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    Clinical Trial Results:
    A Phase II Study Exploring the Safety and Efficacy of Atezolizumab Administered in Combination With Obinutuzumab or Rituximab Anti-CD20 Therapy in Patients With Relapsed/Refractory Mantle Cell Lymphoma, Marginal Zone Lymphoma and Waldenström Macroglobulinemia

    Summary
    EudraCT number
    2016-003579-22
    Trial protocol
    ES   DE   LV   GR   SK   FR   IT  
    Global end of trial date
    14 Jan 2022

    Results information
    Results version number
    v1(current)
    This version publication date
    29 Jan 2023
    First version publication date
    29 Jan 2023
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    MO39107
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    -
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    F. Hoffmann-La Roche AG
    Sponsor organisation address
    Grenzacherstrasse 124, Basel, Switzerland, CH-4070
    Public contact
    F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, 41 616878333, global.trial_information@roche.com
    Scientific contact
    F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, 41 616878333, global.trial_information@roche.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
    14 Jan 2022
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    14 Jan 2022
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    This study evaluated the efficacy, safety and tolerability of atezolizumab in combination with obinutuzumab in participants with relapsed/refractory Mantle Cell Lymphoma (MCL) and Waldenström Macroglobulinemia (WM) or with rituximab in participants with relapsed/refractory Marginal Zone Lymphoma (MZL).
    Protection of trial subjects
    All study subjects were required to read and sign an Informed Consent Form.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    21 Nov 2017
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    Safety, Efficacy
    Long term follow-up duration
    24 Months
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    France: 9
    Country: Number of subjects enrolled
    Latvia: 1
    Country: Number of subjects enrolled
    Germany: 2
    Country: Number of subjects enrolled
    Greece: 11
    Country: Number of subjects enrolled
    Italy: 3
    Country: Number of subjects enrolled
    Spain: 9
    Country: Number of subjects enrolled
    Switzerland: 1
    Country: Number of subjects enrolled
    Bosnia and Herzegovina: 3
    Country: Number of subjects enrolled
    Russian Federation: 14
    Country: Number of subjects enrolled
    Slovakia: 2
    Worldwide total number of subjects
    55
    EEA total number of subjects
    37
    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)
    21
    From 65 to 84 years
    33
    85 years and over
    1

    Subject disposition

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    Recruitment
    Recruitment details
    Initially plan was to enroll 40 patients in each cohort. Enrolment was impacted by a number of limiting factors and most notably the approval of ibrutinib and the availability of this new therapy to patients, thus, sample size was reduced to a planned 30 participants in MCL cohort, 5 patients in WM cohort, and 20 patients in MZL cohort.

    Pre-assignment
    Screening details
    This study included participants with histologically documented, CD20 positive (assessed locally) relapsed or refractory Mantle Cell Lymphoma, Marginal Zone Lymphoma, and Waldenström's Macroglobulinemia and an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0, 1, or 2 (prior to enrolment).

    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
    Atezolizumab + Obinutuzumab for MCL
    Arm description
    Participants with refractory or relapsed Mantle Cell Lymphoma (MCL) received atezolizumab in combination with obinutuzumab during the induction phase (Cycles 1-8), and Atezolizumab during the maintenance phase (Cycles 9-18).
    Arm type
    Experimental

    Investigational medicinal product name
    Obinutuzumab
    Investigational medicinal product code
    Other name
    GAZYVA
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received 1000 mg of obinutuzumab as intravenous infusions on Day 1 of each 21 day cycle for 8 cycles. Participants also received 1000 mg of obinutuzumab on Days 8 and 15 of the first cycle only. The first dose of obinutuzumab may have be split over Day 1 and Day 2 of Cycle 1 (at the discretion of the investigator).

    Investigational medicinal product name
    Atezolizumab
    Investigational medicinal product code
    Other name
    Tecentriq
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received 1200 mg of atezolizumab intravenously on Day 1 of each 21 day cycle for 8 cycles. If the first dose of obinutuzumab was split over Day 1 and Day 2 of Cycle 1, then the atezolizumab dosing occurred on Day 2 of Cycle 1, after the obinutuzumab dosing was completed. From Cycle 9, participants received 1200 mg of atezolizumab only for a further 10 cycles (to a total of 18 cycles for patients that have not progressed).

    Arm title
    Atezolizumab + Obinutuzumab for WM
    Arm description
    Participants with Waldenström Macroglobulinemia (WM) received atezolizumab plus obinutuzumab during the induction phase (Cycles 1-8), and Atezolizumab during the maintenance phase (Cycles 9-18).
    Arm type
    Experimental

    Investigational medicinal product name
    Obinutuzumab
    Investigational medicinal product code
    Other name
    GAZYVA
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received 1000 mg of obinutuzumab as intravenous infusions on Day 1 of each 21 day cycle for 8 cycles. Participants also received 1000 mg of obinutuzumab on Days 8 and 15 of the first cycle only. The first dose of obinutuzumab may have be split over Day 1 and Day 2 of Cycle 1 (at the discretion of the investigator).

    Investigational medicinal product name
    Atezolizumab
    Investigational medicinal product code
    Other name
    Tecentriq
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received 1200 mg of atezolizumab intravenously on Day 1 of each 21 day cycle for 8 cycles. If the first dose of obinutuzumab was split over Day 1 and Day 2 of Cycle 1, then the atezolizumab dosing occurred on Day 2 of Cycle 1, after the obinutuzumab dosing was completed. From Cycle 9, participants received 1200 mg of atezolizumab only for a further 10 cycles (to a total of 18 cycles for patients that have not progressed).

    Arm title
    Atezolizumab + Rituximab for MZL
    Arm description
    Participants with Marginal Zone Lymphoma (MZL) received atezolizumab in combination with rituximab during the induction phase (Cycles 1-8), and Atezolizumab during the maintenance phase (Cycles 9-18).
    Arm type
    Experimental

    Investigational medicinal product name
    Rituximab
    Investigational medicinal product code
    Other name
    RITUXAN
    Pharmaceutical forms
    Infusion, Injection
    Routes of administration
    Intravenous use, Subcutaneous use
    Dosage and administration details
    Participants received 375mg/m2 of rituximab intravenously on Day 1 of Cycle 1. Participants also received 1400 mg of rituximab subcutaneously on Day 1 from Cycles 2-8.

    Investigational medicinal product name
    Atezolizumab
    Investigational medicinal product code
    Other name
    Tecentriq
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received 1200 mg of atezolizumab intravenously on Day 1 of Cycle 1. From Cycle 9, participants received 1200 mg of atezolizumab only for a further 10 cycles.

    Number of subjects in period 1
    Atezolizumab + Obinutuzumab for MCL Atezolizumab + Obinutuzumab for WM Atezolizumab + Rituximab for MZL
    Started
    30
    4
    21
    Completed
    8
    1
    12
    Not completed
    22
    3
    9
         Physician decision
    1
    -
    -
         Consent withdrawn by subject
    1
    1
    1
         Death
    16
    1
    7
         Lost to follow-up
    3
    1
    1
         Protocol deviation
    1
    -
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Atezolizumab + Obinutuzumab for MCL
    Reporting group description
    Participants with refractory or relapsed Mantle Cell Lymphoma (MCL) received atezolizumab in combination with obinutuzumab during the induction phase (Cycles 1-8), and Atezolizumab during the maintenance phase (Cycles 9-18).

    Reporting group title
    Atezolizumab + Obinutuzumab for WM
    Reporting group description
    Participants with Waldenström Macroglobulinemia (WM) received atezolizumab plus obinutuzumab during the induction phase (Cycles 1-8), and Atezolizumab during the maintenance phase (Cycles 9-18).

    Reporting group title
    Atezolizumab + Rituximab for MZL
    Reporting group description
    Participants with Marginal Zone Lymphoma (MZL) received atezolizumab in combination with rituximab during the induction phase (Cycles 1-8), and Atezolizumab during the maintenance phase (Cycles 9-18).

    Reporting group values
    Atezolizumab + Obinutuzumab for MCL Atezolizumab + Obinutuzumab for WM Atezolizumab + Rituximab for MZL Total
    Number of subjects
    30 4 21 55
    Age categorical
    Units: Subjects
        In utero
    0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0 0 0
        Newborns (0-27 days)
    0 0 0 0
        Infants and toddlers (28 days-23 months)
    0 0 0 0
        Children (2-11 years)
    0 0 0 0
        Adolescents (12-17 years)
    0 0 0 0
        Adults (18-64 years)
    11 2 8 21
        From 65-84 years
    19 2 12 33
        85 years and over
    0 0 1 1
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    67.5 ± 8.3 62.3 ± 5.6 68.6 ± 11.5 -
    Gender categorical
    Units: Subjects
        Female
    8 2 14 24
        Male
    22 2 7 31

    End points

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    End points reporting groups
    Reporting group title
    Atezolizumab + Obinutuzumab for MCL
    Reporting group description
    Participants with refractory or relapsed Mantle Cell Lymphoma (MCL) received atezolizumab in combination with obinutuzumab during the induction phase (Cycles 1-8), and Atezolizumab during the maintenance phase (Cycles 9-18).

    Reporting group title
    Atezolizumab + Obinutuzumab for WM
    Reporting group description
    Participants with Waldenström Macroglobulinemia (WM) received atezolizumab plus obinutuzumab during the induction phase (Cycles 1-8), and Atezolizumab during the maintenance phase (Cycles 9-18).

    Reporting group title
    Atezolizumab + Rituximab for MZL
    Reporting group description
    Participants with Marginal Zone Lymphoma (MZL) received atezolizumab in combination with rituximab during the induction phase (Cycles 1-8), and Atezolizumab during the maintenance phase (Cycles 9-18).

    Subject analysis set title
    Atezolizumab + Rituximab for Gastric MZL
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Gastric Marginal Zone Lymphoma (MZL) participants who received atezolizumab plus rituximab in the safety population.

    Subject analysis set title
    Atezolizumab + Rituximab for Splenic MZL
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Splenic Marginal Zone Lymphoma (MZL) participants who received atezolizumab plus rituximab in the safety population.

