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    Clinical Trial Results:
    A Phase I/ II Study to Evaluate the Safety and Preliminary Efficacy of Nivolumab in Combination with Brentuximab Vedotin in Subjects with Relapsed Refractory Non Hodgkin Lymphomas with CD30 Expression CheckMate 436: CHECKpoint pathway and nivolumab clinical Trial Evaluation

    Summary
    EudraCT number
    2015-003286-28
    Trial protocol
    ES   FR   GB   IT  
    Global end of trial date
    07 Feb 2022

    Results information
    Results version number
    v1(current)
    This version publication date
    23 Feb 2023
    First version publication date
    23 Feb 2023
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    CA209-436
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    -
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Bristol-Myers Squibb
    Sponsor organisation address
    Chausse de la Hulpe 185, Brussels, Belgium, 1170
    Public contact
    EU Study Start-Up Unit, Bristol-Myers Squibb International Corporation, Clinical.Trials@bms.com
    Scientific contact
    Bristol-Myers Squibb Study Director, Bristol-Myers Squibb, Clinical.Trials@bms.com
    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
    30 Mar 2022
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    07 Feb 2022
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The purpose of this study is to evaluate the safety profile, tolerability and antitumor activity following administration of nivolumab in combination with brentuximab vedotin in subjects with the diagnosis of relapsed/refractory DLBCL, PTCL (all subtypes excluding ALCL), PMBL. MGZL and CTCL (MF/SS).
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization Good Clinical Practice Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    18 Dec 2015
    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
    France: 15
    Country: Number of subjects enrolled
    Canada: 23
    Country: Number of subjects enrolled
    United States: 6
    Country: Number of subjects enrolled
    Italy: 46
    Country: Number of subjects enrolled
    Spain: 7
    Country: Number of subjects enrolled
    United Kingdom: 47
    Worldwide total number of subjects
    144
    EEA total number of subjects
    68
    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)
    108
    From 65 to 84 years
    35
    85 years and over
    1

    Subject disposition

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    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    The Dose Evaluation Phase (Cohort A) will include a dose limiting toxicity (DLT) evaluation for the dose level of brentuximab vedotin 1.8 mg/kg in combination with nivolumab 240 mg. The reduced dose of brentuximab vedotin at 1.2 mg/kg was not needed based on the safety data reviewed throughout the DLT evaluation period.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Diffuse Large B-cell Lymphoma (DLBCL)
    Arm description
    1.8mg/kg brentuximab vedotin (BV) + 240mg nivolumab
    Arm type
    Experimental

    Investigational medicinal product name
    brentuximab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravascular use
    Dosage and administration details
    1.8mg/kg q3

    Investigational medicinal product name
    nivolumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravascular use
    Dosage and administration details
    240mg

    Arm title
    Peripheral T-cell Lymphoma (PTCL)
    Arm description
    1.8mg/kg brentuximab vedotin (BV) + 240mg nivolumab
    Arm type
    Experimental

    Investigational medicinal product name
    brentuximab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravascular use
    Dosage and administration details
    1.8mg/kg q3

    Investigational medicinal product name
    nivolumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravascular use
    Dosage and administration details
    240mg

    Arm title
    Cutaneous T-cell lymphoma (CTCL)
    Arm description
    1.8mg/kg brentuximab vedotin (BV) + 240mg nivolumab
    Arm type
    Experimental

    Investigational medicinal product name
    brentuximab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravascular use
    Dosage and administration details
    1.8mg/kg q3

    Investigational medicinal product name
    nivolumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravascular use
    Dosage and administration details
    240mg

    Arm title
    Mediastinal Grey Zone Lymphoma (MGZL)
    Arm description
    1.8mg/kg brentuximab vedotin (BV) + 240mg nivolumab
    Arm type
    Experimental

    Investigational medicinal product name
    brentuximab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravascular use
    Dosage and administration details
    1.8mg/kg q3

    Investigational medicinal product name
    nivolumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravascular use
    Dosage and administration details
    240mg

    Arm title
    Primary Mediastinal B-cell Lymphoma (PMBL)
    Arm description
    1.8mg/kg brentuximab vedotin (BV) + 240mg nivolumab
    Arm type
    Experimental

    Investigational medicinal product name
    brentuximab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravascular use
    Dosage and administration details
    1.8mg/kg q3

    Investigational medicinal product name
    nivolumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravascular use
    Dosage and administration details
    240mg

    Number of subjects in period 1
    Diffuse Large B-cell Lymphoma (DLBCL) Peripheral T-cell Lymphoma (PTCL) Cutaneous T-cell lymphoma (CTCL) Mediastinal Grey Zone Lymphoma (MGZL) Primary Mediastinal B-cell Lymphoma (PMBL)
    Started
    42
    33
    29
    10
    30
    Phase 1 DLT evaluable participants
    2
    1
    3
    0
    0
    Completed Phase 1 DLT evaluation
    2
    1
    3
    0
    0
    Completed
    0
    0
    0
    0
    0
    Not completed
    42
    33
    29
    10
    30
         Poor/Non-Compliance
    -
    -
    1
    -
    -
         Disease progression
    29
    19
    13
    5
    8
         Study drug toxicity
    4
    6
    7
    -
    3
         Request to discontinue
    1
    -
    3
    -
    1
         Other Reasons
    1
    -
    2
    2
    3
         Maximum clinical benefit
    1
    7
    1
    3
    13
         AE unrelated to study drug
    3
    1
    1
    -
    2
         participant withdrew consent
    3
    -
    1
    -
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Diffuse Large B-cell Lymphoma (DLBCL)
    Reporting group description
    1.8mg/kg brentuximab vedotin (BV) + 240mg nivolumab

    Reporting group title
    Peripheral T-cell Lymphoma (PTCL)
    Reporting group description
    1.8mg/kg brentuximab vedotin (BV) + 240mg nivolumab

    Reporting group title
    Cutaneous T-cell lymphoma (CTCL)
    Reporting group description
    1.8mg/kg brentuximab vedotin (BV) + 240mg nivolumab

    Reporting group title
    Mediastinal Grey Zone Lymphoma (MGZL)
    Reporting group description
    1.8mg/kg brentuximab vedotin (BV) + 240mg nivolumab

    Reporting group title
    Primary Mediastinal B-cell Lymphoma (PMBL)
    Reporting group description
    1.8mg/kg brentuximab vedotin (BV) + 240mg nivolumab

    Reporting group values
    Diffuse Large B-cell Lymphoma (DLBCL) Peripheral T-cell Lymphoma (PTCL) Cutaneous T-cell lymphoma (CTCL) Mediastinal Grey Zone Lymphoma (MGZL) Primary Mediastinal B-cell Lymphoma (PMBL) Total
    Number of subjects
    42 33 29 10 30 144
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    29 21 20 9 29 108
        From 65-84 years
    12 12 9 1 1 35
        85 years and over
    1 0 0 0 0 1
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    57.7 ± 13.2 59.1 ± 12.0 57.9 ± 12.39 39.9 ± 15.2 37.3 ± 12.9 -
    Sex: Female, Male
    Units: Participants
        Female
    20 11 13 4 17 65
        Male
    22 22 16 6 13 79
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    0 0 0 0 0 0
        Asian
    3 0 0 0 1 4
        Native Hawaiian or Other Pacific Islander
    0 0 0 0 0 0
        Black or African American
    3 2 5 1 2 13
        White
    36 30 24 9 26 125
        More than one race
    0 0 0 0 0 0
        Unknown or Not Reported
    0 1 0 0 1 2
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    1 2 0 0 1 4
        Not Hispanic or Latino
    14 13 16 6 9 58
        Unknown or Not Reported
    27 18 13 4 20 82

    End points

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    End points reporting groups
    Reporting group title
    Diffuse Large B-cell Lymphoma (DLBCL)
    Reporting group description
    1.8mg/kg brentuximab vedotin (BV) + 240mg nivolumab

    Reporting group title
    Peripheral T-cell Lymphoma (PTCL)
    Reporting group description
    1.8mg/kg brentuximab vedotin (BV) + 240mg nivolumab

    Reporting group title
    Cutaneous T-cell lymphoma (CTCL)
    Reporting group description
    1.8mg/kg brentuximab vedotin (BV) + 240mg nivolumab

    Reporting group title
    Mediastinal Grey Zone Lymphoma (MGZL)
    Reporting group description
    1.8mg/kg brentuximab vedotin (BV) + 240mg nivolumab

    Reporting group title
    Primary Mediastinal B-cell Lymphoma (PMBL)
    Reporting group description
    1.8mg/kg brentuximab vedotin (BV) + 240mg nivolumab

    Primary: Safety Analysis - Number of participant deaths

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    End point title
    Safety Analysis - Number of participant deaths [1]
    End point description
    Number of participant Deaths
    End point type
    Primary
    End point timeframe
    CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No Statistical Analysis done for this endpoint
    End point values
    Diffuse Large B-cell Lymphoma (DLBCL) Peripheral T-cell Lymphoma (PTCL) Cutaneous T-cell lymphoma (CTCL) Mediastinal Grey Zone Lymphoma (MGZL) Primary Mediastinal B-cell Lymphoma (PMBL)
    Number of subjects analysed
    42
    33
    29
    10
    30
    Units: Participants
    24
    22
    3
    3
    5
    No statistical analyses for this end point

    Primary: Safety Analysis - Number of participants with adverse advents

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    End point title
    Safety Analysis - Number of participants with adverse advents [2]
    End point description
    An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug.
    End point type
    Primary
    End point timeframe
    CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No Statistical Analysis done for this endpoint
    End point values
    Diffuse Large B-cell Lymphoma (DLBCL) Peripheral T-cell Lymphoma (PTCL) Cutaneous T-cell lymphoma (CTCL) Mediastinal Grey Zone Lymphoma (MGZL) Primary Mediastinal B-cell Lymphoma (PMBL)
    Number of subjects analysed
    42
    33
    29
    10
    30
    Units: Participants
    42
    33
    29
    10
    30
    No statistical analyses for this end point

    Primary: Safety Analysis - Number of participants with serious adverse events

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    End point title
    Safety Analysis - Number of participants with serious adverse events [3]
    End point description
    A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose: - results in death - is life-threatening (defined as an event in which the participant was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe) - requires inpatient hospitalization or causes prolongation of existing hospitalization. - results in persistent or significant disability/incapacity - is a congenital anomaly/birth defect - is an important medical event
    End point type
    Primary
    End point timeframe
    CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No Statistical Analysis done for this endpoint
    End point values
    Diffuse Large B-cell Lymphoma (DLBCL) Peripheral T-cell Lymphoma (PTCL) Cutaneous T-cell lymphoma (CTCL) Mediastinal Grey Zone Lymphoma (MGZL) Primary Mediastinal B-cell Lymphoma (PMBL)
    Number of subjects analysed
    42
    33
    29
    10
    30
    Units: Participants
    22
    19
    14
    4
    10
    No statistical analyses for this end point

    Primary: Safety Analysis - Number of participants with adverse events leading to discontinuation

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    End point title
    Safety Analysis - Number of participants with adverse events leading to discontinuation [4]
    End point description
    Number of participants with adverse events leading to discontinuation
    End point type
    Primary
    End point timeframe
    CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months
    Notes
    [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No Statistical Analysis done for this endpoint
    End point values
    Diffuse Large B-cell Lymphoma (DLBCL) Peripheral T-cell Lymphoma (PTCL) Cutaneous T-cell lymphoma (CTCL) Mediastinal Grey Zone Lymphoma (MGZL) Primary Mediastinal B-cell Lymphoma (PMBL)
    Number of subjects analysed
    42
    33
    29
    10
    30
    Units: Participants
    11
    10
    6
    2
    8
    No statistical analyses for this end point

    Primary: Safety Analysis - Number of participants with adverse events leading to dose delay or reduction

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    End point title
    Safety Analysis - Number of participants with adverse events leading to dose delay or reduction [5]
    End point description
    Number of participants with adverse events leading to dose delay or reduction
    End point type
    Primary
    End point timeframe
    CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months
    Notes
    [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No Statistical Analysis done for this endpoint
    End point values
    Diffuse Large B-cell Lymphoma (DLBCL) Peripheral T-cell Lymphoma (PTCL) Cutaneous T-cell lymphoma (CTCL) Mediastinal Grey Zone Lymphoma (MGZL) Primary Mediastinal B-cell Lymphoma (PMBL)
    Number of subjects analysed
    42
    33
    29
    10
    30
    Units: Participants
    16
    15
    14
    3
    17
    No statistical analyses for this end point

    Primary: Safety Analysis - Number of participants with drug related adverse events

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    End point title
    Safety Analysis - Number of participants with drug related adverse events [6]
    End point description
    Number of participants with Drug Related Adverse Events
    End point type
    Primary
    End point timeframe
    CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months
    Notes
    [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No Statistical Analysis done for this endpoint
    End point values
    Diffuse Large B-cell Lymphoma (DLBCL) Peripheral T-cell Lymphoma (PTCL) Cutaneous T-cell lymphoma (CTCL) Mediastinal Grey Zone Lymphoma (MGZL) Primary Mediastinal B-cell Lymphoma (PMBL)
    Number of subjects analysed
    42
    33
    29
    10
    30
    Units: Participants
    35
    27
    25
    9
    25
    No statistical analyses for this end point

    Primary: Safety Analysis - Percentage of participants with Thyroid test abnormalities

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    End point title
    Safety Analysis - Percentage of participants with Thyroid test abnormalities [7]
    End point description
    Percentage of participants with specific thyroid test abnormalities
    End point type
    Primary
    End point timeframe
    CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months
    Notes
    [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No Statistical Analysis done for this endpoint
    End point values
    Diffuse Large B-cell Lymphoma (DLBCL) Peripheral T-cell Lymphoma (PTCL) Cutaneous T-cell lymphoma (CTCL) Mediastinal Grey Zone Lymphoma (MGZL) Primary Mediastinal B-cell Lymphoma (PMBL)
    Number of subjects analysed
    26
    27
    22
    9
    25
    Units: Percentage of Participants
    number (not applicable)
        TSH > ULN
    34.6
    29.6
    18.2
    11.1
    24.0
        TSH > ULN w/ TSH ≤ ULN at baseline
    26.9
    22.2
    18.2
    0
    8.0
        TSH > ULN w/at least 1 FT3/FT4 value < LLN
    11.5
    11.1
    13.6
    0
    4.0
        TSH > ULN w/all other FT3/FT4 values ≥ LLN
    15.4
    11.1
    0
    11.1
    8.0
        TSH > ULN with FT3/FT4 testing missing
    7.7
    7.4
    4.5
    0
    12.0
        TSH < LLN
    7.7
    7.4
    4.5
    11.1
    24.0
        TSH < LLN w/TSH ≥ LLN at baseline
    7.7
    0
    4.5
    0
    20.0
        TSH < LLN w/at least 1 FT3/FT4 value > ULN
    0
    3.7
    4.5
    0
    20.0
        TSH < LLN w/ all other FT3/FT4 values ≤ ULN
    0
    3.7
    0
    11.1
    0
        TSH < LLN w/ FT3/FT4 test missing
    7.7
    0
    0
    0
    4.0
    No statistical analyses for this end point

    Primary: Safety Analysis - Percentage of participants with Liver test abnormalities

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    End point title
    Safety Analysis - Percentage of participants with Liver test abnormalities [8]
    End point description
    Percentage of participants with specific Liver test abnormalities
    End point type
    Primary
    End point timeframe
    CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months
    Notes
    [8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No Statistical Analysis done for this endpoint
    End point values
    Diffuse Large B-cell Lymphoma (DLBCL) Peripheral T-cell Lymphoma (PTCL) Cutaneous T-cell lymphoma (CTCL) Mediastinal Grey Zone Lymphoma (MGZL) Primary Mediastinal B-cell Lymphoma (PMBL)
    Number of subjects analysed
    42
    33
    29
    10
    30
    Units: Percentage of Participants
    number (not applicable)
        ALT or AST > 3 x ULN
    4.8
    6.1
    13.8
    20.0
    24.0
        ALT or AST > 5 x ULN
    2.4
    0
    6.9
    10.0
    10.0
        ALT or AST > 10 x ULN
    0
    0
    0
    10.0
    6.7
        ALT or AST > 20 x ULN
    0
    0
    0
    10.0
    6.7
        Total Bilirubin > 2 x ULN
    0
    6.1
    3.4
    20.0
    3.3
        ALT/AST elevation > 3xULN w/Bili >2xULN in 1 day
    0
    3.0
    3.4
    10.0
    3.3
        ALT/AST elevation >3xULN w/Bili 2xULN in 30 days
    0
    3.0
    3.4
    10.0
    3.3
    No statistical analyses for this end point

    Primary: Objective Response Rate (ORR)

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    End point title
    Objective Response Rate (ORR) [9]
    End point description
    The percentage of participants with a best overall response (BOR) of CR or PR. DLBCL, PTCL, PMBL & MGZL complete and partial response are outlined in the Lugano Classification 2014 and Lymphoma Response to Immunomodulatory therapy Criteria. CTCL complete and partial response are defined in The consensus Global Response Score assessment.
    End point type
    Primary
    End point timeframe
    CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months
    Notes
    [9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No Statistical Analysis done for this endpoint
    End point values
    Diffuse Large B-cell Lymphoma (DLBCL) Peripheral T-cell Lymphoma (PTCL) Cutaneous T-cell lymphoma (CTCL) Mediastinal Grey Zone Lymphoma (MGZL) Primary Mediastinal B-cell Lymphoma (PMBL)
    Number of subjects analysed
    42
    33
    29
    10
    30
    Units: Percentage of participants
        number (confidence interval 80%)
    28.6 (19.4 to 39.4)
    45.5 (33.3 to 58.0)
    41.4 (28.8 to 55.0)
    70.0 (44.8 to 88.4)
    73.3 (60.3 to 83.8)
    No statistical analyses for this end point

    Primary: Safety Analysis - Number of participants with dose limiting toxicities (DLT) in the DLT evaluation phase

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    End point title
    Safety Analysis - Number of participants with dose limiting toxicities (DLT) in the DLT evaluation phase [10]
    End point description
    DLTs are defined as any study drug-related toxicity (brentuximab vedotin or nivolumab) that requires either a dose reduction or delay of more than 7 days of either study drug in Cycle 2 or delays the Cycle 3 Day 1 administration of combined treatment by more than 7 days.
    End point type
    Primary
    End point timeframe
    From first dose of treatment to 6 weeks after first dose
    Notes
    [10] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No Statistical Analysis done for this endpoint
    End point values
    Diffuse Large B-cell Lymphoma (DLBCL) Peripheral T-cell Lymphoma (PTCL) Cutaneous T-cell lymphoma (CTCL) Mediastinal Grey Zone Lymphoma (MGZL) Primary Mediastinal B-cell Lymphoma (PMBL)
    Number of subjects analysed
    2
    1
    3
    0 [11]
    0 [12]
    Units: Participants
    0
    0
    0
    Notes
    [11] - No subjects with reportable measures
    [12] - No subjects with reportable measures
    No statistical analyses for this end point

    Secondary: Duration of Response (DOR)

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    End point title
    Duration of Response (DOR)
    End point description
    DOR will be calculated from the date of initial documentation of a response (CR, or PR) to the date of first documented evidence of progressive disease (or relapse for participants who experience CR during the study) or death due to any cause, whichever occurs first. DLBCL, PTCL, PMBL & MGZL complete and partial response are outlined in the Lugano Classification 2014 and Lymphoma Response to Immunomodulatory therapy Criteria. CTCL complete and partial response are defined in The consensus Global Response Score assessment. Here "99999" means NA
    End point type
    Secondary
    End point timeframe
    From the first patient first visit to 8 months after the last patient first visit (up to 48 months)
    End point values
    Diffuse Large B-cell Lymphoma (DLBCL) Peripheral T-cell Lymphoma (PTCL) Cutaneous T-cell lymphoma (CTCL) Mediastinal Grey Zone Lymphoma (MGZL) Primary Mediastinal B-cell Lymphoma (PMBL)
    Number of subjects analysed
    12
    15
    12
    7
    22
    Units: Months
        median (confidence interval 95%)
    3.55 (1.18 to 36.53)
    4.60 (2.76 to 12.75)
    26.97 (2.79 to 99999)
    20.76 (1.22 to 99999)
    99999 (23.33 to 99999)
    No statistical analyses for this end point

    Secondary: Complete Response Rate (CRR)

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    End point title
    Complete Response Rate (CRR)
    End point description
    The CRR is defined as the percentage of participants with a BOR (Best overall response) of CR divided by the number of treated participants. DLBCL, PTCL, PMBL & MGZL (CR) 1.Complete disappearance of all detectable clinical evidence of disease. 2.Bone marrow: No evidence of FDG- avid disease in marrow. CTCL (CR) 1. 100% clearance of skin lesions. 2. all lymph nodes ≤1.5 cm, N3 classification and ≤ 1.5 cm in their long axis and > 1 cm in their short axis at baseline, must be ≤ 1 cm in their short axis or biopsy negative for lymphoma. 3. organs should not be enlarged on examination or imaging 4.absence of blood involvement
    End point type
    Secondary
    End point timeframe
    From first dose to the date of initial objectively documented progression or the date of subsequent therapy, whichever occurs first (up to 48 months)
    End point values
    Diffuse Large B-cell Lymphoma (DLBCL) Peripheral T-cell Lymphoma (PTCL) Cutaneous T-cell lymphoma (CTCL) Mediastinal Grey Zone Lymphoma (MGZL) Primary Mediastinal B-cell Lymphoma (PMBL)
    Number of subjects analysed
    42
    33
    29
    10
    30
    Units: Percentage of Participants
        number (not applicable)
    7.1
    33.3
    3.4
    50.0
    40.0
    No statistical analyses for this end point

    Secondary: Duration of Complete Response

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    End point title
    Duration of Complete Response
    End point description
    The duration of CR will only be evaluated in participants with BOR of CR and is defined as the time from first documentation of CR to the date of relapse or death due to any cause, whichever occurs first. DLBCL, PTCL, PMBL & MGZL (CR) 1.Complete disappearance of all detectable clinical evidence of disease. 2.Bone marrow: No evidence of FDG- avid disease in marrow. CTCL (CR) 1. 100% clearance of skin lesions. 2. all lymph nodes ≤1.5 cm, N3 classification and ≤ 1.5 cm in their long axis and > 1 cm in their short axis at baseline, must be ≤ 1 cm in their short axis or biopsy negative for lymphoma. 3. organs should not be enlarged on examination or imaging 4.absence of blood involvement Here "99999" means NA
    End point type
    Secondary
    End point timeframe
    From first dose to the date of relapse or death due to any cause, whichever occurs first. (about 48 months)
    End point values
    Diffuse Large B-cell Lymphoma (DLBCL) Peripheral T-cell Lymphoma (PTCL) Cutaneous T-cell lymphoma (CTCL) Mediastinal Grey Zone Lymphoma (MGZL) Primary Mediastinal B-cell Lymphoma (PMBL)
    Number of subjects analysed
    3
    11
    1
    5
    12
    Units: Months
        median (confidence interval 95%)
    36.53 (9.92 to 99999)
    7.39 (2.17 to 99999)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    99999 (27.89 to 99999)
    No statistical analyses for this end point

    Secondary: Progression Free Survival (PFS)

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    End point title
    Progression Free Survival (PFS)
    End point description
    PFS is defined as the time from the date of first dose of study drug until the date of first documented evidence of progressive disease (or relapse for participants who experience CR during the study) or death due to any cause, whichever comes first. Participants who are progression-free and alive or have unknown status will be censored at the last tumor assessment. Participants who did not have any onstudy tumor assessments and did not die will be censored on the date of first treatment. For participants who received subsequent therapy prior to documented progression, it will be censored on the last tumor assessment date prior to or on subsequent therapy. Here "99999" means NA
    End point type
    Secondary
    End point timeframe
    From first dose of study drug until the date of first documented evidence of progressive disease (or relapse for participants who experience CR during the study) or death due to any cause, whichever comes first. (about 48 months)
    End point values
    Diffuse Large B-cell Lymphoma (DLBCL) Peripheral T-cell Lymphoma (PTCL) Cutaneous T-cell lymphoma (CTCL) Mediastinal Grey Zone Lymphoma (MGZL) Primary Mediastinal B-cell Lymphoma (PMBL)
    Number of subjects analysed
    42
    33
    29
    10
    30
    Units: Months
        median (confidence interval 95%)
    2.60 (1.38 to 2.79)
    4.30 (1.58 to 5.62)
    15.61 (4.86 to 99999)
    21.88 (0.07 to 99999)
    25.95 (2.63 to 99999)
    No statistical analyses for this end point

    Secondary: Overall Survival (OS)

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    End point title
    Overall Survival (OS)
    End point description
    OS is defined as the time from the date of first dose of study drug until the date of death (any reason). If the participant is alive or the vital status is unknown, the participant will be censored at the date the participant was last known to be alive. Here "99999" means NA
    End point type
    Secondary
    End point timeframe
    From the first patient first visit to 8 months after the last patient first visit (about 48 months)
    End point values
    Diffuse Large B-cell Lymphoma (DLBCL) Peripheral T-cell Lymphoma (PTCL) Cutaneous T-cell lymphoma (CTCL) Mediastinal Grey Zone Lymphoma (MGZL) Primary Mediastinal B-cell Lymphoma (PMBL)
    Number of subjects analysed
    42
    33
    29
    10
    30
    Units: Months
        median (confidence interval 95%)
    13.31 (6.57 to 15.87)
    11.07 (5.16 to 15.31)
    37.16 (18.63 to 99999)
    99999 (0.07 to 99999)
    99999 (99999 to 99999)
    No statistical analyses for this end point

    Post-hoc: Safety Analysis - Number of participant deaths - Extended collection

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    End point title
    Safety Analysis - Number of participant deaths - Extended collection
    End point description
    Number of participant Deaths This outcome measure represents an updated version of the primary endpoint to include additional data collection that has occurred after the primary completion date. (Assessments were made until 30-March-2022)
    End point type
    Post-hoc
    End point timeframe
    from first date of treatment to final database lock. Approximately 6 years and 7 months.
    End point values
    Diffuse Large B-cell Lymphoma (DLBCL) Peripheral T-cell Lymphoma (PTCL) Cutaneous T-cell lymphoma (CTCL) Mediastinal Grey Zone Lymphoma (MGZL) Primary Mediastinal B-cell Lymphoma (PMBL)
    Number of subjects analysed
    42
    33
    29
    10
    30
    Units: Participants
    30
    26
    14
    4
    8
    No statistical analyses for this end point

    Post-hoc: Safety Analysis - Number of participants with Adverse Events - Extended Collection

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    End point title
    Safety Analysis - Number of participants with Adverse Events - Extended Collection
    End point description
    An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. This outcome measure represents an updated version of the primary endpoint to include additional data collection that has occurred after the primary completion date. (Assessments were made until 30-March-2022)
    End point type
    Post-hoc
    End point timeframe
    From first patient first treatment to first to 100 days post last treatment. Approximately 6 years and 4 months.
    End point values
    Diffuse Large B-cell Lymphoma (DLBCL) Peripheral T-cell Lymphoma (PTCL) Cutaneous T-cell lymphoma (CTCL) Mediastinal Grey Zone Lymphoma (MGZL) Primary Mediastinal B-cell Lymphoma (PMBL)
    Number of subjects analysed
    42
    33
    29
    10
    30
    Units: Participants
    42
    33
    29
    10
    30
    No statistical analyses for this end point

    Post-hoc: Safety Analysis - Number of participants with Serious Adverse Events - Extended Collection

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    End point title
    Safety Analysis - Number of participants with Serious Adverse Events - Extended Collection
    End point description
    A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose: - results in death - is life-threatening (defined as an event in which the participant was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe) - requires inpatient hospitalization or causes prolongation of existing hospitalization. - results in persistent or significant disability/incapacity - is a congenital anomaly/birth defect - is an important medical event This outcome measure represents an updated version of the primary endpoint to include additional data collection that has occurred after the primary completion date. (Assessments were made until 30-March-2022)
    End point type
    Post-hoc
    End point timeframe
    From first patient first treatment to first to 100 days post last treatment. Approximately 6 years and 4 months.
    End point values
    Diffuse Large B-cell Lymphoma (DLBCL) Peripheral T-cell Lymphoma (PTCL) Cutaneous T-cell lymphoma (CTCL) Mediastinal Grey Zone Lymphoma (MGZL) Primary Mediastinal B-cell Lymphoma (PMBL)
    Number of subjects analysed
    42
    33
    29
    10
    30
    Units: Participants
    22
    19
    14
    4
    10
    No statistical analyses for this end point

    Post-hoc: Safety Analysis - Number of participants with Adverse Events leading to discontinuation - Extended Collection

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    End point title
    Safety Analysis - Number of participants with Adverse Events leading to discontinuation - Extended Collection
    End point description
    Number of Adverse events leading to discontinuation This outcome measure represents an updated version of the primary endpoint to include additional data collection that has occurred after the primary completion date. (Assessments were made until 30-March-2022)
    End point type
    Post-hoc
    End point timeframe
    From first patient first treatment to first to 100 days post last treatment. Approximately 6 years and 4 months.
    End point values
    Diffuse Large B-cell Lymphoma (DLBCL) Peripheral T-cell Lymphoma (PTCL) Cutaneous T-cell lymphoma (CTCL) Mediastinal Grey Zone Lymphoma (MGZL) Primary Mediastinal B-cell Lymphoma (PMBL)
    Number of subjects analysed
    42
    33
    29
    10
    30
    Units: Participants
    12
    11
    10
    2
    9
    No statistical analyses for this end point

    Post-hoc: Safety Analysis - Number of participants with Drug Related Adverse Events - Extended Collection

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    End point title
    Safety Analysis - Number of participants with Drug Related Adverse Events - Extended Collection
    End point description
    Number of Drug Related Adverse Events This outcome measure represents an updated version of the primary endpoint to include additional data collection that has occurred after the primary completion date. (Assessments were made until 30-March-2022)
    End point type
    Post-hoc
    End point timeframe
    From first patient first treatment to first to 100 days post last treatment. Approximately 6 years and 4 months.
    End point values
    Diffuse Large B-cell Lymphoma (DLBCL) Peripheral T-cell Lymphoma (PTCL) Cutaneous T-cell lymphoma (CTCL) Mediastinal Grey Zone Lymphoma (MGZL) Primary Mediastinal B-cell Lymphoma (PMBL)
    Number of subjects analysed
    42
    33
    29
    10
    30
    Units: Participants
    35
    28
    26
    9
    25
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From first patient first visit to first to final data base lock. Approximately 6 years and 7 months. All cause mortality is calculated from first treatment to final data base lock.. Approximately 6 years and 7 months.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    24.1
    Reporting groups
    Reporting group title
    DLBCL
    Reporting group description
    1.8mg/kg brentuximab vedotin (BV) + 240mg nivolumab

    Reporting group title
    PMBL
    Reporting group description
    1.8mg/kg brentuximab vedotin (BV) + 240mg nivolumab

    Reporting group title
    MGZL
    Reporting group description
    1.8mg/kg brentuximab vedotin (BV) + 240mg nivolumab

    Reporting group title
    PTCL
    Reporting group description
    1.8mg/kg brentuximab vedotin (BV) + 240mg nivolumab

    Reporting group title
    CTCL
    Reporting group description
    1.8mg/kg brentuximab vedotin (BV) + 240mg nivolumab

    Serious adverse events
    DLBCL PMBL MGZL PTCL CTCL
    Total subjects affected by serious adverse events
         subjects affected / exposed
    23 / 42 (54.76%)
    12 / 30 (40.00%)
    5 / 10 (50.00%)
    25 / 33 (75.76%)
    18 / 29 (62.07%)
         number of deaths (all causes)
    30
    8
    4
    26
    14
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Bladder transitional cell carcinoma
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lymphoma
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malignant neoplasm progression
         subjects affected / exposed
    13 / 42 (30.95%)
    2 / 30 (6.67%)
    1 / 10 (10.00%)
    9 / 33 (27.27%)
    4 / 29 (13.79%)
         occurrences causally related to treatment / all
    0 / 14
    0 / 2
    0 / 1
    0 / 9
    0 / 4
         deaths causally related to treatment / all
    0 / 10
    0 / 2
    0 / 1
    0 / 9
    0 / 4
    Neoplasm malignant
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    1 / 33 (3.03%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Haematoma
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 30 (3.33%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhage
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Embolism
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 30 (3.33%)
    0 / 10 (0.00%)
    1 / 33 (3.03%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    1 / 33 (3.03%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 30 (0.00%)
    1 / 10 (10.00%)
    0 / 33 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    1 / 33 (3.03%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Influenza like illness
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    1 / 33 (3.03%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 30 (0.00%)
    1 / 10 (10.00%)
    0 / 33 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    0 / 42 (0.00%)
    2 / 30 (6.67%)
    1 / 10 (10.00%)
    10 / 33 (30.30%)
    2 / 29 (6.90%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 1
    3 / 11
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Cytokine release syndrome
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    1 / 33 (3.03%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Oedema genital
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Atelectasis
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 30 (3.33%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute respiratory failure
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    1 / 33 (3.03%)
    2 / 29 (6.90%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 30 (3.33%)
    0 / 10 (0.00%)
    2 / 33 (6.06%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    1 / 42 (2.38%)
    1 / 30 (3.33%)
    0 / 10 (0.00%)
    1 / 33 (3.03%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    Pleural effusion
         subjects affected / exposed
    2 / 42 (4.76%)
    1 / 30 (3.33%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 30 (3.33%)
    0 / 10 (0.00%)
    1 / 33 (3.03%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory distress
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    1 / 33 (3.03%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Psychiatric disorders
    Confusional state
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Delirium
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Lipase increased
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clostridium test positive
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transaminases increased
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    1 / 42 (2.38%)
    1 / 30 (3.33%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infusion related reaction
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    1 / 33 (3.03%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Overdose
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 30 (3.33%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Aplasia
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    1 / 33 (3.03%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrioventricular block complete
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 30 (3.33%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Dysmetria
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    1 / 33 (3.03%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Paraparesis
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 30 (0.00%)
    1 / 10 (10.00%)
    0 / 33 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Neutropenia
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    3 / 42 (7.14%)
    2 / 30 (6.67%)
    1 / 10 (10.00%)
    1 / 33 (3.03%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
    2 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    1 / 33 (3.03%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    1 / 33 (3.03%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 30 (3.33%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 30 (3.33%)
    0 / 10 (0.00%)
    1 / 33 (3.03%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    1 / 33 (3.03%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    2 / 33 (6.06%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholestasis
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 30 (3.33%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune-mediated hepatitis
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 30 (3.33%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatotoxicity
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    1 / 33 (3.03%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Jaundice cholestatic
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Stevens-Johnson syndrome
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rash maculo-papular
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 30 (3.33%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Erythema multiforme
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dermatitis exfoliative generalised
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 42 (0.00%)
    2 / 30 (6.67%)
    0 / 10 (0.00%)
    2 / 33 (6.06%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Nephroangiosclerosis
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    1 / 33 (3.03%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    Adrenal insufficiency
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    1 / 33 (3.03%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Pain in extremity
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Bacteraemia
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    1 / 33 (3.03%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clostridium difficile colitis
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clostridium difficile infection
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Device related infection
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Escherichia urinary tract infection
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    1 / 33 (3.03%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung abscess
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    4 / 42 (9.52%)
    1 / 30 (3.33%)
    0 / 10 (0.00%)
    2 / 33 (6.06%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    2 / 5
    0 / 1
    0 / 0
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Pneumonia pseudomonal
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 30 (3.33%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia staphylococcal
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 42 (2.38%)
    1 / 30 (3.33%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    1 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular device infection
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin infection
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal infection
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    1 / 33 (3.03%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Diabetes mellitus
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    DLBCL PMBL MGZL PTCL CTCL
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    42 / 42 (100.00%)
    28 / 30 (93.33%)
    9 / 10 (90.00%)
    33 / 33 (100.00%)
    28 / 29 (96.55%)
    Vascular disorders
    Hot flush
         subjects affected / exposed
    3 / 42 (7.14%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    4
    0
    0
    0
    0
    Hypotension
         subjects affected / exposed
    9 / 42 (21.43%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    4 / 33 (12.12%)
    2 / 29 (6.90%)
         occurrences all number
    10
    0
    0
    4
    2
    Hypertension
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 30 (0.00%)
    2 / 10 (20.00%)
    3 / 33 (9.09%)
    3 / 29 (10.34%)
         occurrences all number
    0
    0
    2
    3
    3
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    11 / 42 (26.19%)
    4 / 30 (13.33%)
    0 / 10 (0.00%)
    7 / 33 (21.21%)
    5 / 29 (17.24%)
         occurrences all number
    12
    4
    0
    7
    7
    Fatigue
         subjects affected / exposed
    16 / 42 (38.10%)
    2 / 30 (6.67%)
    1 / 10 (10.00%)
    15 / 33 (45.45%)
    8 / 29 (27.59%)
         occurrences all number
    16
    2
    1
    18
    8
    Chills
         subjects affected / exposed
    7 / 42 (16.67%)
    2 / 30 (6.67%)
    0 / 10 (0.00%)
    2 / 33 (6.06%)
    2 / 29 (6.90%)
         occurrences all number
    11
    2
    0
    3
    2
    Chest pain
         subjects affected / exposed
    1 / 42 (2.38%)
    2 / 30 (6.67%)
    1 / 10 (10.00%)
    0 / 33 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    1
    3
    1
    0
    0
    Gait disturbance
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 30 (0.00%)
    1 / 10 (10.00%)
    0 / 33 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    1
    0
    1
    0
    1
    Malaise
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    2 / 33 (6.06%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    Oedema peripheral
         subjects affected / exposed
    4 / 42 (9.52%)
    1 / 30 (3.33%)
    0 / 10 (0.00%)
    2 / 33 (6.06%)
    7 / 29 (24.14%)
         occurrences all number
    4
    1
    0
    2
    7
    Pain
         subjects affected / exposed
    1 / 42 (2.38%)
    4 / 30 (13.33%)
    0 / 10 (0.00%)
    1 / 33 (3.03%)
    0 / 29 (0.00%)
         occurrences all number
    1
    4
    0
    1
    0
    Peripheral swelling
         subjects affected / exposed
    3 / 42 (7.14%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    3
    0
    0
    0
    0
    Pyrexia
         subjects affected / exposed
    13 / 42 (30.95%)
    7 / 30 (23.33%)
    2 / 10 (20.00%)
    12 / 33 (36.36%)
    14 / 29 (48.28%)
         occurrences all number
    17
    10
    3
    20
    17
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    5 / 42 (11.90%)
    3 / 30 (10.00%)
    1 / 10 (10.00%)
    7 / 33 (21.21%)
    4 / 29 (13.79%)
         occurrences all number
    5
    4
    1
    7
    4
    Dysphonia
         subjects affected / exposed
    3 / 42 (7.14%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    1 / 33 (3.03%)
    1 / 29 (3.45%)
         occurrences all number
    4
    0
    0
    1
    2
    Cough
         subjects affected / exposed
    10 / 42 (23.81%)
    13 / 30 (43.33%)
    3 / 10 (30.00%)
    9 / 33 (27.27%)
    6 / 29 (20.69%)
         occurrences all number
    10
    15
    4
    9
    9
    Pneumonitis
         subjects affected / exposed
    2 / 42 (4.76%)
    1 / 30 (3.33%)
    0 / 10 (0.00%)
    2 / 33 (6.06%)
    0 / 29 (0.00%)
         occurrences all number
    2
    1
    0
    2
    0
    Oropharyngeal pain
         subjects affected / exposed
    4 / 42 (9.52%)
    2 / 30 (6.67%)
    0 / 10 (0.00%)
    3 / 33 (9.09%)
    0 / 29 (0.00%)
         occurrences all number
    4
    4
    0
    3
    0
    Nasal congestion
         subjects affected / exposed
    2 / 42 (4.76%)
    1 / 30 (3.33%)
    1 / 10 (10.00%)
    1 / 33 (3.03%)
    1 / 29 (3.45%)
         occurrences all number
    2
    1
    2
    3
    2
    Hypoxia
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 30 (3.33%)
    0 / 10 (0.00%)
    2 / 33 (6.06%)
    0 / 29 (0.00%)
         occurrences all number
    0
    1
    0
    2
    0
    Dyspnoea exertional
         subjects affected / exposed
    6 / 42 (14.29%)
    1 / 30 (3.33%)
    0 / 10 (0.00%)
    2 / 33 (6.06%)
    0 / 29 (0.00%)
         occurrences all number
    7
    1
    0
    2
    0
    Productive cough
         subjects affected / exposed
    4 / 42 (9.52%)
    2 / 30 (6.67%)
    0 / 10 (0.00%)
    1 / 33 (3.03%)
    0 / 29 (0.00%)
         occurrences all number
    9
    3
    0
    2
    0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    3 / 42 (7.14%)
    2 / 30 (6.67%)
    0 / 10 (0.00%)
    2 / 33 (6.06%)
    2 / 29 (6.90%)
         occurrences all number
    3
    2
    0
    2
    2
    Insomnia
         subjects affected / exposed
    5 / 42 (11.90%)
    2 / 30 (6.67%)
    2 / 10 (20.00%)
    1 / 33 (3.03%)
    4 / 29 (13.79%)
         occurrences all number
    6
    2
    2
    1
    4
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 30 (3.33%)
    2 / 10 (20.00%)
    6 / 33 (18.18%)
    2 / 29 (6.90%)
         occurrences all number
    0
    1
    3
    7
    3
    Amylase increased
         subjects affected / exposed
    1 / 42 (2.38%)
    1 / 30 (3.33%)
    0 / 10 (0.00%)
    3 / 33 (9.09%)
    3 / 29 (10.34%)
         occurrences all number
    1
    1
    0
    4
    3
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 30 (0.00%)
    2 / 10 (20.00%)
    6 / 33 (18.18%)
    3 / 29 (10.34%)
         occurrences all number
    0
    0
    2
    8
    4
    Blood alkaline phosphatase increased
         subjects affected / exposed
    2 / 42 (4.76%)
    0 / 30 (0.00%)
    1 / 10 (10.00%)
    2 / 33 (6.06%)
    0 / 29 (0.00%)
         occurrences all number
    2
    0
    1
    3
    0
    Blood bilirubin increased
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 30 (0.00%)
    1 / 10 (10.00%)
    2 / 33 (6.06%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    2
    2
    0
    Blood creatinine increased
         subjects affected / exposed
    3 / 42 (7.14%)
    0 / 30 (0.00%)
    1 / 10 (10.00%)
    1 / 33 (3.03%)
    1 / 29 (3.45%)
         occurrences all number
    3
    0
    1
    1
    1
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    2 / 42 (4.76%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    3 / 33 (9.09%)
    0 / 29 (0.00%)
         occurrences all number
    2
    0
    0
    3
    0
    Lipase increased
         subjects affected / exposed
    2 / 42 (4.76%)
    1 / 30 (3.33%)
    0 / 10 (0.00%)
    3 / 33 (9.09%)
    4 / 29 (13.79%)
         occurrences all number
    2
    1
    0
    3
    6
    Lymphocyte count decreased
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    3 / 33 (9.09%)
    2 / 29 (6.90%)
         occurrences all number
    0
    0
    0
    3
    3
    Neutrophil count decreased
         subjects affected / exposed
    2 / 42 (4.76%)
    2 / 30 (6.67%)
    0 / 10 (0.00%)
    5 / 33 (15.15%)
    0 / 29 (0.00%)
         occurrences all number
    6
    4
    0
    8
    0
    Platelet count decreased
         subjects affected / exposed
    1 / 42 (2.38%)
    1 / 30 (3.33%)
    0 / 10 (0.00%)
    3 / 33 (9.09%)
    2 / 29 (6.90%)
         occurrences all number
    1
    1
    0
    3
    2
    Weight decreased
         subjects affected / exposed
    4 / 42 (9.52%)
    2 / 30 (6.67%)
    1 / 10 (10.00%)
    2 / 33 (6.06%)
    3 / 29 (10.34%)
         occurrences all number
    4
    2
    1
    2
    3
    Weight increased
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 30 (0.00%)
    1 / 10 (10.00%)
    0 / 33 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    1
    0
    1
    White blood cell count decreased
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    2 / 33 (6.06%)
    1 / 29 (3.45%)
         occurrences all number
    1
    0
    0
    3
    1
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    3 / 42 (7.14%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    3
    0
    0
    0
    1
    Infusion related reaction
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 30 (3.33%)
    1 / 10 (10.00%)
    4 / 33 (12.12%)
    6 / 29 (20.69%)
         occurrences all number
    0
    1
    2
    4
    18
    Procedural nausea
         subjects affected / exposed
    0 / 42 (0.00%)
    2 / 30 (6.67%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    Cardiac disorders
    Sinus bradycardia
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 30 (0.00%)
    1 / 10 (10.00%)
    0 / 33 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Sinus tachycardia
         subjects affected / exposed
    2 / 42 (4.76%)
    2 / 30 (6.67%)
    0 / 10 (0.00%)
    1 / 33 (3.03%)
    0 / 29 (0.00%)
         occurrences all number
    2
    2
    0
    1
    0
    Tachycardia
         subjects affected / exposed
    2 / 42 (4.76%)
    2 / 30 (6.67%)
    1 / 10 (10.00%)
    0 / 33 (0.00%)
    2 / 29 (6.90%)
         occurrences all number
    2
    2
    1
    0
    2
    Nervous system disorders
    Neuropathy peripheral
         subjects affected / exposed
    14 / 42 (33.33%)
    9 / 30 (30.00%)
    0 / 10 (0.00%)
    5 / 33 (15.15%)
    9 / 29 (31.03%)
         occurrences all number
    15
    11
    0
    5
    12
    Paraesthesia
         subjects affected / exposed
    3 / 42 (7.14%)
    2 / 30 (6.67%)
    3 / 10 (30.00%)
    5 / 33 (15.15%)
    1 / 29 (3.45%)
         occurrences all number
    3
    2
    3
    5
    1
    Headache
         subjects affected / exposed
    6 / 42 (14.29%)
    6 / 30 (20.00%)
    0 / 10 (0.00%)
    3 / 33 (9.09%)
    4 / 29 (13.79%)
         occurrences all number
    9
    6
    0
    7
    4
    Dysgeusia
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 30 (3.33%)
    0 / 10 (0.00%)
    3 / 33 (9.09%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    0
    3
    1
    Peripheral sensory neuropathy
         subjects affected / exposed
    1 / 42 (2.38%)
    5 / 30 (16.67%)
    2 / 10 (20.00%)
    5 / 33 (15.15%)
    3 / 29 (10.34%)
         occurrences all number
    1
    5
    2
    5
    3
    Dizziness
         subjects affected / exposed
    3 / 42 (7.14%)
    1 / 30 (3.33%)
    0 / 10 (0.00%)
    3 / 33 (9.09%)
    1 / 29 (3.45%)
         occurrences all number
    3
    1
    0
    4
    1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    5 / 42 (11.90%)
    3 / 30 (10.00%)
    6 / 10 (60.00%)
    10 / 33 (30.30%)
    1 / 29 (3.45%)
         occurrences all number
    8
    3
    6
    25
    1
    Eosinophilia
         subjects affected / exposed
    0 / 42 (0.00%)
    2 / 30 (6.67%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    Thrombocytopenia
         subjects affected / exposed
    5 / 42 (11.90%)
    5 / 30 (16.67%)
    3 / 10 (30.00%)
    8 / 33 (24.24%)
    1 / 29 (3.45%)
         occurrences all number
    8
    8
    4
    10
    1
    Neutropenia
         subjects affected / exposed
    8 / 42 (19.05%)
    13 / 30 (43.33%)
    4 / 10 (40.00%)
    9 / 33 (27.27%)
    0 / 29 (0.00%)
         occurrences all number
    20
    23
    5
    23
    0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    2 / 33 (6.06%)
    1 / 29 (3.45%)
         occurrences all number
    1
    0
    0
    2
    1
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    10 / 42 (23.81%)
    4 / 30 (13.33%)
    0 / 10 (0.00%)
    9 / 33 (27.27%)
    1 / 29 (3.45%)
         occurrences all number
    15
    5
    0
    12
    1
    Abdominal pain lower
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    1 / 33 (3.03%)
    2 / 29 (6.90%)
         occurrences all number
    0
    0
    0
    4
    2
    Abdominal pain upper
         subjects affected / exposed
    0 / 42 (0.00%)
    2 / 30 (6.67%)
    1 / 10 (10.00%)
    2 / 33 (6.06%)
    2 / 29 (6.90%)
         occurrences all number
    0
    2
    1
    4
    3
    Diarrhoea
         subjects affected / exposed
    20 / 42 (47.62%)
    4 / 30 (13.33%)
    0 / 10 (0.00%)
    14 / 33 (42.42%)
    15 / 29 (51.72%)
         occurrences all number
    41
    6
    0
    27
    21
    Constipation
         subjects affected / exposed
    9 / 42 (21.43%)
    5 / 30 (16.67%)
    1 / 10 (10.00%)
    8 / 33 (24.24%)
    3 / 29 (10.34%)
         occurrences all number
    13
    5
    1
    11
    3
    Dyspepsia
         subjects affected / exposed
    2 / 42 (4.76%)
    3 / 30 (10.00%)
    0 / 10 (0.00%)
    2 / 33 (6.06%)
    4 / 29 (13.79%)
         occurrences all number
    3
    4
    0
    2
    4
    Dysphagia
         subjects affected / exposed
    3 / 42 (7.14%)
    1 / 30 (3.33%)
    0 / 10 (0.00%)
    2 / 33 (6.06%)
    1 / 29 (3.45%)
         occurrences all number
    4
    1
    0
    2
    1
    Flatulence
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    2 / 33 (6.06%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 42 (0.00%)
    2 / 30 (6.67%)
    0 / 10 (0.00%)
    1 / 33 (3.03%)
    2 / 29 (6.90%)
         occurrences all number
    0
    2
    0
    1
    2
    Haemorrhoids
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    2 / 33 (6.06%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    3
    0
    Stomatitis
         subjects affected / exposed
    0 / 42 (0.00%)
    2 / 30 (6.67%)
    0 / 10 (0.00%)
    2 / 33 (6.06%)
    1 / 29 (3.45%)
         occurrences all number
    0
    2
    0
    3
    1
    Nausea
         subjects affected / exposed
    17 / 42 (40.48%)
    5 / 30 (16.67%)
    0 / 10 (0.00%)
    12 / 33 (36.36%)
    10 / 29 (34.48%)
         occurrences all number
    20
    9
    0
    18
    11
    Toothache
         subjects affected / exposed
    0 / 42 (0.00%)
    2 / 30 (6.67%)
    1 / 10 (10.00%)
    0 / 33 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    2
    1
    0
    0
    Vomiting
         subjects affected / exposed
    9 / 42 (21.43%)
    3 / 30 (10.00%)
    0 / 10 (0.00%)
    8 / 33 (24.24%)
    3 / 29 (10.34%)
         occurrences all number
    10
    5
    0
    12
    3
    Skin and subcutaneous tissue disorders
    Hyperhidrosis
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 30 (3.33%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    2 / 29 (6.90%)
         occurrences all number
    0
    1
    0
    0
    2
    Dry skin
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    4 / 33 (12.12%)
    2 / 29 (6.90%)
         occurrences all number
    1
    0
    0
    4
    2
    Dermatitis exfoliative generalised
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    4 / 29 (13.79%)
         occurrences all number
    0
    0
    0
    0
    4
    Alopecia
         subjects affected / exposed
    4 / 42 (9.52%)
    1 / 30 (3.33%)
    0 / 10 (0.00%)
    3 / 33 (9.09%)
    3 / 29 (10.34%)
         occurrences all number
    5
    1
    0
    4
    3
    Night sweats
         subjects affected / exposed
    6 / 42 (14.29%)
    2 / 30 (6.67%)
    0 / 10 (0.00%)
    2 / 33 (6.06%)
    0 / 29 (0.00%)
         occurrences all number
    10
    2
    0
    2
    0
    Rash maculo-papular
         subjects affected / exposed
    2 / 42 (4.76%)
    0 / 30 (0.00%)
    1 / 10 (10.00%)
    2 / 33 (6.06%)
    3 / 29 (10.34%)
         occurrences all number
    2
    0
    3
    2
    3
    Rash macular
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    2 / 29 (6.90%)
         occurrences all number
    0
    0
    0
    0
    2
    Rash
         subjects affected / exposed
    5 / 42 (11.90%)
    6 / 30 (20.00%)
    0 / 10 (0.00%)
    9 / 33 (27.27%)
    4 / 29 (13.79%)
         occurrences all number
    7
    8
    0
    13
    8
    Pruritus
         subjects affected / exposed
    3 / 42 (7.14%)
    4 / 30 (13.33%)
    1 / 10 (10.00%)
    10 / 33 (30.30%)
    8 / 29 (27.59%)
         occurrences all number
    4
    5
    1
    13
    10
    Petechiae
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    2 / 33 (6.06%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    Skin exfoliation
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    3 / 29 (10.34%)
         occurrences all number
    0
    0
    0
    0
    3
    Skin lesion
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 30 (3.33%)
    0 / 10 (0.00%)
    1 / 33 (3.03%)
    2 / 29 (6.90%)
         occurrences all number
    0
    1
    0
    1
    2
    Skin ulcer
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 30 (0.00%)
    1 / 10 (10.00%)
    0 / 33 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    1 / 33 (3.03%)
    3 / 29 (10.34%)
         occurrences all number
    1
    0
    0
    1
    3
    Endocrine disorders
    Hyperthyroidism
         subjects affected / exposed
    0 / 42 (0.00%)
    4 / 30 (13.33%)
    0 / 10 (0.00%)
    1 / 33 (3.03%)
    0 / 29 (0.00%)
         occurrences all number
    0
    4
    0
    1
    0
    Hypothyroidism
         subjects affected / exposed
    1 / 42 (2.38%)
    2 / 30 (6.67%)
    0 / 10 (0.00%)
    1 / 33 (3.03%)
    2 / 29 (6.90%)
         occurrences all number
    1
    2
    0
    1
    2
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    8 / 42 (19.05%)
    6 / 30 (20.00%)
    1 / 10 (10.00%)
    7 / 33 (21.21%)
    4 / 29 (13.79%)
         occurrences all number
    11
    7
    1
    9
    4
    Bone pain
         subjects affected / exposed
    1 / 42 (2.38%)
    1 / 30 (3.33%)
    1 / 10 (10.00%)
    2 / 33 (6.06%)
    0 / 29 (0.00%)
         occurrences all number
    1
    1
    1
    2
    0
    Back pain
         subjects affected / exposed
    3 / 42 (7.14%)
    3 / 30 (10.00%)
    1 / 10 (10.00%)
    6 / 33 (18.18%)
    1 / 29 (3.45%)
         occurrences all number
    3
    3
    1
    6
    1
    Pain in extremity
         subjects affected / exposed
    4 / 42 (9.52%)
    3 / 30 (10.00%)
    1 / 10 (10.00%)
    4 / 33 (12.12%)
    0 / 29 (0.00%)
         occurrences all number
    5
    4
    1
    5
    0
    Neck pain
         subjects affected / exposed
    1 / 42 (2.38%)
    1 / 30 (3.33%)
    0 / 10 (0.00%)
    1 / 33 (3.03%)
    2 / 29 (6.90%)
         occurrences all number
    1
    1
    0
    2
    2
    Myalgia
         subjects affected / exposed
    2 / 42 (4.76%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    1 / 33 (3.03%)
    3 / 29 (10.34%)
         occurrences all number
    2
    0
    0
    1
    3
    Muscular weakness
         subjects affected / exposed
    2 / 42 (4.76%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    3 / 33 (9.09%)
    1 / 29 (3.45%)
         occurrences all number
    2
    0
    0
    3
    1
    Muscle spasms
         subjects affected / exposed
    3 / 42 (7.14%)
    0 / 30 (0.00%)
    1 / 10 (10.00%)
    1 / 33 (3.03%)
    2 / 29 (6.90%)
         occurrences all number
    3
    0
    1
    1
    2
    Infections and infestations
    Ear infection
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    1 / 33 (3.03%)
    2 / 29 (6.90%)
         occurrences all number
    1
    0
    0
    1
    2
    Nasopharyngitis
         subjects affected / exposed
    3 / 42 (7.14%)
    2 / 30 (6.67%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    3
    2
    0
    0
    0
    Influenza
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    2 / 33 (6.06%)
    1 / 29 (3.45%)
         occurrences all number
    1
    0
    0
    2
    1
    Herpes zoster
         subjects affected / exposed
    3 / 42 (7.14%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    1 / 33 (3.03%)
    1 / 29 (3.45%)
         occurrences all number
    3
    0
    0
    1
    1
    Oral candidiasis
         subjects affected / exposed
    2 / 42 (4.76%)
    2 / 30 (6.67%)
    0 / 10 (0.00%)
    1 / 33 (3.03%)
    0 / 29 (0.00%)
         occurrences all number
    2
    2
    0
    2
    0
    Pneumonia
         subjects affected / exposed
    5 / 42 (11.90%)
    1 / 30 (3.33%)
    2 / 10 (20.00%)
    1 / 33 (3.03%)
    1 / 29 (3.45%)
         occurrences all number
    5
    1
    3
    1
    1
    Rhinitis
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 30 (0.00%)
    1 / 10 (10.00%)
    2 / 33 (6.06%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    1
    3
    0
    Sinusitis
         subjects affected / exposed
    3 / 42 (7.14%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    4
    0
    0
    0
    1
    Skin infection
         subjects affected / exposed
    2 / 42 (4.76%)
    0 / 30 (0.00%)
    1 / 10 (10.00%)
    0 / 33 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    2
    0
    1
    0
    2
    Staphylococcal infection
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 30 (3.33%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    2 / 29 (6.90%)
         occurrences all number
    0
    1
    0
    0
    2
    Upper respiratory tract infection
         subjects affected / exposed
    3 / 42 (7.14%)
    3 / 30 (10.00%)
    0 / 10 (0.00%)
    1 / 33 (3.03%)
    1 / 29 (3.45%)
         occurrences all number
    5
    3
    0
    2
    1
    Urinary tract infection
         subjects affected / exposed
    4 / 42 (9.52%)
    0 / 30 (0.00%)
    1 / 10 (10.00%)
    2 / 33 (6.06%)
    1 / 29 (3.45%)
         occurrences all number
    6
    0
    2
    2
    1
    Viral infection
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    2 / 33 (6.06%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    Metabolism and nutrition disorders
    Diabetes mellitus
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    2 / 29 (6.90%)
         occurrences all number
    0
    0
    0
    0
    2
    Decreased appetite
         subjects affected / exposed
    8 / 42 (19.05%)
    3 / 30 (10.00%)
    2 / 10 (20.00%)
    6 / 33 (18.18%)
    5 / 29 (17.24%)
         occurrences all number
    11
    3
    2
    9
    6
    Hyperuricaemia
         subjects affected / exposed
    2 / 42 (4.76%)
    0 / 30 (0.00%)
    2 / 10 (20.00%)
    1 / 33 (3.03%)
    1 / 29 (3.45%)
         occurrences all number
    2
    0
    3
    1
    1
    Hyperkalaemia
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    2 / 29 (6.90%)
         occurrences all number
    0
    0
    0
    0
    2
    Hyperglycaemia
         subjects affected / exposed
    2 / 42 (4.76%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    4 / 33 (12.12%)
    0 / 29 (0.00%)
         occurrences all number
    5
    0
    0
    4
    0
    Hypoalbuminaemia
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    2 / 33 (6.06%)
    0 / 29 (0.00%)
         occurrences all number
    1
    0
    0
    2
    0
    Hypercalcaemia
         subjects affected / exposed
    3 / 42 (7.14%)
    0 / 30 (0.00%)
    0 / 10 (0.00%)
    0 / 33 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    3
    0
    0
    0
    0
    Hypomagnesaemia
         subjects affected / exposed
    6 / 42 (14.29%)
    1 / 30 (3.33%)
    3 / 10 (30.00%)
    5 / 33 (15.15%)
    1 / 29 (3.45%)
         occurrences all number
    10
    1
    4
    5
    1
    Hypokalaemia
         subjects affected / exposed
    9 / 42 (21.43%)
    0 / 30 (0.00%)
    3 / 10 (30.00%)
    4 / 33 (12.12%)
    1 / 29 (3.45%)
         occurrences all number
    11
    0
    3
    10
    1
    Hypocalcaemia
         subjects affected / exposed
    4 / 42 (9.52%)
    0 / 30 (0.00%)
    1 / 10 (10.00%)
    5 / 33 (15.15%)
    0 / 29 (0.00%)
         occurrences all number
    4
    0
    1
    9
    0

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    14 Sep 2016
    This amendment will allow additional cohorts in subjects with relapsed PMBL & MGZL to participate in the expansion cohort. Additionally, the amendment will also provide defined Indeterminate response (IR) criteria along with changes in the biomarker section. Minor clarification in the inclusion, exclusion criteria and clarification of dose adjustment for brentuximab vedotin for grade 3 neurological toxicity has also been updated

    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.

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