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    Clinical Trial Results:
    A PHASE 2, SINGLE-ARM, MULTI-COHORT, MULTICENTER TRIAL TO DETERMINE THE EFFICACY AND SAFETY OF JCAR017 IN ADULT SUBJECTS WITH AGGRESSIVE B-CELL NON-HODGKIN LYMPHOMA (TRANSCEND WORLD).

    Summary
    EudraCT number
    		 2017-000106-38
    Trial protocol
    		 BE   FR   FI   ES   DE   AT   NL   GB   IT  
    Global end of trial date
    15 Dec 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    07 Dec 2024
    First version publication date
    07 Dec 2024
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    JCAR017-BCM-001
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03484702
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Bristol-Myers Squibb
    Sponsor organisation address
    Chaussée de la Hulpe 185, Brussels, Brussels, Belgium, 1170
    Public contact
    EU Study Start-Up Unit, Bristol-Myers Squibb International, Bristol-Myers Squibb, clinical.trials@bms.com
    Scientific contact
    EU Study Start-Up Unit, Bristol-Myers Squibb International, Bristol-Myers Squibb, clinical.trials@bms.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    23 Feb 2024
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    15 Dec 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Cohorts 1, 2, 3, 4, and 5 • To determine the efficacy, defined as overall response rate (ORR) of JCAR017 in subjects with aggressive B-cell non-Hodgkin lymphoma Cohort 7 • To evaluate the safety of JCAR017 treatment in subjects intended to be treated as outpatients
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization Good Clinical Practice Guidelines. All the local regulatory requirements pertinent to safety of trial participants were followed.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    05 Jun 2018
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Austria: 10
    Country: Number of subjects enrolled
    Belgium: 4
    Country: Number of subjects enrolled
    Finland: 7
    Country: Number of subjects enrolled
    France: 12
    Country: Number of subjects enrolled
    Germany: 8
    Country: Number of subjects enrolled
    Italy: 5
    Country: Number of subjects enrolled
    Japan: 17
    Country: Number of subjects enrolled
    Netherlands: 9
    Country: Number of subjects enrolled
    Spain: 33
    Country: Number of subjects enrolled
    Switzerland: 4
    Country: Number of subjects enrolled
    United Kingdom: 4
    Worldwide total number of subjects
    113
    EEA total number of subjects
    88
    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)
    54
    From 65 to 84 years
    59
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 116 participants underwent leukapheresis, 98 participants started treatment with lymphodepleting chemotherapy. Cohort 6 was planned but subsequently removed from the study. No participants were enrolled into Cohort 6.

    Period 1
    Period 1 title
    Pre-Treatment Period - Leukapheresis
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Cohort 1: Diffuse B-cell Lymphoma Failed ≥ 2 Lines of Therapy
    Arm description
    		 JCAR017 was infused at a dose of 100 x 10^6 JCAR017-positive transfected viable T cells (50 × 10^6 CD8+ CAR+ T cells and 50 × 10^6 CD4+ CAR+ T cells), on Day 1 (2 to 7 days after completion of Lymphodepleting chemotherapy).
    Arm type
    		 Experimental

    Investigational medicinal product name
    JCAR017
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    100 x 10^6 JCAR017-positive transfected viable T cells

    Investigational medicinal product name
    Cyclophosphamide IV
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    300 mg/m2 /day for 3 days

    Investigational medicinal product name
    Fludarabine IV
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    30 mg/m2 /day for 3 days

    Arm title
    		 Cohort 2: Transplant Ineligible Diffuse B-cell Lymphoma
    Arm description
    		 JCAR017 was infused at a dose of 100 x 10^6 JCAR017-positive transfected viable T cells (50 × 10^6 CD8+ CAR+ T cells and 50 × 10^6 CD4+ CAR+ T cells), on Day 1 (2 to 7 days after completion of Lymphodepleting chemotherapy).
    Arm type
    		 Experimental

    Investigational medicinal product name
    JCAR017
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    100 x 10^6 JCAR017-positive transfected viable T cells

    Investigational medicinal product name
    Cyclophosphamide IV
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    300 mg/m2 /day for 3 days

    Investigational medicinal product name
    Fludarabine IV
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    30 mg/m2 /day for 3 days

    Arm title
    		 Cohort 3: Japan Specific
    Arm description
    		 JCAR017 was infused at a dose of 100 x 10^6 JCAR017-positive transfected viable T cells (50 × 10^6 CD8+ CAR+ T cells and 50 × 10^6 CD4+ CAR+ T cells), on Day 1 (2 to 7 days after completion of Lymphodepleting chemotherapy).
    Arm type
    		 Experimental

    Investigational medicinal product name
    JCAR017
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    100 x 10^6 JCAR017-positive transfected viable T cells

    Investigational medicinal product name
    Fludarabine IV
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    30 mg/m2 /day for 3 days

    Investigational medicinal product name
    Cyclophosphamide IV
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    300 mg/m2 /day for 3 days

    Arm title
    		 Cohort 4: Newly Diagnosed High-Grade B-cell Lymphoma
    Arm description
    		 JCAR017 was infused at a dose of 100 x 10^6 JCAR017-positive transfected viable T cells (50 × 10^6 CD8+ CAR+ T cells and 50 × 10^6 CD4+ CAR+ T cells), on Day 1 (2 to 7 days after completion of Lymphodepleting chemotherapy).
    Arm type
    		 Experimental

    Investigational medicinal product name
    JCAR017
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    100 x 10^6 JCAR017-positive transfected viable T cells

    Investigational medicinal product name
    Cyclophosphamide IV
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    300 mg/m2 /day for 3 days

    Investigational medicinal product name
    Fludarabine IV
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    30 mg/m2 /day for 3 days

    Arm title
    		 Cohort 5: Primary Central Nervous System Lymphoma
    Arm description
    		 JCAR017 was infused at a dose of 100 x 10^6 JCAR017-positive transfected viable T cells (50 × 10^6 CD8+ CAR+ T cells and 50 × 10^6 CD4+ CAR+ T cells), on Day 1 (2 to 7 days after completion of Lymphodepleting chemotherapy).
    Arm type
    		 Experimental

    Investigational medicinal product name
    JCAR017
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    100 x 10^6 JCAR017-positive transfected viable T cells

    Investigational medicinal product name
    Cyclophosphamide IV
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    300 mg/m2 /day for 3 days

    Investigational medicinal product name
    Fludarabine IV
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    30 mg/m2 /day for 3 days

    Arm title
    		 Cohort 7: Outpatient Treatment
    Arm description
    		 JCAR017 was infused at a dose of 100 x 10^6 JCAR017-positive transfected viable T cells (50 × 10^6 CD8+ CAR+ T cells and 50 × 10^6 CD4+ CAR+ T cells), on Day 1 (2 to 7 days after completion of Lymphodepleting chemotherapy).
    Arm type
    		 Experimental

    Investigational medicinal product name
    JCAR017
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    100 x 10^6 JCAR017-positive transfected viable T cells

    Investigational medicinal product name
    Cyclophosphamide IV
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    300 mg/m2 /day for 3 days

    Investigational medicinal product name
    Fludarabine IV
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    30 mg/m2 /day for 3 days

    Number of subjects in period 1
    		Cohort 1: Diffuse B-cell Lymphoma Failed ≥ 2 Lines of Therapy Cohort 2: Transplant Ineligible Diffuse B-cell Lymphoma Cohort 3: Japan Specific Cohort 4: Newly Diagnosed High-Grade B-cell Lymphoma Cohort 5: Primary Central Nervous System Lymphoma Cohort 7: Outpatient Treatment
    Started
    45
    32
    14
    4
    7
    11
    Completed
    43
    27
    12
    1
    5
    10
    Not completed
    2
    5
    2
    3
    2
    1
         Other reasons
    2
    5
    2
    3
    2
    1
    Period 2
    Period 2 title
    Treatment Period
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Cohort 1: Diffuse B-cell Lymphoma Failed ≥ 2 Lines of Therapy
    Arm description
    		 JCAR017 was infused at a dose of 100 x 10^6 JCAR017-positive transfected viable T cells (50 × 10^6 CD8+ CAR+ T cells and 50 × 10^6 CD4+ CAR+ T cells), on Day 1 (2 to 7 days after completion of Lymphodepleting chemotherapy).
    Arm type
    		 Experimental

    Investigational medicinal product name
    JCAR017
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    100 x 10^6 JCAR017-positive transfected viable T cells

    Investigational medicinal product name
    Cyclophosphamide IV
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    300 mg/m2 /day for 3 days

    Investigational medicinal product name
    Fludarabine IV
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    30 mg/m2 /day for 3 days

    Arm title
    		 Cohort 2: Transplant Ineligible Diffuse B-cell Lymphoma
    Arm description
    		 JCAR017 was infused at a dose of 100 x 10^6 JCAR017-positive transfected viable T cells (50 × 10^6 CD8+ CAR+ T cells and 50 × 10^6 CD4+ CAR+ T cells), on Day 1 (2 to 7 days after completion of Lymphodepleting chemotherapy).
    Arm type
    		 Experimental

    Investigational medicinal product name
    JCAR017
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    100 x 10^6 JCAR017-positive transfected viable T cells

    Investigational medicinal product name
    Cyclophosphamide IV
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    300 mg/m2 /day for 3 days

    Investigational medicinal product name
    Fludarabine IV
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    30 mg/m2 /day for 3 days

    Arm title
    		 Cohort 3: Japan Specific
    Arm description
    		 JCAR017 was infused at a dose of 100 x 10^6 JCAR017-positive transfected viable T cells (50 × 10^6 CD8+ CAR+ T cells and 50 × 10^6 CD4+ CAR+ T cells), on Day 1 (2 to 7 days after completion of Lymphodepleting chemotherapy).
    Arm type
    		 Experimental

    Investigational medicinal product name
    JCAR017
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    100 x 10^6 JCAR017-positive transfected viable T cells

    Investigational medicinal product name
    Cyclophosphamide IV
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    300 mg/m2 /day for 3 days

    Investigational medicinal product name
    Fludarabine IV
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    30 mg/m2 /day for 3 days

    Arm title
    		 Cohort 4: Newly Diagnosed High-Grade B-cell Lymphoma
    Arm description
    		 JCAR017 was infused at a dose of 100 x 10^6 JCAR017-positive transfected viable T cells (50 × 10^6 CD8+ CAR+ T cells and 50 × 10^6 CD4+ CAR+ T cells), on Day 1 (2 to 7 days after completion of Lymphodepleting chemotherapy).
    Arm type
    		 Experimental

    Investigational medicinal product name
    JCAR017
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    100 x 10^6 JCAR017-positive transfected viable T cells

    Investigational medicinal product name
    Cyclophosphamide IV
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    300 mg/m2 /day for 3 days

    Investigational medicinal product name
    Fludarabine IV
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    30 mg/m2 /day for 3 days

