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    Clinical Trial Results:
    A Phase 1 Multicenter Study Evaluating the Safety and Tolerability of KTE-X19 in Adult Subjects with Relapsed/Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma

    Summary
    EudraCT number
    		 2018-001923-38
    Trial protocol
    		 DE   ES   GB   IT  
    Global end of trial date
    18 Nov 2022

    Results information
    Results version number
    		 v1(current)
    This version publication date
    16 Nov 2023
    First version publication date
    16 Nov 2023
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    KTE-C19-108
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03624036
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Gilead Sciences
    Sponsor organisation address
    333 Lakeside Drive, Foster City, CA, United States, 94404
    Public contact
    Gilead Clinical Study Information Center, Gilead Sciences, GileadClinicalTrials@gilead.com
    Scientific contact
    Gilead Clinical Study Information Center, Gilead Sciences, GileadClinicalTrials@gilead.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    18 Nov 2022
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    12 Feb 2021
    Global end of trial reached?
    Yes
    Global end of trial date
    18 Nov 2022
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The primary objective of this study was to evaluate the safety and tolerability of brexucabtagene autoleucel (KTE-X19) in adults with relapsed/refractory chronic lymphocytic leukemia (r/r CLL) and small lymphocytic lymphoma (r/r SLL) who had received at least 2 prior lines of treatment, one of which must include a Bruton’s tyrosine kinase (BTK) inhibitor. After the end of KTE-C19-108, participants who received an infusion of brexucabtagene autoleucel will complete the remainder of the 15-year follow-up assessments in a separate Long-term Follow-up study, KT-US-982-5968 (2020-005843-21).
    Protection of trial subjects
    The protocol and consent/assent forms were submitted by each investigator to a duly constituted Independent Ethics Committee (IEC) or Institutional Review Board (IRB) for review and approval before study initiation. All revisions to the consent/assent forms (if applicable) after initial IEC/IRB approval were submitted by the investigator to the IEC/IRB for review and approval before implementation in accordance with regulatory requirements. This study was conducted in accordance with recognized international scientific and ethical standards, including but not limited to the International Conference on Harmonization guideline for Good Clinical Practice (ICH GCP) and the original principles embodied in the Declaration of Helsinki.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    15 Nov 2018
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety
    Long term follow-up duration
    		 15 Years
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Italy: 1
    Country: Number of subjects enrolled
    United States: 15
    Worldwide total number of subjects
    16
    EEA total number of subjects
    1
    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)
    9
    From 65 to 84 years
    7
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Participants were enrolled at study sites in the United States and Italy. The study was terminated before enrolling participants in the Cohort 4B.

    Pre-assignment
    Screening details
    		 17 participants were screened.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 First Stage Cohort 1: 1 x 10^6 Anti-CD19 CAR T Cells/kg
    Arm description
    		 Participants with relapsed/refractory (r/r) chronic lymphocytic leukemia (CLL) received conditioning chemotherapy (fludarabine 30 mg/m^2/day over 30 minutes and cyclophosphamide 500 mg/m^2/day over 30-60 minutes) administered intravenously (IV) on Days -5 to -3 with 2 rest days, followed by single infusion of brexucabtagene autoleucel 1 x 10^6 anti-cluster of differentiate 19 (CD19) chimeric antigen receptor (CAR) T cells/kg administered IV on Day 0.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Fludarabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    30 mg/m^2/day administered over 30 minutes on days -5 to -3.

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

    Investigational medicinal product name
    Cyclophosphamide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    500 mg/m^2/day administered over 30-60 minutes on days -5 to -3.

    Arm title
    		 First Stage Cohort 2: 2 x 10^6 Anti-CD19 CAR T Cells/kg
    Arm description
    		 Participants with r/r CLL received conditioning chemotherapy (fludarabine 30 mg/m^2/day over 30 minutes and cyclophosphamide 500 mg/m^2/day over 30-60 minutes) administered IV on Days -5 to -3 with 2 rest days, followed by single infusion of brexucabtagene autoleucel 2 x 10^6 anti-CD19 CAR T cells/kg administered IV on Day 0.
    Arm type
    		 Experimental

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

    Investigational medicinal product name
    Fludarabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    30 mg/m^2/day administered over 30 minutes on days -5 to -3.

    Investigational medicinal product name
    Cyclophosphamide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    500 mg/m^2/day administered over 30-60 minutes on days -5 to -3.

    Arm title
    		 Second Stage Cohort 3: 1 x 10^6 Anti-CD19 CAR T Cells/kg
    Arm description
    		 Participants with r/r CLL and small lymphocytic lymphoma (SLL) with ≤1% malignant cells in peripheral blood or absolute lymphocyte count (ALC) < 5,000 cells/μL received conditioning chemotherapy (fludarabine 30 mg/m^2/day over 30 minutes and cyclophosphamide 500 mg/m^2/day over 30-60 minutes) administered IV on Days -5 to -3 with 2 rest days, followed by single infusion of brexucabtagene autoleucel 1 x 10^6 anti-CD19 CAR T cells/kg administered IV on Day 0.
    Arm type
    		 Experimental

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

    Investigational medicinal product name
    Fludarabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    30 mg/m^2/day administered over 30 minutes on days -5 to -3.

    Investigational medicinal product name
    Cyclophosphamide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    500 mg/m^2/day administered over 30-60 minutes on days -5 to -3.

    Arm title
    		 Second Stage Cohort 4A: 1 x 10^6 Anti-CD19 CAR T Cells/kg
    Arm description
    		 Participants with r/r CLL who previously received two lines of therapy along with ibrutinib with or without anti CD20 antibodies, B-cell lymphoma 2 (BCL-2) and Phosphoinositide 3-kinase (PI3k) inhibitors received ibrutinib up to 30 hours prior to leukapheresis along with conditioning chemotherapy (fludarabine 30 mg/m^2/day over 30 minutes and cyclophosphamide 500 mg/m^2/day over 30-60 minutes) administered IV on Days -5 to -3 with 2 rest days, followed by single infusion of brexucabtagene autoleucel 1 x 10^6 anti-CD19 CAR T cells/kg administered IV on Day 0.
    Arm type
    		 Experimental

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

    Investigational medicinal product name
    Fludarabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    30 mg/m^2/day administered over 30 minutes on days -5 to -3.

    Investigational medicinal product name
    Cyclophosphamide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    500 mg/m^2/day administered over 30-60 minutes on days -5 to -3.

    Number of subjects in period 1
    		First Stage Cohort 1: 1 x 10^6 Anti-CD19 CAR T Cells/kg First Stage Cohort 2: 2 x 10^6 Anti-CD19 CAR T Cells/kg Second Stage Cohort 3: 1 x 10^6 Anti-CD19 CAR T Cells/kg Second Stage Cohort 4A: 1 x 10^6 Anti-CD19 CAR T Cells/kg
    Started
    7
    3
    3
    3
    Completed
    0
    0
    0
    0
    Not completed
    7
    3
    3
    3
         Death
    2
    3
    -
    1
         Withdrawal by Subject
    1
    -
    1
    -
         Reason not Specified
    3
    -
    2
    2
         Enrolled but Never Treated
    1
    -
    -
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    First Stage Cohort 1: 1 x 10^6 Anti-CD19 CAR T Cells/kg
    Reporting group description
    		 Participants with relapsed/refractory (r/r) chronic lymphocytic leukemia (CLL) received conditioning chemotherapy (fludarabine 30 mg/m^2/day over 30 minutes and cyclophosphamide 500 mg/m^2/day over 30-60 minutes) administered intravenously (IV) on Days -5 to -3 with 2 rest days, followed by single infusion of brexucabtagene autoleucel 1 x 10^6 anti-cluster of differentiate 19 (CD19) chimeric antigen receptor (CAR) T cells/kg administered IV on Day 0.

    Reporting group title
    First Stage Cohort 2: 2 x 10^6 Anti-CD19 CAR T Cells/kg
    Reporting group description
    		 Participants with r/r CLL received conditioning chemotherapy (fludarabine 30 mg/m^2/day over 30 minutes and cyclophosphamide 500 mg/m^2/day over 30-60 minutes) administered IV on Days -5 to -3 with 2 rest days, followed by single infusion of brexucabtagene autoleucel 2 x 10^6 anti-CD19 CAR T cells/kg administered IV on Day 0.

    Reporting group title
    Second Stage Cohort 3: 1 x 10^6 Anti-CD19 CAR T Cells/kg
    Reporting group description
    		 Participants with r/r CLL and small lymphocytic lymphoma (SLL) with ≤1% malignant cells in peripheral blood or absolute lymphocyte count (ALC) < 5,000 cells/μL received conditioning chemotherapy (fludarabine 30 mg/m^2/day over 30 minutes and cyclophosphamide 500 mg/m^2/day over 30-60 minutes) administered IV on Days -5 to -3 with 2 rest days, followed by single infusion of brexucabtagene autoleucel 1 x 10^6 anti-CD19 CAR T cells/kg administered IV on Day 0.

    Reporting group title
    Second Stage Cohort 4A: 1 x 10^6 Anti-CD19 CAR T Cells/kg
    Reporting group description
    		 Participants with r/r CLL who previously received two lines of therapy along with ibrutinib with or without anti CD20 antibodies, B-cell lymphoma 2 (BCL-2) and Phosphoinositide 3-kinase (PI3k) inhibitors received ibrutinib up to 30 hours prior to leukapheresis along with conditioning chemotherapy (fludarabine 30 mg/m^2/day over 30 minutes and cyclophosphamide 500 mg/m^2/day over 30-60 minutes) administered IV on Days -5 to -3 with 2 rest days, followed by single infusion of brexucabtagene autoleucel 1 x 10^6 anti-CD19 CAR T cells/kg administered IV on Day 0.

    Reporting group values
    		 First Stage Cohort 1: 1 x 10^6 Anti-CD19 CAR T Cells/kg First Stage Cohort 2: 2 x 10^6 Anti-CD19 CAR T Cells/kg Second Stage Cohort 3: 1 x 10^6 Anti-CD19 CAR T Cells/kg Second Stage Cohort 4A: 1 x 10^6 Anti-CD19 CAR T Cells/kg Total
    Number of subjects
    		 7 3 3 3 16
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 60.8 ( 5.8 ) 58.7 ( 5.9 ) 68.0 ( 11.5 ) 63.3 ( 9.1 ) -
    Gender categorical
    Units: Subjects
        Female
    		 3 1 0 1 5
        Male
    		 4 2 3 2 11
    Race
    Units: Subjects
        Black or African American
    		 1 0 0 1 2
        White
    		 6 3 3 2 14
    Ethnicity
    Units: Subjects
        Not Hispanic or Latino
    		 7 3 3 3 16

    End points

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    End points reporting groups
    Reporting group title
    First Stage Cohort 1: 1 x 10^6 Anti-CD19 CAR T Cells/kg
    Reporting group description
    		 Participants with relapsed/refractory (r/r) chronic lymphocytic leukemia (CLL) received conditioning chemotherapy (fludarabine 30 mg/m^2/day over 30 minutes and cyclophosphamide 500 mg/m^2/day over 30-60 minutes) administered intravenously (IV) on Days -5 to -3 with 2 rest days, followed by single infusion of brexucabtagene autoleucel 1 x 10^6 anti-cluster of differentiate 19 (CD19) chimeric antigen receptor (CAR) T cells/kg administered IV on Day 0.

    Reporting group title
    First Stage Cohort 2: 2 x 10^6 Anti-CD19 CAR T Cells/kg
    Reporting group description
    		 Participants with r/r CLL received conditioning chemotherapy (fludarabine 30 mg/m^2/day over 30 minutes and cyclophosphamide 500 mg/m^2/day over 30-60 minutes) administered IV on Days -5 to -3 with 2 rest days, followed by single infusion of brexucabtagene autoleucel 2 x 10^6 anti-CD19 CAR T cells/kg administered IV on Day 0.

    Reporting group title
    Second Stage Cohort 3: 1 x 10^6 Anti-CD19 CAR T Cells/kg
    Reporting group description
    		 Participants with r/r CLL and small lymphocytic lymphoma (SLL) with ≤1% malignant cells in peripheral blood or absolute lymphocyte count (ALC) < 5,000 cells/μL received conditioning chemotherapy (fludarabine 30 mg/m^2/day over 30 minutes and cyclophosphamide 500 mg/m^2/day over 30-60 minutes) administered IV on Days -5 to -3 with 2 rest days, followed by single infusion of brexucabtagene autoleucel 1 x 10^6 anti-CD19 CAR T cells/kg administered IV on Day 0.

    Reporting group title
    Second Stage Cohort 4A: 1 x 10^6 Anti-CD19 CAR T Cells/kg
    Reporting group description
    		 Participants with r/r CLL who previously received two lines of therapy along with ibrutinib with or without anti CD20 antibodies, B-cell lymphoma 2 (BCL-2) and Phosphoinositide 3-kinase (PI3k) inhibitors received ibrutinib up to 30 hours prior to leukapheresis along with conditioning chemotherapy (fludarabine 30 mg/m^2/day over 30 minutes and cyclophosphamide 500 mg/m^2/day over 30-60 minutes) administered IV on Days -5 to -3 with 2 rest days, followed by single infusion of brexucabtagene autoleucel 1 x 10^6 anti-CD19 CAR T cells/kg administered IV on Day 0.

    Primary: Number of Participants Experiencing Dose Limiting Toxicities (DLTs)

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    End point title
    		 Number of Participants Experiencing Dose Limiting Toxicities (DLTs) [1]
    End point description
    DLTs refer to toxicities with onset experienced during the first 28 days of study treatment that have been judged to be clinically significant and related to study treatment. DLTs evaluated may include with some exceptions: All brexucabtagene autoleucel related Grade 3 non-hematologic toxicities lasting for more than 7 days, Grade 4 non-hematologic toxicities regardless of duration, and Grade 4 hematologic toxicity lasting more than 30 days if not attributable to underlying disease. DLT Evaluable Set included all participants treated with the target brexucabtagene autoleucel dose and followed for at least 28 days.
    End point type
    Primary
    End point timeframe
    First infusion date of brexucabtagene autoleucel up to 28 days. Participants were evaluated in specified period but Grade 4 hematologic toxicity (specified in description) having onset in this period were further observed for 30 days for confirmation.
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical comparison was planned or performed.
    End point values
    		 First Stage Cohort 1: 1 x 10^6 Anti-CD19 CAR T Cells/kg First Stage Cohort 2: 2 x 10^6 Anti-CD19 CAR T Cells/kg Second Stage Cohort 3: 1 x 10^6 Anti-CD19 CAR T Cells/kg Second Stage Cohort 4A: 1 x 10^6 Anti-CD19 CAR T Cells/kg
    Number of subjects analysed
    6
    3
    3
    3
    Units: participants
    0
    0
    1
    0
    No statistical analyses for this end point

    Secondary: Objective Response Rate (ORR) Per Investigator Review Assessed by International Workshop on CLL (IWCLL) 2018 Criteria

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    End point title
    		 Objective Response Rate (ORR) Per Investigator Review Assessed by International Workshop on CLL (IWCLL) 2018 Criteria
    End point description
    ORR: percentage of participants achieving either complete response (CR), CR with incomplete hematopoetic recovery (CRi)/partial response (PR). CR criteria: no lymphadenopathy >1.5 cm/hepatomegaly/splenomegaly, lymphocytes <4000/microliters (μL), bone marrow sample is normocellular with 30% lymphocytes&no B-lymphoid nodules, platelets ≥100,000/µL, hemoglobin ≥11 grams per deciliter (g/dL). CRi: All CR criteria were met except with platelet count <100,000/μL, hemoglobin <11 g/dL or neutrophil count <500/μL.PR: ≥1 of these:≥50% decrease in lymphocytes, lymphadenopathy, size of liver&spleen, 50% decrease in bone marrow infiltrates;&≥1 of these:platelets ≥100,000/µL or ≥50% increase from Baseline, hemoglobin ≥11 g/dL or ≥50% increase from Baseline. Participants who did not meet criteria were considered nonresponders. 95% confidence interval (CI) was calculated by Clopper-Pearson method. All Treated Subjects Set=all participants who were treated with any dose of brexucabtagene autoleucel.
    End point type
    Secondary
    End point timeframe
    First infusion date up to last follow up visit (maximum duration: 42 months)
    End point values
    		 First Stage Cohort 1: 1 x 10^6 Anti-CD19 CAR T Cells/kg First Stage Cohort 2: 2 x 10^6 Anti-CD19 CAR T Cells/kg Second Stage Cohort 3: 1 x 10^6 Anti-CD19 CAR T Cells/kg Second Stage Cohort 4A: 1 x 10^6 Anti-CD19 CAR T Cells/kg
    Number of subjects analysed
    6
    3
    3
    3
    Units: percentage of participants
        number (confidence interval 95%)
    50 (11.8 to 88.2)
    33 (0.8 to 90.6)
    100 (29.2 to 100.0)
    0 (0.0 to 70.8)
    No statistical analyses for this end point

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

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    End point title
    		 Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs)
    End point description
    An AE is defined as any untoward medical occurrence in a clinical trial participant that does not necessarily have a relationship with study treatment or worsening of a pre-existing medical condition. TEAEs were defined as AEs with onset on or after the initiation of brexucabtagene autoleucel infusion. Safety Analysis Set included all participants who were treated with any dose of brexucabtagene autoleucel.
    End point type
    Secondary
    End point timeframe
    First infusion date up to last follow up visit (maximum duration: 42 months)
    End point values
    		 First Stage Cohort 1: 1 x 10^6 Anti-CD19 CAR T Cells/kg First Stage Cohort 2: 2 x 10^6 Anti-CD19 CAR T Cells/kg Second Stage Cohort 3: 1 x 10^6 Anti-CD19 CAR T Cells/kg Second Stage Cohort 4A: 1 x 10^6 Anti-CD19 CAR T Cells/kg
    Number of subjects analysed
    6
    3
    3
    3
    Units: percentage of participants
        number (not applicable)
    100
    100
    100
    100
    No statistical analyses for this end point

    Secondary: Peak Level of Anti-CD19 CAR T-Cells in Blood

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    End point title
    		 Peak Level of Anti-CD19 CAR T-Cells in Blood
    End point description
    Peak was defined as the maximum number of CAR T cells measured post-infusion. Participants in the safety analysis set with available data were analysed.
    End point type
    Secondary
    End point timeframe
    First infusion date up to 3 months post-infusion (approximately 3 months)
    End point values
    		 First Stage Cohort 1: 1 x 10^6 Anti-CD19 CAR T Cells/kg First Stage Cohort 2: 2 x 10^6 Anti-CD19 CAR T Cells/kg Second Stage Cohort 3: 1 x 10^6 Anti-CD19 CAR T Cells/kg Second Stage Cohort 4A: 1 x 10^6 Anti-CD19 CAR T Cells/kg
    Number of subjects analysed
    6
    2
    3
    3
    Units: cells/μL
        median (inter-quartile range (Q1-Q3))
    1.46 (0.58 to 2.35)
    1.08 (0.00 to 2.15)
    42.18 (27.52 to 679.38)
    1.00 (0.00 to 1.27)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    All-Cause Mortality: Enrollment up to last follow up visit (maximum: 43 months); Adverse Events: First infusion date up to last follow up visit (maximum: 42 months)
    Adverse event reporting additional description
    All-Cause Mortality: All Enrolled Analysis Set included all the enrolled participants. Adverse Events: Safety Analysis Set included all participants who were treated with any dose of brexucabtagene autoleucel.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    22
    Reporting groups
    Reporting group title
    First Stage Cohort 1: 1 x 10^6 Anti- CD19 CAR T Cells/kg
    Reporting group description
    		 Participants with r/r CLL received conditioning chemotherapy (fludarabine 30 mg/m^2/day over 30 minutes and cyclophosphamide 500 mg/m^2/day over 30-60 minutes) administered IV on Days -5 to -3 with 2 rest days, followed by single infusion of brexucabtagene autoleucel 1 x 10^6 anti-CD19 CAR T cells/kg administered IV on Day 0.

    Reporting group title
    Second Stage Cohort 4A: 1 x 10^6 Anti-CD19 CAR T Cells/kg
    Reporting group description
    		 Participants with r/r CLL who previously received two lines of therapy along with ibrutinib with or without anti CD20 antibodies, BCL-2 and PI3k inhibitors received ibrutinib up to 30 hours prior to leukapheresis along with conditioning chemotherapy (fludarabine 30 mg/m^2/day over 30 minutes and cyclophosphamide 500 mg/m^2/day over 30-60 minutes) administered IV on Days -5 to -3 with 2 rest days, followed by single infusion of brexucabtagene autoleucel 1 x 10^6 anti-CD19 CAR T cells/kg administered IV on Day 0.

    Reporting group title
    Second Stage Cohort 3: 1 x 10^6 Anti-CD19 CAR T Cells/kg
    Reporting group description
    		 Participants with r/r CLL and SLL with ≤1% malignant cells in peripheral blood or ALC < 5,000 cells/μL received conditioning chemotherapy (fludarabine 30 mg/m^2/day over 30 minutes and cyclophosphamide 500 mg/m^2/day over 30-60 minutes) administered IV on Days -5 to -3 with 2 rest days, followed by single infusion of brexucabtagene autoleucel 1 x 10^6 anti-CD19 CAR T cells/kg administered IV on Day 0.

    Reporting group title
    First Stage Cohort 2: 2 x 10^6 Anti-CD19 CAR T Cells/kg
    Reporting group description
    		 Participants with r/r CLL received conditioning chemotherapy (fludarabine 30 mg/m^2/day over 30 minutes and cyclophosphamide 500 mg/m^2/day over 30-60 minutes) administered IV on Days -5 to -3 with 2 rest days, followed by single infusion of brexucabtagene autoleucel 2 x 10^6 anti-CD19 CAR T cells/kg administered IV on Day 0.

    Serious adverse events
    		 First Stage Cohort 1: 1 x 10^6 Anti- CD19 CAR T Cells/kg Second Stage Cohort 4A: 1 x 10^6 Anti-CD19 CAR T Cells/kg Second Stage Cohort 3: 1 x 10^6 Anti-CD19 CAR T Cells/kg First Stage Cohort 2: 2 x 10^6 Anti-CD19 CAR T Cells/kg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    4 / 6 (66.67%)
    1 / 3 (33.33%)
    3 / 3 (100.00%)
    2 / 3 (66.67%)
         number of deaths (all causes)
    2
    1
    0
    3
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Chronic lymphocytic leukaemia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Vascular disorders
    Hypotension
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    2 / 3 (66.67%)
    1 / 3 (33.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    3 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Embolism
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Tachycardia
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Aphasia
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Malaise
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    2 / 3 (66.67%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chills
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pneumothorax
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Confusional state
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Systemic candida
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rhinovirus infection
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Failure to thrive
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 First Stage Cohort 1: 1 x 10^6 Anti- CD19 CAR T Cells/kg Second Stage Cohort 4A: 1 x 10^6 Anti-CD19 CAR T Cells/kg Second Stage Cohort 3: 1 x 10^6 Anti-CD19 CAR T Cells/kg First Stage Cohort 2: 2 x 10^6 Anti-CD19 CAR T Cells/kg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    6 / 6 (100.00%)
    3 / 3 (100.00%)
    3 / 3 (100.00%)
    3 / 3 (100.00%)
    Vascular disorders
    Hypotension
         subjects affected / exposed
    1 / 6 (16.67%)
    1 / 3 (33.33%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
         occurrences all number
    2
    2
    1
    0
    Hypertension
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    1
    0
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    3 / 6 (50.00%)
    1 / 3 (33.33%)
    1 / 3 (33.33%)
    2 / 3 (66.67%)
         occurrences all number
    3
    1
    1
    2
    Pyrexia
         subjects affected / exposed
    4 / 6 (66.67%)
    2 / 3 (66.67%)
    3 / 3 (100.00%)
    1 / 3 (33.33%)
         occurrences all number
    5
    3
    3
    2
    Pain
         subjects affected / exposed
    2 / 6 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Chills
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Influenza like illness
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Malaise
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Oedema peripheral
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Catheter site pain
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    1
    Reproductive system and breast disorders
    Pruritus genital
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    2 / 3 (66.67%)
         occurrences all number
    0
    0
    1
    2
    Cough
         subjects affected / exposed
    2 / 6 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    2
    0
    0
    1
    Hypoxia
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    2 / 3 (66.67%)
    1 / 3 (33.33%)
         occurrences all number
    1
    0
    2
    1
    Tachypnoea
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Hiccups
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Epistaxis
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Dysphonia
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Psychiatric disorders
    Confusional state
         subjects affected / exposed
    2 / 6 (33.33%)
    1 / 3 (33.33%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
         occurrences all number
    2
    1
    1
    0
    Hallucination
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Frustration tolerance decreased
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    1
    Delirium
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    1
    1
    Anxiety
         subjects affected / exposed
    1 / 6 (16.67%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Insomnia
         subjects affected / exposed
    1 / 6 (16.67%)
    1 / 3 (33.33%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
         occurrences all number
    1
    1
    1
    0
    Investigations
    Neutrophil count decreased
         subjects affected / exposed
    1 / 6 (16.67%)
    1 / 3 (33.33%)
    2 / 3 (66.67%)
    0 / 3 (0.00%)
         occurrences all number
    2
    1
    4
    0
    Platelet count decreased
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    2 / 3 (66.67%)
    0 / 3 (0.00%)
         occurrences all number
    0
    5
    2
    0
    White blood cell count decreased
         subjects affected / exposed
    1 / 6 (16.67%)
    1 / 3 (33.33%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
         occurrences all number
    1
    1
    2
    0
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Aspartate aminotransferase increased
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Blood creatinine increased
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
         occurrences all number
    0
    4
    1
    0
    Blood alkaline phosphatase increased
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Blood bicarbonate decreased
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    1
    Blood bilirubin increased
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    2
    0
    0
    C-reactive protein increased
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Electrocardiogram QT prolonged
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Lymphocyte count decreased
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Lymphocyte count increased
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Cardiac disorders
    Sinus bradycardia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Tachycardia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Pericardial effusion
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Sinus tachycardia
         subjects affected / exposed
    2 / 6 (33.33%)
    1 / 3 (33.33%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
         occurrences all number
    2
    1
    2
    0
    Nervous system disorders
    Encephalopathy
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Headache
         subjects affected / exposed
    5 / 6 (83.33%)
    2 / 3 (66.67%)
    1 / 3 (33.33%)
    1 / 3 (33.33%)
         occurrences all number
    8
    4
    1
    2
    Dizziness
         subjects affected / exposed
    2 / 6 (33.33%)
    0 / 3 (0.00%)
    2 / 3 (66.67%)
    0 / 3 (0.00%)
         occurrences all number
    2
    0
    2
    0
    Tremor
         subjects affected / exposed
    2 / 6 (33.33%)
    0 / 3 (0.00%)
    2 / 3 (66.67%)
    0 / 3 (0.00%)
         occurrences all number
    3
    0
    2
    0
    Aphasia
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    2 / 3 (66.67%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    2
    0
    Cognitive disorder
         subjects affected / exposed
    2 / 6 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    3
    0
    0
    0
    Amnesia
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Ataxia
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Dysgeusia
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Dysgraphia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Transient ischaemic attack
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Taste disorder
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Somnolence
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Nystagmus
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Lethargy
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    2 / 6 (33.33%)
    2 / 3 (66.67%)
    1 / 3 (33.33%)
    2 / 3 (66.67%)
         occurrences all number
    3
    5
    1
    5
    Neutropenia
         subjects affected / exposed
    4 / 6 (66.67%)
    2 / 3 (66.67%)
    0 / 3 (0.00%)
    3 / 3 (100.00%)
         occurrences all number
    9
    4
    0
    7
    Leukopenia
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Thrombocytopenia
         subjects affected / exposed
    2 / 6 (33.33%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    2 / 3 (66.67%)
         occurrences all number
    2
    4
    0
    4
    Pancytopenia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Lymphadenopathy
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    1
    Eye disorders
    Dry eye
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Retinal tear
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Vitreous floaters
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    2
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    2 / 6 (33.33%)
    0 / 3 (0.00%)
    2 / 3 (66.67%)
    1 / 3 (33.33%)
         occurrences all number
    2
    0
    2
    3
    Nausea
         subjects affected / exposed
    2 / 6 (33.33%)
    1 / 3 (33.33%)
    1 / 3 (33.33%)
    1 / 3 (33.33%)
         occurrences all number
    2
    1
    1
    1
    Constipation
         subjects affected / exposed
    2 / 6 (33.33%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    2
    3
    0
    1
    Abdominal pain
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Dry mouth
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    1
    Odynophagia
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Hepatobiliary disorders
    Hepatotoxicity
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Skin and subcutaneous tissue disorders
    Rash pruritic
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Rash
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Pruritus
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Petechiae
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Night sweats
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Rash maculo-papular
         subjects affected / exposed
    2 / 6 (33.33%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    1 / 3 (33.33%)
         occurrences all number
    2
    0
    1
    1
    Erythema
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Renal and urinary disorders
    Urinary incontinence
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    1
    Pollakiuria
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Acute kidney injury
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Musculoskeletal and connective tissue disorders
    Muscular weakness
         subjects affected / exposed
    2 / 6 (33.33%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    1 / 3 (33.33%)
         occurrences all number
    2
    0
    1
    1
    Bone pain
         subjects affected / exposed
    1 / 6 (16.67%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    2
    0
    0
    Arthralgia
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Musculoskeletal pain
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Infections and infestations
    Candida infection
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Covid-19
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Cytomegalovirus viraemia
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Folliculitis
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    1
    Oral candidiasis
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Pneumonia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    1
    Pneumonia aspiration
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Rhinovirus infection
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Metabolism and nutrition disorders
    Hypocalcaemia
         subjects affected / exposed
    1 / 6 (16.67%)
    1 / 3 (33.33%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
         occurrences all number
    1
    2
    1
    0
    Hypophosphataemia
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    2 / 3 (66.67%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    3
    0
    Decreased appetite
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    1
    2
    Hyperglycaemia
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Hypokalaemia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    2 / 3 (66.67%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Hypomagnesaemia
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Hypervolaemia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Hypermagnesaemia
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Hyponatraemia
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Hypoalbuminaemia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    02 May 2019
    • Moved “Levels of anti-CD19 CAR T-cells in blood” to secondary endpoints, removing it from exploratory endpoints • Updated 'bridging therapy' text to clarify language • Added pharmacokinetics to secondary objectives and removed from exploratory objectives • Updated 'study rationale' text to clarify language • Updated the number of participating sites from “30” to “35” • Updated inclusion criteria: to expand participant population and add washout period that was not previously specified • Updated exclusion criteria: removed 'prior' in regard to no prior allo-stem cell transplant (SCT) versus no prior allo-SCT within 6 months, separated criteria into multiple criteria, included participants who may not receive KTE-X19 infusion • Added “The investigational medicinal product (KTE-X19) must be available before initiation of conditioning chemotherapy” • Added “The safety review team (SRT) safety review outcome was communicated to the active clinical study sites after the SRT safety review meeting. • Removed “during the time between the planned interim analysis and primary analysis” • Updated sample size considerations as “The primary analysis occurred when 60 participants in the modified intent to treat (mITT) set have had the opportunity to complete the month 6 disease assessment.” • Updated serious adverse event (SAE) reporting requirements as “reported in accordance with the European Union (EU) guidelines, or if applicable, per local reporting guidelines.” • Added “Post-infusion monitoring of participants must be for a minimum of 7 days unless otherwise required by country regulatory agencies.” • Added language to align with Yescarta label “Participants should be advised to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, for at least 8 weeks following KTE-X19 infusion.”
    27 May 2020
    • Title was updated to “A Phase 1 Multicenter Study Evaluating the Safety and Tolerability of KTE-X19 in Adult Subjects with Relapsed/Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma” • Updated primary, secondary, and exploratory objectives • To account for the addition of SLL, background and updated publication data were added • Updated study design based on suboptimal CAR T expansion seen in Phase 1 Cohort 1 and Cohort 2 • Added rationale for Cohorts 3 and 4 • Updated to reflect that due to the smaller enrollment of the study, limited to activated sites • Updated to reflect enrollment in Phase 1 study to assess expansion of CAR T cell. Clarification throughout protocol that participants enrolled are enrolled and dosed with KTE-X19 • Inclusion criteria updated to include SLL and classified by cohort, imaging to confirm structural defects • Removed sections: Patient Reported Outcomes, Central Review of Response, Data Safety Monitoring Board • Updated to remove Phase 2 data safety monitoring board (DSMB) review criteria as no longer applicable • Revised endpoints with removal of Phase 2: ORR remained as the secondary endpoint for Phase 1, revised secondary endpoints in response to removal of Phase 2 of study, patient reported outcomes no longer a component of the study; ORR secondary endpoint in selected Safe Dose Cohort • Removal of Phase 2 references and planned interim analysis for futility and primary analysis due to the removal of Phase 2; updated sample size considerations to reflect revised study endpoints.
    01 Sep 2021
    • Added footnote in study schema to account for rollover to the long-term follow-up study • Added “Upon completion of Cohort 4A SRT, it was determined not to enroll participants in Cohort 4B.” • Added Long-term follow-up (LTFU). After the end of KTE-C19-108, participants who received an infusion of KTE-X19 will complete the remainder of the 15-year follow-up assessments in a separate LTFU study, KT-US-982-5968 • Updated study duration 'The duration of the study for individual participants vary depending on a participant`s screening requirements, response to treatment, and survival, and if applicable, timing of transition to the separate LTFU study, KT-US-982-5968 • Updated LTFU details: All participants who received an infusion of KTE-X19 were provided the opportunity to transition to a separate LTFU study, KT-US-982-5968, where they were monitored for occurrence of late-onset targeted AEs/SAEs suspected to be possibly related to KTE-X19, presence of replication-competent retrovirus (RCR), and/or insertional mutagenesis for up to 15 years from the time of KTE-X19 infusion; In KT-US-982-5968, participants will continue assessments at timepoints contiguous with the LTFU timepoints in this study • Removed section KTE-X19 Retreatment • Updated SAEs reporting as 'Following completion of KTE-C19-108, any relevant information regarding ongoing SAEs must be submitted to Kite Pharma within 24 hours of the investigator’s knowledge of the event using the hardcopy format SAE Report Form and sent via e-mail to the SAE Reporting mailbox: safety_FC@gilead.com.'

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    18 Nov 2022
    Development program terminated.
    -

    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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