type changes
    15 Jun 2016
    Amendment No. 2 (dated 15 June 2016) to the protocol was issued after 48 patients were enrolled into the study. The following major procedural changes (not all-inclusive) were made to the protocol: • Integration of the Safety Update Letter • Adjustment of the duration of the clinical trial • Update of the Serious Advese Events • Update of the prophylaxis with dexamethasone • Include some minor administrative-type changes/ Changes in the personal responsibility
    19 Mar 2019
    Amendment No. 3 (dated 19 March 2019) to the protocol was issued after 151 patients were enrolled into the study. The following major procedural changes (not all-inclusive) were made to the protocol: • Adjustment of study duration and decrease of sample size from 277 to 203 patients due to slow recruitment • Adjustment of standard chemotherapy as a result of reported delivery shortages of Daunorubicin -> Integration of Idarubicin which can be used in case Daunorubicin is not available • Adaption of Informed Consent Form on the General Data Protection Regulation (EU)

    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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