    Subject analysis set title
    Obinutuzumab Exposure for MCL
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Marginal Cell Lymphoma (MCL) participants with exposure to obinutuzumab in the safety population.

    Subject analysis set title
    Atezolizumab Exposure for MCL
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Marginal Cell Lymphoma (MCL) participants with exposure to atezolizumab in the safety population.

    Subject analysis set title
    Obinutuzumab Exposure for WM
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Waldenström Macroglobulinemia (WM) participants with obinutuzumab exposure in the safety population.

    Subject analysis set title
    Atezolizumab Exposure for WM
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Waldenström Macroglobulinemia (WM) participants with atezolizumab exposure in the safety population.

    Subject analysis set title
    Rituximab Exposure for MZL
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Marginal Zone lymphoma (MZL) participants with rituximab exposure in the safety population.

    Subject analysis set title
    Atezolizumab Exposure for MZL
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Marginal Zone lymphoma (MZL) participants with atezolizumab exposure in the safety population.

    Primary: For MCL and Nodal and Extra-Nodal MZL, Objective Response at End of Induction (EOI)

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    End point title
    For MCL and Nodal and Extra-Nodal MZL, Objective Response at End of Induction (EOI) [1] [2]
    End point description
    For Mantle Cell Lymphoma (MCL) and nodal and extra-nodal Marginal Zone Lymphoma (MZL), objective response at End of Induction (EOI) was defined as a Complete Response (CR) or Partial Response (PR) based on modified Cheson 2007 criteria (excluding PET).
    End point type
    Primary
    End point timeframe
    End of induction (approximately 6 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 for this end point.
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No statistical analysis for this end point.
    End point values
    Atezolizumab + Obinutuzumab for MCL Atezolizumab + Rituximab for MZL
    Number of subjects analysed
    30
    21
    Units: Percentage
        number (confidence interval 95%)
    16.7 (5.6 to 34.7)
    42.9 (21.8 to 66.0)
    No statistical analyses for this end point

    Primary: Best Overall Objective Response (BOR) for WM

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    End point title
    Best Overall Objective Response (BOR) for WM [3] [4]
    End point description
    For Waldenström's Macroglobulinemia (WM), Best Overall Objective Response (BOR) was defined as a Complete Response (CR), Very Good Partial Response (VGPR), Partial Response (PR), or Minimum Response (MR), based on Owen 2013 criteria, at any time during the study.
    End point type
    Primary
    End point timeframe
    At any time during the study (up to approximately 49 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 for this end point.
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No statistical analysis for this end point.
    End point values
    Atezolizumab + Obinutuzumab for WM
    Number of subjects analysed
    4
    Units: Percentage
        number (confidence interval 95%)
    0 (0.0 to 60.2)
    No statistical analyses for this end point

    Primary: Objective Response at End of Induction (EOI) for Gastric MZL

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    End point title
    Objective Response at End of Induction (EOI) for Gastric MZL [5]
    End point description
    For gastric Marginal Zone Lymphoma (MZL), objective response at End of Induction (EOI), was defined as a Complete Response (CR) or Probable Minimal Residual Disease (pMRD) or Responding Residual Disease (rRD), based on the histological grading system of GELA 2003 criteria.
    End point type
    Primary
    End point timeframe
    End of induction (approximately 6 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 for this end point.
    End point values
    Atezolizumab + Rituximab for Gastric MZL
    Number of subjects analysed
    3
    Units: Percentage
        number (confidence interval 95%)
    66.7 (9.4 to 99.2)
    No statistical analyses for this end point

    Primary: Objective Response at End of Induction (EOI) for Splenic MZL

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    End point title
    Objective Response at End of Induction (EOI) for Splenic MZL [6]
    End point description
    For splenic MZL, objective response at End of Induction (EOI) was defined as a CR or PR based on Matutes (2008).
    End point type
    Primary
    End point timeframe
    End of induction (approximately 6 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 for this end point.
    End point values
    Atezolizumab + Rituximab for Splenic MZL
    Number of subjects analysed
    8
    Units: Percentage
        number (confidence interval 95%)
    12.5 (0.3 to 52.7)
    No statistical analyses for this end point

    Primary: Percentage of Participants with Treatment-Emergent Adverse Events

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    End point title
    Percentage of Participants with Treatment-Emergent Adverse Events [7]
    End point description
    Percentage of participants with treatment-emergent adverse events
    End point type
    Primary
    End point timeframe
    Baseline up to to the data cutoff date: 14 January 2022 (up to approximately 49 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 for this end point.
    End point values
    Atezolizumab + Obinutuzumab for MCL Atezolizumab + Obinutuzumab for WM Atezolizumab + Rituximab for MZL
    Number of subjects analysed
    30
    4
    21
    Units: Percentage of participants
        number (not applicable)
    93.3
    100
    95.2
    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
    Progression-free survival (PFS) is defined as the time from enrolment to the first occurrence of disease progression or death from any cause, whichever occurs first, as determined by the investigator. Participants who have experienced none of these events at the time of analysis (clinical-cut off) and participants who were lost to follow-up will be censored at the time of the last evaluable tumor assessment. Participants with no tumor assessment after the baseline visit were censored at the time of enrolment plus one day. Note: 999999=Non-Estimated.
    End point type
    Secondary
    End point timeframe
    Enrolment to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 49 months).
    End point values
    Atezolizumab + Obinutuzumab for MCL Atezolizumab + Obinutuzumab for WM Atezolizumab + Rituximab for MZL
    Number of subjects analysed
    30
    4
    21
    Units: Months
        median (confidence interval 95%)
    10.1 (3.4 to 14.0)
    7.2 (6.2 to 999999)
    23.5 (10.1 to 999999)
    No statistical analyses for this end point

    Secondary: Best Overall Response (BOR)

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    End point title
    Best Overall Response (BOR)
    End point description
    Best overall response (BOR) is defined as best response seen throughout study, of CR or PR for MCL, nodal and extra-nodal MZL and splenic MZL. CR, pMRD or rRD for gastric MZL. And for WM, this includes CR, VGPR, PR or MR.
    End point type
    Secondary
    End point timeframe
    Throughout study (up to approximately 49 months).
    End point values
    Atezolizumab + Obinutuzumab for MCL Atezolizumab + Obinutuzumab for WM Atezolizumab + Rituximab for MZL
    Number of subjects analysed
    30
    4
    21
    Units: Percentage
        number (confidence interval 95%)
    33.3 (17.3 to 52.8)
    0 (0.0 to 60.2)
    61.9 (38.4 to 81.9)
    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
    Complete Response Rate (CRR) is defined as best response of CR.
    End point type
    Secondary
    End point timeframe
    Throughout study (up to approximately 49 months).
    End point values
    Atezolizumab + Obinutuzumab for MCL Atezolizumab + Obinutuzumab for WM Atezolizumab + Rituximab for MZL
    Number of subjects analysed
    30
    4
    21
    Units: Percentage
        number (confidence interval 95%)
    10.0 (2.1 to 26.5)
    0 (0.0 to 60.2)
    38.1 (18.1 to 61.6)
    No statistical analyses for this end point

    Secondary: Duration of Objective Response (DOR)

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    End point title
    Duration of Objective Response (DOR)
    End point description
    Duration of objective response (DOR) is defined for responding patients as the time from first occurrence of a documented objective response to the time of progression or death from any cause, whichever occurs first, as determined by the investigator. Note: 999999=Non-Estimated.
    End point type
    Secondary
    End point timeframe
    From first occurrence of a documented objective response to the time of progression or death from any cause (up to approximately 49 months).
    End point values
    Atezolizumab + Obinutuzumab for MCL Atezolizumab + Obinutuzumab for WM Atezolizumab + Rituximab for MZL
    Number of subjects analysed
    5 [8]
    0 [9]
    9
    Units: Months
        median (confidence interval 95%)
    999999 (999999 to 999999)
    ( to )
    27.8 (3.4 to 999999)
    Notes
    [8] - DOR ascertained at first percentile.Of 5 responders,2 patients had events,& 3 observations censored.
    [9] - The DOR was not applicable to WM patients due to no responders.
    No statistical analyses for this end point

    Secondary: Time to Next Treatment (TTNT)

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    End point title
    Time to Next Treatment (TTNT)
    End point description
    Time to next treatment (TTNT) is defined as the time from the date of enrolment to the start date of the next anti-lymphoma treatment (NALT) or death from any cause, whichever occurred first. Note: 999999=Non-Estimated.
    End point type
    Secondary
    End point timeframe
    Time from the date of enrolment to the start date of the next anti-lymphoma treatment (NALT) or death from any cause, whichever occurred first (up to approximately 49 months).
    End point values
    Atezolizumab + Obinutuzumab for MCL Atezolizumab + Obinutuzumab for WM Atezolizumab + Rituximab for MZL
    Number of subjects analysed
    20
    1 [10]
    12
    Units: Months
        median (confidence interval 95%)
    10.5 (6.7 to 22.6)
    999999 (999999 to 999999)
    30.5 (16.6 to 999999)
    Notes
    [10] - As median TTNT was not established, first quartile presented was 6.2 months (95% CI: 6.2, Non-Est)..
    No statistical analyses for this end point

    Secondary: Overall Survival (OS)

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    End point title
    Overall Survival (OS)
    End point description
    Overall survival (OS) is defined as the time from enrolment to death from any cause (up to approximately 49 months). Note: 999999=Non-Estimated.
    End point type
    Secondary
    End point timeframe
    From enrolment to death from any cause.
    End point values
    Atezolizumab + Obinutuzumab for MCL Atezolizumab + Obinutuzumab for WM Atezolizumab + Rituximab for MZL
    Number of subjects analysed
    30
    4
    21
    Units: Months
        median (confidence interval 95%)
    30.9 (12.3 to 999999)
    999999 (999999 to 999999)
    999999 (999999 to 999999)
    No statistical analyses for this end point

    Secondary: Event-Free Survival (EFS)

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    End point title
    Event-Free Survival (EFS)
    End point description
    Event-free survival (EFS) is defined as the time from enrolment to first occurrence of disease progression or relapse, death from any cause, as assessed by the investigator, or initiation of any non-protocol-specified NALT, whichever occurred first. Note: 999999=Non-Estimated.
    End point type
    Secondary
    End point timeframe
    From enrolment to first occurrence of disease progression or relapse, death from any cause (up to approximately 49 months).
    End point values
    Atezolizumab + Obinutuzumab for MCL Atezolizumab + Obinutuzumab for WM Atezolizumab + Rituximab for MZL
    Number of subjects analysed
    30
    4
    21
    Units: Months
        median (confidence interval 95%)
    7.4 (3.4 to 12.5)
    7.2 (6.2 to 999999)
    23.5 (10.1 to 999999)
    No statistical analyses for this end point

    Secondary: Disease-Free Survival (DFS)

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    End point title
    Disease-Free Survival (DFS)
    End point description
    Disease-free survival (DFS) is defined as the time from the date of the first occurrence of a documented CR to the date of disease progression, relapse, or death from any cause, whichever occurred first, as assessed by the investigator, for the subgroup of patients with a BOR of CR. Note: 999999=Non-Estimated.
    End point type
    Secondary
    End point timeframe
    From the date of the first occurrence of a documented CR to the date of disease progression, relapse, or death from any cause, whichever occurred first (up to approximately 49 months).
    End point values
    Atezolizumab + Obinutuzumab for MCL Atezolizumab + Obinutuzumab for WM Atezolizumab + Rituximab for MZL
    Number of subjects analysed
    3 [11]
    0 [12]
    8 [13]
    Units: Months
        median (confidence interval 95%)
    999999 (999999 to 999999)
    ( to )
    999999 (999999 to 999999)
    Notes
    [11] - Due to a lack of events, only the first quartile of DFS was reached.
    [12] - No patients with a best overall response of CR.
    [13] - Due to a lack of events, only the first quartile of DFS was reached.
    No statistical analyses for this end point

    Secondary: Dose Intensity

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    End point title
    Dose Intensity
    End point description
    Dose intensity = 100 * cumulative dose / total planned dose.
    End point type
    Secondary
    End point timeframe
    Up to approximately 49 months
    End point values
    Obinutuzumab Exposure for MCL Atezolizumab Exposure for MCL Obinutuzumab Exposure for WM Atezolizumab Exposure for WM Rituximab Exposure for MZL Atezolizumab Exposure for MZL
    Number of subjects analysed
    30
    30
    4
    4
    21
    21
    Units: Percentage
        arithmetic mean (standard deviation)
    100.0 ± 0.00
    100.0 ± 0.00
    100.0 ± 0.00
    100.0 ± 0.00
    100.1 ± 0.21
    100.0 ± 0.00
    No statistical analyses for this end point

    Secondary: Total Number of Infusions/Injections Modified

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    End point title
    Total Number of Infusions/Injections Modified
    End point description
    Total number of infusions/injections modified (dose reductions and interruptions).
    End point type
    Secondary
    End point timeframe
    Up to approximately 49 months
    End point values
    Obinutuzumab Exposure for MCL Atezolizumab Exposure for MCL Obinutuzumab Exposure for WM Atezolizumab Exposure for WM Rituximab Exposure for MZL Atezolizumab Exposure for MZL
    Number of subjects analysed
    30
    30
    4
    4
    21
    21
    Units: Number of infusions/injections
        arithmetic mean (standard deviation)
    0.1 ± 0.35
    0.00 ± 0.00
    0.00 ± 0.00
    0.0 ± 0.00
    0.2 ± 0.40
    0.0 ± 0.00
    No statistical analyses for this end point

    Secondary: Atezolizumab PK Concentration

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    End point title
    Atezolizumab PK Concentration
    End point description
    Atezolizumab PK Concentration. Note: 888888=Non-Reportable. 999999=non evaluable
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 (pre-dose and 30 minutes), Cycle 2 pre-dose, Cycle 3 pre-dose, Cycle 4 pre-dose, Cycle 8 pre-dose, Cycle 12 pre-dose, Cycle 16 pre-dose, End of treatment, Post treatment follow-up period. (Cycle length=21 days)
    End point values
    Atezolizumab + Obinutuzumab for MCL Atezolizumab + Obinutuzumab for WM Atezolizumab + Rituximab for MZL
    Number of subjects analysed
    28
    4
    21
    Units: ug/mL
    arithmetic mean (standard deviation)
        Cycle 1 Day 1/ Predose (n=28, 21, 4)
    888888 ± 888888
    888888 ± 888888
    888888 ± 888888
        Cycle 1 Day 1/ 30 Min (n=28, 21, 4)
    371 ± 92.2
    308 ± 70.4
    366 ± 161
        Cycle 2/ Predose (n=28, 20, 3)
    90.4 ± 35.6
    76.5 ± 29.8
    101 ± 28.6
        Cycle 3/ Predose (n=24, 18, 3)
    176 ± 109
    138 ± 77.4
    189 ± 47.8
        Cycle 4/ Predose (n=23, 17, 3)
    209 ± 77.8
    189 ± 103
    214 ± 58.1
        Cycle 8/ Predose (n=13, 14, 2)
    303 ± 90.3
    371 ± 58.7
    297 ± 96.7
        Cycle 12/ Predose (n=10, 14, 1)
    399 ± 114
    89.7 ± 999999
    317 ± 101
        Cycle 16/ Predose (n=8, 11, 1)
    447 ± 135
    104 ± 999999
    357 ± 142
        End of Treatment (n=23, 18, 2)
    272 ± 167
    185 ± 124
    249 ± 140
        Pose Trt FU Period (n=9, 6, 1)
    67.2 ± 63.2
    2.26 ± 999999
    46.0 ± 38.0
    No statistical analyses for this end point

    Secondary: Obinutuzumab PK Concentration

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    End point title
    Obinutuzumab PK Concentration [14]
    End point description
    Obinutuzumab PK Concentration. Note: 888888=Non-Reportable
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 (pre-dose and 4 hours), Cycle 2 pre-dose, Cycle 4 pre-dose, End of treatment, Post treatment follow-up period. (Cycle length=21 days)
    Notes
    [14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No statistical analysis for this end point.
    End point values
    Atezolizumab + Obinutuzumab for MCL Atezolizumab + Obinutuzumab for WM
    Number of subjects analysed
    27
    4
    Units: ug/mL
    arithmetic mean (standard deviation)
        Cycle 1 Day 1, Predose (n=27,3)
    888888 ± 888888
    888888 ± 888888
        Cycle 1 day 1,4 hours (n=24, 4)
    268 ± 81.7
    231 ± 79.4
        Cycle 2,Predose (n=27, 3)
    313 ± 144
    216 ± 214
        Cycle 4,Predose (n=22, 3)
    320 ± 221
    209 ± 263
        End of Treatment (n=14, 2)
    167 ± 217
    264 ± 6.36
        Post Trt Follow-Up Period (n=4)
    31.9 ± 53.6
    888888 ± 888888
    No statistical analyses for this end point

    Secondary: Rituximab PK Concentrations

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    End point title
    Rituximab PK Concentrations [15]
    End point description
    Rituximab PK concentrations Note: 888888=non-reportable.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 pre-dose, Cycle 1 Day 1 30 minutes, Cycle 2 pre-dose, Cycle 4 pre-dose, Cycle 8 pre-dose, End of Treatment, Post Treatment Follow-Up Period
    Notes
    [15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No statistical analysis for this end point.
    End point values
    Atezolizumab + Rituximab for MZL
    Number of subjects analysed
    21
    Units: ug/mL
    arithmetic mean (standard deviation)
        Cycle 1 Day 1/pre-dose (n=21)
    888888 ± 888888
        Cycle 1 Day 1/ 30 min (n=21)
    124 ± 98.2
        Cycle 2/ pre-dose (n=20)
    31.5 ± 24.1
        Cycle 4/ pre-dose (n=18)
    89.3 ± 56.7
        Cycle 8/ pre-dose (n=14)
    175 ± 64.0
        End of Treatment (n=18)
    19.7 ± 46.4
        Post TRT FU Period (n=6)
    888888 ± 888888
    No statistical analyses for this end point

    Secondary: Incidence of anti-drug antibodies (ADAs) to Atezolizumab

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    End point title
    Incidence of anti-drug antibodies (ADAs) to Atezolizumab
    End point description
    Incidence of anti-drug antibodies (ADAs) to atezolizumab.
    End point type
    Secondary
    End point timeframe
    Baseline and Post Baseline
    End point values
    Atezolizumab + Obinutuzumab for MCL Atezolizumab + Obinutuzumab for WM Atezolizumab + Rituximab for MZL
    Number of subjects analysed
    28
    4
    21
    Units: Number of participants
        Baseline Prevalence of ADAs
    0
    0
    1
        Post-Baseline Incidence of ADAs
    1
    0
    0
    No statistical analyses for this end point

    Secondary: Incidence of anti-drug antibodies (ADAs) to Rituximab

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    End point title
    Incidence of anti-drug antibodies (ADAs) to Rituximab [16]
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline and Post Baseline
    Notes
    [16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No statistical analysis for this end point.
    End point values
    Atezolizumab + Rituximab for MZL
    Number of subjects analysed
    21
    Units: Number of Participants
        Baseline Prevalence of ADAs
    4
        Post-Baseline Incidence of ADAs
    19
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From the first study drug to the data cutoff date: January 14, 2022 (up to approximately 49 months)
    Adverse event reporting additional description
    The safety population will include all enrolled patients who received at least one dose of study drug (atezolizumab, obinutuzumab or rituximab). Data cutoff date: 14 January 2022 (up to approximately 49 months).
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    18
    Reporting groups
    Reporting group title
    Atezolizumab + Obinutuzumab for MCL
    Reporting group description
    Participants with refractory or relapsed Mantle Cell Lymphoma (MCL) received atezolizumab in combination with obinutuzumab during the induction phase (Cycles 1-8), and Atezolizumab during the maintenance phase (Cycles 9-18).

    Reporting group title
    Atezolizumab + Rituximab for MZL
    Reporting group description
    Participants with Marginal Zone Lymphoma (MZL) received atezolizumab in combination with rituximab during the induction phase (Cycles 1-8), and Atezolizumab during the maintenance phase (Cycles 9-18).

    Reporting group title
    Atezolizumab + Obinutuzumab for WM
    Reporting group description
    Participants with Waldenström Macroglobulinemia (WM) received atezolizumab plus obinutuzumab during the induction phase (Cycles 1-8), and Atezolizumab during the maintenance phase (Cycles 9-18).

    Serious adverse events
    Atezolizumab + Obinutuzumab for MCL Atezolizumab + Rituximab for MZL Atezolizumab + Obinutuzumab for WM
    Total subjects affected by serious adverse events
         subjects affected / exposed
    9 / 30 (30.00%)
    5 / 21 (23.81%)
    0 / 4 (0.00%)
         number of deaths (all causes)
    16
    7
    1
         number of deaths resulting from adverse events
    0
    0
    0
    Injury, poisoning and procedural complications
    Hip fracture
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 21 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Pelvic venous thrombosis
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 21 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 21 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 21 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 21 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Syncope
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 21 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 21 (4.76%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 21 (4.76%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 21 (4.76%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Ascites
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 21 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Dermatitis allergic
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 21 (4.76%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Infection
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 21 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    2 / 30 (6.67%)
    1 / 21 (4.76%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    Cytomegalovirus infection
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 21 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    2 / 30 (6.67%)
    0 / 21 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 21 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bacterial sepsis
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 21 (4.76%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Atezolizumab + Obinutuzumab for MCL Atezolizumab + Rituximab for MZL Atezolizumab + Obinutuzumab for WM
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    27 / 30 (90.00%)
    18 / 21 (85.71%)
    4 / 4 (100.00%)
    Vascular disorders
    Lymphoedema
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 21 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    1
    Hypotension
         subjects affected / exposed
    1 / 30 (3.33%)
    2 / 21 (9.52%)
    0 / 4 (0.00%)
         occurrences all number
    1
    2
    0
    Phlebitis
         subjects affected / exposed
    2 / 30 (6.67%)
    0 / 21 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    2
    0
    0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    3 / 30 (10.00%)
    3 / 21 (14.29%)
    0 / 4 (0.00%)
         occurrences all number
    4
    7
    0
    Fatigue
         subjects affected / exposed
    2 / 30 (6.67%)
    4 / 21 (19.05%)
    1 / 4 (25.00%)
         occurrences all number
    2
    4
    1
    Asthenia
         subjects affected / exposed
    4 / 30 (13.33%)
    2 / 21 (9.52%)
    0 / 4 (0.00%)
         occurrences all number
    5
    2
    0
    Pain
         subjects affected / exposed
    0 / 30 (0.00%)
    2 / 21 (9.52%)
    0 / 4 (0.00%)
         occurrences all number
    0
    2
    0
    Oedema peripheral
         subjects affected / exposed
    3 / 30 (10.00%)
    1 / 21 (4.76%)
    0 / 4 (0.00%)
         occurrences all number
    3
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    2 / 30 (6.67%)
    1 / 21 (4.76%)
    0 / 4 (0.00%)
         occurrences all number
    2
    1
    0
    Cough
         subjects affected / exposed
    3 / 30 (10.00%)
    2 / 21 (9.52%)
    2 / 4 (50.00%)
         occurrences all number
    4
    3
    2
    Rhinorrhoea
         subjects affected / exposed
    3 / 30 (10.00%)
    0 / 21 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    3
    0
    0
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    1 / 30 (3.33%)
    2 / 21 (9.52%)
    0 / 4 (0.00%)
         occurrences all number
    1
    2
    0
    Anxiety
         subjects affected / exposed
    1 / 30 (3.33%)
    2 / 21 (9.52%)
    0 / 4 (0.00%)
         occurrences all number
    1
    2
    0
    Investigations
    Lymphocyte count decreased
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 21 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    1
    Blood alkaline phosphatase increased
         subjects affected / exposed
    2 / 30 (6.67%)
    0 / 21 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    5
    0
    0
    Neutrophil count decreased
         subjects affected / exposed
    2 / 30 (6.67%)
    0 / 21 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    4
    0
    2
    Platelet count decreased
         subjects affected / exposed
    5 / 30 (16.67%)
    0 / 21 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    7
    0
    1
    Injury, poisoning and procedural complications
    Infusion related reaction
         subjects affected / exposed
    0 / 30 (0.00%)
    2 / 21 (9.52%)
    1 / 4 (25.00%)
         occurrences all number
    0
    2
    1
    Cardiac disorders
    Palpitations
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 21 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    1
    Nervous system disorders
    Headache
         subjects affected / exposed
    2 / 30 (6.67%)
    4 / 21 (19.05%)
    1 / 4 (25.00%)
         occurrences all number
    2
    4
    1
    Dysgeusia
         subjects affected / exposed
    1 / 30 (3.33%)
    2 / 21 (9.52%)
    0 / 4 (0.00%)
         occurrences all number
    2
    2
    0
    Dizziness
         subjects affected / exposed
    2 / 30 (6.67%)
    1 / 21 (4.76%)
    0 / 4 (0.00%)
         occurrences all number
    2
    2
    0
    Paraesthesia
         subjects affected / exposed
    0 / 30 (0.00%)
    2 / 21 (9.52%)
    1 / 4 (25.00%)
         occurrences all number
    0
    2
    2
    Neuropathy peripheral
         subjects affected / exposed
    0 / 30 (0.00%)
    2 / 21 (9.52%)
    0 / 4 (0.00%)
         occurrences all number
    0
    2
    0
    Blood and lymphatic system disorders
    Thrombocytopenia
         subjects affected / exposed
    6 / 30 (20.00%)
    1 / 21 (4.76%)
    3 / 4 (75.00%)
         occurrences all number
    11
    1
    6
    Autoimmune haemolytic anaemia
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 21 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    1
    Leukopenia
         subjects affected / exposed
    1 / 30 (3.33%)
    1 / 21 (4.76%)
    2 / 4 (50.00%)
         occurrences all number
    1
    1
    3
    Anaemia
         subjects affected / exposed
    6 / 30 (20.00%)
    4 / 21 (19.05%)
    0 / 4 (0.00%)
         occurrences all number
    8
    4
    0
    Lymphopenia
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 21 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    1
    0
    1
    Iron deficiency anaemia
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 21 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    1
    0
    3
    Febrile neutropenia
         subjects affected / exposed
    2 / 30 (6.67%)
    0 / 21 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    2
    0
    0
    Neutropenia
         subjects affected / exposed
    6 / 30 (20.00%)
    3 / 21 (14.29%)
    1 / 4 (25.00%)
         occurrences all number
    12
    5
    1
    Ear and labyrinth disorders
    Hypoacusis
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 21 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    1
    Vertigo
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 21 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    1
    Gastrointestinal disorders
    Toothache
         subjects affected / exposed
    2 / 30 (6.67%)
    1 / 21 (4.76%)
    0 / 4 (0.00%)
         occurrences all number
    2
    1
    0
    Dyspepsia
         subjects affected / exposed
    1 / 30 (3.33%)
    1 / 21 (4.76%)
    1 / 4 (25.00%)
         occurrences all number
    1
    1
    1
    Vomiting
         subjects affected / exposed
    2 / 30 (6.67%)
    3 / 21 (14.29%)
    0 / 4 (0.00%)
         occurrences all number
    2
    3
    0
    Diarrhoea
         subjects affected / exposed
    3 / 30 (10.00%)
    3 / 21 (14.29%)
    0 / 4 (0.00%)
         occurrences all number
    5
    3
    0
    Constipation
         subjects affected / exposed
    1 / 30 (3.33%)
    2 / 21 (9.52%)
    1 / 4 (25.00%)
         occurrences all number
    1
    2
    1
    Hepatobiliary disorders
    Hepatitis toxic
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 21 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    1
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    1 / 30 (3.33%)
    2 / 21 (9.52%)
    0 / 4 (0.00%)
         occurrences all number
    1
    2
    0
    Renal and urinary disorders
    Dysuria
         subjects affected / exposed
    2 / 30 (6.67%)
    0 / 21 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    2
    0
    0
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    2 / 30 (6.67%)
    1 / 21 (4.76%)
    0 / 4 (0.00%)
         occurrences all number
    2
    1
    0
    Musculoskeletal and connective tissue disorders
    Pain in extremity
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 21 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    1
    Arthralgia
         subjects affected / exposed
    2 / 30 (6.67%)
    3 / 21 (14.29%)
    1 / 4 (25.00%)
         occurrences all number
    2
    7
    1
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    1 / 30 (3.33%)
    2 / 21 (9.52%)
    0 / 4 (0.00%)
         occurrences all number
    1
    3
    0
    Urinary tract infection
         subjects affected / exposed
    2 / 30 (6.67%)
    0 / 21 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    2
    0
    0
    Upper respiratory tract infection
         subjects affected / exposed
    2 / 30 (6.67%)
    0 / 21 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    2
    0
    0
    Bronchitis
         subjects affected / exposed
    3 / 30 (10.00%)
    1 / 21 (4.76%)
    0 / 4 (0.00%)
         occurrences all number
    3
    1
    0
    Pharyngitis
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 21 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    1
    Respiratory tract infection
         subjects affected / exposed
    3 / 30 (10.00%)
    0 / 21 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    3
    0
    0
    Nasopharyngitis
         subjects affected / exposed
    1 / 30 (3.33%)
    2 / 21 (9.52%)
    0 / 4 (0.00%)
         occurrences all number
    1
    2
    0
    Metabolism and nutrition disorders
    Hyperglycaemia
         subjects affected / exposed
    2 / 30 (6.67%)
    0 / 21 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    2
    0
    0
    Decreased appetite
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 21 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    1
    0
    1

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    07 Nov 2018
    Protocol was amended to include adjustment to the study sample size, and to clarify that access to atezolizumab is only within the 18 cycles of study treatment per the study design. In addition, several clarifications have been made relating to the conduct of the study and to update all safety, efficacy, and licensing status text for atezolizumab, obinutuzumab, and rituximab.

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

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