    Arm title
    		 Cohort 5: Primary Central Nervous System Lymphoma
    Arm description
    		 JCAR017 was infused at a dose of 100 x 10^6 JCAR017-positive transfected viable T cells (50 × 10^6 CD8+ CAR+ T cells and 50 × 10^6 CD4+ CAR+ T cells), on Day 1 (2 to 7 days after completion of Lymphodepleting chemotherapy).
    Arm type
    		 Experimental

    Investigational medicinal product name
    JCAR017
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    100 x 10^6 JCAR017-positive transfected viable T cells

    Investigational medicinal product name
    Cyclophosphamide IV
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    300 mg/m2 /day for 3 days

    Investigational medicinal product name
    Fludarabine IV
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    30 mg/m2 /day for 3 days

    Arm title
    		 Cohort 7: Outpatient Treatment
    Arm description
    		 JCAR017 was infused at a dose of 100 x 10^6 JCAR017-positive transfected viable T cells (50 × 10^6 CD8+ CAR+ T cells and 50 × 10^6 CD4+ CAR+ T cells), on Day 1 (2 to 7 days after completion of Lymphodepleting chemotherapy).
    Arm type
    		 Experimental

    Investigational medicinal product name
    JCAR017
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    100 x 10^6 JCAR017-positive transfected viable T cells

    Investigational medicinal product name
    Fludarabine IV
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    30 mg/m2 /day for 3 days

    Investigational medicinal product name
    Cyclophosphamide IV
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    300 mg/m2 /day for 3 days

    Number of subjects in period 2
    		Cohort 1: Diffuse B-cell Lymphoma Failed ≥ 2 Lines of Therapy Cohort 2: Transplant Ineligible Diffuse B-cell Lymphoma Cohort 3: Japan Specific Cohort 4: Newly Diagnosed High-Grade B-cell Lymphoma Cohort 5: Primary Central Nervous System Lymphoma Cohort 7: Outpatient Treatment
    Started
    43
    27
    12
    1
    5
    10
    JCAR017 Treated Set
    36 [1]
    27
    10 [2]
    1
    5
    9
    Completed
    39
    24
    12
    1
    5
    9
    Not completed
    4
    3
    0
    0
    0
    1
         Adverse event, serious fatal
    3
    1
    -
    -
    -
    -
         Participant Withdrew from Study
    -
    1
    -
    -
    -
    -
         Physician decision
    -
    1
    -
    -
    -
    1
         Adverse event, non-fatal
    1
    -
    -
    -
    -
    -
    Notes
    [1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Not all LDC treated participants received JCAR017
    [2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Not all LDC treated participants received JCAR017

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Cohort 1: Diffuse B-cell Lymphoma Failed ≥ 2 Lines of Therapy
    Reporting group description
    		 JCAR017 was infused at a dose of 100 x 10^6 JCAR017-positive transfected viable T cells (50 × 10^6 CD8+ CAR+ T cells and 50 × 10^6 CD4+ CAR+ T cells), on Day 1 (2 to 7 days after completion of Lymphodepleting chemotherapy).

    Reporting group title
    Cohort 2: Transplant Ineligible Diffuse B-cell Lymphoma
    Reporting group description
    		 JCAR017 was infused at a dose of 100 x 10^6 JCAR017-positive transfected viable T cells (50 × 10^6 CD8+ CAR+ T cells and 50 × 10^6 CD4+ CAR+ T cells), on Day 1 (2 to 7 days after completion of Lymphodepleting chemotherapy).

    Reporting group title
    Cohort 3: Japan Specific
    Reporting group description
    		 JCAR017 was infused at a dose of 100 x 10^6 JCAR017-positive transfected viable T cells (50 × 10^6 CD8+ CAR+ T cells and 50 × 10^6 CD4+ CAR+ T cells), on Day 1 (2 to 7 days after completion of Lymphodepleting chemotherapy).

    Reporting group title
    Cohort 4: Newly Diagnosed High-Grade B-cell Lymphoma
    Reporting group description
    		 JCAR017 was infused at a dose of 100 x 10^6 JCAR017-positive transfected viable T cells (50 × 10^6 CD8+ CAR+ T cells and 50 × 10^6 CD4+ CAR+ T cells), on Day 1 (2 to 7 days after completion of Lymphodepleting chemotherapy).

    Reporting group title
    Cohort 5: Primary Central Nervous System Lymphoma
    Reporting group description
    		 JCAR017 was infused at a dose of 100 x 10^6 JCAR017-positive transfected viable T cells (50 × 10^6 CD8+ CAR+ T cells and 50 × 10^6 CD4+ CAR+ T cells), on Day 1 (2 to 7 days after completion of Lymphodepleting chemotherapy).

    Reporting group title
    Cohort 7: Outpatient Treatment
    Reporting group description
    		 JCAR017 was infused at a dose of 100 x 10^6 JCAR017-positive transfected viable T cells (50 × 10^6 CD8+ CAR+ T cells and 50 × 10^6 CD4+ CAR+ T cells), on Day 1 (2 to 7 days after completion of Lymphodepleting chemotherapy).

    Reporting group values
    		 Cohort 1: Diffuse B-cell Lymphoma Failed ≥ 2 Lines of Therapy Cohort 2: Transplant Ineligible Diffuse B-cell Lymphoma Cohort 3: Japan Specific Cohort 4: Newly Diagnosed High-Grade B-cell Lymphoma Cohort 5: Primary Central Nervous System Lymphoma Cohort 7: Outpatient Treatment Total
    Number of subjects
    		 45 32 14 4 7 11 113
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0 0 0 0
        Adults (18-64 years)
    		 26 1 11 1 7 8 54
        From 65-84 years
    		 19 31 3 3 0 3 59
        85 years and over
    		 0 0 0 0 0 0 0
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 60.2 ( 10.60 ) 73.3 ( 5.50 ) 57.6 ( 10.08 ) 63.5 ( 21.11 ) 57.0 ( 5.74 ) 58.1 ( 12.47 ) -
    Sex: Female, Male
    Units: Participants
        Female
    		 15 13 6 1 3 4 42
        Male
    		 30 19 8 3 4 7 71
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 7 1 0 1 0 1 10
        Not Hispanic or Latino
    		 29 22 14 2 5 7 79
        Unknown or Not Reported
    		 9 9 0 1 2 3 24
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0 0 0 0 0
        Asian
    		 0 3 14 0 0 0 17
        Native Hawaiian or Other Pacific Islander
    		 0 0 0 0 0 0 0
        Black or African American
    		 0 0 0 0 0 0 0
        White
    		 37 19 0 3 5 7 71
        More than one race
    		 0 0 0 0 0 0 0
        Unknown or Not Reported
    		 8 10 0 1 2 4 25

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Cohort 1: Diffuse B-cell Lymphoma Failed ≥ 2 Lines of Therapy
    Reporting group description
    		 JCAR017 was infused at a dose of 100 x 10^6 JCAR017-positive transfected viable T cells (50 × 10^6 CD8+ CAR+ T cells and 50 × 10^6 CD4+ CAR+ T cells), on Day 1 (2 to 7 days after completion of Lymphodepleting chemotherapy).

    Reporting group title
    Cohort 2: Transplant Ineligible Diffuse B-cell Lymphoma
    Reporting group description
    		 JCAR017 was infused at a dose of 100 x 10^6 JCAR017-positive transfected viable T cells (50 × 10^6 CD8+ CAR+ T cells and 50 × 10^6 CD4+ CAR+ T cells), on Day 1 (2 to 7 days after completion of Lymphodepleting chemotherapy).

    Reporting group title
    Cohort 3: Japan Specific
    Reporting group description
    		 JCAR017 was infused at a dose of 100 x 10^6 JCAR017-positive transfected viable T cells (50 × 10^6 CD8+ CAR+ T cells and 50 × 10^6 CD4+ CAR+ T cells), on Day 1 (2 to 7 days after completion of Lymphodepleting chemotherapy).

    Reporting group title
    Cohort 4: Newly Diagnosed High-Grade B-cell Lymphoma
    Reporting group description
    		 JCAR017 was infused at a dose of 100 x 10^6 JCAR017-positive transfected viable T cells (50 × 10^6 CD8+ CAR+ T cells and 50 × 10^6 CD4+ CAR+ T cells), on Day 1 (2 to 7 days after completion of Lymphodepleting chemotherapy).

    Reporting group title
    Cohort 5: Primary Central Nervous System Lymphoma
    Reporting group description
    		 JCAR017 was infused at a dose of 100 x 10^6 JCAR017-positive transfected viable T cells (50 × 10^6 CD8+ CAR+ T cells and 50 × 10^6 CD4+ CAR+ T cells), on Day 1 (2 to 7 days after completion of Lymphodepleting chemotherapy).

    Reporting group title
    Cohort 7: Outpatient Treatment
    Reporting group description
    		 JCAR017 was infused at a dose of 100 x 10^6 JCAR017-positive transfected viable T cells (50 × 10^6 CD8+ CAR+ T cells and 50 × 10^6 CD4+ CAR+ T cells), on Day 1 (2 to 7 days after completion of Lymphodepleting chemotherapy).
    Reporting group title
    Cohort 1: Diffuse B-cell Lymphoma Failed ≥ 2 Lines of Therapy
    Reporting group description
    		 JCAR017 was infused at a dose of 100 x 10^6 JCAR017-positive transfected viable T cells (50 × 10^6 CD8+ CAR+ T cells and 50 × 10^6 CD4+ CAR+ T cells), on Day 1 (2 to 7 days after completion of Lymphodepleting chemotherapy).

    Reporting group title
    Cohort 2: Transplant Ineligible Diffuse B-cell Lymphoma
    Reporting group description
    		 JCAR017 was infused at a dose of 100 x 10^6 JCAR017-positive transfected viable T cells (50 × 10^6 CD8+ CAR+ T cells and 50 × 10^6 CD4+ CAR+ T cells), on Day 1 (2 to 7 days after completion of Lymphodepleting chemotherapy).

    Reporting group title
    Cohort 3: Japan Specific
    Reporting group description
    		 JCAR017 was infused at a dose of 100 x 10^6 JCAR017-positive transfected viable T cells (50 × 10^6 CD8+ CAR+ T cells and 50 × 10^6 CD4+ CAR+ T cells), on Day 1 (2 to 7 days after completion of Lymphodepleting chemotherapy).

    Reporting group title
    Cohort 4: Newly Diagnosed High-Grade B-cell Lymphoma
    Reporting group description
    		 JCAR017 was infused at a dose of 100 x 10^6 JCAR017-positive transfected viable T cells (50 × 10^6 CD8+ CAR+ T cells and 50 × 10^6 CD4+ CAR+ T cells), on Day 1 (2 to 7 days after completion of Lymphodepleting chemotherapy).

    Reporting group title
    Cohort 5: Primary Central Nervous System Lymphoma
    Reporting group description
    		 JCAR017 was infused at a dose of 100 x 10^6 JCAR017-positive transfected viable T cells (50 × 10^6 CD8+ CAR+ T cells and 50 × 10^6 CD4+ CAR+ T cells), on Day 1 (2 to 7 days after completion of Lymphodepleting chemotherapy).

    Reporting group title
    Cohort 7: Outpatient Treatment
    Reporting group description
    		 JCAR017 was infused at a dose of 100 x 10^6 JCAR017-positive transfected viable T cells (50 × 10^6 CD8+ CAR+ T cells and 50 × 10^6 CD4+ CAR+ T cells), on Day 1 (2 to 7 days after completion of Lymphodepleting chemotherapy).

    Primary: Overall Response Rate (ORR) in Cohorts 1, 2, 3, 4

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    End point title
    		 Overall Response Rate (ORR) in Cohorts 1, 2, 3, 4 [1] [2]
    End point description
    ORR by Independent Review Committee (Cohorts 1, 2, 3) or Investigator (Cohort 4). ORR is the percent of participants with best overall response of complete response (CR) or partial response (PR). Complete response via PET-CT: • Lymph nodes/extralymphatic: Score 1, 2, 3a with/w-out residual mass on 5-point scale • New lesions: No • Bone marrow: No FDG-avid disease Complete response via CT scan: • Lymph nodes/extralymphatic: Target nodes/nodal masses ≤ 1.5 cm longest transverse diameter. • Nonmeasured lesion: None • New lesions: No • Bone marrow: Normal Partial response via PET-CT: • Lymph nodes/extralymphatic: Score 4, 5b, reduced uptake from baseline • New lesions: No • Bone marrow: Residual uptake higher than normal, reduced from baseline Partial response via CT scan: • Lymph nodes/extralymphatic: 50% decrease in sum of diameters of <= 6 target measurable nodes/extranodal sites • Nonmeasured lesion: No • Organ enlargement: Spleen length decreased > 50% • New lesions: No
    End point type
    Primary
    End point timeframe
    From JCAR017 infusion until disease progression, end of study, the start of another anticancer therapy, or hemopoietic stem cell transplant (HSCT) (up to approximately 24 months)
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive statistics were planned for this endpoint.
    [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: Prespecified to be reported for Cohorts 1, 2, 3, 4 only.
    End point values
    		 Cohort 1: Diffuse B-cell Lymphoma Failed ≥ 2 Lines of Therapy Cohort 2: Transplant Ineligible Diffuse B-cell Lymphoma Cohort 3: Japan Specific Cohort 4: Newly Diagnosed High-Grade B-cell Lymphoma
    Number of subjects analysed
    36
    27
    10
    1
    Units: Percent of Participants
        number (confidence interval 95%)
    61.1 (43.5 to 76.9)
    63.0 (42.4 to 80.6)
    70.0 (34.8 to 93.3)
    100 (100 to 100)
    No statistical analyses for this end point

    Primary: Number of Participants with Adverse Events in Cohort 7

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    End point title
    		 Number of Participants with Adverse Events in Cohort 7 [3] [4]
    End point description
    An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant’s health, including laboratory test values, regardless of etiology. Any worsening (i.e., any clinically significant adverse change in the frequency or intensity of a preexisting condition) should be considered an AE. Graded according to NCI CTCAE (Version 4.03) guidelines where grade 1 = mild, grade 2 = moderate, grade 3 = severe, grade 4 = life threatening, grade 5 = death.
    End point type
    Primary
    End point timeframe
    From leukapheresis to end of study (up to approximately 24 months)
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive statistics were planned for this endpoint.
    [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: Prespecified to be reported for Cohort 7 only.
    End point values
    		 Cohort 7: Outpatient Treatment
    Number of subjects analysed
    9
    Units: Participants
        AEs between leukapheresis and LDC
    0
        AEs occurring LDC and JCAR017 infusion
    2
        AEs between JCAR017 infusion and Day 30
    9
        AEs between Day 31 and Day 90
    7
        AEs between Day 91 and end of study
    7
    No statistical analyses for this end point

    Primary: Overall Response Rate (ORR) in Cohort 5

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    End point title
    		 Overall Response Rate (ORR) in Cohort 5 [5] [6]
    End point description
    ORR determined by Investigator assessment after JCAR017 infusion. The ORR is the percent of participants with best overall response (BOR) of either complete response (CR), complete response unconfirmed (Cru) or partial response (PR). Complete response (CR): • Brain imaging: No contrast enhancement • Corticosteroid dose: None • Eye examination: Normal • Cerebrospinal fluid cytology: Negative Complete response unconfirmed (CRu): • Brain imaging: No contrast enhancement, Minimal abnormality • Corticosteroid dose: Any • Eye examination: Normal, minor RPE abnormality • Cerebrospinal fluid cytology: Negative Partial response (PR): • Brain imaging: 50% decrease in enhancing tumor, no contrast enhancement. • Corticosteroid dose: Irrelevant • Eye examination: Minor RPE abnormality, decrease in vitreous cells or retinal infiltrate. • Cerebrospinal fluid cytology: Negative, persistent or suspicious
    End point type
    Primary
    End point timeframe
    From JCAR017 infusion until disease progression, end of study, the start of another anticancer therapy, or hemopoietic stem cell transplant (HSCT) (up to approximately 24 months)
    Notes
    [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive statistics were planned for this endpoint.
    [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: Prespecified to be reported for Cohort 5 only.
    End point values
    		 Cohort 1: Diffuse B-cell Lymphoma Failed ≥ 2 Lines of Therapy
    Number of subjects analysed
    5
    Units: Percent of Participants
        number (confidence interval 95%)
    80.0 (28.4 to 99.5)
    No statistical analyses for this end point

    Primary: Number of Participants with Serious Adverse Events (SAEs) in Cohort 7

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    End point title
    		 Number of Participants with Serious Adverse Events (SAEs) in Cohort 7 [7] [8]
    End point description
    A serious adverse event (SAE) is defined as any adverse event (AE) occurring at any dose that: • Results in death; • Is life-threatening (ie, in the opinion of the Investigator, the participant is at immediate risk of death from the AE); • Requires inpatient hospitalization or prolongation of existing hospitalization (hospitalization is defined as an inpatient admission, regardless of length of stay). • Results in persistent or significant disability/incapacity (a substantial disruption of the participant’s ability to conduct normal life functions); • Is a congenital anomaly/birth defect; • Constitutes an important medical event. Graded according to NCI CTCAE (Version 4.03) guidelines where grade 1 = mild, grade 2 = moderate, grade 3 = severe, grade 4 = life threatening, grade 5 = death.
    End point type
    Primary
    End point timeframe
    From leukapheresis to end of study (up to approximately 24 months)
    Notes
    [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive statistics were planned for this endpoint.
    [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: Prespecified to be reported for Cohort 7 only.
    End point values
    		 Cohort 7: Outpatient Treatment
    Number of subjects analysed
    9
    Units: Participants
        SAEs between leukapheresis and LDC
    0
        SAEs between LDC and JCAR017 infusion
    0
        SAEs between JCAR017 infusion and Day 30
    1
        SAEs between Day 31 and Day 90
    0
        SAEs between Day 91 and end of study
    1
    No statistical analyses for this end point

    Primary: Number of Participants with Increase from Baseline in Select Serum Chemistry Parameters - Cohort 7

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    End point title
    		 Number of Participants with Increase from Baseline in Select Serum Chemistry Parameters - Cohort 7 [9] [10]
    End point description
    JCAR017 treatment-emergent laboratory abnormalities are defined as an abnormality that, compared to baseline, worsens by at least one grade after JCAR017 infusion. The baseline value is defined as the last available recorded value on or prior to the date of JCAR017 infusion.
    End point type
    Primary
    End point timeframe
    At Baseline and Day 29 after JCAR017 infusion
    Notes
    [9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive statistics were planned for this endpoint.
    [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: Prespecified to be reported for Cohort 7 only.
    End point values
    		 Cohort 7: Outpatient Treatment
    Number of subjects analysed
    9
    Units: Participants
        Albumin (g/L) - Day 29
    0
        Phosphate (mmol/L) - Day 29
    0
        Alkaline Phosphatase (U/L) - Day 29
    0
        Alanine Aminotransferase (U/L) - Day 29
    0
        Aspartate Aminotransferase (U/L) - Day 29
    1
        Bilirubin (umol/L) - Day 29
    0
        Creatinine (umol/L) - Day 29
    7
        Triglycerides (mmol/L) - Day 29
    3
        Urate (umol/L) - Day 29
    0
    No statistical analyses for this end point

    Primary: Number of Participants with Increase from Baseline in Select Hematology Parameters - Cohort 7

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    End point title
    		 Number of Participants with Increase from Baseline in Select Hematology Parameters - Cohort 7 [11] [12]
    End point description
    JCAR017 treatment-emergent laboratory abnormalities are defined as an abnormality that, compared to baseline, worsens by at least one grade after JCAR017 infusion. The baseline value is defined as the last available recorded value on or prior to the date of JCAR017 infusion.
    End point type
    Primary
    End point timeframe
    At Baseline and Day 29 after JCAR017 infusion
    Notes
    [11] - 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: Only descriptive statistics were planned for this endpoint.
    [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: Prespecified to be reported for Cohort 7 only.
    End point values
    		 Cohort 7: Outpatient Treatment
    Number of subjects analysed
    9
    Units: Participants
        Leukocytes (10^9/L) - Day 29
    0
        Neutrophils, Segmented (10^9/L) - Day 29
    2
        Platelets (10^9/L) - Day 29
    5
        Activated Partial Thromboplastin Time (sec) Day 29
    0
        Prothrombin Intl. Normalized Ratio - Day 29
    1
    No statistical analyses for this end point

    Secondary: Number of Participants with Adverse Events in Cohorts 1, 2, 3, 4, and 5

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    End point title
    		 Number of Participants with Adverse Events in Cohorts 1, 2, 3, 4, and 5 [13]
    End point description
    An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant’s health, including laboratory test values, regardless of etiology. Any worsening (i.e., any clinically significant adverse change in the frequency or intensity of a preexisting condition) should be considered an AE. Graded according to NCI CTCAE (Version 4.03) guidelines where grade 1 = mild, grade 2 = moderate, grade 3 = severe, grade 4 = life threatening, grade 5 = death.
    End point type
    Secondary
    End point timeframe
    From leukapheresis to end of study (up to approximately 24 months)
    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: Only descriptive statistics were planned for this endpoint.
    End point values
    		 Cohort 1: Diffuse B-cell Lymphoma Failed ≥ 2 Lines of Therapy Cohort 2: Transplant Ineligible Diffuse B-cell Lymphoma Cohort 3: Japan Specific Cohort 4: Newly Diagnosed High-Grade B-cell Lymphoma Cohort 5: Primary Central Nervous System Lymphoma
    Number of subjects analysed
    36
    27
    10
    1
    5
    Units: Participants
        AEs between leukapheresis and LDC
    5
    5
    0
    0
    0
        AEs between LDC and JCAR017 infusion
    29
    23
    8
    0
    4
        AEs between JCAR017 infusion and Day 30
    36
    26
    10
    1
    5
        AEs between Day 31 and Day 90
    25
    10
    8
    1
    3
        AEs between Day 91 and end of study
    10
    9
    7
    0
    2
    No statistical analyses for this end point

    Secondary: Number of Participants with Serious Adverse Events (SAEs) in Cohorts 1, 2, 3, 4, and 5

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    End point title
    		 Number of Participants with Serious Adverse Events (SAEs) in Cohorts 1, 2, 3, 4, and 5 [14]
    End point description
    A serious adverse event (SAE) is defined as any adverse event (AE) occurring at any dose that: • Results in death; • Is life-threatening (ie, in the opinion of the Investigator, the participant is at immediate risk of death from the AE); • Requires inpatient hospitalization or prolongation of existing hospitalization (hospitalization is defined as an inpatient admission, regardless of length of stay). • Results in persistent or significant disability/incapacity (a substantial disruption of the participant’s ability to conduct normal life functions); • Is a congenital anomaly/birth defect; • Constitutes an important medical event. Graded according to NCI CTCAE (Version 4) guidelines where grade 1 = mild, grade 2 = moderate, grade 3 = severe, grade 4 = life threatening, grade 5 = death.
    End point type
    Secondary
    End point timeframe
    From leukapheresis to end of study (up to approximately 24 months)
    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: Prespecified to be reported for Cohorts 1, 2, 3, 4, and 5 only.
    End point values
    		 Cohort 1: Diffuse B-cell Lymphoma Failed ≥ 2 Lines of Therapy Cohort 2: Transplant Ineligible Diffuse B-cell Lymphoma Cohort 3: Japan Specific Cohort 4: Newly Diagnosed High-Grade B-cell Lymphoma Cohort 5: Primary Central Nervous System Lymphoma
    Number of subjects analysed
    36
    27
    10
    1
    5
    Units: Participants
        SAEs between leukapheresis and LDC
    0
    1
    0
    0
    0
        SAEs between LDC and JCAR017 infusion
    1
    0
    0
    0
    0
        SAEs between JCAR017 infusion and Day 30
    16
    7
    0
    0
    1
        SAEs between Day 31 and Day 90
    7
    3
    2
    0
    1
        SAEs between Day 91 and end of study
    5
    3
    1
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Participants with Increase from Baseline in Select Hematology Parameters - Cohorts 1, 2, 3, 4, and 5

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    End point title
    		 Number of Participants with Increase from Baseline in Select Hematology Parameters - Cohorts 1, 2, 3, 4, and 5 [15]
    End point description
    JCAR017 treatment-emergent laboratory abnormalities are defined as an abnormality that, compared to baseline, worsens by at least one grade after JCAR017 infusion. The baseline value is defined as the last available recorded value on or prior to the date of JCAR017 infusion.
    End point type
    Secondary
    End point timeframe
    At Baseline and Day 29 after JCAR017 infusion
    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: Prespecified to be reported for Cohorts 1, 2, 3, 4, and 5 only.
    End point values
    		 Cohort 1: Diffuse B-cell Lymphoma Failed ≥ 2 Lines of Therapy Cohort 2: Transplant Ineligible Diffuse B-cell Lymphoma Cohort 3: Japan Specific Cohort 4: Newly Diagnosed High-Grade B-cell Lymphoma Cohort 5: Primary Central Nervous System Lymphoma
    Number of subjects analysed
    33
    21
    10
    1
    5
    Units: Participants
        Leukocytes (10^9/L) - Day 29
    4
    2
    1
    0
    1
        Neutrophils, Segmented (10^9/L) - Day 29
    11
    6
    3
    0
    1
        Platelets (10^9/L) - Day 29
    13
    8
    9
    1
    3
        Activated Partial Thromboplastin Time (sec) Day 29
    0
    1
    1
    0
    1
        Prothrombin Intl. Normalized Ratio - Day 29
    1
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Participants with Increase from Baseline in Select Serum Chemistry Parameters - Cohorts 1, 2, 3, 4, and 5

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    End point title
    		 Number of Participants with Increase from Baseline in Select Serum Chemistry Parameters - Cohorts 1, 2, 3, 4, and 5 [16]
    End point description
    JCAR017 treatment-emergent laboratory abnormalities are defined as an abnormality that, compared to baseline, worsens by at least one grade after JCAR017 infusion. The baseline value is defined as the last available recorded value on or prior to the date of JCAR017 infusion.
    End point type
    Secondary
    End point timeframe
    At Baseline and Day 29 after JCAR017 infusion
    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: Prespecified to be reported for Cohorts 1, 2, 3, 4, and 5 only.
    End point values
    		 Cohort 1: Diffuse B-cell Lymphoma Failed ≥ 2 Lines of Therapy Cohort 2: Transplant Ineligible Diffuse B-cell Lymphoma Cohort 3: Japan Specific Cohort 4: Newly Diagnosed High-Grade B-cell Lymphoma Cohort 5: Primary Central Nervous System Lymphoma
    Number of subjects analysed
    35
    24
    10
    1
    4
    Units: Participants
        Albumin (g/L) - Day 29
    0
    0
    0
    0
    0
        Phosphate (mmol/L) - Day 29
    0
    1
    0
    0
    0
        Alkaline Phosphatase (U/L) - Day 29
    2
    1
    0
    0
    1
        Alanine Aminotransferase (U/L) - Day 29
    10
    3
    1
    0
    2
        Aspartate Aminotransferase (U/L) - Day 29
    6
    3
    1
    0
    3
        Bilirubin (umol/L) - Day 29
    2
    0
    0
    0
    0
        Creatinine (umol/L) - Day 29
    23
    20
    6
    1
    3
        Triglycerides (mmol/L) - Day 29
    10
    6
    2
    0
    2
        Urate (umol/L) - Day 29
    1
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Overall Response Rate (ORR) in Cohort 7

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    End point title
    		 Overall Response Rate (ORR) in Cohort 7 [17]
    End point description
    ORR by Independent Review Committee. ORR is the percent of participants with best overall response of complete response (CR) or partial response (PR). Complete response via PET-CT: • Lymph nodes/extralymphatic: Score 1, 2, 3a with/without residual mass on 5-point scale • New lesions: No • Bone marrow: No FDG-avid disease Complete response via CT scan: • Lymph nodes/extralymphatic: Target nodes/nodal masses ≤ 1.5 cm longest transverse diameter. • Nonmeasured lesion: None • New lesions: No • Bone marrow: Normal Partial response via PET-CT: • Lymph nodes/extralymphatic: Score 4, 5b, reduced uptake from baseline • New lesions: None • Bone marrow: Residual uptake higher than normal, reduced from baseline Partial response via CT scan: • Lymph nodes/extralymphatic: 50% decrease in sum of diameters of <= 6 target measurable nodes/extranodal sites • Nonmeasured lesion: None/normal • Organ enlargement: Spleen length decreased > 50% • New lesions: No
    End point type
    Secondary
    End point timeframe
    From JCAR017 infusion until disease progression, end of study, the start of another anticancer therapy, or hemopoietic stem cell transplant (HSCT) (up to approximately 24 months)
    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: Prespecified to be reported for Cohort 7 only.
    End point values
    		 Cohort 7: Outpatient Treatment
    Number of subjects analysed
    9
    Units: Percent of Participants
        number (confidence interval 95%)
    88.9 (51.8 to 99.7)
    No statistical analyses for this end point

    Secondary: Complete Response Rate (CRR)

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    End point title
    		 Complete Response Rate (CRR)
    End point description
    Complete response rate is defined as percentage of participants achieving a best overall response of complete response. Complete response via PET-CT: • Lymph nodes/extralymphatic: Score 1, 2, 3a with/without residual mass on 5-point scale • New lesions: No • Bone marrow: No FDG-avid disease Complete response via CT scan: • Lymph nodes/extralymphatic: Target nodes/nodal masses ≤ 1.5 cm longest transverse diameter. • Nonmeasured lesion: None • New lesions: No • Bone marrow: Normal Complete response (CR) (Cohort 5): • Brain imaging: No contrast enhancement • Corticosteroid dose: None • Eye examination: Normal • Cerebrospinal fluid cytology: Negative Complete response unconfirmed (CRu) (Cohort 5): • Brain imaging: No contrast enhancement, Minimal abnormality • Corticosteroid dose: Any • Eye examination: Normal, minor RPE abnormality • Cerebrospinal fluid cytology: Negative
    End point type
    Secondary
    End point timeframe
    From JCAR017 infusion until disease progression, end of study, the start of another anticancer therapy, or hemopoietic stem cell transplant (HSCT) (up to approximately 24 months)
    End point values
    		 Cohort 1: Diffuse B-cell Lymphoma Failed ≥ 2 Lines of Therapy Cohort 2: Transplant Ineligible Diffuse B-cell Lymphoma Cohort 3: Japan Specific Cohort 4: Newly Diagnosed High-Grade B-cell Lymphoma Cohort 5: Primary Central Nervous System Lymphoma Cohort 7: Outpatient Treatment
    Number of subjects analysed
    36
    27
    10
    1
    5
    9
    Units: Percent of Participants
        number (confidence interval 95%)
    33.3 (18.6 to 51.0)
    48.1 (28.7 to 68.1)
    50.0 (18.7 to 81.3)
    0 (0 to 0)
    0 (0 to 0)
    88.9 (51.8 to 99.7)
    No statistical analyses for this end point

    Secondary: Event Free Survival (EFS)

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    End point title
    		 Event Free Survival (EFS)
    End point description
    Event-free survival is defined as the interval from the date of JCAR017 infusion to the earliest of the following events: death from any cause, progressive disease, or starting a new anticancer therapy. If a participant did not have an EFS event prior to data cutoff date, EFS was censored at the date of the last adequate disease assessment. Estimated using Kaplan-Meier product-limit estimates. "99999" = N/A
    End point type
    Secondary
    End point timeframe
    From JCAR017 infusion to death due to any reason, progressive disease, or starting a new anticancer therapy (up to approximately 24 months).
    End point values
    		 Cohort 1: Diffuse B-cell Lymphoma Failed ≥ 2 Lines of Therapy Cohort 2: Transplant Ineligible Diffuse B-cell Lymphoma Cohort 3: Japan Specific Cohort 4: Newly Diagnosed High-Grade B-cell Lymphoma Cohort 5: Primary Central Nervous System Lymphoma Cohort 7: Outpatient Treatment
    Number of subjects analysed
    36
    27
    10
    1
    5
    9
    Units: Months
        median (confidence interval 95%)
    2.99 (2.60 to 5.22)
    3.12 (1.97 to 7.36)
    6.33 (0.56 to 99999)
    23.95 (23.95 to 23.95)
    14.23 (0.76 to 24.02)
    99999 (5.65 to 99999)
    No statistical analyses for this end point

    Secondary: Progression Free Survival (PFS) using European Medicines Agency (EMA) Criteria

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    End point title
    		 Progression Free Survival (PFS) using European Medicines Agency (EMA) Criteria
    End point description
    Progression-free survival is defined as the interval from the date of JCAR017 infusion to progressive disease or death due to any cause, whichever occurred first. Participants who did not experience progressive disease and who did not die before the data cutoff date were censored at the time of the last visit with adequate response assessment when the participants were known not to have progressed. Estimated using Kaplan-Meier product-limit estimates. "99999" = N/A
    End point type
    Secondary
    End point timeframe
    From JCAR017 infusion to progressive disease or death due to any reason, whichever occurred first (up to approximately 24 months)
    End point values
    		 Cohort 1: Diffuse B-cell Lymphoma Failed ≥ 2 Lines of Therapy Cohort 2: Transplant Ineligible Diffuse B-cell Lymphoma Cohort 3: Japan Specific Cohort 4: Newly Diagnosed High-Grade B-cell Lymphoma Cohort 5: Primary Central Nervous System Lymphoma Cohort 7: Outpatient Treatment
    Number of subjects analysed
    36
    27
    10
    1
    5
    9
    Units: Months
        median (confidence interval 95%)
    2.99 (2.76 to 5.22)
    3.12 (1.97 to 7.36)
    6.33 (0.56 to 99999)
    14.23 (0.76 to 24.02)
    23.95 (23.95 to 23.95)
    99999 (5.65 to 99999)
    No statistical analyses for this end point

    Secondary: Overall Survival (OS)

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    End point title
    		 Overall Survival (OS)
    End point description
    Overall survival is defined as the interval from the date of JCAR017 infusion to the date of death due to any reason. Data from surviving participants was censored at the last time that the participant was known to be alive. Estimated using Kaplan-Meier product-limit estimates. "99999" = N/A
    End point type
    Secondary
    End point timeframe
    From the date of JCAR017 infusion to the date of death due to any reason (up to approximately 24 months).
    End point values
    		 Cohort 1: Diffuse B-cell Lymphoma Failed ≥ 2 Lines of Therapy Cohort 2: Transplant Ineligible Diffuse B-cell Lymphoma Cohort 3: Japan Specific Cohort 4: Newly Diagnosed High-Grade B-cell Lymphoma Cohort 5: Primary Central Nervous System Lymphoma Cohort 7: Outpatient Treatment
    Number of subjects analysed
    36
    27
    10
    1
    5
    9
    Units: Months
        arithmetic mean (confidence interval 95%)
    15.84 (5.82 to 23.95)
    16.82 (4.27 to 99999)
    14.72 (1.71 to 99999)
    31.74 (31.74 to 31.74)
    14.23 (4.30 to 99999)
    99999 (11.60 to 99999)
    No statistical analyses for this end point

    Secondary: Duration of Response (DOR)

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    End point title
    		 Duration of Response (DOR)
    End point description
    DoR is the time from first response to progressive disease or death due to any reason. Estimated using Kaplan-Meier estimates. Those without progressive disease/did not die were censored at last response assessment visit. Complete response - PET-CT: • Lymph nodes/extralymphatic: Score 1/2/3a w/w-out residual mass on 5-point scale • New lesions: No • Bone marrow: No FDG-avid disease Complete response - CT scan: • Lymph nodes/extralymphatic: Target nodes/nodal masses ≤ 1.5 cm longest transverse diameter. • Nonmeasured lesion: No • New lesions: No • Bone marrow: Normal Partial response - PET-CT: • Lymph nodes/extralymphatic: Score 4/5b, reduced uptake from baseline • New lesions: No • Bone marrow: Residual uptake higher than normal, reduced from baseline Partial response - CT scan: • Lymph nodes/extralymphatic: 50% decrease in sum of diameters of <= 6 target measurable nodes/extranodal • Nonmeasured lesion: No • Organ enlargement: Spleen decreased > 50% • New lesions: No "99999" = N/A
    End point type
    Secondary
    End point timeframe
    From JCAR017 infusion until disease progression, death due to any reason, end of study, the start of another anticancer therapy, or hemopoietic stem cell transplant (HSCT) (up to approximately 24 months)
    End point values
    		 Cohort 1: Diffuse B-cell Lymphoma Failed ≥ 2 Lines of Therapy Cohort 2: Transplant Ineligible Diffuse B-cell Lymphoma Cohort 3: Japan Specific Cohort 4: Newly Diagnosed High-Grade B-cell Lymphoma Cohort 5: Primary Central Nervous System Lymphoma Cohort 7: Outpatient Treatment
    Number of subjects analysed
    24
    20
    7
    1
    4
    8
    Units: Months
        median (confidence interval 95%)
    3.83 (2.07 to 17.05)
    3.91 (1.87 to 99999)
    9.07 (2.04 to 99999)
    17.97 (17.97 to 17.97)
    17.63 (2.46 to 23.10)
    99999 (2.69 to 99999)
    No statistical analyses for this end point

    Secondary: Maximum Concentration (Cmax) of JCAR017 by qPCR

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    End point title
    		 Maximum Concentration (Cmax) of JCAR017 by qPCR
    End point description
    Cmax is the maximum or peak concentration of drug reached in the plasma following a dose of the drug. Quantitative polymerase chain reaction (qPCR) was used to determine Cmax by detecting the JCAR017 transgene. "99999" = N/A Baseline is defined as the last available recorded value on or prior to the date of JCAR017 infusion.
    End point type
    Secondary
    End point timeframe
    At baseline and up until 24 months post JCAR017 infusion
    End point values
    		 Cohort 1: Diffuse B-cell Lymphoma Failed ≥ 2 Lines of Therapy Cohort 2: Transplant Ineligible Diffuse B-cell Lymphoma Cohort 3: Japan Specific Cohort 4: Newly Diagnosed High-Grade B-cell Lymphoma Cohort 5: Primary Central Nervous System Lymphoma Cohort 7: Outpatient Treatment
    Number of subjects analysed
    34
    22
    10
    1
    5
    9
    Units: Copies/ug
        geometric mean (geometric coefficient of variation)
    23132.1 ( 434.6 )
    21960.0 ( 278.1 )
    17337.8 ( 894.4 )
    51121.0 ( 99999 )
    7661.6 ( 1730.0 )
    32027.1 ( 101.4 )
    No statistical analyses for this end point

    Secondary: Time to Peak Concentration (Tmax) of JCAR017 by qPCR

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    End point title
    		 Time to Peak Concentration (Tmax) of JCAR017 by qPCR
    End point description
    Time to maximum concentration (Tmax) is the time it takes for a drug to reach the maximum concentration (Cmax) after administration. Quantitative polymerase chain reaction (qPCR) was used to determine Tmax by detecting the JCAR017 transgene. Baseline is defined as the last available recorded value on or prior to the date of JCAR017 infusion.
    End point type
    Secondary
    End point timeframe
    At baseline and up until 24 months post JCAR017 infusion
    End point values
    		 Cohort 1: Diffuse B-cell Lymphoma Failed ≥ 2 Lines of Therapy Cohort 2: Transplant Ineligible Diffuse B-cell Lymphoma Cohort 3: Japan Specific Cohort 4: Newly Diagnosed High-Grade B-cell Lymphoma Cohort 5: Primary Central Nervous System Lymphoma Cohort 7: Outpatient Treatment
    Number of subjects analysed
    34
    22
    10
    1
    5
    9
    Units: Days
        median (full range (min-max))
    11.6 (3.0 to 28.0)
    9.0 (7.0 to 14.0)
    84.1 (7.0 to 733.0)
    10.0 (10.0 to 10.0)
    9.0 (7.0 to 14.0)
    12.2 (10.0 to 21.0)
    No statistical analyses for this end point

    Secondary: Total Exposure to JCAR017 as Measured by Area Under the Curve (AUC) of JCAR017 by qPCR

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    End point title
    		 Total Exposure to JCAR017 as Measured by Area Under the Curve (AUC) of JCAR017 by qPCR
    End point description
    Area Under the Curve (AUC) represents the total exposure of participants to study drug. Quantitative polymerase chain reaction (qPCR) was used to determine AUC by detecting the JCAR017 transgene. "99999" = N/A Baseline is defined as the last available recorded value on or prior to the date of JCAR017 infusion.
    End point type
    Secondary
    End point timeframe
    At baseline and up until 24 months post JCAR017 infusion
    End point values
    		 Cohort 1: Diffuse B-cell Lymphoma Failed ≥ 2 Lines of Therapy Cohort 2: Transplant Ineligible Diffuse B-cell Lymphoma Cohort 3: Japan Specific Cohort 4: Newly Diagnosed High-Grade B-cell Lymphoma Cohort 5: Primary Central Nervous System Lymphoma Cohort 7: Outpatient Treatment
    Number of subjects analysed
    34
    22
    10
    1
    5
    9
    Units: Days*copies/ug
        geometric mean (geometric coefficient of variation)
    185586.667 ( 325.6 )
    157499.362 ( 211.9 )
    134819.085 ( 1268.9 )
    286119.439 ( 99999 )
    64945.715 ( 1345.7 )
    199731.737 ( 136.8 )
    No statistical analyses for this end point

    Secondary: Percent of Participants with Presence of JCAR017 Transgene in Peripheral Blood by qPCR

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    End point title
    		 Percent of Participants with Presence of JCAR017 Transgene in Peripheral Blood by qPCR
    End point description
    Persistence is defined as a transgene count greater than or equal to the lower limit of detection (LLOD) of 5 copies per reaction. Data obtained after the start of a new anti-cancer therapy were excluded. qPCR = Quantitative polymerase chain reaction
    End point type
    Secondary
    End point timeframe
    At Day 29 and Months 2, 3, 6, 9, 12, 18, and 24 post JCAR017 infusion.
    End point values
    		 Cohort 1: Diffuse B-cell Lymphoma Failed ≥ 2 Lines of Therapy Cohort 2: Transplant Ineligible Diffuse B-cell Lymphoma Cohort 3: Japan Specific Cohort 4: Newly Diagnosed High-Grade B-cell Lymphoma Cohort 5: Primary Central Nervous System Lymphoma Cohort 7: Outpatient Treatment
    Number of subjects analysed
    34
    21
    10
    1
    5
    9
    Units: Percent of Participants
    number (not applicable)
        Day 29
    88.2
    95.2
    100.0
    100.0
    80.0
    100.0
        Month 2
    70.0
    66.7
    100.0
    100.0
    100.0
    62.5
        Month 3
    61.5
    50.0
    100.0
    100.0
    100.0
    37.5
        Month 6
    33.3
    45.5
    71.4
    0.0
    100.0
    16.7
        Month 9
    41.7
    40.0
    60.0
    0.0
    100.0
    25.0
        Month 12
    40.0
    57.1
    100.0
    0.0
    66.7
    0.0
        Month 18
    25.0
    57.1
    75.0
    0.0
    100.0
    20.0
        Month 24
    28.6
    50.0
    100.0
    0.0
    100.0
    20.0
    No statistical analyses for this end point

    Secondary: Change from Baseline in European Organisation for Research and Treatment of Cancer – Quality of Life C30 questionnaire (EORTC QLQ-C30) Scores

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    End point title
    		 Change from Baseline in European Organisation for Research and Treatment of Cancer – Quality of Life C30 questionnaire (EORTC QLQ-C30) Scores
    End point description
    The EORTC QLQ-C30 consists of five functional scales (physical, role, emotional, cognitive, social), three symptom scales (fatigue, nausea/vomiting, pain), a global health status/health-related quality of life (HRQoL) scale, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, financial difficulties). The questionnaire is scored on a 4-point Likert scale: 1 = not at all, 2 = a little, 3 = quite a bit, 4 = very much. The raw score is the average of the items contributing to the scale. The final scores are calculated via linear transformation of raw scores and range from 0 to 100. For functional scales higher scores indicate better QoL. For symptom scales and single items lower scores indicate fewer symptoms, i.e. better QoL. Baseline the last available recorded scores on or prior to the date of JCAR017 infusion. Only global health, fatigue, physical and cognitive functioning subscales were assessed. "99999" = N/A
    End point type
    Secondary
    End point timeframe
    At baseline and Day 1, 29, 60, 90, 180, 270, 365, 545, and 730 post JCAR017 infusion.
    End point values
    		 Cohort 1: Diffuse B-cell Lymphoma Failed ≥ 2 Lines of Therapy Cohort 2: Transplant Ineligible Diffuse B-cell Lymphoma Cohort 3: Japan Specific Cohort 4: Newly Diagnosed High-Grade B-cell Lymphoma Cohort 5: Primary Central Nervous System Lymphoma Cohort 7: Outpatient Treatment
    Number of subjects analysed
    34
    23
    10
    1
    5
    9
    Units: Scores on a Scale
    arithmetic mean (standard deviation)
        Global Health Status: Change from baseline Day 1
    -4.41 ( 17.070 )
    -5.07 ( 17.898 )
    -6.67 ( 10.244 )
    -8.33 ( 99999 )
    8.33 ( 25.685 )
    -7.41 ( 12.108 )
        Global Health Status: Change from baseline Day 29
    -1.26 ( 14.301 )
    0.00 ( 18.002 )
    -4.17 ( 17.236 )
    0.00 ( 99999 )
    16.67 ( 11.785 )
    -1.85 ( 14.299 )
        Global Health Status: Change from baseline Day 60
    5.00 ( 14.778 )
    7.84 ( 17.547 )
    4.17 ( 16.457 )
    0.00 ( 99999 )
    13.89 ( 26.788 )
    9.26 ( 8.784 )
        Global Health Status: Change from baseline Day 90
    2.47 ( 14.766 )
    1.28 ( 22.527 )
    -5.95 ( 17.817 )
    0.00 ( 99999 )
    22.22 ( 41.107 )
    4.63 ( 8.448 )
        Global Health Status: Change from baseline Day 180
    6.94 ( 13.685 )
    1.04 ( 23.332 )
    -13.10 ( 35.635 )
    -16.67 ( 99999 )
    25.00 ( 22.048 )
    2.78 ( 8.607 )
        Global Health Status: Change from baseline Day 270
    6.25 ( 20.140 )
    9.72 ( 9.742 )
    -3.33 ( 26.745 )
    0.00 ( 99999 )
    25.00 ( 22.048 )
    3.33 ( 9.501 )
        Global Health Status: Change from baseline Day 365
    -6.67 ( 20.337 )
    3.57 ( 11.664 )
    -12.50 ( 25.909 )
    0.00 ( 99999 )
    30.56 ( 26.788 )
    3.33 ( 7.454 )
        Global Health Status: Change from baseline Day 545
    -6.48 ( 18.530 )
    3.57 ( 26.726 )
    -5.56 ( 24.056 )
    0.00 ( 99999 )
    0.00 ( 47.140 )
    1.67 ( 9.129 )
        Global Health Status: Change from baseline Day 730
    -11.11 ( 12.975 )
    -4.17 ( 12.638 )
    -6.25 ( 7.979 )
    0.00 ( 99999 )
    20.83 ( 29.463 )
    -2.08 ( 21.916 )
        Physical Functioning: Change from baseline Day 1
    -3.33 ( 20.970 )
    -6.09 ( 21.074 )
    -3.33 ( 11.440 )
    -6.67 ( 99999 )
    -2.67 ( 19.777 )
    -3.70 ( 14.948 )
        Physical Functioning: Change from baseline Day 29
    -2.63 ( 18.555 )
    -4.21 ( 10.706 )
    -10.00 ( 14.824 )
    6.67 ( 99999 )
    -8.33 ( 16.667 )
    -8.15 ( 18.493 )
        Physical Functioning: Change from baseline Day 60
    3.11 ( 15.135 )
    -0.39 ( 21.275 )
    -4.44 ( 15.587 )
    0.00 ( 99999 )
    -2.22 ( 10.184 )
    -2.96 ( 10.062 )
        Physical Functioning: Change from baseline Day 90
    3.46 ( 16.781 )
    3.59 ( 12.054 )
    -5.71 ( 11.174 )
    6.67 ( 99999 )
    11.11 ( 23.413 )
    -0.74 ( 18.692 )
        Physical Functioning: Change from baseline Day 180
    7.78 ( 12.975 )
    -8.33 ( 31.219 )
    -5.71 ( 19.024 )
    -6.67 ( 99999 )
    15.56 ( 27.756 )
    -2.22 ( 24.825 )
        Physical Functioning: Change from baseline Day 270
    3.33 ( 10.050 )
    1.11 ( 19.052 )
    -2.67 ( 22.410 )
    6.67 ( 99999 )
    24.44 ( 27.756 )
    -6.67 ( 31.972 )
        Physical Functioning: Change from baseline Day 365
    0.67 ( 16.163 )
    0.95 ( 16.069 )
    -16.67 ( 20.000 )
    6.67 ( 99999 )
    22.22 ( 26.943 )
    5.33 ( 11.926 )
        Physical Functioning: Change from baseline Day 545
    -3.70 ( 26.690 )
    -1.90 ( 19.135 )
    -13.33 ( 23.094 )
    6.67 ( 99999 )
    13.33 ( 47.140 )
    9.33 ( 11.155 )
        Physical Functioning: Change from baseline Day 730
    1.11 ( 15.785 )
    -8.89 ( 28.493 )
    -3.33 ( 8.607 )
    6.67 ( 99999 )
    3.33 ( 42.426 )
    -3.33 ( 11.547 )
        Cognitive Functioning: Change from baseline Day 1
    -3.43 ( 17.301 )
    -3.62 ( 17.376 )
    -1.67 ( 9.461 )
    0.00 ( 99999 )
    -3.33 ( 13.944 )
    -1.85 ( 10.015 )
        Cognitive Functioning: Change from baseline Day 29
    -2.53 ( 16.203 )
    3.51 ( 14.250 )
    3.33 ( 13.147 )
    0.00 ( 99999 )
    8.33 ( 21.517 )
    -7.41 ( 12.108 )
        Cognitive Functioning: Change from baseline Day 60
    2.78 ( 12.444 )
    0.98 ( 10.978 )
    0.00 ( 27.889 )
    0.00 ( 99999 )
    33.33 ( 44.096 )
    -1.85 ( 13.029 )
        Cognitive Functioning: Change from baseline Day 90
    0.00 ( 13.074 )
    -1.28 ( 12.659 )
    4.76 ( 20.893 )
    0.00 ( 99999 )
    11.11 ( 19.245 )
    0.00 ( 8.333 )
        Cognitive Functioning: Change frm baseline Day 180
    -2.78 ( 15.624 )
    -2.08 ( 5.893 )
    11.90 ( 20.893 )
    0.00 ( 99999 )
    16.67 ( 28.868 )
    -5.56 ( 8.607 )
        Cognitive Functioning: Change frm baseline Day 270
    0.00 ( 22.473 )
    0.00 ( 0.000 )
    3.33 ( 13.944 )
    0.00 ( 99999 )
    33.33 ( 44.096 )
    3.33 ( 7.454 )
        Cognitive Functioning: Change frm baseline Day 365
    -11.67 ( 22.292 )
    0.00 ( 0.000 )
    -4.17 ( 8.333 )
    0.00 ( 99999 )
    22.22 ( 38.490 )
    6.67 ( 9.129 )
        Cognitive Functioning: Change frm baseline Day 545
    -7.41 ( 18.840 )
    2.38 ( 11.501 )
    -5.56 ( 19.245 )
    0.00 ( 99999 )
    -41.67 ( 82.496 )
    3.33 ( 7.454 )
        Cognitive Functioning: Change frm baseline Day 730
    -1.39 ( 18.060 )
    -5.56 ( 8.607 )
    -4.17 ( 15.957 )
    0.00 ( 99999 )
    -16.67 ( 23.570 )
    -4.17 ( 8.333 )
        Fatigue: Change from baseline Day 1
    1.63 ( 26.959 )
    1.45 ( 16.173 )
    3.33 ( 20.320 )
    0.00 ( 99999 )
    -20.00 ( 30.832 )
    1.23 ( 18.794 )
        Fatigue: Change from baseline Day 29
    3.03 ( 24.418 )
    2.34 ( 12.046 )
    5.56 ( 17.568 )
    -11.11 ( 99999 )
    -13.89 ( 27.778 )
    6.17 ( 14.815 )
        Fatigue: Change from baseline Day 60
    -9.63 ( 18.623 )
    -1.31 ( 20.743 )
    3.70 ( 31.946 )
    11.11 ( 99999 )
    -14.81 ( 35.717 )
    0.00 ( 17.568 )
        Fatigue: Change from baseline Day 90
    -4.53 ( 19.795 )
    -4.27 ( 17.881 )
    4.76 ( 35.635 )
    -11.11 ( 99999 )
    -37.04 ( 12.830 )
    -3.70 ( 22.906 )
        Fatigue: Change from baseline Day 180
    -8.33 ( 21.254 )
    2.78 ( 34.503 )
    -4.76 ( 38.946 )
    22.22 ( 99999 )
    -37.04 ( 23.130 )
    0.00 ( 33.702 )
        Fatigue: Change from baseline Day 270
    -9.26 ( 15.594 )
    0.00 ( 22.222 )
    -6.67 ( 14.907 )
    -11.11 ( 99999 )
    -29.63 ( 42.066 )
    -2.22 ( 34.605 )
        Fatigue: Change from baseline Day 365
    -3.33 ( 14.861 )
    -4.76 ( 20.141 )
    13.89 ( 33.179 )
    -11.11 ( 99999 )
    -44.44 ( 22.222 )
    -13.33 ( 14.487 )
        Fatigue: Change from baseline Day 545
    4.94 ( 25.526 )
    -1.59 ( 19.698 )
    -3.70 ( 27.962 )
    -11.11 ( 99999 )
    -5.56 ( 23.570 )
    -11.11 ( 15.713 )
        Fatigue: Change from baseline Day 730
    0.93 ( 22.947 )
    3.70 ( 9.072 )
    5.56 ( 14.344 )
    -11.11 ( 99999 )
    -16.67 ( 7.857 )
    -8.33 ( 16.667 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Functional Assessment of Cancer Treatment-Lymphoma “Additional Concerns” Subscale (FACT-LymS) Scores

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    End point title
    		 Change from Baseline in Functional Assessment of Cancer Treatment-Lymphoma “Additional Concerns” Subscale (FACT-LymS) Scores
    End point description
    The Functional Assessment of Cancer Treatment-Lymphoma “Additional concerns” subscale (FACT-LymS) consists of the FACT-General scale and a 15-item lymphoma-specific additional concerns subscale (LYM). This scale addresses symptoms and functional limitations that are important to lymphoma patients. Only the LYM subscale was administered in this study. The LYM items are scored on a 0 (“Not at all”) to 4 (“Very much”) response scale. Items are aggregated to a single score on a 0-60 scale. Lower scores indicate better health outcomes. Baseline the last available recorded scores on or prior to the date of JCAR017 infusion. "99999" = N/A
    End point type
    Secondary
    End point timeframe
    At baseline and Day 1, 29, 60, 90, 180, 270, 365, 545, and 730 post JCAR017 infusion.
    End point values
    		 Cohort 1: Diffuse B-cell Lymphoma Failed ≥ 2 Lines of Therapy Cohort 2: Transplant Ineligible Diffuse B-cell Lymphoma Cohort 3: Japan Specific Cohort 4: Newly Diagnosed High-Grade B-cell Lymphoma Cohort 5: Primary Central Nervous System Lymphoma Cohort 7: Outpatient Treatment
    Number of subjects analysed
    33
    23
    10
    1
    5
    9
    Units: Scores on a Scale
    arithmetic mean (standard deviation)
        Change from baseline Day 1
    0.7 ( 8.17 )
    0.1 ( 7.05 )
    1.9 ( 5.92 )
    1.0 ( 99999 )
    -4.0 ( 6.52 )
    -1.2 ( 11.08 )
        Change from baseline Day 29
    -1.7 ( 7.14 )
    -2.7 ( 4.56 )
    1.3 ( 7.24 )
    -4.0 ( 99999 )
    -6.5 ( 8.10 )
    1.0 ( 9.08 )
        Change from baseline Day 60
    -2.8 ( 5.42 )
    -2.0 ( 4.20 )
    -3.3 ( 9.99 )
    -4.0 ( 99999 )
    -4.7 ( 8.33 )
    -0.4 ( 9.95 )
        Change from baseline Day 90
    -0.4 ( 5.42 )
    -2.8 ( 3.83 )
    0.6 ( 9.25 )
    -5.0 ( 99999 )
    -6.7 ( 8.50 )
    -1.7 ( 8.67 )
        Change from baseline Day 180
    0.6 ( 5.14 )
    -1.8 ( 5.65 )
    -3.6 ( 10.20 )
    2.0 ( 99999 )
    -8.0 ( 7.00 )
    1.0 ( 7.27 )
        Change from baseline Day 270
    -0.3 ( 6.78 )
    -3.7 ( 2.25 )
    -1.0 ( 10.07 )
    -8.0 ( 99999 )
    -10.00 ( 12.53 )
    2.4 ( 5.22 )
        Change from baseline Day 365
    1.3 ( 7.01 )
    -3.3 ( 3.30 )
    2.0 ( 12.03 )
    -6.0 ( 99999 )
    -6.7 ( 10.69 )
    1.4 ( 7.33 )
        Change from baseline Day 545
    0.7 ( 7.14 )
    -3.7 ( 4.35 )
    -4.7 ( 4.16 )
    -3.0 ( 99999 )
    3.5 ( 6.36 )
    -1.0 ( 4.85 )
        Change from baseline Day 730
    1.4 ( 7.12 )
    -0.8 ( 1.33 )
    -1.8 ( 5.32 )
    -2.0 ( 99999 )
    -1.5 ( 12.02 )
    -1.5 ( 1.29 )
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Participants were assessed for All-Cause Mortality, Serious Adverse Events and Other (Not Including Serious) Adverse Events from the date of leukapheresis until study completion (assessed up to approximately 25 months).
    Adverse event reporting additional description
    All-Cause Mortality, Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that underwent leukapheresis and may or may not have received at least 1 dose of JCAR017.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    26.0
    Reporting groups
    Reporting group title
    Cohort 1: Diffuse B-cell Lymphoma Failed ≥ 2 Lines of Therapy
    Reporting group description
    		 JCAR017 was infused at a dose of 100 x 10^6 JCAR017-positive transfected viable T cells (50 × 10^6 CD8+ CAR+ T cells and 50 × 10^6 CD4+ CAR+ T cells), on Day 1 (2 to 7 days after completion of Lymphodepleting chemotherapy).

    Reporting group title
    Cohort 2: Transplant Ineligible Diffuse B-cell Lymphoma
    Reporting group description
    		 JCAR017 was infused at a dose of 100 x 10^6 JCAR017-positive transfected viable T cells (50 × 10^6 CD8+ CAR+ T cells and 50 × 10^6 CD4+ CAR+ T cells), on Day 1 (2 to 7 days after completion of Lymphodepleting chemotherapy).

    Reporting group title
    Cohort 7: Outpatient Treatment
    Reporting group description
    		 JCAR017 was infused at a dose of 100 x 10^6 JCAR017-positive transfected viable T cells (50 × 10^6 CD8+ CAR+ T cells and 50 × 10^6 CD4+ CAR+ T cells), on Day 1 (2 to 7 days after completion of Lymphodepleting chemotherapy).

    Reporting group title
    Cohort 4: Newly Diagnosed High-Grade B-cell Lymphoma
    Reporting group description
    		 JCAR017 was infused at a dose of 100 x 10^6 JCAR017-positive transfected viable T cells (50 × 10^6 CD8+ CAR+ T cells and 50 × 10^6 CD4+ CAR+ T cells), on Day 1 (2 to 7 days after completion of Lymphodepleting chemotherapy).

    Reporting group title
    Cohort 5: Primary Central Nervous System Lymphoma
    Reporting group description
    		 JCAR017 was infused at a dose of 100 x 10^6 JCAR017-positive transfected viable T cells (50 × 10^6 CD8+ CAR+ T cells and 50 × 10^6 CD4+ CAR+ T cells), on Day 1 (2 to 7 days after completion of Lymphodepleting chemotherapy).

    Reporting group title
    Cohort 3: Japan Specific
    Reporting group description
    		 JCAR017 was infused at a dose of 100 x 10^6 JCAR017-positive transfected viable T cells (50 × 10^6 CD8+ CAR+ T cells and 50 × 10^6 CD4+ CAR+ T cells), on Day 1 (2 to 7 days after completion of Lymphodepleting chemotherapy).

    Serious adverse events
    		 Cohort 1: Diffuse B-cell Lymphoma Failed ≥ 2 Lines of Therapy Cohort 2: Transplant Ineligible Diffuse B-cell Lymphoma Cohort 7: Outpatient Treatment Cohort 4: Newly Diagnosed High-Grade B-cell Lymphoma Cohort 5: Primary Central Nervous System Lymphoma Cohort 3: Japan Specific
    Total subjects affected by serious adverse events
         subjects affected / exposed
    19 / 45 (42.22%)
    8 / 32 (25.00%)
    1 / 11 (9.09%)
    0 / 4 (0.00%)
    2 / 7 (28.57%)
    2 / 14 (14.29%)
         number of deaths (all causes)
    32
    22
    4
    0
    5
    9
         number of deaths resulting from adverse events
    2
    1
    0
    0
    0
    1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Squamous cell carcinoma of head and neck
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 32 (3.13%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Capillary leak syndrome
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 32 (0.00%)
    1 / 11 (9.09%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 14 (7.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Immune system disorders
    Cytokine release syndrome
         subjects affected / exposed
    7 / 45 (15.56%)
    1 / 32 (3.13%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    7 / 7
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemophagocytic lymphohistiocytosis
         subjects affected / exposed
    2 / 45 (4.44%)
    1 / 32 (3.13%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Hypoxia
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Agitation
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bradyphrenia
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Confusional state
         subjects affected / exposed
    5 / 45 (11.11%)
    1 / 32 (3.13%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    5 / 5
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Delirium
         subjects affected / exposed
    2 / 45 (4.44%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Disorientation
         subjects affected / exposed
    2 / 45 (4.44%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hallucination
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac failure
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 32 (3.13%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Ataxia
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aphasia
         subjects affected / exposed
    4 / 45 (8.89%)
    1 / 32 (3.13%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    4 / 4
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Amnesia
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 32 (3.13%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Depressed level of consciousness
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dysarthria
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 32 (3.13%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyskinesia
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Somnolence
         subjects affected / exposed
    2 / 45 (4.44%)
    1 / 32 (3.13%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    1 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Memory impairment
         subjects affected / exposed
    2 / 45 (4.44%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lethargy
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 32 (3.13%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Stupor
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tremor
         subjects affected / exposed
    5 / 45 (11.11%)
    1 / 32 (3.13%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    5 / 5
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Febrile neutropenia
         subjects affected / exposed
    4 / 45 (8.89%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    3 / 4
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anaemia
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    1 / 45 (2.22%)
    1 / 32 (3.13%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Ulcerative keratitis
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 32 (3.13%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    2 / 45 (4.44%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 32 (3.13%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 32 (3.13%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastric haemorrhage
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 32 (3.13%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Melaena
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 14 (7.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hypertransaminasaemia
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    Hypercalcaemia of malignancy
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Muscular weakness
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 32 (3.13%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Conjunctivitis
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 32 (3.13%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clostridium colitis
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Candida sepsis
         subjects affected / exposed
    2 / 45 (4.44%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cystitis
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Device related sepsis
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cytomegalovirus infection
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 32 (3.13%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 32 (3.13%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal sepsis
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Cohort 1: Diffuse B-cell Lymphoma Failed ≥ 2 Lines of Therapy Cohort 2: Transplant Ineligible Diffuse B-cell Lymphoma Cohort 7: Outpatient Treatment Cohort 4: Newly Diagnosed High-Grade B-cell Lymphoma Cohort 5: Primary Central Nervous System Lymphoma Cohort 3: Japan Specific
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    40 / 45 (88.89%)
    25 / 32 (78.13%)
    9 / 11 (81.82%)
    1 / 4 (25.00%)
    5 / 7 (71.43%)
    12 / 14 (85.71%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Peritumoural oedema
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Skin papilloma
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 32 (0.00%)
    1 / 11 (9.09%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Tumour flare
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 32 (3.13%)
    1 / 11 (9.09%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    1 / 45 (2.22%)
    3 / 32 (9.38%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    3
    0
    0
    0
    0
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    3 / 45 (6.67%)
    1 / 32 (3.13%)
    1 / 11 (9.09%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    4 / 14 (28.57%)
         occurrences all number
    3
    1
    1
    0
    0
    4
    Asthenia
         subjects affected / exposed
    3 / 45 (6.67%)
    2 / 32 (6.25%)
    1 / 11 (9.09%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    3
    2
    2
    0
    0
    0
    Catheter site related reaction
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    2 / 14 (14.29%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    Pyrexia
         subjects affected / exposed
    20 / 45 (44.44%)
    10 / 32 (31.25%)
    1 / 11 (9.09%)
    0 / 4 (0.00%)
    2 / 7 (28.57%)
    2 / 14 (14.29%)
         occurrences all number
    21
    11
    1
    0
    2
    2
    Oedema peripheral
         subjects affected / exposed
    2 / 45 (4.44%)
    5 / 32 (15.63%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    2
    5
    0
    0
    0
    1
    Immune system disorders
    Cytokine release syndrome
         subjects affected / exposed
    12 / 45 (26.67%)
    12 / 32 (37.50%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    3 / 7 (42.86%)
    6 / 14 (42.86%)
         occurrences all number
    12
    12
    0
    0
    3
    7
    Hypogammaglobulinaemia
         subjects affected / exposed
    6 / 45 (13.33%)
    3 / 32 (9.38%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    4 / 14 (28.57%)
         occurrences all number
    6
    3
    0
    0
    0
    6
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    4 / 45 (8.89%)
    0 / 32 (0.00%)
    3 / 11 (27.27%)
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 14 (0.00%)
         occurrences all number
    6
    0
    3
    0
    1
    0
    Hypoxia
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Hiccups
         subjects affected / exposed
    2 / 45 (4.44%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    2
    0
    0
    0
    0
    1
    Pleural effusion
         subjects affected / exposed
    0 / 45 (0.00%)
    2 / 32 (6.25%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    Psychiatric disorders
    Delirium
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 32 (3.13%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    1
    0
    0
    0
    2
    Confusional state
         subjects affected / exposed
    2 / 45 (4.44%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    2
    0
    0
    0
    0
    1
    Investigations
    Aspartate aminotransferase increased
         subjects affected / exposed
    3 / 45 (6.67%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    5
    0
    0
    0
    0
    0
    Alanine aminotransferase increased
         subjects affected / exposed
    2 / 45 (4.44%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    2 / 7 (28.57%)
    0 / 14 (0.00%)
         occurrences all number
    2
    0
    0
    0
    2
    0
    Blood fibrinogen decreased
         subjects affected / exposed
    0 / 45 (0.00%)
    2 / 32 (6.25%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    0
    4
    0
    0
    0
    0
    Injury, poisoning and procedural complications
    Post procedural haemorrhage
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Allergic transfusion reaction
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    2 / 14 (14.29%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    Nervous system disorders
    Seizure
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 14 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Post herpetic neuralgia
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Hemiparesis
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 14 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Headache
         subjects affected / exposed
    7 / 45 (15.56%)
    4 / 32 (12.50%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 14 (0.00%)
         occurrences all number
    8
    4
    0
    0
    1
    0
    Blood and lymphatic system disorders
    Acquired antithrombin III deficiency
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Anaemia
         subjects affected / exposed
    21 / 45 (46.67%)
    8 / 32 (25.00%)
    2 / 11 (18.18%)
    0 / 4 (0.00%)
    3 / 7 (42.86%)
    10 / 14 (71.43%)
         occurrences all number
    35
    15
    2
    0
    8
    10
    Leukopenia
         subjects affected / exposed
    9 / 45 (20.00%)
    5 / 32 (15.63%)
    2 / 11 (18.18%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    11 / 14 (78.57%)
         occurrences all number
    12
    8
    6
    0
    0
    34
    Lymphopenia
         subjects affected / exposed
    9 / 45 (20.00%)
    4 / 32 (12.50%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    12
    8
    0
    0
    0
    0
    Hypofibrinogenaemia
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    4 / 14 (28.57%)
         occurrences all number
    1
    0
    0
    0
    0
    5
    Febrile neutropenia
         subjects affected / exposed
    5 / 45 (11.11%)
    1 / 32 (3.13%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    6
    1
    0
    0
    0
    0
    Eosinophilia
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Neutropenia
         subjects affected / exposed
    35 / 45 (77.78%)
    22 / 32 (68.75%)
    9 / 11 (81.82%)
    1 / 4 (25.00%)
    5 / 7 (71.43%)
    11 / 14 (78.57%)
         occurrences all number
    54
    40
    14
    3
    7
    37
    Thrombocytopenia
         subjects affected / exposed
    16 / 45 (35.56%)
    11 / 32 (34.38%)
    3 / 11 (27.27%)
    1 / 4 (25.00%)
    3 / 7 (42.86%)
    11 / 14 (78.57%)
         occurrences all number
    20
    16
    3
    1
    7
    12
    Ear and labyrinth disorders
    Hypoacusis
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 14 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Eye disorders
    Keratopathy
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 14 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    5 / 45 (11.11%)
    2 / 32 (6.25%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    6
    2
    0
    0
    0
    0
    Constipation
         subjects affected / exposed
    7 / 45 (15.56%)
    2 / 32 (6.25%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    7
    2
    0
    0
    0
    1
    Nausea
         subjects affected / exposed
    6 / 45 (13.33%)
    3 / 32 (9.38%)
    1 / 11 (9.09%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    7
    3
    1
    0
    0
    1
    Diarrhoea
         subjects affected / exposed
    7 / 45 (15.56%)
    3 / 32 (9.38%)
    2 / 11 (18.18%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    2 / 14 (14.29%)
         occurrences all number
    8
    3
    2
    0
    0
    2
    Vomiting
         subjects affected / exposed
    3 / 45 (6.67%)
    2 / 32 (6.25%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    2 / 14 (14.29%)
         occurrences all number
    5
    2
    0
    0
    0
    4
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    Dermatitis acneiform
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    Pruritus
         subjects affected / exposed
    3 / 45 (6.67%)
    1 / 32 (3.13%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    3
    1
    0
    0
    0
    0
    Renal and urinary disorders
    Micturition disorder
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 32 (3.13%)
    1 / 11 (9.09%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    2 / 45 (4.44%)
    0 / 32 (0.00%)
    1 / 11 (9.09%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    2
    0
    1
    0
    0
    0
    Bone pain
         subjects affected / exposed
    4 / 45 (8.89%)
    0 / 32 (0.00%)
    1 / 11 (9.09%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    4
    0
    1
    0
    0
    0
    Neck pain
         subjects affected / exposed
    2 / 45 (4.44%)
    2 / 32 (6.25%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    2
    2
    0
    0
    0
    0
    Pain in extremity
         subjects affected / exposed
    4 / 45 (8.89%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 14 (0.00%)
         occurrences all number
    4
    0
    0
    0
    1
    0
    Infections and infestations
    Varicella zoster virus infection
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Urinary tract infection
         subjects affected / exposed
    2 / 45 (4.44%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 14 (0.00%)
         occurrences all number
    2
    0
    0
    0
    1
    0
    Pneumonia
         subjects affected / exposed
    4 / 45 (8.89%)
    0 / 32 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    4
    0
    0
    0
    0
    0
    Escherichia urinary tract infection
         subjects affected / exposed
    1 / 45 (2.22%)
    3 / 32 (9.38%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    3
    0
    0
    0
    0
    COVID-19
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 32 (0.00%)
    1 / 11 (9.09%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Metabolism and nutrition disorders
    Hypomagnesaemia
         subjects affected / exposed
    6 / 45 (13.33%)
    1 / 32 (3.13%)
    1 / 11 (9.09%)
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    1 / 14 (7.14%)
         occurrences all number
    7
    1
    1
    0
    1
    1
    Hypokalaemia
         subjects affected / exposed
    6 / 45 (13.33%)
    3 / 32 (9.38%)
    1 / 11 (9.09%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    6
    9
    1
    0
    0
    1
    Decreased appetite
         subjects affected / exposed
    2 / 45 (4.44%)
    1 / 32 (3.13%)
    1 / 11 (9.09%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    2
    1
    1
    0
    0
    1
    Hypophosphataemia
         subjects affected / exposed
    3 / 45 (6.67%)
    3 / 32 (9.38%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    4
    4
    0
    0
    0
    0

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    08 Jan 2018
    Restricted transformed indolent B-NHL to transformed follicular lymphoma - Revised definition of TNE subjects - Revised eligibility criteria for Cohort 3 (Japan only), Cohort 5(PCNSL), Cohort 6 (Richter’s transformation) - Added safety run-in for Cohort 3 - Revised inclusion criterion for subjects with secondary DLBCL CNS involvement
    28 Dec 2018
    An ad hoc DSMB meeting (14-Dec-2018) held after a Grade 5 respiratory failure on 10-Dec-2018. Implemented an urgent safety measure following trial pause with revision of I/E criteria; enrollment restricted to subjects with ECOG PS 0 to1(except TNE subjects) and excluded subjects with vascular tumor invasion, DVT or PE within 3 mos, or requiring therapeutic levels of anticoagulation. - Added requirement for subjects to be clinically stable prior to liso-cel infusion, including absence of active infection, supplemental oxygen, uncontrolled cardiac arrhythmias, and vasopressor support - Clarified the selection of subjects with primary or secondary CNS involvement
    21 Nov 2019
    Cohort 4 (HGBCL) clarified to allow for consolidation with liso-cel after 1L therapy; Cohort 5 modified to 2L population; Cohort 6 removed; Cohort 7 added - Updated criteria for pausing/stopping the study, patient interviews, inclusion criteria, and pregnancy risk - Removed exclusion criteria of DVT/PE/ anticoagulation; added statements on stable disease/ anticoagulation - Added 2 exclusion criteria per HA requirements: - Excluded subjects with known severe hypersensitivity to DMSO or dextran - Excluded systemic immunostimulatory agents (including but not limited to IFN and IL-2) ≤ 6 wks or 5 half-lives of the drug, whichever was shorter, prior to liso-cel infusion. - Updated planned sample size from 124 to 116 - Added new conditions to be reported as SAEs
    16 Nov 2020
    Modified Cohort 2 sample size from ≥ 28 to ≤ 28 subjects - Revised Cohort 2 primary analysis to be descriptive without formal hypothesis testing. Analysis triggered when last subject treated with liso-cel was followed for at ≥1post- baseline efficacy assessment instead of 6 months -Pooled analysis from Cohort 2 and Study 017006 (PILOT) to be reported outside of the BCM-001 CSR - Aligned screening, baseline, and post-baseline evaluations for Cohort 5 with standardized evaluations for PCNSL -Added inclusion criterion #8 back for subjects with NHL: “For subjects with NHL (except Cohort 5): Subjects must have PET-positive disease as per Lugano Classification
    12 Aug 2021
    Cohort 2 sample size was modified from a maximum of 28 to approximately 28 subjects. Specified that Cohort 2 will have formal hypothesis testing at the time of the primary analysis. · Cohort 5 inclusion criteria were amended to allow for enrollment of subjects who failed to proceed to HDCT and ASCT following induction therapy. Timing of cohort 7 analysis was added.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

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