Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

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

    The EU Clinical Trials Register currently displays   44334   clinical trials with a EudraCT protocol, of which   7366   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    International Study for Treatment of Standard Risk Childhood Relapsed ALL 2010 - A randomized Phase III Study Conducted by the Resistant Disease Committee of the International BFM Study Group

    Summary
    EudraCT number
    		 2012-000793-30
    Trial protocol
    		 SE   PT   GB   DE   BE   AT   IE   FI   DK   CZ   IT   NL   FR   PL   ES   NO  
    Global end of trial date
    31 Jul 2023

    Results information
    Results version number
    		 v2(current)
    This version publication date
    06 Mar 2025
    First version publication date
    26 Sep 2024
    Other versions
    		 v1
    Version creation reason
    • Correction of full data set
    update some values

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    IntReALL-SR-2010
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01802814
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Charité Universitätsmedizin Berlin
    Sponsor organisation address
    Campus Virchow Klinikum - Augustenburger Platz 1, Berlin, Germany, 13353
    Public contact
    PD Dr. Arend von Stackelberg, Charité Universitätsmedizin Berlin, +49 30450666833, arend.stackelberg@charite.de
    Scientific contact
    PD Dr. Arend von Stackelberg, Charité Universitätsmedizin Berlin, +49 30450666833, arend.stackelberg@charite.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
    01 Jul 2024
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    31 Jul 2023
    Global end of trial reached?
    Yes
    Global end of trial date
    31 Jul 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    - Overall: Improvement of event-free survival (EFS) probabilities in childhood relapsed ALL - Randomization 1: EFS of Arm A (ALL-REZ BFM 2002) versus B (ALLR3) in SR patients - Randomization 2: Influence of epratuzumab on EFS in consolidation of SR patients
    Protection of trial subjects
    This study was conducted in accordance with applicable laws and regulations including, but not limited to, the ethical principles that have their origins in the Declaration of Helsinki and the International Conference on Harmonisation Guideline for Good Clinical Practice (GCP). Prior to recruitment of subjects, the relevant authorities and ethics committees had to approve and authorize this clinical trial. Amendments were only implemented after approval. Before the procedures mentioned in the protocol were performed, the subject or his/her parent/legal guardian had to sign and date the approved informed consent form according to the requirements of national law. Post trial treatment is not different from the expected normal treatment of that condition. After termination of the study, patients will be followed up by national children’s cancer registries to capture safety relevant late effects, secondary malignancies and to have the opportunity to give feed back to the patients, if necessary. Patients who are off study continue to be observed including a report of death in order to allow the assessment of overall survival.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    27 May 2014
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety, Efficacy
    Long term follow-up duration
    		 3 Years
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    New Zealand: 3
    Country: Number of subjects enrolled
    United Kingdom: 4
    Country: Number of subjects enrolled
    Austria: 17
    Country: Number of subjects enrolled
    Belgium: 7
    Country: Number of subjects enrolled
    Czechia: 22
    Country: Number of subjects enrolled
    Denmark: 14
    Country: Number of subjects enrolled
    Finland: 15
    Country: Number of subjects enrolled
    France: 141
    Country: Number of subjects enrolled
    Germany: 141
    Country: Number of subjects enrolled
    Italy: 179
    Country: Number of subjects enrolled
    Netherlands: 14
    Country: Number of subjects enrolled
    Norway: 9
    Country: Number of subjects enrolled
    Poland: 1
    Country: Number of subjects enrolled
    Portugal: 17
    Country: Number of subjects enrolled
    Switzerland: 14
    Country: Number of subjects enrolled
    Australia: 35
    Country: Number of subjects enrolled
    Israel: 21
    Country: Number of subjects enrolled
    Japan: 39
    Worldwide total number of subjects
    693
    EEA total number of subjects
    577
    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)
    501
    Adolescents (12-17 years)
    192
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Patients with a first standard-risk (SR) ALL relapse aged 1 to 17 years were recruited in the trial from 23.10.2014 to 31.07.2020 in 17 countries (210 centers).

    Pre-assignment
    Screening details
    		 confirmed 1st relapsed B-cell or T-cell ALL; less than 18 years of age; meeting SR criteria: late isolated or late/early combined BCP BM relapse, late/early isolated extramedullary relapse; enrollment in a participating centre; written informed consent; start of treatment falling into the study period; no other clinical trials 30 days prior

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 SR arm A (ALL-REZ BFM 2002 arm Prot II-IDA)
    Arm description
    		 SR arm A (ALL-REZ BFM 2002 arm Prot II-IDA): Induction: SIA (F1, F2); Post induction: SCA1 and SCA2, 5 courses SCA3-7 (R1/2/1/2/1), 24 months maintenance (6MP, MTX) with 6 x TIT / 4 weeks. Cranial irradiation 18Gy for CNS relapse.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    ALL-REZ BFM 2002 arm Prot II-IDA
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Kit for radiopharmaceutical preparation, Solution for injection/infusion, Syrup, Tablet
    Routes of administration
    Intrathecal use, Intravenous use, Oral use, Percutaneous use
    Dosage and administration details
    Induction: SIA (F1, F2);Consolidation: SCA1 and SCA2, 5 courses SCA3-7 (R1/2/1/2/1); Maintenance 24 months (6-MP, MTX) with 6 x TIT / 4 weeks. Cranial irradiation with 18 Gy for CNS relapse.

    Arm title
    		 SR arm B (UK-R3, arm mitoxantrone)
    Arm description
    		 SR arm B (ALL R3): Induction (1st randomization): SIB (phase I); Consolidation: SCB1 and SCB2 (consolidation and intensification), 2 courses SCB3-4 (interim maintenance 1 and 2); Maintenance 20 months (6-MP, MTX, 4-weekly VCR/DEX/IT reinduction pulses). Cranial irradiation with 18 Gy for CNS relapse.
    Arm type
    		 Experimental

    Investigational medicinal product name
    ALL R3
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Kit for radiopharmaceutical preparation, Solution for injection/infusion, Syrup, Tablet
    Routes of administration
    Intrathecal use, Intravenous use, Oral use, Percutaneous use
    Dosage and administration details
    Induction: SIB (phase I); Consolidation: SCB1 and SCB2 (consolidation and intensification), 2 courses SCB3-4 (interim maintenance 1 and 2); Maintenance 20 months (6-MP, MTX, 4-weekly VCR/DEX/IT reinduction pulses). Cranial irradiation with 18 Gy for CNS relapse.

    Number of subjects in period 1 [1]
    		SR arm A (ALL-REZ BFM 2002 arm Prot II-IDA) SR arm B (UK-R3, arm mitoxantrone)
    Started
    303
    316
    Completed
    282
    293
    Not completed
    21
    23
         no CR or death in CR without SCT
    21
    23
    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: Of the 693 subjects that were enrolled in the trial worldwide, 619 (303 in Arm A, 316 in Arm B) could be randomized in Randomization 1 and are therefore available for assessment in Reporting Groups "SR arm A" and "SR arm B".

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    SR arm A (ALL-REZ BFM 2002 arm Prot II-IDA)
    Reporting group description
    		 SR arm A (ALL-REZ BFM 2002 arm Prot II-IDA): Induction: SIA (F1, F2); Post induction: SCA1 and SCA2, 5 courses SCA3-7 (R1/2/1/2/1), 24 months maintenance (6MP, MTX) with 6 x TIT / 4 weeks. Cranial irradiation 18Gy for CNS relapse.

    Reporting group title
    SR arm B (UK-R3, arm mitoxantrone)
    Reporting group description
    		 SR arm B (ALL R3): Induction (1st randomization): SIB (phase I); Consolidation: SCB1 and SCB2 (consolidation and intensification), 2 courses SCB3-4 (interim maintenance 1 and 2); Maintenance 20 months (6-MP, MTX, 4-weekly VCR/DEX/IT reinduction pulses). Cranial irradiation with 18 Gy for CNS relapse.

    Reporting group values
    		 SR arm A (ALL-REZ BFM 2002 arm Prot II-IDA) SR arm B (UK-R3, arm mitoxantrone) Total
    Number of subjects
    		 303 316 619
    Age categorical
    Units: Subjects
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 229 221 450
        Adolescents (12-17 years)
    		 74 95 169
        Adults (18-64 years)
    		 0 0 0
    Gender categorical
    Units: Subjects
        Female
    		 104 104 208
        Male
    		 199 212 411

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    SR arm A (ALL-REZ BFM 2002 arm Prot II-IDA)
    Reporting group description
    		 SR arm A (ALL-REZ BFM 2002 arm Prot II-IDA): Induction: SIA (F1, F2); Post induction: SCA1 and SCA2, 5 courses SCA3-7 (R1/2/1/2/1), 24 months maintenance (6MP, MTX) with 6 x TIT / 4 weeks. Cranial irradiation 18Gy for CNS relapse.

    Reporting group title
    SR arm B (UK-R3, arm mitoxantrone)
    Reporting group description
    		 SR arm B (ALL R3): Induction (1st randomization): SIB (phase I); Consolidation: SCB1 and SCB2 (consolidation and intensification), 2 courses SCB3-4 (interim maintenance 1 and 2); Maintenance 20 months (6-MP, MTX, 4-weekly VCR/DEX/IT reinduction pulses). Cranial irradiation with 18 Gy for CNS relapse.

    Primary: 4-year Event Free Survival probability - ITT

    		 Close Top of page
    End point title
    		 4-year Event Free Survival probability - ITT
    End point description
    The probability of Event Free Survival (pEFS) at 4 years was estimated according to the Kaplan-Meier method. The analysis was performed using the “intention to treat” (ITT) principle for all randomized study patients.
    End point type
    Primary
    End point timeframe
    Event free survival (EFS) for is defined as the time from randomization to the first of induction failure, relapse, death from any cause or second malignancy or is censored at the date of last follow-up.
    End point values
    		 SR arm A (ALL-REZ BFM 2002 arm Prot II-IDA) SR arm B (UK-R3, arm mitoxantrone)
    Number of subjects analysed
    303
    316
    Units: percentage
        number (confidence interval 95%)
    68.6 (62.6 to 73.9)
    69.0 (63.2 to 74.2)
    Statistical analysis title
    		 Final analysis (Intention to treat)
    Statistical analysis description
    The log-rank test was used to compare the groups.
    Comparison groups
    SR arm A (ALL-REZ BFM 2002 arm Prot II-IDA) v SR arm B (UK-R3, arm mitoxantrone)
    Number of subjects included in analysis
    619
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Logrank
    Confidence interval

    Secondary: 4-year Overall Survival probability - ITT

    		 Close Top of page
    End point title
    		 4-year Overall Survival probability - ITT
    End point description
    The probability of Overall Survival (pOS) at 4 years was estimated according to the Kaplan-Meier method. The analysis was performed using the “intention to treat” (ITT) principle for all randomized study patients.
    End point type
    Secondary
    End point timeframe
    Overall Survival (OS) is defined as the time from randomization to death from any cause. Stem-cell transplantation is not considered as event and is also not censored in the EFS/OS analyses.
    End point values
    		 SR arm A (ALL-REZ BFM 2002 arm Prot II-IDA) SR arm B (UK-R3, arm mitoxantrone)
    Number of subjects analysed
    303
    316
    Units: percentage
        number (confidence interval 95%)
    84.0 (79.0 to 87.9)
    84.8 (80.1 to 88.4)
    Statistical analysis title
    		 Final analysis (Intention to treat)
    Statistical analysis description
    The log-rank test was used to compare the groups.
    Comparison groups
    SR arm A (ALL-REZ BFM 2002 arm Prot II-IDA) v SR arm B (UK-R3, arm mitoxantrone)
    Number of subjects included in analysis
    619
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Logrank
    Confidence interval

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    From first day of study treatment until end of study follow-up (3 years after treatment initiation).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 CTCAE
    Dictionary version
    4.03
    Reporting groups
    Reporting group title
    SR arm B (UK-R3, arm mitoxantrone)
    Reporting group description
    		 SR arm B (ALL R3): Induction (1st randomization): SIB (phase I); Consolidation: SCB1 and SCB2 (consolidation and intensification), 2 courses SCB3-4 (interim maintenance 1 and 2); Maintenance 20 months (6-MP, MTX, 4-weekly VCR/DEX/IT reinduction pulses). Cranial irradiation with 18 Gy for CNS relapse.

    Reporting group title
    SR arm A (ALL-REZ BFM 2002 arm Prot II-IDA)
    Reporting group description
    		 SR arm A (ALL-REZ BFM 2002 arm Prot II-IDA): Induction: SIA (F1, F2); Post induction: SCA1 and SCA2, 5 courses SCA3-7 (R1/2/1/2/1), 24 months maintenance (6MP, MTX) with 6 x TIT / 4 weeks. Cranial irradiation 18Gy for CNS relapse.

    Serious adverse events
    		 SR arm B (UK-R3, arm mitoxantrone) SR arm A (ALL-REZ BFM 2002 arm Prot II-IDA)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    213 / 316 (67.41%)
    191 / 303 (63.04%)
         number of deaths (all causes)
    35
    24
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify
         subjects affected / exposed
    3 / 316 (0.95%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 3
    0 / 1
    Vascular disorders
    Hypertension
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    2 / 316 (0.63%)
    2 / 303 (0.66%)
         occurrences causally related to treatment / all
    2 / 2
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Thromboembolic event
         subjects affected / exposed
    2 / 316 (0.63%)
    3 / 303 (0.99%)
         occurrences causally related to treatment / all
    2 / 2
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Vascular disorders - Other, specify
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Death NOS
         subjects affected / exposed
    6 / 316 (1.90%)
    2 / 303 (0.66%)
         occurrences causally related to treatment / all
    1 / 6
    0 / 2
         deaths causally related to treatment / all
    1 / 6
    0 / 2
    Fever
         subjects affected / exposed
    1 / 316 (0.32%)
    5 / 303 (1.65%)
         occurrences causally related to treatment / all
    1 / 1
    3 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypothermia
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multi-organ failure
         subjects affected / exposed
    3 / 316 (0.95%)
    4 / 303 (1.32%)
         occurrences causally related to treatment / all
    1 / 3
    1 / 4
         deaths causally related to treatment / all
    0 / 2
    1 / 4
    Sudden death NOS
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Immune system disorders
    Allergic reaction
         subjects affected / exposed
    2 / 316 (0.63%)
    5 / 303 (1.65%)
         occurrences causally related to treatment / all
    2 / 2
    5 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anaphylaxis treatment
         subjects affected / exposed
    7 / 316 (2.22%)
    7 / 303 (2.31%)
         occurrences causally related to treatment / all
    5 / 7
    7 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders - Other, specify
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cytokine release syndrome
         subjects affected / exposed
    1 / 316 (0.32%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Adult respiratory distress syndrome
         subjects affected / exposed
    1 / 316 (0.32%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Apnea
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 303 (0.33%)
         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
    2 / 316 (0.63%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 1
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Pneumonitis
         subjects affected / exposed
    3 / 316 (0.95%)
    4 / 303 (1.32%)
         occurrences causally related to treatment / all
    3 / 3
    3 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Respiratory failure
         subjects affected / exposed
    3 / 316 (0.95%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    2 / 3
    1 / 1
         deaths causally related to treatment / all
    1 / 2
    0 / 0
    Bronchial infection
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung infection
         subjects affected / exposed
    19 / 316 (6.01%)
    10 / 303 (3.30%)
         occurrences causally related to treatment / all
    18 / 19
    9 / 10
         deaths causally related to treatment / all
    1 / 2
    0 / 0
    Psychiatric disorders
    Agitation
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Delirium
         subjects affected / exposed
    0 / 316 (0.00%)
    2 / 303 (0.66%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Suicide attempt
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood bilirubin increased
         subjects affected / exposed
    3 / 316 (0.95%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Creatinine increased
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations - Other, specify
         subjects affected / exposed
    0 / 316 (0.00%)
    2 / 303 (0.66%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Injury, poisoning and procedural complications
    Intestinal stoma site bleeding
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular access complication
         subjects affected / exposed
    1 / 316 (0.32%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac arrest
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cardiac disorders - Other, specify
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Heart failure
         subjects affected / exposed
    0 / 316 (0.00%)
    2 / 303 (0.66%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Sinus tachycardia
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Depressed level of consciousness
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Edema cerebral
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Encephalopathy
         subjects affected / exposed
    3 / 316 (0.95%)
    2 / 303 (0.66%)
         occurrences causally related to treatment / all
    3 / 3
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Extrapyramidal disorder
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hydrocephalus
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intracranial hemorrhage
         subjects affected / exposed
    1 / 316 (0.32%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    1 / 1
    1 / 1
    Ischemia cerebrovascular
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 303 (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 - Other, specify
         subjects affected / exposed
    0 / 316 (0.00%)
    4 / 303 (1.32%)
         occurrences causally related to treatment / all
    0 / 0
    4 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral motor neuropathy
         subjects affected / exposed
    0 / 316 (0.00%)
    2 / 303 (0.66%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral sensory neuropathy
         subjects affected / exposed
    1 / 316 (0.32%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    4 / 316 (1.27%)
    8 / 303 (2.64%)
         occurrences causally related to treatment / all
    3 / 4
    8 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reversible posterior leukencephalopathy syndrome
         subjects affected / exposed
    3 / 316 (0.95%)
    2 / 303 (0.66%)
         occurrences causally related to treatment / all
    3 / 3
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Blood and lymphatic system disorders - Other, specify
         subjects affected / exposed
    2 / 316 (0.63%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    21 / 316 (6.65%)
    7 / 303 (2.31%)
         occurrences causally related to treatment / all
    25 / 26
    11 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bone marrow hypocellular
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    White blood cell count decreased
         subjects affected / exposed
    1 / 316 (0.32%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Eye disorders - Other, specify
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retinopathy
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anal fistula
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colonic hemorrhage
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colonic perforation
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Esophagitis
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders - Other, specify
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    0 / 316 (0.00%)
    2 / 303 (0.66%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mucositis oral
         subjects affected / exposed
    2 / 316 (0.63%)
    3 / 303 (0.99%)
         occurrences causally related to treatment / all
    2 / 2
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oral pain
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    9 / 316 (2.85%)
    10 / 303 (3.30%)
         occurrences causally related to treatment / all
    11 / 11
    9 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal hemorrhage
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal perforation
         subjects affected / exposed
    1 / 316 (0.32%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stomach pain
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Typhlitis
         subjects affected / exposed
    1 / 316 (0.32%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatic necrosis
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anal mucositis
         subjects affected / exposed
    2 / 316 (0.63%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Jejunal obstruction
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hepatic failure
         subjects affected / exposed
    1 / 316 (0.32%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Hepatobiliay disorders - Other, specify
         subjects affected / exposed
    1 / 316 (0.32%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Skin and subcutaneous tissue disorders - Other, specify
         subjects affected / exposed
    2 / 316 (0.63%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin ulceration
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Toxic epidermal necrolysis
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Papulopustular rash
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Renal colic
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute kidney injury
         subjects affected / exposed
    1 / 316 (0.32%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscle weakness right-sided
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Avascular necrosis
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Appendicitis
         subjects affected / exposed
    4 / 316 (1.27%)
    4 / 303 (1.32%)
         occurrences causally related to treatment / all
    4 / 4
    2 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Appendicitis perforated
         subjects affected / exposed
    1 / 316 (0.32%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Catheter related infection
         subjects affected / exposed
    4 / 316 (1.27%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    3 / 4
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Encephalitis infection
         subjects affected / exposed
    3 / 316 (0.95%)
    2 / 303 (0.66%)
         occurrences causally related to treatment / all
    3 / 3
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endophthalmitis
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterocolitis
         subjects affected / exposed
    1 / 316 (0.32%)
    2 / 303 (0.66%)
         occurrences causally related to treatment / all
    1 / 1
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations - Other, specify
         subjects affected / exposed
    14 / 316 (4.43%)
    5 / 303 (1.65%)
         occurrences causally related to treatment / all
    13 / 13
    1 / 5
         deaths causally related to treatment / all
    1 / 2
    0 / 2
    Kidney infection
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Meningitis
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    32 / 316 (10.13%)
    40 / 303 (13.20%)
         occurrences causally related to treatment / all
    29 / 31
    36 / 37
         deaths causally related to treatment / all
    9 / 11
    5 / 7
    Urinary tract infection
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal infection
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Soft tissue infection
         subjects affected / exposed
    1 / 316 (0.32%)
    2 / 303 (0.66%)
         occurrences causally related to treatment / all
    1 / 1
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lip infection
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mucosal infection
         subjects affected / exposed
    1 / 316 (0.32%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vulval infection
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    1 / 316 (0.32%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperglycemia
         subjects affected / exposed
    6 / 316 (1.90%)
    1 / 303 (0.33%)
         occurrences causally related to treatment / all
    7 / 7
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertriglyceridaemia
         subjects affected / exposed
    0 / 316 (0.00%)
    5 / 303 (1.65%)
         occurrences causally related to treatment / all
    0 / 0
    4 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypokalemia
         subjects affected / exposed
    4 / 316 (1.27%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    3 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 303 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 SR arm B (UK-R3, arm mitoxantrone) SR arm A (ALL-REZ BFM 2002 arm Prot II-IDA)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    142 / 316 (44.94%)
    190 / 303 (62.71%)
    Vascular disorders
    Capillary leak syndrome
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 303 (0.00%)
         occurrences all number
    1
    0
    Hypertension
         subjects affected / exposed
    1 / 316 (0.32%)
    1 / 303 (0.33%)
         occurrences all number
    1
    1
    Hypotension
         subjects affected / exposed
    0 / 316 (0.00%)
    2 / 303 (0.66%)
         occurrences all number
    0
    2
    Thromboembolic event
         subjects affected / exposed
    9 / 316 (2.85%)
    7 / 303 (2.31%)
         occurrences all number
    9
    15
    Surgical and medical procedures
    Surgical and medical procedures - Other, specify
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 303 (0.00%)
         occurrences all number
    1
    0
    General disorders and administration site conditions
    Fever
         subjects affected / exposed
    43 / 316 (13.61%)
    42 / 303 (13.86%)
         occurrences all number
    54
    48
    Pain
         subjects affected / exposed
    2 / 316 (0.63%)
    0 / 303 (0.00%)
         occurrences all number
    2
    0
    Edema limbs
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 303 (0.33%)
         occurrences all number
    0
    1
    Immune system disorders
    Allergic reaction
         subjects affected / exposed
    6 / 316 (1.90%)
    6 / 303 (1.98%)
         occurrences all number
    7
    6
    Anaphylaxis
         subjects affected / exposed
    3 / 316 (0.95%)
    4 / 303 (1.32%)
         occurrences all number
    3
    4
    Immune system disorders - Other, specify
         subjects affected / exposed
    2 / 316 (0.63%)
    1 / 303 (0.33%)
         occurrences all number
    2
    1
    Respiratory, thoracic and mediastinal disorders
    Epistaxis
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 303 (0.33%)
         occurrences all number
    0
    1
    Pneumonitis
         subjects affected / exposed
    2 / 316 (0.63%)
    0 / 303 (0.00%)
         occurrences all number
    2
    0
    Pulmonary edema
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 303 (0.33%)
         occurrences all number
    0
    1
    Pulmonary fibrosis
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 303 (0.33%)
         occurrences all number
    0
    1
    Respiratory failure
         subjects affected / exposed
    1 / 316 (0.32%)
    1 / 303 (0.33%)
         occurrences all number
    1
    1
    Psychiatric disorders
    Agitation
         subjects affected / exposed
    1 / 316 (0.32%)
    2 / 303 (0.66%)
         occurrences all number
    1
    2
    Anxiety
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 303 (0.33%)
         occurrences all number
    0
    1
    Confusion
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 303 (0.33%)
         occurrences all number
    0
    1
    Psychiatric disorders - Other, specify
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 303 (0.33%)
         occurrences all number
    0
    1
    Psychosis
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 303 (0.00%)
         occurrences all number
    2
    0
    Investigations
    Blood bilirubin increased
         subjects affected / exposed
    56 / 316 (17.72%)
    53 / 303 (17.49%)
         occurrences all number
    82
    84
    Cholesterol high
         subjects affected / exposed
    1 / 316 (0.32%)
    4 / 303 (1.32%)
         occurrences all number
    1
    5
    Creatinine increased
         subjects affected / exposed
    8 / 316 (2.53%)
    6 / 303 (1.98%)
         occurrences all number
    8
    6
    Fibrinogen decreased
         subjects affected / exposed
    0 / 316 (0.00%)
    6 / 303 (1.98%)
         occurrences all number
    0
    11
    Investigations - Other, specify
         subjects affected / exposed
    4 / 316 (1.27%)
    3 / 303 (0.99%)
         occurrences all number
    5
    21
    Lipase increased
         subjects affected / exposed
    2 / 316 (0.63%)
    12 / 303 (3.96%)
         occurrences all number
    2
    16
    Lymphocyte count decreased
         subjects affected / exposed
    3 / 316 (0.95%)
    2 / 303 (0.66%)
         occurrences all number
    15
    3
    Serum amylase increased
         subjects affected / exposed
    1 / 316 (0.32%)
    3 / 303 (0.99%)
         occurrences all number
    1
    5
    Weight loss
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 303 (0.00%)
         occurrences all number
    3
    0
    GGT increased
         subjects affected / exposed
    5 / 316 (1.58%)
    5 / 303 (1.65%)
         occurrences all number
    8
    7
    Injury, poisoning and procedural complications
    Fracture
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 303 (0.33%)
         occurrences all number
    0
    2
    Injury, poisoning and procedural complications - Other, specify
         subjects affected / exposed
    2 / 316 (0.63%)
    0 / 303 (0.00%)
         occurrences all number
    2
    0
    Cardiac disorders
    Cardiac disorders - Other, specify
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 303 (0.00%)
         occurrences all number
    1
    0
    Pericardial effusion
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 303 (0.33%)
         occurrences all number
    0
    1
    Nervous system disorders
    Edema cerebral
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 303 (0.33%)
         occurrences all number
    0
    1
    Encephalopathy
         subjects affected / exposed
    0 / 316 (0.00%)
    2 / 303 (0.66%)
         occurrences all number
    0
    2
    Headache
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 303 (0.33%)
         occurrences all number
    0
    1
    Nervous system disorders - Other, specify
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 303 (0.33%)
         occurrences all number
    0
    1
    Peripheral motor neuropathy
         subjects affected / exposed
    0 / 316 (0.00%)
    4 / 303 (1.32%)
         occurrences all number
    0
    4
    Peripheral sensory neuropathy
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 303 (0.33%)
         occurrences all number
    0
    1
    Seizure
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 303 (0.33%)
         occurrences all number
    0
    1
    Vasovagal reaction
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 303 (0.33%)
         occurrences all number
    0
    1
    Paresthesia
         subjects affected / exposed
    7 / 316 (2.22%)
    16 / 303 (5.28%)
         occurrences all number
    13
    19
    Blood and lymphatic system disorders
    Blood and lymphatic system disorders - Other, specify
         subjects affected / exposed
    5 / 316 (1.58%)
    0 / 303 (0.00%)
         occurrences all number
    11
    0
    Febrile neutropenia
         subjects affected / exposed
    8 / 316 (2.53%)
    11 / 303 (3.63%)
         occurrences all number
    13
    16
    Bone marrow hypocellular
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 303 (0.33%)
         occurrences all number
    0
    1
    Ear and labyrinth disorders
    Hearing impaired
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 303 (0.00%)
         occurrences all number
    1
    0
    Otitis media
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 303 (0.00%)
         occurrences all number
    1
    0
    Eye disorders
    Conjunctivitis
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 303 (0.00%)
         occurrences all number
    1
    0
    Eye disorders - Other, specify
         subjects affected / exposed
    2 / 316 (0.63%)
    0 / 303 (0.00%)
         occurrences all number
    2
    0
    Uveitis
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 303 (0.00%)
         occurrences all number
    1
    0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 303 (0.00%)
         occurrences all number
    1
    0
    Anal ulcer
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 303 (0.33%)
         occurrences all number
    0
    1
    Appendicitis
         subjects affected / exposed
    1 / 316 (0.32%)
    1 / 303 (0.33%)
         occurrences all number
    1
    1
    Appendicitis perforated
         subjects affected / exposed
    0 / 316 (0.00%)
    2 / 303 (0.66%)
         occurrences all number
    0
    2
    Ascites
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 303 (0.33%)
         occurrences all number
    0
    1
    Colitis
         subjects affected / exposed
    2 / 316 (0.63%)
    0 / 303 (0.00%)
         occurrences all number
    2
    0
    Diarrhoea
         subjects affected / exposed
    21 / 316 (6.65%)
    30 / 303 (9.90%)
         occurrences all number
    23
    36
    Gastrointestinal disorders - Other, specify
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 303 (0.33%)
         occurrences all number
    0
    1
    Ileus
         subjects affected / exposed
    2 / 316 (0.63%)
    2 / 303 (0.66%)
         occurrences all number
    2
    3
    Mucositis oral
         subjects affected / exposed
    121 / 316 (38.29%)
    111 / 303 (36.63%)
         occurrences all number
    156
    156
    Nausea
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 303 (0.00%)
         occurrences all number
    1
    0
    Oral hemorrhage
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 303 (0.33%)
         occurrences all number
    0
    1
    Pancreatitis
         subjects affected / exposed
    2 / 316 (0.63%)
    8 / 303 (2.64%)
         occurrences all number
    2
    8
    Typhlitis
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 303 (0.00%)
         occurrences all number
    1
    0
    Vomiting
         subjects affected / exposed
    13 / 316 (4.11%)
    23 / 303 (7.59%)
         occurrences all number
    14
    26
    Pancreatic necrosis
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 303 (0.33%)
         occurrences all number
    0
    1
    Anal mucositis
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 303 (0.00%)
         occurrences all number
    1
    0
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 303 (0.33%)
         occurrences all number
    0
    1
    Bullous dermatitis
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 303 (0.00%)
         occurrences all number
    1
    0
    Skin and subcutaneous tissue disorders - Other, specify
         subjects affected / exposed
    2 / 316 (0.63%)
    1 / 303 (0.33%)
         occurrences all number
    2
    1
    Skin ulceration
         subjects affected / exposed
    1 / 316 (0.32%)
    1 / 303 (0.33%)
         occurrences all number
    1
    1
    Urticaria
         subjects affected / exposed
    0 / 316 (0.00%)
    2 / 303 (0.66%)
         occurrences all number
    0
    2
    Rash maculo-papular
         subjects affected / exposed
    19 / 316 (6.01%)
    4 / 303 (1.32%)
         occurrences all number
    21
    4
    Renal and urinary disorders
    Renal and urinary disorders - Other, specify
         subjects affected / exposed
    1 / 316 (0.32%)
    1 / 303 (0.33%)
         occurrences all number
    1
    1
    Acute kidney injury
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 303 (0.33%)
         occurrences all number
    0
    1
    Endocrine disorders
    Adrenal insufficiency
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 303 (0.33%)
         occurrences all number
    0
    1
    Delayed puberty
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 303 (0.00%)
         occurrences all number
    1
    0
    Hypothyroidism
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 303 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 303 (0.33%)
         occurrences all number
    0
    1
    Myalgia
         subjects affected / exposed
    1 / 316 (0.32%)
    0 / 303 (0.00%)
         occurrences all number
    1
    0
    Infections and infestations
    Catheter related infection
         subjects affected / exposed
    1 / 316 (0.32%)
    1 / 303 (0.33%)
         occurrences all number
    1
    1
    Sepsis
         subjects affected / exposed
    3 / 316 (0.95%)
    4 / 303 (1.32%)
         occurrences all number
    3
    4
    Skin infection
         subjects affected / exposed
    2 / 316 (0.63%)
    0 / 303 (0.00%)
         occurrences all number
    2
    0
    Vaginal infection
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 303 (0.33%)
         occurrences all number
    0
    1
    Pancreas infection
         subjects affected / exposed
    1 / 316 (0.32%)
    1 / 303 (0.33%)
         occurrences all number
    1
    1
    Lung infection
         subjects affected / exposed
    2 / 316 (0.63%)
    1 / 303 (0.33%)
         occurrences all number
    2
    1
    Soft tissue infection
         subjects affected / exposed
    2 / 316 (0.63%)
    0 / 303 (0.00%)
         occurrences all number
    2
    0
    Lip infection
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 303 (0.33%)
         occurrences all number
    0
    1
    Metabolism and nutrition disorders
    Anorexia
         subjects affected / exposed
    3 / 316 (0.95%)
    0 / 303 (0.00%)
         occurrences all number
    5
    0
    Dehydration
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 303 (0.33%)
         occurrences all number
    0
    1
    Hyperglycaemia
         subjects affected / exposed
    10 / 316 (3.16%)
    13 / 303 (4.29%)
         occurrences all number
    11
    21
    Hypertriglyceridaemia
         subjects affected / exposed
    3 / 316 (0.95%)
    17 / 303 (5.61%)
         occurrences all number
    3
    31
    Hyperuricaemia
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 303 (0.33%)
         occurrences all number
    0
    1
    Hypoalbuminaemia
         subjects affected / exposed
    3 / 316 (0.95%)
    0 / 303 (0.00%)
         occurrences all number
    6
    0
    Hypocalcaemia
         subjects affected / exposed
    1 / 316 (0.32%)
    2 / 303 (0.66%)
         occurrences all number
    1
    2
    Hypoglycaemia
         subjects affected / exposed
    0 / 316 (0.00%)
    1 / 303 (0.33%)
         occurrences all number
    0
    1
    Hypokalemia
         subjects affected / exposed
    10 / 316 (3.16%)
    7 / 303 (2.31%)
         occurrences all number
    13
    11
    Hypomagnesaemia
         subjects affected / exposed
    1 / 316 (0.32%)
    1 / 303 (0.33%)
         occurrences all number
    1
    1
    Hyponatraemia
         subjects affected / exposed
    5 / 316 (1.58%)
    5 / 303 (1.65%)
         occurrences all number
    5
    9
    Hypophosphataemia
         subjects affected / exposed
    1 / 316 (0.32%)
    2 / 303 (0.66%)
         occurrences all number
    1
    3
    Metabolism and nutrition disorders - Other, specify
         subjects affected / exposed
    4 / 316 (1.27%)
    3 / 303 (0.99%)
         occurrences all number
    7
    3
    Iron overload
         subjects affected / exposed
    2 / 316 (0.63%)
    0 / 303 (0.00%)
         occurrences all number
    2
    0

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    25 Feb 2015
    Amended Protocol Version 1.9: Minor changes and clarifications.
    01 Nov 2018
    Amended Protocol Version 2.0: Stop of second randomization since 01.02.2019 due to discontinued supply of Epratuzumab. All patients receive the full standard chemotherapy of arm A or B. Recruitment time and follow-up time extended.

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

    European Medicines Agency © 1995-Fri May 02 21:20:20 CEST 2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA