Flag of the European Union EU Clinical Trials Register Help

Clinical trials

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

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

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

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

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Phase 1/2 Multi-Center Study Evaluating the Safety and Efficacy of KTE-X19 in Adult Subjects with Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (r/r ALL) (ZUMA-3)

    Summary
    EudraCT number
    		 2015-005009-35
    Trial protocol
    		 DE   NL   FR  
    Global end of trial date
    03 Nov 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    15 Nov 2024
    First version publication date
    15 Nov 2024
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    KTE-C19-103
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02614066
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Gilead Sciences
    Sponsor organisation address
    333 Lakeside Drive, Foster City, CA, United States, 94404
    Public contact
    Gilead Clinical Study Information Center, Gilead Sciences, GileadClinicalTrials@gilead.com
    Scientific contact
    Gilead Clinical Study Information Center, Gilead Sciences, GileadClinicalTrials@gilead.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
    03 Nov 2023
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    23 Jul 2022
    Global end of trial reached?
    Yes
    Global end of trial date
    03 Nov 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objectives of this study were to determine the safety and efficacy of brexucabtagene autoleucel (KTE-X19) in adult participants with relapsed/refractory (r/r) B-precursor acute lymphoblastic leukemia (ALL).
    Protection of trial subjects
    The protocol and consent/assent forms were submitted by each investigator to a duly constituted Independent Ethics Committee (IEC) or Institutional Review Board (IRB) for review and approval before study initiation. All revisions to the consent/assent forms (if applicable) after initial IEC/IRB approval were submitted by the investigator to the IEC/IRB for review and approval before implementation in accordance with regulatory requirements. This study was conducted in accordance with recognized international scientific and ethical standards, including but not limited to the International Conference on Harmonization guideline for Good Clinical Practice (ICH GCP) and the original principles embodied in the Declaration of Helsinki.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    07 Mar 2016
    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
    Canada: 1
    Country: Number of subjects enrolled
    France: 12
    Country: Number of subjects enrolled
    Germany: 5
    Country: Number of subjects enrolled
    Netherlands: 1
    Country: Number of subjects enrolled
    United States: 106
    Worldwide total number of subjects
    125
    EEA total number of subjects
    18
    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)
    105
    From 65 to 84 years
    20
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Participants were enrolled at study sites in Canada, France, Germany, the Netherlands, and the United States.

    Pre-assignment
    Screening details
    		 173 participants were screened. Bridging therapy was recommended for all participants particularly those participants with high disease burden at baseline (M3 marrow [> 25% leukemic blasts] or ≥ 1,000 blasts/mm^3 in the peripheral circulation) to control participant's disease post apheresis/enrollment and prior to conditioning chemotherapy.

    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
    		 Phase 1: 2 x 10^6 anti-CD19 CAR T Cells/kg
    Arm description
    		 Participants with relapsed or refractory B-precursor acute lymphoblastic leukemia (r/r B-ALL) received conditioning chemotherapy (fludarabine 25 mg/m^2 intravenously [IV] over 30 minutes on Day -4, Day -3, and Day -2 and cyclophosphamide 900 mg/m^2 IV over 60 minutes on Day -2) followed by a single infusion of brexucabtagene autoleucel (KTE-X19) chimeric antigen receptor (CAR) transduced autologous T cells administered IV at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg of body weight on Day 0. For participants weighing > 100 kg, a maximum flat dose of 2 x 10^8 anti-CD19 CAR T cells/kg of body weight was administered.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Brexucabtagene autoleucel
    Investigational medicinal product code
    Other name
    KTE-X19
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Single infusion of 2 x 10^6 anti-CD19 CAR T cells/kg administered on Day 0.

    Investigational medicinal product name
    Cyclophosphamide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    900 mg/m^2 administered over 60 minutes on Day -2

    Investigational medicinal product name
    Fludarabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    25 mg/m^2 administered over 30 minutes on Day -4, Day -3, and Day -2

    Arm title
    		 Phase 1: 1 x 10^6 anti-CD19 CAR T Cells/kg
    Arm description
    		 Participants with r/r B-ALL received conditioning chemotherapy (fludarabine 25 mg/m^2 IV over 30 minutes on Day -4, Day -3, and Day -2 and cyclophosphamide 900 mg/m^2 IV over 60 minutes on Day -2) followed by a single infusion of brexucabtagene autoleucel CAR transduced autologous T cells administered IV at a target dose of 1 x 10^6 anti-CD19 CAR T cells/kg of body weight on Day 0. For participants weighing > 100 kg, a maximum flat dose of 1 x 10^8 anti-CD19 CAR T cells/kg of body weight was administered.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Brexucabtagene autoleucel
    Investigational medicinal product code
    Other name
    KTE-X19
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Single infusion of 1 x 10^6 anti-CD19 CAR T cells/kg administered on Day 0.

    Investigational medicinal product name
    Fludarabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    25 mg/m^2 administered over 30 minutes on Day -4, Day -3, and Day -2

    Investigational medicinal product name
    Cyclophosphamide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    900 mg/m^2 administered over 60 minutes on Day -2

    Arm title
    		 Phase 1: 0.5 x 10^6 anti-CD19 CAR T Cells/kg
    Arm description
    		 Participants with r/r B-ALL received conditioning chemotherapy (fludarabine 25 mg/m^2 IV over 30 minutes on Day -4, Day -3, and Day -2 and cyclophosphamide 900 mg/m^2 IV over 60 minutes on Day -2) followed by a single infusion of brexucabtagene autoleucel CAR transduced autologous T cells administered IV at a target dose of 0.5 x 10^6 anti-CD19 CAR T cells/kg of body weight on Day 0. For participants weighing > 100 kg, a maximum flat dose of 0.5 x 10^8 anti-CD19 CAR T cells/kg of body weight was administered.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Brexucabtagene autoleucel
    Investigational medicinal product code
    Other name
    KTE-X19
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Single infusion of 0.5 x 10^6 anti-CD19 CAR T cells/kg administered on Day 0.

    Investigational medicinal product name
    Cyclophosphamide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    900 mg/m^2 administered over 60 minutes on Day -2

    Investigational medicinal product name
    Fludarabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    25 mg/m^2 administered over 30 minutes on Day -4, Day -3, and Day -2

    Arm title
    		 Phase 2: 1 x 10^6 anti-CD19 CAR T Cells/kg
    Arm description
    		 Participants with r/r B-ALL received conditioning chemotherapy (fludarabine 25 mg/m^2 IV over 30 minutes on Day -4, Day -3, and Day -2 and cyclophosphamide 900 mg/m^2 IV over 60 minutes on Day -2) followed by a single infusion of brexucabtagene autoleucel CAR transduced autologous T cells administered IV at a target dose of 1 x 10^6 anti-CD19 CAR T cells/kg of body weight on Day 0. For participants weighing > 100 kg, a maximum flat dose of 1 x 10^8 anti-CD19 CAR T cells/kg of body weight was administered.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Brexucabtagene autoleucel
    Investigational medicinal product code
    Other name
    KTE-X19
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Single infusion of 1 x 10^6 anti-CD19 CAR T cells/kg administered on Day 0.

    Investigational medicinal product name
    Cyclophosphamide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    900 mg/m^2 administered over 60 minutes on Day -2

    Investigational medicinal product name
    Fludarabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    25 mg/m^2 administered over 30 minutes on Day -4, Day -3, and Day -2

    Number of subjects in period 1
    		Phase 1: 2 x 10^6 anti-CD19 CAR T Cells/kg Phase 1: 1 x 10^6 anti-CD19 CAR T Cells/kg Phase 1: 0.5 x 10^6 anti-CD19 CAR T Cells/kg Phase 2: 1 x 10^6 anti-CD19 CAR T Cells/kg
    Started
    6
    28
    20
    71
    Completed
    0
    0
    0
    0
    Not completed
    6
    28
    20
    71
         Full consent withdrawn
    -
    1
    -
    8
         Enrolled but did not Initiate KTE-X19
    -
    5
    4
    16
         Death
    6
    14
    11
    29
         Rolled over or consented to a long term follow-up
    -
    4
    2
    15
         Lost to follow-up
    -
    2
    2
    2
         Reason not specified
    -
    2
    1
    1

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Phase 1: 2 x 10^6 anti-CD19 CAR T Cells/kg
    Reporting group description
    		 Participants with relapsed or refractory B-precursor acute lymphoblastic leukemia (r/r B-ALL) received conditioning chemotherapy (fludarabine 25 mg/m^2 intravenously [IV] over 30 minutes on Day -4, Day -3, and Day -2 and cyclophosphamide 900 mg/m^2 IV over 60 minutes on Day -2) followed by a single infusion of brexucabtagene autoleucel (KTE-X19) chimeric antigen receptor (CAR) transduced autologous T cells administered IV at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg of body weight on Day 0. For participants weighing > 100 kg, a maximum flat dose of 2 x 10^8 anti-CD19 CAR T cells/kg of body weight was administered.

    Reporting group title
    Phase 1: 1 x 10^6 anti-CD19 CAR T Cells/kg
    Reporting group description
    		 Participants with r/r B-ALL received conditioning chemotherapy (fludarabine 25 mg/m^2 IV over 30 minutes on Day -4, Day -3, and Day -2 and cyclophosphamide 900 mg/m^2 IV over 60 minutes on Day -2) followed by a single infusion of brexucabtagene autoleucel CAR transduced autologous T cells administered IV at a target dose of 1 x 10^6 anti-CD19 CAR T cells/kg of body weight on Day 0. For participants weighing > 100 kg, a maximum flat dose of 1 x 10^8 anti-CD19 CAR T cells/kg of body weight was administered.

    Reporting group title
    Phase 1: 0.5 x 10^6 anti-CD19 CAR T Cells/kg
    Reporting group description
    		 Participants with r/r B-ALL received conditioning chemotherapy (fludarabine 25 mg/m^2 IV over 30 minutes on Day -4, Day -3, and Day -2 and cyclophosphamide 900 mg/m^2 IV over 60 minutes on Day -2) followed by a single infusion of brexucabtagene autoleucel CAR transduced autologous T cells administered IV at a target dose of 0.5 x 10^6 anti-CD19 CAR T cells/kg of body weight on Day 0. For participants weighing > 100 kg, a maximum flat dose of 0.5 x 10^8 anti-CD19 CAR T cells/kg of body weight was administered.

    Reporting group title
    Phase 2: 1 x 10^6 anti-CD19 CAR T Cells/kg
    Reporting group description
    		 Participants with r/r B-ALL received conditioning chemotherapy (fludarabine 25 mg/m^2 IV over 30 minutes on Day -4, Day -3, and Day -2 and cyclophosphamide 900 mg/m^2 IV over 60 minutes on Day -2) followed by a single infusion of brexucabtagene autoleucel CAR transduced autologous T cells administered IV at a target dose of 1 x 10^6 anti-CD19 CAR T cells/kg of body weight on Day 0. For participants weighing > 100 kg, a maximum flat dose of 1 x 10^8 anti-CD19 CAR T cells/kg of body weight was administered.

    Reporting group values
    		 Phase 1: 2 x 10^6 anti-CD19 CAR T Cells/kg Phase 1: 1 x 10^6 anti-CD19 CAR T Cells/kg Phase 1: 0.5 x 10^6 anti-CD19 CAR T Cells/kg Phase 2: 1 x 10^6 anti-CD19 CAR T Cells/kg Total
    Number of subjects
    		 6 28 20 71 125
    Age categorical
    Units: Subjects
        18 – 64 Years
    		 6 22 17 60 105
        65 – 84 Years
    		 0 6 3 11 20
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 38 ( 13.8 ) 46 ( 18.2 ) 44 ( 16.1 ) 44 ( 16.2 ) -
    Gender categorical
    Units: Subjects
        Female
    		 1 16 10 30 57
        Male
    		 5 12 10 41 68
    Race
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0 1 1
        Asian
    		 1 3 2 4 10
        Black or African American
    		 0 0 1 2 3
        White
    		 4 23 16 51 94
        Native Hawaiian or Other Pacific Islander
    		 0 1 0 0 1
        Not Collected
    		 0 0 0 4 4
        Other or More Than One Race
    		 1 1 1 9 12
    Ethnicity
    Units: Subjects
        Not Hispanic or Latino
    		 3 16 16 57 92
        Hispanic or Latino
    		 3 12 4 12 31
        Not Collected
    		 0 0 0 2 2

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Phase 1: 2 x 10^6 anti-CD19 CAR T Cells/kg
    Reporting group description
    		 Participants with relapsed or refractory B-precursor acute lymphoblastic leukemia (r/r B-ALL) received conditioning chemotherapy (fludarabine 25 mg/m^2 intravenously [IV] over 30 minutes on Day -4, Day -3, and Day -2 and cyclophosphamide 900 mg/m^2 IV over 60 minutes on Day -2) followed by a single infusion of brexucabtagene autoleucel (KTE-X19) chimeric antigen receptor (CAR) transduced autologous T cells administered IV at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg of body weight on Day 0. For participants weighing > 100 kg, a maximum flat dose of 2 x 10^8 anti-CD19 CAR T cells/kg of body weight was administered.

    Reporting group title
    Phase 1: 1 x 10^6 anti-CD19 CAR T Cells/kg
    Reporting group description
    		 Participants with r/r B-ALL received conditioning chemotherapy (fludarabine 25 mg/m^2 IV over 30 minutes on Day -4, Day -3, and Day -2 and cyclophosphamide 900 mg/m^2 IV over 60 minutes on Day -2) followed by a single infusion of brexucabtagene autoleucel CAR transduced autologous T cells administered IV at a target dose of 1 x 10^6 anti-CD19 CAR T cells/kg of body weight on Day 0. For participants weighing > 100 kg, a maximum flat dose of 1 x 10^8 anti-CD19 CAR T cells/kg of body weight was administered.

    Reporting group title
    Phase 1: 0.5 x 10^6 anti-CD19 CAR T Cells/kg
    Reporting group description
    		 Participants with r/r B-ALL received conditioning chemotherapy (fludarabine 25 mg/m^2 IV over 30 minutes on Day -4, Day -3, and Day -2 and cyclophosphamide 900 mg/m^2 IV over 60 minutes on Day -2) followed by a single infusion of brexucabtagene autoleucel CAR transduced autologous T cells administered IV at a target dose of 0.5 x 10^6 anti-CD19 CAR T cells/kg of body weight on Day 0. For participants weighing > 100 kg, a maximum flat dose of 0.5 x 10^8 anti-CD19 CAR T cells/kg of body weight was administered.

    Reporting group title
    Phase 2: 1 x 10^6 anti-CD19 CAR T Cells/kg
    Reporting group description
    		 Participants with r/r B-ALL received conditioning chemotherapy (fludarabine 25 mg/m^2 IV over 30 minutes on Day -4, Day -3, and Day -2 and cyclophosphamide 900 mg/m^2 IV over 60 minutes on Day -2) followed by a single infusion of brexucabtagene autoleucel CAR transduced autologous T cells administered IV at a target dose of 1 x 10^6 anti-CD19 CAR T cells/kg of body weight on Day 0. For participants weighing > 100 kg, a maximum flat dose of 1 x 10^8 anti-CD19 CAR T cells/kg of body weight was administered.

    Primary: Phase 1: Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs)

    		 Close Top of page
    End point title
    		 Phase 1: Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs) [1] [2]
    End point description
    DLT is drug-related events within first 28 days post infusion:Grade(GR)4 hematologic toxicity lasting more than 30 days (except lymphopenia) if not attributed to underlying disease and related GR 3 lasting for >7 days or 4 non-hematologic toxicities regardless of duration (except: aphasia/dysphasia or confusion/cognitive disturbance which resolves to at least GR 1/baseline within 2 weeks or baseline within 4 weeks, fever GR 3/ 4, immediate hypersensitivity reactions(2 hours of infusion) that are reversible ≤ GR 2 within 24 hours, renal toxicity(dialysis for ≤ 7 days), intubation for airway protection if ≤ 7 days, tumor lysis syndrome, GR 3 liver function test elevation (if resolution to ≤ GR 2 in 14 days), GR 4 transient serum hepatic enzyme abnormalities (if resolution to ≤ GR 3 within < 72 hours),hypogammaglobulinemia GR 3/ 4 and GR 3 nausea and/or anorexia).DLT-Evaluable Analysis Set included first 3 participants in Phase 1 treated with target dose and followed for 28 days.
    End point type
    Primary
    End point timeframe
    First infusion date of brexucabtagene autoleucel up to 28 days. Participants were evaluated in specified period but GR 4 hematologic toxicity (specified in description) having onset in this period were further observed for 30 days for confirmation
    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 comparison was planned or performed.
    [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: Per prespecified analysis, only participants from Phase 1: 2 X 10^6 Anti-CD19 CAR T Cells/kg were pre-specified to be assessed for this Outcome Measure.
    End point values
    		 Phase 1: 2 x 10^6 anti-CD19 CAR T Cells/kg
    Number of subjects analysed
    3
    Units: percentage of participants
        number (not applicable)
    0
    No statistical analyses for this end point

    Primary: Phase 2: Overall complete remission (OCR) Rate (Complete remission [CR]+ complete remission with incomplete hematologic recovery [CRi]) as Assessed per Independent Review

    		 Close Top of page
    End point title
    		 Phase 2: Overall complete remission (OCR) Rate (Complete remission [CR]+ complete remission with incomplete hematologic recovery [CRi]) as Assessed per Independent Review [3] [4]
    End point description
    OCR rate:percentage of participants achieving CR+CRi.CR: ≤5% blasts by morphology in bone marrow(BM);ANC≥1000/μL and platelets(Plt) ≥100000/μL in peripheral blood(PB);CNS extramedullary disease(CNS EMD) of CNS-1(no detectable leukemia in CSF);Non-CNS baselineEMD:if present(images shows CR),if no(images not needed),if performed shows negative PET baseline,baseline lesions shows CR as disappearance of measurable and nonmeasurable nodal lesions(Nodal masses >1.5 cm in greatest transverse diameter[GTD] at baseline have regressed to ≤l.5 cm GTD,nodes that were 1.1 to 1.5 cm[long axis] and >1.0 cm[short axis] have decreased to 1.0 cm in their short axis, spleen and/or liver must be normal size) and no new lesions.CRi:all CR criteria except in PB ANC≥1000/μL and Plt<100000/μL or ANC<1000/μL and Plt ≥100000/μL.95% CI was calculated by Clopper-Pearson method.The modified Intent-to-Treat (mITT) Analysis Set included all enrolled participants treated with brexucabtagene autoleucel in Phase 2.
    End point type
    Primary
    End point timeframe
    First infusion date of brexucabtagene autoleucel (Phase 2) up to 3.7 years
    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 comparison was planned or performed.
    [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: Per prespecified analysis, the data for this endpoint was collected only for Phase 2 of the study. Hence the data for Phase 1 arms is not reported for this endpoint.
    End point values
    		 Phase 2: 1 x 10^6 anti-CD19 CAR T Cells/kg
    Number of subjects analysed
    55
    Units: percentage of participants
        number (confidence interval 95%)
    70.9 (57 to 82)
    No statistical analyses for this end point

    Secondary: Phase 2: Complete Remission (CR) Rate per Independent Review

    		 Close Top of page
    End point title
    		 Phase 2: Complete Remission (CR) Rate per Independent Review [5]
    End point description
    CR: ≤ 5% blasts by morphology in BM; ANC ≥ 1000/µL and Plt ≥ 100000/µL in PB; CNS EMD of CNS-1 (no detectable leukemia in CSF); Non-CNS EMD: if baseline EMD present (images must show CR), if no baseline EMD (then images not required), but if performed should show negative PET baseline, baseline lesions must show CR as disappearance of measurable and nonmeasurable nodal lesions (Nodal masses > 1.5 cm in GTD at baseline must have regressed to ≤ l.5 cm GTD, nodes that were 1.1 to 1.5 cm [long axis] and > 1.0 cm [short axis] must have decreased to 1.0 cm in their short axis, spleen and/or liver must be normal size) and no new lesions. Percentage of participants with CR was reported. 95% CI was calculated by Clopper-Pearson method. Participants in mITT Analysis Set were analyzed.
    End point type
    Secondary
    End point timeframe
    First infusion date of brexucabtagene autoleucel (Phase 2) up to 3.7 years
    Notes
    [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per prespecified analysis, the data for this endpoint was collected only for Phase 2 of the study. Hence the data for Phase 1 arms is not reported for this endpoint.
    End point values
    		 Phase 2: 1 x 10^6 anti-CD19 CAR T Cells/kg
    Number of subjects analysed
    55
    Units: percentage of participants
        number (confidence interval 95%)
    56.4 (42 to 70)
    No statistical analyses for this end point

    Secondary: Phase 2: Minimum Residual Disease (MRD) Negative Remission Rate

    		 Close Top of page
    End point title
    		 Phase 2: Minimum Residual Disease (MRD) Negative Remission Rate [6]
    End point description
    MRD was assessed utilizing multicolor flow cytometry to detect residual cancerous cells with a sensitivity of 10^-4. MRD negative remission was defined as MRD < 10^-4 threshold. Percentage of participants with MRD negative remission was reported. 95% CI was calculated by Clopper-Pearson method. Participants in mITT Analysis Set were analyzed.
    End point type
    Secondary
    End point timeframe
    First infusion date of brexucabtagene autoleucel (Phase 2) up to 3.7 years
    Notes
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per prespecified analysis, the data for this endpoint was collected only for Phase 2 of the study. Hence the data for Phase 1 arms is not reported for this endpoint.
    End point values
    		 Phase 2: 1 x 10^6 anti-CD19 CAR T Cells/kg
    Number of subjects analysed
    55
    Units: percentage of participants
        number (confidence interval 95%)
    76 (63 to 87)
    No statistical analyses for this end point

    Secondary: Phase 2: Percentage of Participants With Allogeneic stem cell transplant (allo-SCT)

    		 Close Top of page
    End point title
    		 Phase 2: Percentage of Participants With Allogeneic stem cell transplant (allo-SCT) [7]
    End point description
    Participants in mITT Analysis Set were analyzed.
    End point type
    Secondary
    End point timeframe
    First infusion date of brexucabtagene autoleucel (Phase 2) up to 5 years
    Notes
    [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per prespecified analysis, the data for this endpoint was collected only for Phase 2 of the study. Hence the data for Phase 1 arms is not reported for this endpoint.
    End point values
    		 Phase 2: 1 x 10^6 anti-CD19 CAR T Cells/kg
    Number of subjects analysed
    55
    Units: percentage of participants
        number (not applicable)
    20
    No statistical analyses for this end point

    Secondary: Phase 2: OCR Rate (CR + CRi) Per Investigator Review

    		 Close Top of page
    End point title
    		 Phase 2: OCR Rate (CR + CRi) Per Investigator Review [8]
    End point description
    OCR rate: percentage of participants achieving CR+CRi. CR: ≤ 5% blasts by morphology in BM; ANC ≥1000/µL and Plt ≥ 100000/µL in PB; CNS EMD of CNS-1 (no detectable leukemia in CSF); Non-CNS EMD: if baseline EMD present (images must show CR), if no baseline EMD (then images not required), but if performed should show negative PET baseline, baseline lesions must show CR as disappearance of measurable and nonmeasurable nodal lesions (Nodal masses >1.5 cm in GTD at baseline must have regressed to ≤l.5 cm GTD, nodes that were 1.1 to 1.5 cm [long axis] and >1.0 cm [short axis] must have decreased to 1.0 cm in their short axis, spleen and/or liver must be normal size, if tested) and no new lesions. CRi: all CR criteria except in PB ANC ≥1000/µL and Plt <100000/µL or ANC <1000/µL and Plt ≥100000/µL. 95% CI was calculated by Clopper-Pearson method. Participants in mITT Analysis Set were analyzed.
    End point type
    Secondary
    End point timeframe
    First infusion date of brexucabtagene autoleucel (Phase 2) up to 5 years
    Notes
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per prespecified analysis, the data for this endpoint was collected only for Phase 2 of the study. Hence the data for Phase 1 arms is not reported for this endpoint.
    End point values
    		 Phase 2: 1 x 10^6 anti-CD19 CAR T Cells/kg
    Number of subjects analysed
    55
    Units: percentage of participants
        number (confidence interval 95%)
    72.7 (59 to 84)
    No statistical analyses for this end point

    Secondary: Phase 2: Duration of Remission (DOR) per Independent Review

    		 Close Top of page
    End point title
    		 Phase 2: Duration of Remission (DOR) per Independent Review [9]
    End point description
    DOR is the time from first CR or CRi to relapse or any death in the absence of documented relapse. Relapse: ≤ 5% blasts by morphology in BM; or circulating leukemia present in PB; or CNS EMD of CNS-2 (detectable CSF blast cells in a sample of CSF with < 5 white blood cells [WBCs] per mm^3 with neurological changes) or CNS-3 (detectable CSF blast cells in a sample of CSF with ≥ 5 WBCs per mm^3 with or without neurological changes); or PD: at least one of the following (≥ 50% increase from nadir in the sum of at least two lymph nodes, or if a single node is involved at least a 50% increase in the product of the diameters of this one node; at least a 50% increase in the longest diameter of any single previously identified node more than 1 cm in its short axis; ≥ 50% increase in size of splenic, hepatic or any other non-nodal lesion). Kaplan-Meier (KM) estimates was used for analyses. Participants in the mITT Analysis Set with overall complete remission (CR or CRi ) were analyzed.
    End point type
    Secondary
    End point timeframe
    From first CR or CRi (Phase 2) up to 3.7 years
    Notes
    [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per prespecified analysis, the data for this endpoint was collected only for Phase 2 of the study. Hence the data for Phase 1 arms is not reported for this endpoint.
    End point values
    		 Phase 2: 1 x 10^6 anti-CD19 CAR T Cells/kg
    Number of subjects analysed
    39
    Units: months
        median (confidence interval 95%)
    14.6 (9.4 to 24.1)
    No statistical analyses for this end point

    Secondary: Phase 2: Complete Remission With Incomplete Hematologic Recovery (CRi) Rate per Independent Review

    		 Close Top of page
    End point title
    		 Phase 2: Complete Remission With Incomplete Hematologic Recovery (CRi) Rate per Independent Review [10]
    End point description
    CRi: ≤ 5% blasts by morphology in BM; ANC ≥ 1000/µL and Plt < 100000/µL or ANC < 1000/µL and Plt ≥ 100000/µL in PB; CNS EMD of CNS-1 (no detectable leukemia in CSF); Non-CNS EMD: if baseline EMD present (images must show CR), if no baseline EMD (then images not required), but if performed should show negative PET baseline, baseline lesions must show CR as disappearance of measurable and nonmeasurable nodal lesions (Nodal masses > 1.5 cm in GTD at baseline must have regressed to ≤ l.5 cm GTD, nodes that were 1.1 to 1.5 cm [long axis] and > 1.0 cm [short axis] must have decreased to 1.0 cm in their short axis, spleen and/or liver must be normal size, if tested) and no new lesions. Percentage of participants with CRi was reported. 95% CI was calculated by Clopper-Pearson method. Participants in mITT Analysis Set were analyzed.
    End point type
    Secondary
    End point timeframe
    First infusion date of brexucabtagene autoleucel (Phase 2) up to 3.7 years
    Notes
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per prespecified analysis, the data for this endpoint was collected only for Phase 2 of the study. Hence the data for Phase 1 arms is not reported for this endpoint.
    End point values
    		 Phase 2: 1 x 10^6 anti-CD19 CAR T Cells/kg
    Number of subjects analysed
    55
    Units: percentage of participants
        number (confidence interval 95%)
    14.5 (6 to 27)
    No statistical analyses for this end point

    Secondary: Phase 2: MRD Negative Remission Rate Among Complete Remission (CR) Participants

    		 Close Top of page
    End point title
    		 Phase 2: MRD Negative Remission Rate Among Complete Remission (CR) Participants [11]
    End point description
    Percentage of participants with MRD negative remission among CR participants was reported. MRD was assessed by multicolor flow cytometry to detect residual cancerous cells with a sensitivity of 10^-4. Remission was defined as MRD < 10^-4 threshold. CR: ≤5% blasts by morphology in BM; ANC ≥ 1000/µL and Plt ≥ 100000/µL in PB; CNS EMD of CNS-1 (no detectable leukemia in CSF); Non-CNS EMD: if baseline EMD present (images must show CR), if no baseline EMD (images not required), but if performed should show negative PET baseline, baseline lesions must show CR as disappearance of measurable and nonmeasurable nodal lesions (Nodal masses > 1.5 cm in GTD at baseline must have regressed to ≤ l.5 cm GTD, nodes that were 1.1 to 1.5 cm [long axis] and > 1.0 cm [short axis] must have decreased to 1.0 cm in their short axis, spleen and/or liver must be normal size) and no new lesions. 95% CI was calculated by Clopper-Pearson method. Participants in mITT Analysis Set with CR were analyzed.
    End point type
    Secondary
    End point timeframe
    First infusion date of brexucabtagene autoleucel (Phase 2) up to 3.7 years
    Notes
    [11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per prespecified analysis, the data for this endpoint was collected only for Phase 2 of the study. Hence the data for Phase 1 arms is not reported for this endpoint.
    End point values
    		 Phase 2: 1 x 10^6 anti-CD19 CAR T Cells/kg
    Number of subjects analysed
    31
    Units: percentage of participants
        number (confidence interval 95%)
    97 (83 to 100)
    No statistical analyses for this end point

    Secondary: Phase 2: MRD Negative Remission Rate Among Complete Remission With Incomplete Hematologic Recovery (CRi) Participants

    		 Close Top of page
    End point title
    		 Phase 2: MRD Negative Remission Rate Among Complete Remission With Incomplete Hematologic Recovery (CRi) Participants [12]
    End point description
    Percentage of participants with MRD negative remission among CRi participants was reported. MRD by multicolor flow cytometry to detect residual cancerous cells(sensitivity of 10^-4).Remission was defined as MRD < 10^-4 threshold. CRi: ≤ 5% blasts by morphology in BM; ANC ≥ 1000/µL and Plt < 100000/µL or ANC < 1000/µL and Plt ≥ 100000/µL in PB; CNS EMD of CNS-1(no detectable leukemia in CSF); Non-CNS EMD: if baseline EMD(images must show CR), if no baseline EMD (then images not required), if performed should show negative PET baseline, baseline lesions must show CR as disappearance of measurable and nonmeasurable nodal lesions (Nodal masses >1.5 cm in GTD at baseline must have regressed to ≤l.5 cm GTD, nodes that were 1.1 to 1.5 cm [long axis] and >1.0 cm [short axis] must have decreased to 1.0 cm in their short axis, spleen and/or liver must be normal size) and no new lesions. 95% CI was calculated by Clopper-Pearson method. Participants in mITT Analysis Set with CRi were analyzed.
    End point type
    Secondary
    End point timeframe
    First infusion date of brexucabtagene autoleucel (Phase 2) up to 3.7 years
    Notes
    [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per prespecified analysis, the data for this endpoint was collected only for Phase 2 of the study. Hence the data for Phase 1 arms is not reported for this endpoint.
    End point values
    		 Phase 2: 1 x 10^6 anti-CD19 CAR T Cells/kg
    Number of subjects analysed
    8
    Units: percentage of participants
        number (confidence interval 95%)
    100 (63 to 100)
    No statistical analyses for this end point

    Secondary: Phase 2: Overall survival (OS)

    		 Close Top of page
    End point title
    		 Phase 2: Overall survival (OS) [13]
    End point description
    OS was defined as the time from brexucabtagene autoleucel infusion to the date of death from any cause. Participants who had not died by the analysis data cutoff date were censored at their last contact date. KM estimates was used for analyses. Participants in mITT Analysis Set were analyzed. 9999 indicates that the upper limit of confidence interval was not estimable due to insufficient number of events.
    End point type
    Secondary
    End point timeframe
    First infusion date of brexucabtagene autoleucel (Phase 2) up to 5 years
    Notes
    [13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per prespecified analysis, the data for this endpoint was collected only for Phase 2 of the study. Hence the data for Phase 1 arms is not reported for this endpoint.
    End point values
    		 Phase 2: 1 x 10^6 anti-CD19 CAR T Cells/kg
    Number of subjects analysed
    55
    Units: months
        median (confidence interval 95%)
    26.0 (16.2 to 9999)
    No statistical analyses for this end point

    Secondary: Phase 2: Relapse-free survival (RFS)

    		 Close Top of page
    End point title
    		 Phase 2: Relapse-free survival (RFS) [14]
    End point description
    RFS: time from brexucabtagene autoleucel infusion to date of disease relapse or death from any cause. Participants not meeting criteria for relapse by the analysis data cutoff date were censored at their last evaluable disease assessment date. Participants who had not achieved a CR or CRi at analysis data cutoff were evaluated as an RFS event at Day 0. CR and CRi are defined in Outcome Measures 4 and 5. Relapse is defined in Outcome Measure 6. KM estimates was used for analyses. Participants in mITT Analysis Set were analyzed.
    End point type
    Secondary
    End point timeframe
    First infusion date of brexucabtagene autoleucel (Phase 2) up to 3.7 years
    Notes
    [14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per prespecified analysis, the data for this endpoint was collected only for Phase 2 of the study. Hence the data for Phase 1 arms is not reported for this endpoint.
    End point values
    		 Phase 2: 1 x 10^6 anti-CD19 CAR T Cells/kg
    Number of subjects analysed
    55
    Units: months
        median (confidence interval 95%)
    11.6 (2.7 to 20.5)
    No statistical analyses for this end point

    Secondary: Phase 2: Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs)

    		 Close Top of page
    End point title
    		 Phase 2: Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs) [15]
    End point description
    An AE was any untoward medical occurrence in a participant after brexucabtagene autoleucel infusion, which did not necessarily have a causal relationship with the treatment. An AE could therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. TEAEs included all AEs with onset on or after initiation of the brexucabtagene autoleucel infusion. The Safety Analysis Set included all participants treated with any dose of brexucabtagene autoleucel.
    End point type
    Secondary
    End point timeframe
    Up to 5 years
    Notes
    [15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per prespecified analysis, the data for this endpoint was collected only for Phase 2 of the study. Hence the data for Phase 1 arms is not reported for this endpoint.
    End point values
    		 Phase 2: 1 x 10^6 anti-CD19 CAR T Cells/kg
    Number of subjects analysed
    55
    Units: percentage of participants
        number (not applicable)
    100
    No statistical analyses for this end point

    Secondary: Phase 2: Number of Participants Experiencing Laboratory Toxicity Grade 3 or Higher TEAEs Resulting From Increased Parameter Value

    		 Close Top of page
    End point title
    		 Phase 2: Number of Participants Experiencing Laboratory Toxicity Grade 3 or Higher TEAEs Resulting From Increased Parameter Value [16]
    End point description
    Grading categories are determined by Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Grade 1: mild, Grade 2: moderate, Grade 3: severe or medically significant, Grade 4: life-threatening. Participants in Safety Analysis Set were analyzed.
    End point type
    Secondary
    End point timeframe
    Up to 5 years
    Notes
    [16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per prespecified analysis, the data for this endpoint was collected only for Phase 2 of the study. Hence the data for Phase 1 arms is not reported for this endpoint.
    End point values
    		 Phase 2: 1 x 10^6 anti-CD19 CAR T Cells/kg
    Number of subjects analysed
    55
    Units: participants
        Hematology: Lymphocytes
    1
        Hematology: Leukocytes
    4
        Hematology: Hemoglobin
    0
        Hematology: Neutrophils
    0
        Hematology: Platelets
    0
        Chemistry: Creatinine
    4
        Chemistry: Glucose
    13
        Chemistry: Aspartate Aminotransferase
    14
        Chemistry: Alanine Aminotransferase
    17
        Chemistry: Bilirubin
    5
        Chemistry: Alkaline Phosphatase
    3
        Chemistry: Direct Bilirubin
    8
        Chemistry: Urate
    12
        Chemistry: Sodium
    1
        Chemistry: Potassium
    2
        Chemistry: Magnesium
    3
        Chemistry: Calcium
    0
        Chemistry: Albumin
    0
        Chemistry: Phosphate
    0
    No statistical analyses for this end point

    Secondary: Phase 2: Number of Participants Experiencing Laboratory Toxicity Grade 3 or Higher TEAEs Resulting From Decreased Parameter Value

    		 Close Top of page
    End point title
    		 Phase 2: Number of Participants Experiencing Laboratory Toxicity Grade 3 or Higher TEAEs Resulting From Decreased Parameter Value [17]
    End point description
    Grading categories are determined by CTCAE version 4.03. Grade 1: mild, Grade 2: moderate, Grade 3: severe or medically significant, Grade 4: life-threatening. Participants in Safety Analysis Set were analyzed.
    End point type
    Secondary
    End point timeframe
    Up to 5 years
    Notes
    [17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per prespecified analysis, the data for this endpoint was collected only for Phase 2 of the study. Hence the data for Phase 1 arms is not reported for this endpoint.
    End point values
    		 Phase 2: 1 x 10^6 anti-CD19 CAR T Cells/kg
    Number of subjects analysed
    55
    Units: participants
        Hematology: Hemoglobin
    42
        Hematology: Leukocytes
    54
        Hematology: Platelets
    46
        Hematology: Lymphocytes
    52
        Hematology: Neutrophils
    53
        Chemistry: Calcium
    9
        Chemistry: Albumin
    5
        Chemistry: Phosphate
    27
        Chemistry: Magnesium
    0
        Chemistry: Sodium
    11
        Chemistry: Potassium
    7
        Chemistry: Glucose
    0
        Chemistry: Alanine Aminotransferase
    0
        Chemistry: Alkaline Phosphatase
    0
        Chemistry: Aspartate Aminotransferase
    0
        Chemistry: Bilirubin
    0
        Chemistry: Creatinine
    0
        Chemistry: Direct Bilirubin
    0
        Chemistry: Urate
    0
    No statistical analyses for this end point

    Secondary: Phase 2: Percentage of Participants With Anti-KTE-X19 Antibodies

    		 Close Top of page
    End point title
    		 Phase 2: Percentage of Participants With Anti-KTE-X19 Antibodies [18]
    End point description
    Participants in Safety Analysis Set were analyzed.
    End point type
    Secondary
    End point timeframe
    First infusion date of brexucabtagene autoleucel (Phase 2) up to 2.7 years
    Notes
    [18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per prespecified analysis, the data for this endpoint was collected only for Phase 2 of the study. Hence the data for Phase 1 arms is not reported for this endpoint.
    End point values
    		 Phase 2: 1 x 10^6 anti-CD19 CAR T Cells/kg
    Number of subjects analysed
    55
    Units: percentage of participants
        number (not applicable)
    7
    No statistical analyses for this end point

    Secondary: Phase 2: Number of Participants With 5-Level European Quality of Life-5 Dimensions (EQ-5D-5L): Health Utility Index scale

    		 Close Top of page
    End point title
    		 Phase 2: Number of Participants With 5-Level European Quality of Life-5 Dimensions (EQ-5D-5L): Health Utility Index scale [19]
    End point description
    The EQ-5D-5 levels (EQ-5D-5L) is a standardized measure of health status of the participant that provides a simple, generic measure of health for clinical and economic appraisal. It is a self-reported questionnaire used for assessing the overall health status of a participant scoring 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. EQ-5D health states, defined by the EQ-5D descriptive system, are converted into a single summary index by applying a formula that attaches values (also called QOL utilities) to each of the levels in each dimension. EQ-5D Summary Index values range from -0.11 (worst health) to 1.00 (perfect health).This results in a 1-digit number. The digits for 5 dimensions can be combined into a 5-digit number. Higher scores=better health. Participants in Safety Analysis Set with available data were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 28, Month 3, Month 6, Month 9, Month 12, Month 15, Month 18, and Month 24
    Notes
    [19] - 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: Per prespecified analysis, the data for this endpoint was collected only for Phase 2 of the study. Hence the data for Phase 1 arms is not reported for this endpoint. .
    End point values
    		 Phase 2: 1 x 10^6 anti-CD19 CAR T Cells/kg
    Number of subjects analysed
    51
    Units: participants
        Baseline: Mobility (No problem)
    39
        Baseline: Mobility (Slight problem)
    7
        Baseline: Mobility (Moderate problem)
    4
        Baseline: Mobility (Severe problem)
    1
        Baseline: Mobility (Unable to walk)
    0
        D 28: Mobility (No problem) N=42
    19
        D 28: Mobility (Slight problem) N=42
    10
        D 28: Mobility (Moderate problem) N=42
    9
        D 28: Mobility (Severe problem) N=42
    1
        D 28: Mobility (Unable to walk) N=42
    3
        Month 3: Mobility (No problem) N=26
    19
        Month 3: Mobility (Slight problem) N=26
    5
        Month 3: Mobility (Moderate problem) N=26
    1
        Month 3: Mobility (Severe problem) N=26
    0
        Month 3: Mobility (Unable to walk) N=26
    1
        Month 6: Mobility (No problem) N=25
    16
        Month 6: Mobility (Slight problem) N=25
    6
        Month 6: Mobility (Moderate problem) N=25
    2
        Month 6: Mobility (Severe problem) N=25
    0
        Month 6: Mobility (Unable to walk) N=25
    1
        Month 9: Mobility (No problem) N=10
    8
        Month 9: Mobility (Slight problem) N=10
    1
        Month 9: Mobility (Moderate problem) N=10
    0
        Month 9: Mobility (Severe problem) N=10
    0
        Month 9: Mobility (Unable to walk) N=10
    1
        Month 12: Mobility (No problem) N=14
    11
        Month 12: Mobility (Slight problem) N=14
    3
        Month 12: Mobility (Moderate problem) N=14
    0
        Month 12: Mobility (Severe problem) N=14
    0
        Month 12: Mobility (Unable to walk) N=14
    0
        Month 15: Mobility (No problem) N=10
    7
        Month 15: Mobility (Slight problem) N=10
    2
        Month 15: Mobility (Moderate problem) N=10
    1
        Month 15: Mobility (Severity problem) N=10
    0
        Month 15: Mobility (Unable to walk) N=10
    0
        Month 18: Mobility (No problem) N=4
    3
        Month 18: Mobility (Slight problem) N=4
    1
        Month 18: Mobility (Moderate problem) N=4
    0
        Month 18: Mobility (Severe problem) N=4
    0
        Month 18: Mobility (Unable to walk) N=4
    0
        Month 24: Mobility (No problem) N=4
    3
        Month 24: Mobility (Slight problem) N=4
    1
        Month 24: Mobility (Moderate problem) N=4
    0
        Month 24: Mobility (Severe problem) N=4
    0
        Month 24: Mobility (Unable to Walk) N=4
    0
        Baseline: Self-care (No problem)
    44
        Baseline: Self-care (Slight problem)
    5
        Baseline: Self-care (Moderate problem)
    1
        Baseline: Self-care (Severe problem)
    1
        Baseline: Self-care (Unable to wash or dress)
    0
        D 28: Self-care (No problem) N=42
    31
        D 28: Self-care (Slight problem) N=42
    6
        D 28: Self-care (Moderate problem) N=42
    1
        D 28: Self-care (Severe problem) N=42
    2
        D 28: Self-care (Unable to wash or dress) N=42
    2
        Month 3: Self-care (No problem) N=25
    23
        Month 3: Self-care (Slight problem) N=25
    1
        Month 3: Self-care (Moderate problem) N=25
    1
        Month 3: Self-care (Severe problem) N=25
    0
        Month 3: Self-care (Unable to wash or dress) N=25
    0
        Month 6: Self-care (No problem) N=25
    23
        Month 6: Self-care (Slight problem)
    0
        Month 6: Self-care (Moderate problem)
    1
        Month 6: Self-care (Severe problem)
    1
        Month 6: Self-care (Unable to wash or dress) N=10
    0
        Month 9: Self-care (No problem) N=10
    9
        Month 9: Self-care (Slight problem) N=10
    0
        Month 9: Self-care (Moderate problem) N=10
    0
        Month 9: Self-care (Severe problem) N=10
    1
        Month 9: Self-care (Unable to wash or dress)
    0
        Month 12: Self-care (No problem) N=14
    14
        Month 12: Self-care (Slight problem) N=14
    0
        Month 12: Self-care (Moderate problem) N=14
    0
        Month 12: Self-care (Severe problem) N=14
    0
        Mon 12: Self-care (Unable to wash or dress) N=14
    0
        Month 15: Self-care (No problem) N=10
    10
        Month 15: Self-care (Slight problem) N=10
    0
        Month 15: Self-care (Moderate problem) N=10
    0
        Month 15: Self-care (Severe problem) N=10
    0
        Mon 15: Self-care (Unable to wash or dress) N=10
    0
        Month 18: Self-care (No problem) N=4
    4
        Month 18: Self-care (Slight problem) N=4
    0
        Month 18: Self-care (Moderate problem) N=4
    0
        Month 18: Self-care (Severe problem) N=4
    0
        Month 18: Self-care (Unable to wash or dress) N=4
    0
        Month 24: Self-care (No problem) N=4
    4
        Month 24: Self-care (Slight problem) N=4
    0
        Month 24: Self-care (Moderate problem) N=4
    0
        Month 24: Self-care (Severe problem) N=4
    0
        Month 24: Self-care (Unable to wash or dress) N=4
    0
        Baseline: Usual activities (No problem)
    24
        Baseline: Usual activities (Slight problem)
    14
        Baseline: Usual activities (Moderate problem)
    9
        Baseline: Usual activities (Severe problem)
    3
        Bas Usu activities (Unable to do usual activities)
    1
        D 28: Usual activities (No problem) N=42
    17
        D 28: Usual activities (Slight problem) N=42
    13
        D 28: Usual activities (Moderate problem) N=42
    8
        D 28: Usual activities (Severe problem) N=42
    3
        D 28: Usu act (Unable to do usual activities) N=42
    1
        Month 3: Usual activities (No problem) N=25
    14
        Month 3: Usual activities (Slight problem) N=25
    9
        Month 3: Usual activities (Moderate problem) N=25
    1
        Month 3: Usual activities (Severe problem) N=25
    1
        Mon 3: Usu act (Un to do usual activities) N=25
    0
        Month 6: Usual activities (No problem) N=25
    17
        Month 6: Usual activities (Slight problem) N=25
    4
        Month 6: Usual activities (Moderate problem) N=25
    2
        Month 6: Usual activities (Severe problem) N=25
    2
        Mon 6: Usu act (Un to do usual activities) N=25
    0
        Month 9: Usual activities (No problem) N=10
    9
        Month 9: Usual activities (Slight problem) N=10
    0
        Month 9: Usual activities (Moderate problem) N=10
    0
        Month 9: Usual activities (Severe problem) N=10
    0
        Mon 9: Usu act (Un to do usual activities) N=10
    1
        Month 12: Usual activities (No problem) N=14
    11
        Month 12: Usual activities (Slight problem) N=14
    3
        Month 12: Usual activities (Moderate problem) N=14
    0
        Month 12: Usual activities (Severe problem) N=14
    0
        Mon 12: Usu act (Un to do usual activities) N=14
    0
        Month 15: Usual activities (No problem) N=10
    8
        Month 15: Usual activities (Slight problem) N=10
    2
        Month 15: Usual activities (Moderate problem) N=10
    0
        Month 15: Usual activities (Severe problem) N=10
    0
        Mon 15: Usu act (Un to do usual activities) N=10
    0
        Month 18: Usual activities (No problem) N=4
    1
        Month 18: Usual activities (Slight problem) N=4
    3
        Month 18: Usual activities (Moderate problem) N=4
    0
        Month 18: Usual activities (Severe problem) N=4
    0
        Mon 18: Usu act (Un to do usual activities) N=4
    0
        Month 24: Usual activities (No problem) N=4
    4
        Month 24: Usual activities (Slight problem) N=4
    0
        Month 24: Usual activities (Moderate problem) N=4
    0
        Month 24: Usual activities (Severe problem) N=4
    0
        Mon 24: Usu act (Un to do usual activities) N=4
    0
        Baseline: Pain/Discomfort (No Problem)
    23
        Baseline: Pain/Discomfort (Slight Problem)
    16
        Baseline: Pain/Discomfort (Moderate Problem)
    12
        Baseline: Pain/Discomfort (Severe Problem)
    0
        Bas Pain/Discomfort (Extreme Pain or discomfort)
    0
        D 28: Pain/Discomfort (No Problem) N=42
    19
        D 28: Pain/Discomfort (Slight Problem) N=42
    14
        D 28: Pain/Discomfort (Moderate Problem) N=42
    9
        D 28: Pain/Discomfort (Severe Problem) N=42
    0
        D 28: Pai (Extreme Pain or discomfort) N=42
    0
        Month 3: Pain/Discomfort (No Problem) N=26
    11
        Month 3: Pain/Discomfort (Slight Problem) N=26
    9
        Month 3: Pain/Discomfort (Moderate Problem) N=26
    6
        Month 3: Pain/Discomfort (Severe Problem) N=26
    0
        Mon 3: Pai (Extreme Pain or discomfort) N=26
    0
        Month 6: Pain/Discomfort (No Problem) N=25
    11
        Month 6: Pain/Discomfort (Slight Problem) N=25
    5
        Month 6: Pain/Discomfort (Moderate Problem) N=25
    7
        Month 6: Pain/Discomfort (Severe Problem) N=25
    2
        Mon 6: Pai (Extreme Pain or discomfort) N=25
    0
        Month 9: Pain/Discomfort (No Problem) N=10
    7
        Month 9: Pain/Discomfort (Slight Problem) N=10
    1
        Month 9: Pain/Discomfort (Moderate Problem) N=10
    2
        Month 9: Pain/Discomfort (Severe Problem) N=10
    0
        Mon 9: Pai (Extreme Pain or discomfort) N=10
    0
        Month 12: Pain/Discomfort (No Problem) N=14
    7
        Month 12: Pain/Discomfort (Slight Problem) N=14
    6
        Month 12: Pain/Discomfort (Moderate Problem) N=14
    1
        Month 12: Pain/Discomfort (Severe Problem) N=14
    0
        Mon 12: Pai (Extreme Pain or discomfort) N=14
    0
        Month 15: Pain/Discomfort (No Problem) N=10
    6
        Month 15: Pain/Discomfort (Slight Problem) N=10
    4
        Month 15: Pain/Discomfort (Moderate Problem) N=10
    0
        Month 15: Pain/Discomfort (Severe Problem) N=10
    0
        Mon 15: Pai (Extreme Pain or discomfort) N=10
    0
        Month 18: Pain/Discomfort (No Problem) N=4
    1
        Month 18: Pain/Discomfort (Slight Problem) N=4
    3
        Month 18: Pain/Discomfort (Moderate Problem) N=4
    0
        Month 18: Pain/Discomfort (Severe Problem) N=4
    0
        Mon 18: Pai (Extreme Pain or discomfort) N=4
    0
        Month 24: Pain/Discomfort (No Problem) N=4
    3
        Month 24: Pain/Discomfort (Slight Problem) N=4
    1
        Month 24: Pain/Discomfort (Moderate Problem) N=4
    0
        Month 24: Pain/Discomfort (Severe Problem) N=4
    0
        Mon 24: Pai (Extreme Pain or discomfort) N=4
    0
        Baseline: Anxiety/Depression (No problem)
    30
        Baseline: Anxiety/Depression (Slight problem)
    12
        Baseline: Anxiety/Depression (Moderate problem)
    7
        Baseline: Anxiety/Depression (Severe problem)
    2
        Bas Anx (Extreme Anxious or Depressed)
    0
        D 28: Anxiety/Depression (No problem) N=42
    28
        D 28: Anxiety/Depression (Slight problem) N=42
    11
        D 28: Anxiety/Depression (Moderate problem) N=42
    3
        D 28: Anxiety/Depression (Severe problem) N=42
    0
        D 28: Anx (Extreme Anxious or Depressed) N=42
    0
        Month 3: Anxiety/Depression (No problem) N=26
    17
        Month 3: Anxiety/Depression (Slight problem) N=26
    6
        Mon 3: Anxiety/Depression (Moderate problem) N=26
    3
        Month 3: Anxiety/Depression (Severe problem) N=26
    0
        Mon 3: Anx (Extreme Anxious or Depressed) N=26
    0
        Month 6: Anxiety/Depression (No problem) N=25
    18
        Month 6: Anxiety/Depression (Slight problem) N=25
    4
        Mon 6: Anxiety/Depression (Moderate problem) N=25
    3
        Month 6: Anxiety/Depression (Severe problem) N=25
    0
        Mon 6: Anx (Extreme Anxious or Depressed) N=25
    0
        Month 9: Anxiety/Depression (No problem) N=10
    9
        Month 9: Anxiety/Depression (Slight problem) N=10
    0
        Mon 9: Anxiety/Depression (Moderate problem) N=10
    1
        Month 9: Anxiety/Depression (Severe problem) N=10
    0
        Mon 9: Anx (Extreme Anxious or Depressed) N=10
    0
        Month 12: Anxiety/Depression (No problem) N=14
    10
        Month 12: Anxiety/Depression (Slight problem) N=14
    2
        Mon 12: Anxiety/Depression (Moderate problem) N=14
    2
        Month 12: Anxiety/Depression (Severe problem) N=14
    0
        Mon 12: Anx (Extreme Anxious or Depressed) N=14
    0
        Month 15: Anxiety/Depression (No problem) N=10
    7
        Month 15: Anxiety/Depression (Slight problem) N=10
    2
        Mon 15: Anxiety/Depression (Moderate problem) N=10
    1
        Month 15: Anxiety/Depression (Severe problem) N=10
    0
        Mon 15: Anx (Extreme Anxious or Depressed) N=10
    0
        Month 18: Anxiety/Depression (No problem) N=4
    3
        Month 18: Anxiety/Depression (Slight problem) N=4
    1
        Mon 18: Anxiety/Depression (Moderate problem) N=4
    0
        Month 18: Anxiety/Depression (Severe problem) N=4
    0
        Mon 18: Anx (Extreme Anxious or Depressed) N=4
    0
        Month 24: Anxiety/Depression (No problem) N=4
    4
        Month 24: Anxiety/Depression (Slight problem) N=4
    0
        Mon 24: Anxiety/Depression (Moderate problem) N=4
    0
        Month 24: Anxiety/Depression (Severe problem) N=4
    0
        Mon 24: Anx (Extreme Anxious or Depressed) N=4
    0
    No statistical analyses for this end point

    Secondary: Phase 2: EQ-5D Visual Analogue Scale (VAS) Score

    		 Close Top of page
    End point title
    		 Phase 2: EQ-5D Visual Analogue Scale (VAS) Score [20]
    End point description
    EQ-5D is a self-reported questionnaire used for assessing the overall health status of a participant. The EQ-5D is a participant rated questionnaire to assess health-related quality of life in terms of a single index value. The EQ-5D-VAS records the participant's self-rated health on a 20-cm vertical visual analogue scale and is asked to make a global assessment of their current state of health with 0 indicating the worst health they can imagine and 100 indicating the best health they can imagine. Higher scores indicate a better health state. Participants in Safety Analysis Set with available data were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 28, Month 3, Month 6, Month 9, Month 12, Month 15, Month 18, and Month 24
    Notes
    [20] - 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: Per prespecified analysis, the data for this endpoint was collected only for Phase 2 of the study. Hence the data for Phase 1 arms is not reported for this endpoint.
    End point values
    		 Phase 2: 1 x 10^6 anti-CD19 CAR T Cells/kg
    Number of subjects analysed
    51
    Units: score on a scale
    arithmetic mean (standard deviation)
        Baseline
    68.2 ( 21.8 )
        Day 28 N=41
    74.7 ( 17.9 )
        Month 3 N=26
    79.7 ( 12.2 )
        Month 6 N=25
    81.0 ( 17.6 )
        Month 9 N=10
    81.7 ( 23.1 )
        Month 12 N=14
    86.9 ( 10.0 )
        Month 15 N=10
    87.8 ( 11.6 )
        Month 18 N=4
    93.3 ( 5.9 )
        Month 24 N=4
    97.5 ( 2.9 )
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Adverse Event: Up to 5 years; All-Cause mortality: Up to 7.1 years
    Adverse event reporting additional description
    Adverse Events: The Safety Analysis Set included all participants treated with any dose of brexucabtagene autoleucel. All-cause mortality: All Enrolled Analysis Set included all enrolled participants in the study.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    26.1
    Reporting groups
    Reporting group title
    Phase 1: 2 x 10^6 Anti-CD19 CAR T Cells/kg
    Reporting group description
    		 Participants with r/r B-ALL received conditioning chemotherapy (fludarabine 25 mg/m^2 IV over 30 minutes on Day -4, Day -3, and Day -2 and cyclophosphamide 900 mg/m^2 IV over 60 minutes on Day -2) followed by a single infusion of brexucabtagene autoleucel CAR transduced autologous T cells administered IV at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg of body weight on Day 0. For participants weighing > 100 kg, a maximum flat dose of 2 x 10^8 anti-CD19 CAR T cells/kg of body weight was administered.

    Reporting group title
    Phase 2: 1 x 10^6 Anti-CD19 CAR T Cells/kg
    Reporting group description
    		 Participants with r/r B-ALL received conditioning chemotherapy (fludarabine 25 mg/m^2 IV over 30 minutes on Day -4, Day -3, and Day -2 and cyclophosphamide 900 mg/m^2 IV over 60 minutes on Day -2) followed by a single infusion of brexucabtagene autoleucel CAR transduced autologous T cells administered IV at a target dose of 1 x 10^6 anti-CD19 CAR T cells/kg of body weight on Day 0. For participants weighing > 100 kg, a maximum flat dose of 1 x 10^8 anti-CD19 CAR T cells/kg of body weight was administered.

    Reporting group title
    Phase 1: 0.5 x 10^6 Anti-CD19 CAR T Cells/kg
    Reporting group description
    		 Participants with r/r B-ALL received conditioning chemotherapy (fludarabine 25 mg/m^2 IV over 30 minutes on Day -4, Day -3, and Day -2 and cyclophosphamide 900 mg/m^2 IV over 60 minutes on Day -2) followed by a single infusion of brexucabtagene autoleucel CAR transduced autologous T cells administered IV at a target dose of 0.5 x 10^6 anti-CD19 CAR T cells/kg of body weight on Day 0. For participants weighing > 100 kg, a maximum flat dose of 0.5 x 10^8 anti-CD19 CAR T cells/kg of body weight was administered.

    Reporting group title
    Phase 1: 1 x 10^6 Anti-CD19 CAR T Cells/kg
    Reporting group description
    		 Participants with r/r B-ALL received conditioning chemotherapy (fludarabine 25 mg/m^2 IV over 30 minutes on Day -4, Day -3, and Day -2 and cyclophosphamide 900 mg/m^2 IV over 60 minutes on Day -2) followed by a single infusion of brexucabtagene autoleucel CAR transduced autologous T cells administered IV at a target dose of 1 x 10^6 anti-CD19 CAR T cells/kg of body weight on Day 0. For participants weighing > 100 kg, a maximum flat dose of 1 x 10^8 anti-CD19 CAR T cells/kg of body weight was administered.

    Serious adverse events
    		 Phase 1: 2 x 10^6 Anti-CD19 CAR T Cells/kg Phase 2: 1 x 10^6 Anti-CD19 CAR T Cells/kg Phase 1: 0.5 x 10^6 Anti-CD19 CAR T Cells/kg Phase 1: 1 x 10^6 Anti-CD19 CAR T Cells/kg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    6 / 6 (100.00%)
    41 / 55 (74.55%)
    12 / 16 (75.00%)
    21 / 23 (91.30%)
         number of deaths (all causes)
    6
    39
    15
    17
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Myelodysplastic syndrome
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    1 / 16 (6.25%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Carcinoma in situ
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    0 / 16 (0.00%)
    1 / 23 (4.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute lymphocytic leukaemia
         subjects affected / exposed
    0 / 6 (0.00%)
    4 / 55 (7.27%)
    4 / 16 (25.00%)
    1 / 23 (4.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 4
    0 / 4
    0 / 1
    Vascular disorders
    Hypotension
         subjects affected / exposed
    3 / 6 (50.00%)
    16 / 55 (29.09%)
    3 / 16 (18.75%)
    9 / 23 (39.13%)
         occurrences causally related to treatment / all
    2 / 3
    16 / 16
    2 / 4
    8 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    0 / 16 (0.00%)
    1 / 23 (4.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Shock
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    1 / 16 (6.25%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    0 / 6 (0.00%)
    2 / 55 (3.64%)
    0 / 16 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    0 / 6 (0.00%)
    15 / 55 (27.27%)
    1 / 16 (6.25%)
    4 / 23 (17.39%)
         occurrences causally related to treatment / all
    0 / 0
    16 / 17
    1 / 1
    3 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chills
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    0 / 16 (0.00%)
    1 / 23 (4.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Face oedema
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 55 (1.82%)
    0 / 16 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 55 (0.00%)
    0 / 16 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Hypogammaglobulinaemia
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 55 (1.82%)
    0 / 16 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Drug hypersensitivity
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 55 (1.82%)
    0 / 16 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemophagocytic lymphohistiocytosis
         subjects affected / exposed
    0 / 6 (0.00%)
    2 / 55 (3.64%)
    0 / 16 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Graft versus host disease
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 55 (1.82%)
    0 / 16 (0.00%)
    1 / 23 (4.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory distress syndrome
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    2 / 16 (12.50%)
    1 / 23 (4.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoxia
         subjects affected / exposed
    1 / 6 (16.67%)
    7 / 55 (12.73%)
    2 / 16 (12.50%)
    3 / 23 (13.04%)
         occurrences causally related to treatment / all
    0 / 1
    7 / 7
    3 / 3
    4 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    0 / 6 (0.00%)
    3 / 55 (5.45%)
    0 / 16 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tachypnoea
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    0 / 16 (0.00%)
    1 / 23 (4.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    0 / 6 (0.00%)
    2 / 55 (3.64%)
    1 / 16 (6.25%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Acute respiratory failure
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 55 (1.82%)
    0 / 16 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    1 / 16 (6.25%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary alveolar haemorrhage
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    0 / 16 (0.00%)
    1 / 23 (4.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 55 (0.00%)
    0 / 16 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Confusional state
         subjects affected / exposed
    0 / 6 (0.00%)
    3 / 55 (5.45%)
    0 / 16 (0.00%)
    2 / 23 (8.70%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 3
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Delirium
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 55 (1.82%)
    0 / 16 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Disorientation
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    0 / 16 (0.00%)
    1 / 23 (4.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Restlessness
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    0 / 16 (0.00%)
    1 / 23 (4.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mental status changes
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    1 / 16 (6.25%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Platelet count decreased
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 55 (1.82%)
    1 / 16 (6.25%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutrophil count decreased
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 55 (1.82%)
    0 / 16 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Brain herniation
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 55 (1.82%)
    0 / 16 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiomyopathy
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    1 / 16 (6.25%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sinus tachycardia
         subjects affected / exposed
    0 / 6 (0.00%)
    2 / 55 (3.64%)
    0 / 16 (0.00%)
    2 / 23 (8.70%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tachycardia
         subjects affected / exposed
    0 / 6 (0.00%)
    3 / 55 (5.45%)
    0 / 16 (0.00%)
    2 / 23 (8.70%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 3
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulseless electrical activity
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 55 (0.00%)
    0 / 16 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Encephalopathy
         subjects affected / exposed
    2 / 6 (33.33%)
    4 / 55 (7.27%)
    1 / 16 (6.25%)
    8 / 23 (34.78%)
         occurrences causally related to treatment / all
    2 / 2
    4 / 4
    1 / 1
    10 / 12
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Monoplegia
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 55 (1.82%)
    0 / 16 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune effector cell-associated ~ neurotoxicity syndrome
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 55 (1.82%)
    0 / 16 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    0 / 16 (0.00%)
    1 / 23 (4.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Facial paralysis
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 55 (1.82%)
    0 / 16 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cauda equina syndrome
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 55 (1.82%)
    0 / 16 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Brain oedema
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 55 (1.82%)
    0 / 16 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Paraparesis
         subjects affected / exposed
    0 / 6 (0.00%)
    2 / 55 (3.64%)
    0 / 16 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    2 / 16 (12.50%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
    0 / 0
    Seizure
         subjects affected / exposed
    0 / 6 (0.00%)
    3 / 55 (5.45%)
    1 / 16 (6.25%)
    1 / 23 (4.35%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 3
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aphasia
         subjects affected / exposed
    0 / 6 (0.00%)
    3 / 55 (5.45%)
    1 / 16 (6.25%)
    3 / 23 (13.04%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 3
    1 / 1
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Status epilepticus
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    1 / 16 (6.25%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    0 / 16 (0.00%)
    1 / 23 (4.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    0 / 16 (0.00%)
    1 / 23 (4.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Febrile neutropenia
         subjects affected / exposed
    0 / 6 (0.00%)
    2 / 55 (3.64%)
    4 / 16 (25.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    2 / 6
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 55 (1.82%)
    0 / 16 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cytopenia
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 55 (1.82%)
    0 / 16 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 55 (1.82%)
    1 / 16 (6.25%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Disseminated intravascular ~ coagulation
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 55 (1.82%)
    0 / 16 (0.00%)
    1 / 23 (4.35%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Tongue oedema
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 55 (1.82%)
    0 / 16 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoaesthesia oral
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 55 (1.82%)
    0 / 16 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 55 (1.82%)
    0 / 16 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 55 (1.82%)
    0 / 16 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    1 / 16 (6.25%)
    1 / 23 (4.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 55 (1.82%)
    0 / 16 (0.00%)
    1 / 23 (4.35%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 55 (1.82%)
    0 / 16 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    0 / 16 (0.00%)
    1 / 23 (4.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Muscular weakness
         subjects affected / exposed
    2 / 6 (33.33%)
    0 / 55 (0.00%)
    0 / 16 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 55 (1.82%)
    0 / 16 (0.00%)
    1 / 23 (4.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bone pain
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 55 (0.00%)
    0 / 16 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Enterococcal bacteraemia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    2 / 16 (12.50%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bacteraemia
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 55 (1.82%)
    1 / 16 (6.25%)
    1 / 23 (4.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 6 (0.00%)
    3 / 55 (5.45%)
    1 / 16 (6.25%)
    1 / 23 (4.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 6 (0.00%)
    2 / 55 (3.64%)
    3 / 16 (18.75%)
    4 / 23 (17.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 1
    Herpes simplex viraemia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    0 / 16 (0.00%)
    1 / 23 (4.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Escherichia sepsis
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 55 (1.82%)
    0 / 16 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Escherichia infection
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 55 (1.82%)
    0 / 16 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Escherichia bacteraemia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    0 / 16 (0.00%)
    1 / 23 (4.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteomyelitis fungal
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 55 (1.82%)
    0 / 16 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    0 / 16 (0.00%)
    1 / 23 (4.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 6 (0.00%)
    2 / 55 (3.64%)
    0 / 16 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 55 (1.82%)
    0 / 16 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Device related bacteraemia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    0 / 16 (0.00%)
    1 / 23 (4.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peritonitis
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 55 (0.00%)
    0 / 16 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumocystis jirovecii pneumonia
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 55 (1.82%)
    0 / 16 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia fungal
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 55 (1.82%)
    0 / 16 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Pneumonia respiratory syncytial ~ viral
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 55 (1.82%)
    0 / 16 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sinusitis
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 55 (1.82%)
    0 / 16 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    0 / 16 (0.00%)
    1 / 23 (4.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    0 / 16 (0.00%)
    1 / 23 (4.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Tumour lysis syndrome
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    1 / 16 (6.25%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypervolaemia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    1 / 16 (6.25%)
    1 / 23 (4.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Phase 1: 2 x 10^6 Anti-CD19 CAR T Cells/kg Phase 2: 1 x 10^6 Anti-CD19 CAR T Cells/kg Phase 1: 0.5 x 10^6 Anti-CD19 CAR T Cells/kg Phase 1: 1 x 10^6 Anti-CD19 CAR T Cells/kg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    6 / 6 (100.00%)
    55 / 55 (100.00%)
    16 / 16 (100.00%)
    23 / 23 (100.00%)
    Vascular disorders
    Thrombosis
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    1 / 16 (6.25%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Hypotension
         subjects affected / exposed
    5 / 6 (83.33%)
    27 / 55 (49.09%)
    7 / 16 (43.75%)
    13 / 23 (56.52%)
         occurrences all number
    6
    41
    12
    16
    Hypertension
         subjects affected / exposed
    0 / 6 (0.00%)
    7 / 55 (12.73%)
    2 / 16 (12.50%)
    3 / 23 (13.04%)
         occurrences all number
    0
    10
    2
    6
    Flushing
         subjects affected / exposed
    0 / 6 (0.00%)
    3 / 55 (5.45%)
    1 / 16 (6.25%)
    3 / 23 (13.04%)
         occurrences all number
    0
    3
    1
    3
    Distributive shock
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 55 (1.82%)
    1 / 16 (6.25%)
    0 / 23 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Haematoma
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    1 / 16 (6.25%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    General disorders and administration site conditions
    Face oedema
         subjects affected / exposed
    0 / 6 (0.00%)
    3 / 55 (5.45%)
    1 / 16 (6.25%)
    0 / 23 (0.00%)
         occurrences all number
    0
    3
    1
    0
    Pyrexia
         subjects affected / exposed
    6 / 6 (100.00%)
    49 / 55 (89.09%)
    11 / 16 (68.75%)
    21 / 23 (91.30%)
         occurrences all number
    7
    66
    13
    26
    Chills
         subjects affected / exposed
    3 / 6 (50.00%)
    18 / 55 (32.73%)
    3 / 16 (18.75%)
    12 / 23 (52.17%)
         occurrences all number
    5
    21
    4
    14
    Fatigue
         subjects affected / exposed
    1 / 6 (16.67%)
    13 / 55 (23.64%)
    6 / 16 (37.50%)
    7 / 23 (30.43%)
         occurrences all number
    2
    14
    6
    7
    Oedema peripheral
         subjects affected / exposed
    1 / 6 (16.67%)
    10 / 55 (18.18%)
    4 / 16 (25.00%)
    7 / 23 (30.43%)
         occurrences all number
    1
    13
    4
    8
    Pain
         subjects affected / exposed
    0 / 6 (0.00%)
    7 / 55 (12.73%)
    0 / 16 (0.00%)
    3 / 23 (13.04%)
         occurrences all number
    0
    9
    0
    3
    Asthenia
         subjects affected / exposed
    0 / 6 (0.00%)
    3 / 55 (5.45%)
    1 / 16 (6.25%)
    3 / 23 (13.04%)
         occurrences all number
    0
    4
    1
    3
    Malaise
         subjects affected / exposed
    0 / 6 (0.00%)
    5 / 55 (9.09%)
    1 / 16 (6.25%)
    0 / 23 (0.00%)
         occurrences all number
    0
    5
    1
    0
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 6 (0.00%)
    2 / 55 (3.64%)
    1 / 16 (6.25%)
    2 / 23 (8.70%)
         occurrences all number
    0
    3
    1
    2
    Catheter site pain
         subjects affected / exposed
    1 / 6 (16.67%)
    1 / 55 (1.82%)
    0 / 16 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Oedema
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 55 (1.82%)
    1 / 16 (6.25%)
    0 / 23 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Gravitational oedema
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 55 (0.00%)
    0 / 16 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Hypothermia
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 55 (0.00%)
    0 / 16 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Peripheral swelling
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    1 / 16 (6.25%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Immune system disorders
    Hypogammaglobulinaemia
         subjects affected / exposed
    0 / 6 (0.00%)
    3 / 55 (5.45%)
    0 / 16 (0.00%)
    3 / 23 (13.04%)
         occurrences all number
    0
    3
    0
    3
    Drug hypersensitivity
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 55 (0.00%)
    0 / 16 (0.00%)
    1 / 23 (4.35%)
         occurrences all number
    1
    0
    0
    1
    Reproductive system and breast disorders
    Gynaecomastia
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 55 (0.00%)
    0 / 16 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Vaginal haemorrhage
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    1 / 16 (6.25%)
    1 / 23 (4.35%)
         occurrences all number
    0
    0
    1
    1
    Pelvic pain
         subjects affected / exposed
    1 / 6 (16.67%)
    1 / 55 (1.82%)
    0 / 16 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Hypoxia
         subjects affected / exposed
    2 / 6 (33.33%)
    12 / 55 (21.82%)
    5 / 16 (31.25%)
    5 / 23 (21.74%)
         occurrences all number
    2
    17
    7
    6
    Pulmonary oedema
         subjects affected / exposed
    1 / 6 (16.67%)
    3 / 55 (5.45%)
    1 / 16 (6.25%)
    2 / 23 (8.70%)
         occurrences all number
    1
    3
    1
    2
    Dyspnoea
         subjects affected / exposed
    1 / 6 (16.67%)
    4 / 55 (7.27%)
    3 / 16 (18.75%)
    3 / 23 (13.04%)
         occurrences all number
    1
    4
    3
    5
    Cough
         subjects affected / exposed
    1 / 6 (16.67%)
    7 / 55 (12.73%)
    2 / 16 (12.50%)
    2 / 23 (8.70%)
         occurrences all number
    1
    7
    2
    3
    Pneumonitis
         subjects affected / exposed
    1 / 6 (16.67%)
    3 / 55 (5.45%)
    0 / 16 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    3
    0
    0
    Wheezing
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 55 (1.82%)
    1 / 16 (6.25%)
    2 / 23 (8.70%)
         occurrences all number
    0
    1
    1
    2
    Atelectasis
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    1 / 16 (6.25%)
    1 / 23 (4.35%)
         occurrences all number
    0
    0
    1
    1
    Paranasal sinus discomfort
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    2 / 16 (12.50%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Productive cough
         subjects affected / exposed
    1 / 6 (16.67%)
    1 / 55 (1.82%)
    0 / 16 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    2
    0
    0
    Rhinitis allergic
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    1 / 16 (6.25%)
    1 / 23 (4.35%)
         occurrences all number
    0
    0
    1
    1
    Rales
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    1 / 16 (6.25%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Sinus pain
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    1 / 16 (6.25%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Oropharyngeal pain
         subjects affected / exposed
    0 / 6 (0.00%)
    2 / 55 (3.64%)
    0 / 16 (0.00%)
    4 / 23 (17.39%)
         occurrences all number
    0
    3
    0
    5
    Pleural effusion
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    2 / 16 (12.50%)
    3 / 23 (13.04%)
         occurrences all number
    0
    0
    2
    3
    Tachypnoea
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 55 (1.82%)
    0 / 16 (0.00%)
    4 / 23 (17.39%)
         occurrences all number
    0
    2
    0
    4
    Epistaxis
         subjects affected / exposed
    0 / 6 (0.00%)
    3 / 55 (5.45%)
    0 / 16 (0.00%)
    1 / 23 (4.35%)
         occurrences all number
    0
    3
    0
    1
    Nasal congestion
         subjects affected / exposed
    0 / 6 (0.00%)
    3 / 55 (5.45%)
    1 / 16 (6.25%)
    0 / 23 (0.00%)
         occurrences all number
    0
    3
    2
    0
    Psychiatric disorders
    Abnormal dreams
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 55 (0.00%)
    0 / 16 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Depression
         subjects affected / exposed
    1 / 6 (16.67%)
    2 / 55 (3.64%)
    0 / 16 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    2
    0
    0
    Mental status changes
         subjects affected / exposed
    0 / 6 (0.00%)
    2 / 55 (3.64%)
    0 / 16 (0.00%)
    2 / 23 (8.70%)
         occurrences all number
    0
    2
    0
    2
    Delirium
         subjects affected / exposed
    2 / 6 (33.33%)
    1 / 55 (1.82%)
    2 / 16 (12.50%)
    0 / 23 (0.00%)
         occurrences all number
    2
    1
    2
    0
    Insomnia
         subjects affected / exposed
    1 / 6 (16.67%)
    7 / 55 (12.73%)
    0 / 16 (0.00%)
    3 / 23 (13.04%)
         occurrences all number
    1
    10
    0
    3
    Anxiety
         subjects affected / exposed
    1 / 6 (16.67%)
    4 / 55 (7.27%)
    2 / 16 (12.50%)
    5 / 23 (21.74%)
         occurrences all number
    1
    5
    2
    5
    Agitation
         subjects affected / exposed
    0 / 6 (0.00%)
    7 / 55 (12.73%)
    2 / 16 (12.50%)
    4 / 23 (17.39%)
         occurrences all number
    0
    7
    2
    5
    Confusional state
         subjects affected / exposed
    2 / 6 (33.33%)
    11 / 55 (20.00%)
    6 / 16 (37.50%)
    6 / 23 (26.09%)
         occurrences all number
    2
    14
    6
    9
    Investigations
    Blood bilirubin increased
         subjects affected / exposed
    2 / 6 (33.33%)
    3 / 55 (5.45%)
    0 / 16 (0.00%)
    4 / 23 (17.39%)
         occurrences all number
    3
    4
    0
    4
    Platelet count decreased
         subjects affected / exposed
    1 / 6 (16.67%)
    18 / 55 (32.73%)
    5 / 16 (31.25%)
    10 / 23 (43.48%)
         occurrences all number
    1
    61
    18
    22
    Neutrophil count decreased
         subjects affected / exposed
    0 / 6 (0.00%)
    15 / 55 (27.27%)
    4 / 16 (25.00%)
    8 / 23 (34.78%)
         occurrences all number
    0
    67
    6
    12
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 6 (16.67%)
    12 / 55 (21.82%)
    0 / 16 (0.00%)
    8 / 23 (34.78%)
         occurrences all number
    1
    16
    0
    10
    Aspartate aminotransferase increased
         subjects affected / exposed
    1 / 6 (16.67%)
    10 / 55 (18.18%)
    0 / 16 (0.00%)
    9 / 23 (39.13%)
         occurrences all number
    1
    18
    0
    12
    White blood cell count decreased
         subjects affected / exposed
    0 / 6 (0.00%)
    14 / 55 (25.45%)
    4 / 16 (25.00%)
    2 / 23 (8.70%)
         occurrences all number
    0
    24
    5
    6
    Weight decreased
         subjects affected / exposed
    3 / 6 (50.00%)
    1 / 55 (1.82%)
    0 / 16 (0.00%)
    3 / 23 (13.04%)
         occurrences all number
    6
    1
    0
    6
    Blood fibrinogen decreased
         subjects affected / exposed
    0 / 6 (0.00%)
    2 / 55 (3.64%)
    0 / 16 (0.00%)
    4 / 23 (17.39%)
         occurrences all number
    0
    2
    0
    4
    Blood alkaline phosphatase increased
         subjects affected / exposed
    0 / 6 (0.00%)
    4 / 55 (7.27%)
    0 / 16 (0.00%)
    1 / 23 (4.35%)
         occurrences all number
    0
    6
    0
    1
    Lymphocyte count decreased
         subjects affected / exposed
    0 / 6 (0.00%)
    4 / 55 (7.27%)
    1 / 16 (6.25%)
    0 / 23 (0.00%)
         occurrences all number
    0
    8
    1
    0
    Weight increased
         subjects affected / exposed
    2 / 6 (33.33%)
    0 / 55 (0.00%)
    1 / 16 (6.25%)
    2 / 23 (8.70%)
         occurrences all number
    4
    0
    1
    3
    Blood creatinine increased
         subjects affected / exposed
    2 / 6 (33.33%)
    2 / 55 (3.64%)
    0 / 16 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    2
    2
    0
    0
    C-reactive protein increased
         subjects affected / exposed
    0 / 6 (0.00%)
    3 / 55 (5.45%)
    0 / 16 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    3
    0
    0
    Electrocardiogram QT prolonged
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    1 / 16 (6.25%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    0 / 6 (0.00%)
    3 / 55 (5.45%)
    2 / 16 (12.50%)
    2 / 23 (8.70%)
         occurrences all number
    0
    3
    2
    2
    Procedural pain
         subjects affected / exposed
    1 / 6 (16.67%)
    2 / 55 (3.64%)
    0 / 16 (0.00%)
    2 / 23 (8.70%)
         occurrences all number
    1
    3
    0
    2
    Cardiac disorders
    Sinus tachycardia
         subjects affected / exposed
    2 / 6 (33.33%)
    19 / 55 (34.55%)
    2 / 16 (12.50%)
    8 / 23 (34.78%)
         occurrences all number
    4
    21
    2
    12
    Tachycardia
         subjects affected / exposed
    2 / 6 (33.33%)
    13 / 55 (23.64%)
    6 / 16 (37.50%)
    4 / 23 (17.39%)
         occurrences all number
    2
    15
    7
    6
    Bradycardia
         subjects affected / exposed
    0 / 6 (0.00%)
    5 / 55 (9.09%)
    2 / 16 (12.50%)
    0 / 23 (0.00%)
         occurrences all number
    0
    5
    2
    0
    Sinus bradycardia
         subjects affected / exposed
    1 / 6 (16.67%)
    2 / 55 (3.64%)
    0 / 16 (0.00%)
    4 / 23 (17.39%)
         occurrences all number
    1
    3
    0
    5
    Pericardial effusion
         subjects affected / exposed
    0 / 6 (0.00%)
    2 / 55 (3.64%)
    1 / 16 (6.25%)
    0 / 23 (0.00%)
         occurrences all number
    0
    2
    1
    0
    Angina pectoris
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 55 (0.00%)
    1 / 16 (6.25%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Supraventricular tachycardia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    1 / 16 (6.25%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    3
    0
    Ventricular tachycardia
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 55 (0.00%)
    0 / 16 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Nervous system disorders
    Lethargy
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    2 / 16 (12.50%)
    3 / 23 (13.04%)
         occurrences all number
    0
    0
    2
    3
    Somnolence
         subjects affected / exposed
    0 / 6 (0.00%)
    3 / 55 (5.45%)
    1 / 16 (6.25%)
    2 / 23 (8.70%)
         occurrences all number
    0
    3
    1
    2
    Dizziness
         subjects affected / exposed
    1 / 6 (16.67%)
    8 / 55 (14.55%)
    2 / 16 (12.50%)
    2 / 23 (8.70%)
         occurrences all number
    1
    11
    2
    2
    Aphasia
         subjects affected / exposed
    0 / 6 (0.00%)
    6 / 55 (10.91%)
    3 / 16 (18.75%)
    8 / 23 (34.78%)
         occurrences all number
    0
    6
    3
    9
    Encephalopathy
         subjects affected / exposed
    4 / 6 (66.67%)
    9 / 55 (16.36%)
    1 / 16 (6.25%)
    6 / 23 (26.09%)
         occurrences all number
    5
    11
    1
    9
    Tremor
         subjects affected / exposed
    1 / 6 (16.67%)
    15 / 55 (27.27%)
    4 / 16 (25.00%)
    8 / 23 (34.78%)
         occurrences all number
    2
    17
    4
    9
    Cognitive disorder
         subjects affected / exposed
    0 / 6 (0.00%)
    3 / 55 (5.45%)
    0 / 16 (0.00%)
    1 / 23 (4.35%)
         occurrences all number
    0
    3
    0
    1
    Headache
         subjects affected / exposed
    1 / 6 (16.67%)
    20 / 55 (36.36%)
    8 / 16 (50.00%)
    10 / 23 (43.48%)
         occurrences all number
    2
    24
    12
    19
    Neuropathy peripheral
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 55 (0.00%)
    2 / 16 (12.50%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    2
    0
    Dysgeusia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    1 / 16 (6.25%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Cerebral ischaemia
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 55 (0.00%)
    0 / 16 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Brain fog
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    1 / 16 (6.25%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Peripheral sensory neuropathy
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 55 (0.00%)
    1 / 16 (6.25%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Memory impairment
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 55 (1.82%)
    1 / 16 (6.25%)
    0 / 23 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Seizure
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 55 (0.00%)
    0 / 16 (0.00%)
    2 / 23 (8.70%)
         occurrences all number
    1
    0
    0
    4
    Ataxia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    0 / 16 (0.00%)
    2 / 23 (8.70%)
         occurrences all number
    0
    0
    0
    2
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    3 / 6 (50.00%)
    29 / 55 (52.73%)
    4 / 16 (25.00%)
    14 / 23 (60.87%)
         occurrences all number
    4
    67
    9
    32
    Neutropenia
         subjects affected / exposed
    1 / 6 (16.67%)
    8 / 55 (14.55%)
    1 / 16 (6.25%)
    7 / 23 (30.43%)
         occurrences all number
    1
    13
    1
    15
    Thrombocytopenia
         subjects affected / exposed
    1 / 6 (16.67%)
    9 / 55 (16.36%)
    1 / 16 (6.25%)
    3 / 23 (13.04%)
         occurrences all number
    1
    13
    3
    4
    Febrile neutropenia
         subjects affected / exposed
    1 / 6 (16.67%)
    5 / 55 (9.09%)
    2 / 16 (12.50%)
    4 / 23 (17.39%)
         occurrences all number
    1
    8
    2
    6
    Disseminated intravascular coagulation
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 55 (1.82%)
    0 / 16 (0.00%)
    2 / 23 (8.70%)
         occurrences all number
    0
    1
    0
    2
    Leukocytosis
         subjects affected / exposed
    0 / 6 (0.00%)
    2 / 55 (3.64%)
    1 / 16 (6.25%)
    0 / 23 (0.00%)
         occurrences all number
    0
    2
    1
    0
    Bone marrow failure
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 55 (1.82%)
    1 / 16 (6.25%)
    0 / 23 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Bone marrow reticulin fibrosis
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 55 (0.00%)
    0 / 16 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Splenic infarction
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    1 / 16 (6.25%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Hypofibrinogenaemia
         subjects affected / exposed
    0 / 6 (0.00%)
    3 / 55 (5.45%)
    0 / 16 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    3
    0
    0
    Ear and labyrinth disorders
    Tinnitus
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    0 / 16 (0.00%)
    2 / 23 (8.70%)
         occurrences all number
    0
    0
    0
    3
    Eye disorders
    Vitreous floaters
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 55 (1.82%)
    1 / 16 (6.25%)
    0 / 23 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Vision blurred
         subjects affected / exposed
    0 / 6 (0.00%)
    4 / 55 (7.27%)
    2 / 16 (12.50%)
    3 / 23 (13.04%)
         occurrences all number
    0
    4
    2
    3
    Photophobia
         subjects affected / exposed
    0 / 6 (0.00%)
    2 / 55 (3.64%)
    1 / 16 (6.25%)
    1 / 23 (4.35%)
         occurrences all number
    0
    2
    1
    1
    Dry eye
         subjects affected / exposed
    0 / 6 (0.00%)
    3 / 55 (5.45%)
    0 / 16 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    3
    0
    0
    Eye pain
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 55 (1.82%)
    1 / 16 (6.25%)
    0 / 23 (0.00%)
         occurrences all number
    0
    1
    2
    0
    Ocular hyperaemia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    1 / 16 (6.25%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Visual impairment
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    1 / 16 (6.25%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Gastrointestinal disorders
    Ascites
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 55 (0.00%)
    0 / 16 (0.00%)
    1 / 23 (4.35%)
         occurrences all number
    1
    0
    0
    1
    Nausea
         subjects affected / exposed
    1 / 6 (16.67%)
    21 / 55 (38.18%)
    3 / 16 (18.75%)
    11 / 23 (47.83%)
         occurrences all number
    1
    24
    4
    16
    Diarrhoea
         subjects affected / exposed
    3 / 6 (50.00%)
    11 / 55 (20.00%)
    6 / 16 (37.50%)
    11 / 23 (47.83%)
         occurrences all number
    6
    15
    7
    15
    Constipation
         subjects affected / exposed
    1 / 6 (16.67%)
    8 / 55 (14.55%)
    2 / 16 (12.50%)
    11 / 23 (47.83%)
         occurrences all number
    1
    8
    2
    15
    Abdominal pain
         subjects affected / exposed
    3 / 6 (50.00%)
    10 / 55 (18.18%)
    2 / 16 (12.50%)
    5 / 23 (21.74%)
         occurrences all number
    6
    13
    4
    6
    Vomiting
         subjects affected / exposed
    1 / 6 (16.67%)
    9 / 55 (16.36%)
    2 / 16 (12.50%)
    7 / 23 (30.43%)
         occurrences all number
    1
    10
    2
    11
    Abdominal distension
         subjects affected / exposed
    1 / 6 (16.67%)
    4 / 55 (7.27%)
    1 / 16 (6.25%)
    2 / 23 (8.70%)
         occurrences all number
    1
    5
    2
    2
    Dry mouth
         subjects affected / exposed
    2 / 6 (33.33%)
    3 / 55 (5.45%)
    1 / 16 (6.25%)
    2 / 23 (8.70%)
         occurrences all number
    2
    3
    1
    3
    Dyspepsia
         subjects affected / exposed
    0 / 6 (0.00%)
    3 / 55 (5.45%)
    0 / 16 (0.00%)
    2 / 23 (8.70%)
         occurrences all number
    0
    3
    0
    2
    Haemorrhoids
         subjects affected / exposed
    0 / 6 (0.00%)
    3 / 55 (5.45%)
    1 / 16 (6.25%)
    1 / 23 (4.35%)
         occurrences all number
    0
    3
    1
    1
    Dysphagia
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 55 (1.82%)
    0 / 16 (0.00%)
    2 / 23 (8.70%)
         occurrences all number
    0
    1
    0
    3
    Stomatitis
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 55 (1.82%)
    1 / 16 (6.25%)
    1 / 23 (4.35%)
         occurrences all number
    0
    1
    1
    1
    Abdominal pain upper
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 55 (1.82%)
    1 / 16 (6.25%)
    0 / 23 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Ileus
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    1 / 16 (6.25%)
    1 / 23 (4.35%)
         occurrences all number
    0
    0
    1
    1
    Haematochezia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    1 / 16 (6.25%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Lower gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    1 / 16 (6.25%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Mucous stools
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    1 / 16 (6.25%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Rectal haemorrhage
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    1 / 16 (6.25%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Toothache
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 55 (0.00%)
    0 / 16 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Anal incontinence
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    1 / 16 (6.25%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Hepatobiliary disorders
    Hypertransaminasaemia
         subjects affected / exposed
    1 / 6 (16.67%)
    1 / 55 (1.82%)
    3 / 16 (18.75%)
    1 / 23 (4.35%)
         occurrences all number
    1
    1
    4
    1
    Hyperbilirubinaemia
         subjects affected / exposed
    0 / 6 (0.00%)
    3 / 55 (5.45%)
    0 / 16 (0.00%)
    2 / 23 (8.70%)
         occurrences all number
    0
    5
    0
    2
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    0 / 6 (0.00%)
    5 / 55 (9.09%)
    2 / 16 (12.50%)
    4 / 23 (17.39%)
         occurrences all number
    0
    5
    4
    4
    Pruritus
         subjects affected / exposed
    0 / 6 (0.00%)
    3 / 55 (5.45%)
    1 / 16 (6.25%)
    3 / 23 (13.04%)
         occurrences all number
    0
    3
    1
    3
    Dry skin
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 55 (0.00%)
    1 / 16 (6.25%)
    2 / 23 (8.70%)
         occurrences all number
    1
    0
    1
    2
    Night sweats
         subjects affected / exposed
    0 / 6 (0.00%)
    3 / 55 (5.45%)
    0 / 16 (0.00%)
    1 / 23 (4.35%)
         occurrences all number
    0
    3
    0
    1
    Rash maculo-papular
         subjects affected / exposed
    0 / 6 (0.00%)
    2 / 55 (3.64%)
    0 / 16 (0.00%)
    2 / 23 (8.70%)
         occurrences all number
    0
    2
    0
    2
    Decubitus ulcer
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    1 / 16 (6.25%)
    2 / 23 (8.70%)
         occurrences all number
    0
    0
    1
    2
    Rash macular
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 55 (1.82%)
    1 / 16 (6.25%)
    1 / 23 (4.35%)
         occurrences all number
    0
    1
    1
    1
    Skin lesion
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    0 / 16 (0.00%)
    3 / 23 (13.04%)
         occurrences all number
    0
    0
    0
    3
    Alopecia
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 55 (1.82%)
    1 / 16 (6.25%)
    0 / 23 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Drug eruption
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    1 / 16 (6.25%)
    1 / 23 (4.35%)
         occurrences all number
    0
    0
    1
    1
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    1 / 16 (6.25%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Micturition urgency
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    1 / 16 (6.25%)
    1 / 23 (4.35%)
         occurrences all number
    0
    0
    1
    1
    Dysuria
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 55 (0.00%)
    1 / 16 (6.25%)
    1 / 23 (4.35%)
         occurrences all number
    1
    0
    1
    2
    Acute kidney injury
         subjects affected / exposed
    1 / 6 (16.67%)
    1 / 55 (1.82%)
    1 / 16 (6.25%)
    1 / 23 (4.35%)
         occurrences all number
    1
    2
    1
    1
    Urinary incontinence
         subjects affected / exposed
    0 / 6 (0.00%)
    3 / 55 (5.45%)
    2 / 16 (12.50%)
    1 / 23 (4.35%)
         occurrences all number
    0
    3
    2
    1
    Urinary retention
         subjects affected / exposed
    1 / 6 (16.67%)
    2 / 55 (3.64%)
    2 / 16 (12.50%)
    3 / 23 (13.04%)
         occurrences all number
    1
    2
    2
    3
    Pollakiuria
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    1 / 16 (6.25%)
    2 / 23 (8.70%)
         occurrences all number
    0
    0
    1
    2
    Musculoskeletal and connective tissue disorders
    Pain in extremity
         subjects affected / exposed
    1 / 6 (16.67%)
    2 / 55 (3.64%)
    1 / 16 (6.25%)
    2 / 23 (8.70%)
         occurrences all number
    1
    2
    1
    2
    Bone pain
         subjects affected / exposed
    1 / 6 (16.67%)
    3 / 55 (5.45%)
    2 / 16 (12.50%)
    1 / 23 (4.35%)
         occurrences all number
    2
    3
    2
    1
    Back pain
         subjects affected / exposed
    1 / 6 (16.67%)
    2 / 55 (3.64%)
    0 / 16 (0.00%)
    4 / 23 (17.39%)
         occurrences all number
    1
    4
    0
    6
    Myalgia
         subjects affected / exposed
    0 / 6 (0.00%)
    6 / 55 (10.91%)
    1 / 16 (6.25%)
    1 / 23 (4.35%)
         occurrences all number
    0
    8
    1
    1
    Muscular weakness
         subjects affected / exposed
    2 / 6 (33.33%)
    6 / 55 (10.91%)
    0 / 16 (0.00%)
    5 / 23 (21.74%)
         occurrences all number
    4
    6
    0
    8
    Coccydynia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    1 / 16 (6.25%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Bone lesion
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    1 / 16 (6.25%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Musculoskeletal stiffness
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    0 / 16 (0.00%)
    2 / 23 (8.70%)
         occurrences all number
    0
    0
    0
    2
    Flank pain
         subjects affected / exposed
    2 / 6 (33.33%)
    0 / 55 (0.00%)
    0 / 16 (0.00%)
    1 / 23 (4.35%)
         occurrences all number
    3
    0
    0
    1
    Neck pain
         subjects affected / exposed
    0 / 6 (0.00%)
    3 / 55 (5.45%)
    0 / 16 (0.00%)
    2 / 23 (8.70%)
         occurrences all number
    0
    3
    0
    2
    Arthralgia
         subjects affected / exposed
    0 / 6 (0.00%)
    3 / 55 (5.45%)
    1 / 16 (6.25%)
    1 / 23 (4.35%)
         occurrences all number
    0
    3
    1
    1
    Infections and infestations
    Oral candidiasis
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    0 / 16 (0.00%)
    2 / 23 (8.70%)
         occurrences all number
    0
    0
    0
    2
    Bacteraemia
         subjects affected / exposed
    1 / 6 (16.67%)
    1 / 55 (1.82%)
    1 / 16 (6.25%)
    1 / 23 (4.35%)
         occurrences all number
    1
    1
    1
    1
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 6 (16.67%)
    2 / 55 (3.64%)
    0 / 16 (0.00%)
    1 / 23 (4.35%)
         occurrences all number
    1
    2
    0
    1
    Clostridium difficile infection
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 55 (1.82%)
    1 / 16 (6.25%)
    0 / 23 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Pneumonia
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 55 (1.82%)
    1 / 16 (6.25%)
    0 / 23 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Infection
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    1 / 16 (6.25%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Rhinovirus infection
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    1 / 16 (6.25%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Skin infection
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 55 (0.00%)
    0 / 16 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Staphylococcal infection
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    1 / 16 (6.25%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Metabolism and nutrition disorders
    Hypophosphataemia
         subjects affected / exposed
    2 / 6 (33.33%)
    15 / 55 (27.27%)
    3 / 16 (18.75%)
    13 / 23 (56.52%)
         occurrences all number
    5
    18
    5
    24
    Hypokalaemia
         subjects affected / exposed
    1 / 6 (16.67%)
    15 / 55 (27.27%)
    2 / 16 (12.50%)
    11 / 23 (47.83%)
         occurrences all number
    1
    24
    2
    14
    Hyperglycaemia
         subjects affected / exposed
    1 / 6 (16.67%)
    8 / 55 (14.55%)
    5 / 16 (31.25%)
    8 / 23 (34.78%)
         occurrences all number
    1
    9
    5
    9
    Hypomagnesaemia
         subjects affected / exposed
    1 / 6 (16.67%)
    12 / 55 (21.82%)
    1 / 16 (6.25%)
    8 / 23 (34.78%)
         occurrences all number
    1
    15
    1
    9
    Decreased appetite
         subjects affected / exposed
    0 / 6 (0.00%)
    8 / 55 (14.55%)
    4 / 16 (25.00%)
    9 / 23 (39.13%)
         occurrences all number
    0
    8
    4
    9
    Hypocalcaemia
         subjects affected / exposed
    2 / 6 (33.33%)
    9 / 55 (16.36%)
    1 / 16 (6.25%)
    8 / 23 (34.78%)
         occurrences all number
    3
    13
    1
    12
    Hyponatraemia
         subjects affected / exposed
    3 / 6 (50.00%)
    4 / 55 (7.27%)
    2 / 16 (12.50%)
    7 / 23 (30.43%)
         occurrences all number
    4
    4
    4
    8
    Hypoalbuminaemia
         subjects affected / exposed
    3 / 6 (50.00%)
    1 / 55 (1.82%)
    0 / 16 (0.00%)
    5 / 23 (21.74%)
         occurrences all number
    7
    3
    0
    8
    Hypermagnesaemia
         subjects affected / exposed
    3 / 6 (50.00%)
    1 / 55 (1.82%)
    0 / 16 (0.00%)
    2 / 23 (8.70%)
         occurrences all number
    5
    2
    0
    3
    Dehydration
         subjects affected / exposed
    2 / 6 (33.33%)
    1 / 55 (1.82%)
    1 / 16 (6.25%)
    1 / 23 (4.35%)
         occurrences all number
    2
    1
    1
    1
    Vitamin D deficiency
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    1 / 16 (6.25%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Metabolic alkalosis
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    1 / 16 (6.25%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Iron overload
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    1 / 16 (6.25%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Acidosis hyperchloraemic
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 55 (0.00%)
    1 / 16 (6.25%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Hypervolaemia
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 55 (1.82%)
    1 / 16 (6.25%)
    0 / 23 (0.00%)
         occurrences all number
    0
    2
    1
    0
    Hyperkalaemia
         subjects affected / exposed
    2 / 6 (33.33%)
    0 / 55 (0.00%)
    0 / 16 (0.00%)
    1 / 23 (4.35%)
         occurrences all number
    2
    0
    0
    1
    Hypercalcaemia
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 55 (1.82%)
    0 / 16 (0.00%)
    2 / 23 (8.70%)
         occurrences all number
    0
    1
    0
    2
    Hypernatraemia
         subjects affected / exposed
    1 / 6 (16.67%)
    2 / 55 (3.64%)
    1 / 16 (6.25%)
    1 / 23 (4.35%)
         occurrences all number
    1
    3
    1
    2

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    04 Oct 2015
    • Modified study design in Phase 1 from a 6+6 to a 3+3 • Updated secondary and exploratory endpoints • Updated eligibility criteria • Added medical assessments and monitoring requirements prior to the initiation of • leukapheresis, lymphodepleting chemotherapy, and KTE-C19 • Aligned enrollment into the study with initiation of leukapheresis to ensure that subjects were • not prematurely enrolled into the study prior to meeting all eligibility criteria • Clarified expectations for bone marrow and extramedullary disease assessments • Updated toxicity management guidelines, including addition of more detailed guidance for the management of neurotoxicity
    09 Nov 2015
    • Clarified response criteria and definitions for CR, CRh, CRi, and CRp • Introduced criteria to pause enrollment to be assessed at regular intervals during the study • Refined eligibility criteria • Clarified timing and requirements for disease assessments
    28 Nov 2016
    • Updated eligibility criteria, including allowance for prior blinatumomab treatment and exclusion of subjects with a history of autoimmune disease • Provided additional toxicity management guidance related to CRS, neurotoxicity, cardiac function, and hemophagocytic lymphohistiocytosis (HLH) • Added laboratory assessments: CD3 count at enrollment, CD19 expression, MRD analysis at Month 3 (central analysis), and collection of a PBMC sample at time of progression (for central analysis) • Updated targeted AE, SAE, and concomitant medication reporting requirements • Clarified possible SRT recommendations based on the incidence of DLTs among subjects treated in Phase 1 • Updated primary, secondary, and exploratory endpoints to clarify definitions for CR, CRh, CRi, BFBM, and RFS • Provided further guidance regarding the administration of CSF prophylaxis • Updated statistical considerations: the timing of the 2 interim analyses in Phase 2 were revised to occur after 20 and 35 subjects in the mITT analysis set had had the opportunity to complete the Month 3 disease assessment. A review of efficacy data by the DSMB was added after 7 subjects previously treated with blinatumomab in the mITT analysis set had had the opportunity to complete the Day 28 disease assessment. • Added additional requirements and conditions for retreatment
    10 Mar 2017
    • Based on the outcome of SRT review: • Updated sample size in Phase 1 to allow additional subjects to be enrolled at the 1 x 106 anti-CD19 CAR T cells/kg dose level and added a new lower dose of 0.5 x 106 anti-CD19 CAR T cells/kg • Added a mandatory dose of tocilizumab at 36 hours (± 2 hours) after KTE-C19 infusion • Added new exclusion criteria related to severe hypersensitivity to aminoglycosides or any agent used in the study • Added requirement for subjects to be closely monitored and aggressively treated for possible infection • Added requirement to complete a lumbar puncture for subjects with a first onset of Grade 2 or higher neurological symptoms • Added option for redose for subjects who were MRD+ (≤ 5% lymphoblasts in bone marrow) ≥ 2 weeks after the initial KTE-C19 infusion; following this change, subjects could receive up to 3 doses of KTE-C19 (ie, original infusion, redose for MRD+ disease, and retreatment following PD with > 5% bone marrow lymphoblasts) • Updated toxicity management guidance related to HLH, neurologic events, and cerebral edema • Updated laboratory assessments: updated and clarified bone marrow sample collection requirements, added mandatory bone marrow biopsy at Day −4, and added PBMC sample at Week 8 • Updated AE, SAE, and concomitant medication reporting requirements • Updated timing of the 2 interim safety analyses in Phase 2 to occur after 20 and 35 subjects in the mITT analysis set had had the opportunity to be followed for 30 days after the KTE-C19 infusion • Updated timing of the first interim efficacy analysis in Phase 2 to occur after 20 subjects in the mITT analysis set had had the opportunity to be followed for 30 days after the KTE-C19 infusion; removed the second planned interim efficacy analysis of 35 subjects • Added MRD− rate per central assessment as a secondary endpoint
    25 Oct 2017
    • Updated the definition of OCR rate in the primary objective from CR + CRh to CR + CRi • Added requirement for EQ-5D for subjects in Phase 2 and added secondary objective of changes in EQ-5D scores • Updated sample size in Phase 1 from 30 to 40 subjects and total sample size from 90 to 100 subjects • Refined eligibility criteria, including the definition of r/r disease • Updated timing of completion of bridging chemotherapy: bridging therapy was to be completed at least 7 days or 5 half-lives, whichever is shorter, prior to initiating lymphodepleting chemotherapy • Removed requirement for MMSE • Updated timing of Day 28 lumbar puncture: for subjects with CNS-2 at baseline, a CSF sample was required at the time of first presumed response (ie, bone marrow blasts < 5%) • Updated imaging requirements for subjects with known non-CNS extramedullary disease at baseline: the first on-study images were to occur at the time of first presumed response (ie, bone marrow blasts ≤ 5%), rather than at the first occurrence of PR or better based on the bone marrow evaluation • Clarified time points for RCR testing • Updated requirements to be met at the time of leukapheresis regarding the need to meet all eligibility criteria and avoiding corticosteroid therapy for 7 days prior to leukapheresis • Added requirement to assess peripheral blast counts prior to lymphodepleting chemotherapy (ie, Day −4) for subjects who did not have a Day −4 bone marrow evaluation • Eliminated the requirement to administer tocilizumab at 36 hours after the KTE-C19 infusion • Changed analysis of applicable endpoints from local review to independent review per the updated overall disease response classification appendix • Updated definitions of OCR, DOR, and RFS used for study endpoints
    31 Oct 2018
    • Updated number of participating sites to 35 • Added rationale for the recommended Phase 2 dose of 1 x 106 anti-CD19 CAR T cells/kg • Added lumbar punctures for subjects with CNS-2 disease at screening and described that for subjects with new onset of a Grade 2 or higher neurologic event after KTE-X19 infusion, a lumbar puncture may be performed as applicable • Added a requirement for the IP to be available before initiation of lymphodepletingchemotherapy • Added language for safety criteria to be met prior to initiation of lymphodepleting chemotherapy, including timing of fever prior to lymphodepleting chemotherapy, infection/inflammation assessment, treatment with antimicrobials, and anti-infective workup • Added section to include safety criteria to be met prior to KTE-X19 infusion, including timing of fever and high C-reactive protein (CRP) prior to infusion, WBC counts, infection/inflammation assessment, treatment with antimicrobials, and anti-infective workup • Clarified the required length of hospitalization to be aligned with country-specific Requirements • Added EQ-5D time points during the long-term follow-up period • Updated AE and SAE reporting requirements • Updated guidelines for use of contraception during the course of the study • Added appendix for monitoring of subjects after IP administration per German country requirements
    14 Dec 2021
    • A Long-term Follow-up (LTFU) protocol, KT-US-982-5968 has been developed to allow for rollover of subjects to complete the 15-year follow-up after infusion of KTE-X19 on the KTE-C19-103 study. Subjects were provided the opportunity to rollover to the LTFU protocol for safety followup and reduced burden of study-specific assessments.

    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

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/34097852
    http://www.ncbi.nlm.nih.gov/pubmed/33827116
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Sun May 04 02:17:38 CEST 2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA