A Study to Evaluate the Safety and Efficacy of JCAR017 in... | NCT03743246

ID	Type	Description	Link
U1111-1220-3324	Registry Identifier	WHO
2018-001246-34	EudraCT Number

Label	Type	Description	Intervention Names
Administration of JCAR017	Experimental	Subjects will receive Lymphodepleting chemotherapy with intravenous (IV) fludarabine (30 mg/m2/day for 3 days) plus cyclophosphamide IV (300 mg/m2/day for 3 days) (flu/cy) concurrently, followed by JCAR017 cells infusion. Phase 1 will evaluate up to 5 JCAR017 cells dose levels and dose escalation/de-escalation will follow a modified toxicity probability interval (mTPI-2) algorithm. The declared RP2D in Phase 1 will be applied to the subjects enrolled in Phase 2	Drug: JCAR017 Drug: Lymphodepleting Drug: Fludarabine Drug: Cyclophosphamide

Name	Type	Description	Arm Group Labels	Other Names
JCAR017	Drug	JCAR017	Administration of JCAR017
Lymphodepleting

Measure	Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events up to 30 Days Post JCAR017 Infusion	An AE is defined as any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. Treatment Emergent Adverse Events (TEAEs) are defined as any AE occurring or worsening on the day of the JCAR017 infusion until 30 days post-treatment (JCAR017 infusion) using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 or greater.	From first JCAR017 infusion (Day 1) to 30 days after JCAR017 infusion
Number of Participants With Dose Limiting Toxicities	A DLT was defined as: Death not related to disease progression Grade (Gr) 4 (Life-threatening) neurotoxicity Gr 3 (Severe) neurotoxicity of greater than 7 days Gr 3 neurotoxicity does not revert to baseline within 28 days of the start date of the Grade 3 event Seizures of grade that do not resolve within 7 days Gr 4 cytokine release syndrome (CRS) that does not resolve to Grade ≤ 3 within 3 days Gr 3 CRS that does not resolve to Grade ≤ 2 within 7 days Any increase in aspartate aminotransferase (AST) or ALT > 3 × ULN and concurrent increase in total bilirubin > 2 × ULN that is unrelated to CRS and has no other probable reason to explain the combination of increases Any cardiac, dermatologic, gastrointestinal, hepatic, pulmonary, renal/genitourinary, or neurologic Gr 3 or 4 event not pre-existing or not due to the underlying malignancy Any other Gr 3 or 4 event deemed unexpected by the Investigator and considered a DLT upon evaluation by the safety review committee	From first JCAR017 infusion (Day 1) to 28 days after JCAR017 infusion
Concentration of JCAR017 in Peripheral Blood at Day 28 Post JCAR017 Infusion	Concentration of JCAR017 in Peripheral Blood was assessed by droplet digital polymerase chain reaction.	At day 28 post JCAR017 infusion

Measure	Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events up to 90 Days Post JCAR017 Infusion	An AE is defined as any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. Treatment Emergent Adverse Events (TEAEs) are defined as any AE occurring or worsening on the day of the JCAR017 infusion until 90 days post-treatment (JCAR017 infusion) using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 or greater. The following scale for grading was used - Grade 3 = Severe, Grade 4 = Life-Threatening.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Subjects must satisfy the following criteria to be enrolled in the study:

Phase 1: Subject < 18 years of age and weighs ≥ 6 kg at the time of signing the informed consent form (ICF)/informed assent form (IAF).

Phase 2: Subject ≤ 25 years of age and weighs ≥ 6 kg at the time of signing the ICF/IAF.
Subject (when applicable, parental/legal representative) must understand and voluntarily provide permission to the ICF/IAF prior to conducting any study-related assessments/procedures.
Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
Investigator considers the subject is appropriate for adoptive T cell therapy.
Evidence of CD19 expression via flow cytometry (peripheral blood or bone marrow) or immunohistochemistry (bone marrow biopsy)
Subject has a Karnofsky score of ≥ 50 (subjects ≥ 16 years of age) or a Lansky score ≥ 50 (subjects < 16 years of age).
Diagnosis of B-cell ALL or B-cell NHL as defined below:

Phase 1: Subjects with r/r B-ALL, defined as morphological evidence of disease in BM (5% or greater lymphoblast by morphology) and either of the following:
- First or greater marrow relapse, or
- Any marrow relapse after allogeneic HSCT, or
- Primary refractory defined as not achieving a CR or a CRi after 2 or more separate induction regimens (or chemo-refractory as not achieving CR/CRi after 1 cycle of standard chemotherapy for relapsed leukemia), or
- Ineligible for allogeneic HSCT Note: Subjects will be included regardless of MRD status.
Phase 2: Subjects with one of the following:
- Cohort 1: r/r B-ALL, defined as morphological evidence of disease in BM (5% or greater lymphoblast by morphology) and either:
  - First or greater marrow relapse, or
  - Any marrow relapse after allogeneic HSCT, or
  - Primary refractory defined as not achieving a CR or a CRi after 2 or more separate induction regimens (or chemo-refractory as not achieving CR/CRi after 1 cycle of standard chemotherapy for relapsed leukemia), or
  - Ineligible for allogeneic HSCT.
- Cohort 2: MRD+ B-ALL, defined as:
  - < 5% lymphoblasts by morphology with,
  - MRD detected by a validated assay at a frequency of 1 x10-4 or greater in BM cells. Subjects eligible for enrollment in Cohort 2 are those with MRD positive morphologic CR2 after re-induction when these subjects had previously experienced an early relapse (< 36 months) after first-line chemotherapy. Subjects who are in MRD+ morphologic CR3 and later, regardless of time to relapse in earlier lines, are also eligible. Subjects who are in morphologic relapse at screening (r/r B-ALL) and become MRD+ after bridging chemotherapy are also eligible for treatment in Cohort 2.
- Cohort 3: r/r B-NHL (DLBCL, BL or PMBCL), defined as measurable disease after 1 or more lines of chemotherapy and/or having failed HSCT or being ineligible for HSCT.
Note: B-NHL subjects with secondary CNS lymphoma involvement are eligible however subject selection must consider clinical risk factors for severe neurological AEs and alternative treatment options. Subjects should only be enrolled if the Investigator considers the potential benefit outweighs the risk for the subject.
Subjects with Philadelphia chromosome positive ALL are eligible if they are intolerant to or have failed one or more lines of tyrosine-kinase inhibitor (TKI) therapy or if TKI therapy is contraindicated.
Adequate organ function, defined as:
- Adequate BM function to receive LD chemotherapy as assessed by the Investigator.
- Subject with adequate renal function, which is defined as:
Serum creatinine based on age/gender as described below. Subjects that do not meet the criteria but who have a creatinine clearance or radioisotope glomerular filtration rate (GFR) > 70 mL/min/1.73 m2 are eligible.• Alanine aminotransferase (ALT) ≤ 5 x upper limit of normal (ULN) and total bilirubin < 2.0 mg/dL (or < 3.0 mg/dL for subjects with Gilbert's syndrome or leukemic/lymphomatous infiltration of the liver).
- Adequate pulmonary function, defined as ≤ Grade 1 dyspnea according to Common Toxicity Criteria for Adverse Events (CTCAE) and oxygen saturation (SaO2) ≥ 92% on room air.
- Adequate cardiac function, defined as left ventricular ejection fraction (LVEF) ≥ 40% as assessed by echocardiogram (ECHO) or multi-gated acquisition scan (MUGA) within 4 weeks prior to leukapheresis.
Adequate vascular access for leukapheresis procedure.
Participants must agree to use effective contraception

Exclusion Criteria:

The presence of any of the following will exclude a subject from enrollment:

Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
Subject has any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
Subject has any condition that confounds the ability to interpret data from the study.
Subject with a history of another primary malignancy that has not been in remission for at least 2 years prior to enrollment.
Subjects who have received previous CD19-targeted therapy must have CD19-positive disease confirmed since completing the prior CD19-targeted therapy.
Prior CAR T cell or other genetically-modified T cell therapy.
Subject with a previous history of or active hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection.
Subjects with uncontrolled systemic fungal, bacterial, viral or other infection (including tuberculosis) despite appropriate antibiotics or other treatment at the time of leukapheresis or JCAR017 infusion.
Subject has presence of acute or chronic graft-versus-host disease (GVHD).
Subject with active autoimmune disease requiring immunosuppressive therapy.
Subject has cardiac disorders (CTCAE version 4.03 Grade 3 or 4) within the past 6 months.
Subject with a concomitant genetic syndrome, with the exception of Down's syndrome.
Subject with active CNS disease and significant neurological deterioration. Subjects with CNS-2 or CNS-3 involvement are eligible provided they are asymptomatic and do not have significant neurological deterioration and, in the opinion of the study investigator, the CNS disease burden can be controlled until JCAR017 infusion.
Subject with a history or presence of clinically relevant CNS pathology such as epilepsy, seizure, paresis, aphasia, stroke, cerebral edema, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis.
Subject is pregnant or nursing.
Subject has used the following:
- Therapeutic doses of corticosteroids (defined as > 0.4 mg/kg maximum 20 mg/day prednisone or equivalent) within 7 days prior to leukapheresis or 72 hours prior to JCAR017 infusion. Physiologic replacement, topical, and inhaled steroids are permitted.
- Low-dose chemotherapy (eg, vincristine, rituximab, cyclophosphamide ≤ 300 mg/m2) given after leukapheresis to maintain disease control must be stopped ≥ 7 days prior to LD chemotherapy.
- Cytotoxic chemotherapeutic agents that are not considered lymphotoxic within 1 week prior to leukapheresis. Oral anticancer agents are allowed if at least 3 half-lives have elapsed prior to leukapheresis.
- Lymphotoxic chemotherapeutic agents (eg, cyclophosphamide, ifosfamide, bendamustine) within 2 weeks prior to leukapheresis.
- Experimental agents within 4 weeks prior to leukapheresis unless no response or PD is documented on the experimental therapy and at least 3 half-lives have elapsed prior to leukapheresis.
- Immunosuppressive therapies within 4 weeks prior to leukapheresis and JCAR017 infusion (eg, calcineurin inhibitors, methotrexate or other chemotherapeutics, mycophenolate, rapamycin, thalidomide, immunosuppressive antibodies such as antitumor necrosis factor [TNF], anti-IL-6, or anti-IL-6R).
- Donor lymphocyte infusions (DLI) within 6 weeks prior to JCAR017 infusion.
- Radiation within 6 weeks prior to leukapheresis. Subjects must have PD in irradiated lesions or have additional non-irradiated lesions to be eligible. Radiation to a single lesion, if additional non-irradiated, measurable lesions are present, is allowed up to 2 weeks prior to leukapheresis.
- Allogeneic HSCT within 90 days prior to leukapheresis.
Tumor invasion of venous or arterial vessels (B-NHL subjects only).
Deep Venous Thrombosis (DVT) or Pulmonary Embolism (PE) within 3 months prior to leukapheresis. Subjects with DVT or PE that occurred longer than 3 months prior to leukapheresis, who still require ongoing therapeutic levels of anti-coagulation therapy, are also excluded.
Existence of CD19-negative clone(s) of leukemia cells

Name	Affiliation	Role
Bristol-Myers Squibb	Bristol-Myers Squibb	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Local Institution - 163		Duarte	California	91010	United States
Local Institution - 167

Label	URL
BMS Clinical Trial Information	View source
BMS Clinical Trial Patient Recruiting	View source

ID	Title	Description
FG000	0.05 x 10^6 CAR+ T Cells/kg	Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.05 x 10^6 CAR+ T cells per kilogram (kg) post leukapheresis.
FG001	0.15 x 10^6 CAR+ T Cells/kg

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Sep 10, 2019

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Participants With Treatment Emergent Adverse Events up to 30 Days Post JCAR017 Infusion

An AE is defined as any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. Treatment Emergent Adverse Events (TEAEs) are defined as any AE occurring or worsening on the day of the JCAR017 infusion until 30 days post-treatment (JCAR017 infusion) using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 or greater.

Safety Analysis Set included all participants who received conforming JCAR017 infusion with baseline and post-baseline measurements.

Posted

Count of Participants

Participants

From first JCAR017 infusion (Day 1) to 30 days after JCAR017 infusion

ID	Title	Description
OG000	0.05 x 10^6 CAR+ T Cells/kg	Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.05 x 10^6 CAR+ T cells per kilogram (kg) post leukapheresis.
OG001	0.15 x 10^6 CAR+ T Cells/kg	Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.15 x 106 CAR+ T cells/kg post leukapheresis.
OG002	0.50 x 106 CAR+T Cells/kg	Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.50 x 106 CAR+T cells/kg post leukapheresis.

Units	Counts
Participants	OG0007 OG0016 OG0021

Title

Denominators

Categories

Title	Measurements
	OG0007 OG0016 OG0021

Primary

Number of Participants With Dose Limiting Toxicities

A DLT was defined as:

Death not related to disease progression
Grade (Gr) 4 (Life-threatening) neurotoxicity
Gr 3 (Severe) neurotoxicity of greater than 7 days
Gr 3 neurotoxicity does not revert to baseline within 28 days of the start date of the Grade 3 event
Seizures of grade that do not resolve within 7 days
Gr 4 cytokine release syndrome (CRS) that does not resolve to Grade ≤ 3 within 3 days
Gr 3 CRS that does not resolve to Grade ≤ 2 within 7 days
Any increase in aspartate aminotransferase (AST) or ALT > 3 × ULN and concurrent increase in total bilirubin > 2 × ULN that is unrelated to CRS and has no other probable reason to explain the combination of increases
Any cardiac, dermatologic, gastrointestinal, hepatic, pulmonary, renal/genitourinary, or neurologic Gr 3 or 4 event not pre-existing or not due to the underlying malignancy
Any other Gr 3 or 4 event deemed unexpected by the Investigator and considered a DLT upon evaluation by the safety review committee

Dose-Limiting Toxicity Analysis Set included all participants who received conforming JCAR017 infusion and completed 28 days post JCAR017 infusion.

Posted

Count of Participants

Participants

From first JCAR017 infusion (Day 1) to 28 days after JCAR017 infusion

ID	Title	Description
OG000	0.05 x 10^6 CAR+ T Cells/kg	Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.05 x 10^6 CAR+ T cells per kilogram (kg) post leukapheresis.
OG001	0.15 x 10^6 CAR+ T Cells/kg

Primary

Concentration of JCAR017 in Peripheral Blood at Day 28 Post JCAR017 Infusion

Concentration of JCAR017 in Peripheral Blood was assessed by droplet digital polymerase chain reaction.

The PK Analysis Set include all participants who received JCAR017 infusion and have at least one measurable JCAR017 concentration. Participants available at specific timepoints have been analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

copies per microgram

At day 28 post JCAR017 infusion

ID	Title	Description
OG000	0.05 x 10^6 CAR+ T Cells/kg	Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.05 x 10^6 CAR+ T cells per kilogram (kg) post leukapheresis.
OG001	0.15 x 10^6 CAR+ T Cells/kg	Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.15 x 106 CAR+ T cells/kg post leukapheresis.
OG002	0.50 x 106 CAR+T Cells/kg	Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.50 x 106 CAR+T cells/kg post leukapheresis.

Secondary

Number of Participants With Treatment-Emergent Adverse Events up to 90 Days Post JCAR017 Infusion

An AE is defined as any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. Treatment Emergent Adverse Events (TEAEs) are defined as any AE occurring or worsening on the day of the JCAR017 infusion until 90 days post-treatment (JCAR017 infusion) using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 or greater. The following scale for grading was used - Grade 3 = Severe, Grade 4 = Life-Threatening.

Safety Analysis Set included all participants who received conforming JCAR017 infusion with baseline and post-baseline measurements.

Posted

Count of Participants

Participants

From first JCAR017 infusion (Day 1) to 90 days after JCAR017 infusion

ID	Title	Description
OG000	0.05 x 10^6 CAR+ T Cells/kg	Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.05 x 10^6 CAR+ T cells per kilogram (kg) post leukapheresis.
OG001	0.15 x 10^6 CAR+ T Cells/kg	Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.15 x 106 CAR+ T cells/kg post leukapheresis.
OG002

Secondary

Number of Participants With Serious Treatment-Emergent Adverse Events up to 90 Days Post JCAR017 Infusion

Serious adverse events (SAE) are defined as any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/ birth defect; constitutes an important medical event. Treatment Emergent Adverse Events (TEAEs) are defined as any AE occurring or worsening on the day of the JCAR017 infusion until 90 days post-treatment (JCAR017 infusion) using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 or greater.

Safety Analysis Set included all participants who received conforming JCAR017 infusion with baseline and post-baseline measurements.

Posted

Count of Participants

Participants

From first JCAR017 infusion (Day 1) to 90 days after JCAR017 infusion

ID	Title	Description
OG000	0.05 x 10^6 CAR+ T Cells/kg	Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.05 x 10^6 CAR+ T cells per kilogram (kg) post leukapheresis.
OG001	0.15 x 10^6 CAR+ T Cells/kg	Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.15 x 106 CAR+ T cells/kg post leukapheresis.

Secondary

Change From Baseline at Day 28 in Hematology Laboratory Parameters- Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets

Baseline is defined as the last assessment with non-missing value on or prior to the first date of the lymphodepletion chemotherapy.

Safety Analysis Set included all participants who received conforming JCAR017 infusion with baseline and post-baseline measurements. Participants available at specific timepoints have been analyzed.

Posted

Mean

Standard Deviation

10^9 cells/L

Baseline and at Day 28

ID	Title	Description
OG000	0.05 x 10^6 CAR+ T Cells/kg	Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.05 x 10^6 CAR+ T cells per kilogram (kg) post leukapheresis.
OG001	0.15 x 10^6 CAR+ T Cells/kg	Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.15 x 106 CAR+ T cells/kg post leukapheresis.
OG002	0.50 x 106 CAR+T Cells/kg	Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.50 x 106 CAR+T cells/kg post leukapheresis.

Secondary

Change From Baseline at Day 28 in Hematology Laboratory Parameters- Basophils/Leukocytes; Eosinophils/Leukocytes; Lymphocytes/Leukocytes; Neutrophils/Leukocytes; Monocytes/Leukocytes

Baseline is defined as the last assessment with non-missing value on or prior to the first date of the lymphodepletion chemotherapy.

Safety Analysis Set included all participants who received conforming JCAR017 infusion with baseline and post-baseline measurements. Participants available at specific timepoints have been analyzed.

Posted

Mean

Standard Deviation

Ratio

Baseline and at Day 28

ID	Title	Description
OG000	0.05 x 10^6 CAR+ T Cells/kg	Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.05 x 10^6 CAR+ T cells per kilogram (kg) post leukapheresis.
OG001	0.15 x 10^6 CAR+ T Cells/kg	Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.15 x 106 CAR+ T cells/kg post leukapheresis.
OG002	0.50 x 106 CAR+T Cells/kg	Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.50 x 106 CAR+T cells/kg post leukapheresis.

Secondary

Change From Baseline at Day 28 in Hematology Laboratory Parameters- Erythrocytes

Baseline is defined as the last assessment with non-missing value on or prior to the first date of the lymphodepletion chemotherapy.

Safety Analysis Set included all participants who received conforming JCAR017 infusion with baseline and post-baseline measurements. Participants available at specific timepoints have been analyzed.

Posted

Mean

Standard Deviation

10^12 cells/L

Baseline and at Day 28

ID	Title	Description
OG000	0.05 x 10^6 CAR+ T Cells/kg	Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.05 x 10^6 CAR+ T cells per kilogram (kg) post leukapheresis.
OG001	0.15 x 10^6 CAR+ T Cells/kg	Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.15 x 106 CAR+ T cells/kg post leukapheresis.
OG002	0.50 x 106 CAR+T Cells/kg	Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.50 x 106 CAR+T cells/kg post leukapheresis.

Secondary

Change From Baseline at Day 28 in Hematology Laboratory Parameters- Hematocrit

Baseline is defined as the last assessment with non-missing value on or prior to the first date of the lymphodepletion chemotherapy.

Safety Analysis Set included all participants who received conforming JCAR017 infusion with baseline and post-baseline measurements. Participants available at specific timepoints have been analyzed.

Posted

Mean

Standard Deviation

proportion of red blood cells in blood

Baseline and at Day 28

ID	Title	Description
OG000	0.05 x 10^6 CAR+ T Cells/kg	Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.05 x 10^6 CAR+ T cells per kilogram (kg) post leukapheresis.
OG001	0.15 x 10^6 CAR+ T Cells/kg	Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.15 x 106 CAR+ T cells/kg post leukapheresis.
OG002	0.50 x 106 CAR+T Cells/kg	Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.50 x 106 CAR+T cells/kg post leukapheresis.

Secondary

Change From Baseline at Day 28 in Hematology Laboratory Parameters- Hemoglobin

Baseline is defined as the last assessment with non-missing value on or prior to the first date of the lymphodepletion chemotherapy.

Safety Analysis Set included all participants who received conforming JCAR017 infusion with baseline and post-baseline measurements. Participants available at specific timepoints have been analyzed.

Posted

Mean

Standard Deviation

grams per liter

Baseline and at Day 28

ID	Title	Description
OG000	0.05 x 10^6 CAR+ T Cells/kg	Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.05 x 10^6 CAR+ T cells per kilogram (kg) post leukapheresis.
OG001	0.15 x 10^6 CAR+ T Cells/kg	Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.15 x 106 CAR+ T cells/kg post leukapheresis.
OG002	0.50 x 106 CAR+T Cells/kg	Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.50 x 106 CAR+T cells/kg post leukapheresis.

Secondary

Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Alanine Aminotransferase; Alkaline Phosphatase; Aspartate Aminotransferase; Lactate Dehydrogenase

Baseline is defined as the last assessment with non-missing value on or prior to the first date of the lymphodepletion chemotherapy.

Safety Analysis Set included all participants who received conforming JCAR017 infusion with baseline and post-baseline measurements. Participants available at specific timepoints have been analyzed.

Posted

Mean

Standard Deviation

units per liter

Baseline and at Day 28

ID	Title	Description
OG000	0.05 x 10^6 CAR+ T Cells/kg	Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.05 x 10^6 CAR+ T cells per kilogram (kg) post leukapheresis.
OG001	0.15 x 10^6 CAR+ T Cells/kg	Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.15 x 106 CAR+ T cells/kg post leukapheresis.
OG002	0.50 x 106 CAR+T Cells/kg	Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.50 x 106 CAR+T cells/kg post leukapheresis.

Secondary

Change From Baseline at Day 28 in Laboratory Parameters- Albumin; Protein

Baseline is defined as the last assessment with non-missing value on or prior to the first date of the lymphodepletion chemotherapy.

Safety Analysis Set included all participants who received conforming JCAR017 infusion with baseline and post-baseline measurements. Participants available at specific timepoints have been analyzed.

Posted

Mean

Standard Deviation

grams per liter

Baseline and at Day 28

ID	Title	Description
OG000	0.05 x 10^6 CAR+ T Cells/kg	Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.05 x 10^6 CAR+ T cells per kilogram (kg) post leukapheresis.
OG001	0.15 x 10^6 CAR+ T Cells/kg	Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.15 x 106 CAR+ T cells/kg post leukapheresis.
OG002	0.50 x 106 CAR+T Cells/kg	Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.50 x 106 CAR+T cells/kg post leukapheresis.

Secondary

Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Bicarbonate; Blood Urea Nitrogen; Calcium; Chloride; Glucose; Magnesium; Phosphate; Potassium; Sodium, Triglyceride

Baseline is defined as the last assessment with non-missing value on or prior to the first date of the lymphodepletion chemotherapy.

Safety Analysis Set included all participants who received conforming JCAR017 infusion with baseline and post-baseline measurements. Participants available at specific timepoints have been analyzed.

Posted

Mean

Standard Deviation

mmol/L

Baseline and at Day 28

ID	Title	Description
OG000	0.05 x 10^6 CAR+ T Cells/kg	Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.05 x 10^6 CAR+ T cells per kilogram (kg) post leukapheresis.
OG001	0.15 x 10^6 CAR+ T Cells/kg	Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.15 x 106 CAR+ T cells/kg post leukapheresis.
OG002	0.50 x 106 CAR+T Cells/kg	Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.50 x 106 CAR+T cells/kg post leukapheresis.

Secondary

Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Bilirubin; Creatinine; Direct Bilirubin; Urate

Baseline is defined as the last assessment with non-missing value on or prior to the first date of the lymphodepletion chemotherapy.

Safety Analysis Set included all participants who received conforming JCAR017 infusion with baseline and post-baseline measurements. Participants available at specific timepoints have been analyzed.

Posted

Mean

Standard Error

umol/L

Baseline and at Day 28

ID	Title	Description
OG000	0.05 x 10^6 CAR+ T Cells/kg	Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.05 x 10^6 CAR+ T cells per kilogram (kg) post leukapheresis.
OG001	0.15 x 10^6 CAR+ T Cells/kg	Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.15 x 106 CAR+ T cells/kg post leukapheresis.
OG002	0.50 x 106 CAR+T Cells/kg	Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.50 x 106 CAR+T cells/kg post leukapheresis.

Secondary

Number of Participants With Manufacturing Success of JCAR017 Product

Successful product was defined as JCAR017 product was generated and able to be QC released (including nonconforming product) for infusion. Unsuccessful product is defined as no JCAR017 product could be generated after two manufacturing attempts using a single apheresis product for starting material or product was unable to be QC released for infusion.

Pre-Treatment Set included all participants who have screened successfully into the study and underwent leukapheresis.

Posted

Count of Participants

Participants

From screening to JCAR017 infusion (day -35 to day 1)

ID	Title	Description
OG000	0.05 x 10^6 CAR+ T Cells/kg	Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.05 x 10^6 CAR+ T cells per kilogram (kg) post leukapheresis.
OG001	0.15 x 10^6 CAR+ T Cells/kg	Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.15 x 106 CAR+ T cells/kg post leukapheresis.
OG002	0.50 x 106 CAR+T Cells/kg	Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.50 x 106 CAR+T cells/kg post leukapheresis.

Secondary

Overall Response Rate (ORR)

ORR is defined as the percentage of participants who achieved either a complete response (CR) or complete response with incomplete blood recovery (CRi) on Day 28 that is confirmed on Day 56. Response assessment was performed according to the 2019 Comprehensive Cancer Network (NCCN) response criteria guidelines for pediatric acute lymphoblastic leukemia (ALL). CR is defined as absence of circulating blasts, extramedullary disease, lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement, Trilineage hematopoiesis (TLH) and < 5%, Absolute neutrophil count (ANC) > 1000 per microliter, Platelets > 100,000 per microliter and no recurrence for 4 weeks. CRi is defined as meeting all criteria for CR except platelets < 100,000/μL or ANC is < 1000/μL.

Efficacy Analysis Set included all participants who fulfilled all study eligibility criteria, received conforming JCAR017 infusion, who did not demonstrate morphological remission at screening and who are not MRD negative upon restaging prior to initiation of lymphodepleting (LD) chemotherapy.

Posted

Number

95% Confidence Interval

percentage of participants

Up to Day 56

ID	Title	Description
OG000	0.05 x 10^6 CAR+ T Cells/kg	Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.05 x 10^6 CAR+ T cells per kilogram (kg) post leukapheresis.
OG001	0.15 x 10^6 CAR+ T Cells/kg

Secondary

Duration of Response (DOR)

DOR is defined as time from first response (either CR or CRi) until progressive disease (PD), disease relapse, or death from any cause, whichever occurs first. Response assessment was performed according to the 2019 Comprehensive Cancer Network (NCCN) response criteria guidelines for pediatric ALL. CR is defined as absence of circulating blasts, extramedullary disease, lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement, Trilineage hematopoiesis (TLH) and < 5%, Absolute neutrophil count (ANC) > 1000 per microliter, Platelets > 100,000 per microliter and no recurrence for 4 weeks. CRi is defined as meeting all criteria for CR except platelets < 100,000/μL or ANC is < 1000/μL. Disease progression is defined as increase of at least 25% in the absolute number of circulating or bone marrow blasts or development of extramedullary disease.

Posted

Median

Full Range

months

From first response (either CR or CRi) until progressive disease (PD), disease relapse, or death from any cause, whichever occurs first (Up to approximately 14 months)

ID	Title	Description
OG000	0.05 x 10^6 CAR+ T Cells/kg	Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.05 x 10^6 CAR+ T cells per kilogram (kg) post leukapheresis.

Secondary

Relapse Free Survival (RFS)

RFS is defined as time from conforming JCAR017 infusion to the first progressive disease (PD), relapsed disease or death from any cause, whichever occurs first. Disease progression is defined as increase of at least 25% in the absolute number of circulating or bone marrow blasts or development of extramedullary disease. Relapsed disease is defined as Reappearance of blasts in the blood or bone marrow (> 5%) or > 1% with previous/supportive molecular findings or in any extramedullary site after a CR. CR is defined as absence of circulating blasts, extramedullary disease, lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement, Trilineage hematopoiesis (TLH) and < 5%, Absolute neutrophil count (ANC) > 1000 per microliter, Platelets > 100,000 per microliter and no recurrence for 4 weeks.

Posted

Median

Full Range

months

Up to approximately 15 months

ID	Title	Description
OG000	0.05 x 10^6 CAR+ T Cells/kg	Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.05 x 10^6 CAR+ T cells per kilogram (kg) post leukapheresis.
OG001	0.15 x 10^6 CAR+ T Cells/kg

Secondary

Event Free Survival (EFS)

EFS is defined as time from conforming JCAR017 infusion to progressive disease (PD), relapsed disease, start of a new anticancer therapy including HSCT or death from any cause, whichever occurs first. Disease progression is defined as increase of at least 25% in the absolute number of circulating or bone marrow blasts or development of extramedullary disease. Relapsed disease is defined as Reappearance of blasts in the blood or bone marrow (> 5%) or > 1% with previous/supportive molecular findings or in any extramedullary site after a CR. CR is defined as absence of circulating blasts, extramedullary disease, lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement, Trilineage hematopoiesis (TLH) and < 5%, Absolute neutrophil count (ANC) > 1000 per microliter, Platelets > 100,000 per microliter and no recurrence for 4 weeks. Only responders are included in he analysis. Censored participants were also analyzed.

Posted

Median

Full Range

months

From conforming JCAR017 infusion to PD, relapsed disease, start of a new anticancer therapy including Hematopoietic Stem Cell Transplant (HSCT) or death from any cause, whichever occurs first (Up to approximately 15 months)

ID	Title	Description
OG000	0.05 x 10^6 CAR+ T Cells/kg	Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.05 x 10^6 CAR+ T cells per kilogram (kg) post leukapheresis.

Secondary

Overall Survival (OS)

OS is defined as the interval from the date of first confirming JCAR017 infusion to the date of death due to any reason.

Posted

Median

95% Confidence Interval

months

From the date of first confirming JCAR017 infusion to the date of death due to any reason (Up to approximately 24 months)

ID	Title	Description
OG000	0.05 x 10^6 CAR+ T Cells/kg	Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.05 x 10^6 CAR+ T cells per kilogram (kg) post leukapheresis.
OG001	0.15 x 10^6 CAR+ T Cells/kg	Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.15 x 106 CAR+ T cells/kg post leukapheresis.
OG002	0.50 x 106 CAR+T Cells/kg	Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.50 x 106 CAR+T cells/kg post leukapheresis.

Secondary

Minimal Residual Response (MRD) Negative Response Rate

Minimal Residual Disease (MRD) Negative Response Rate is defined as the percentage of participants achieving either a CR or CRi with a MRD negative bone marrow on Day 28, confirmed on Day 56. CR is defined as absence of circulating blasts, extramedullary disease, lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement, Trilineage hematopoiesis (TLH) and < 5%, Absolute neutrophil count (ANC) > 1000 per microliter, Platelets > 100,000 per microliter and no recurrence for 4 weeks. CRi is defined as meeting all criteria for CR except platelets < 100,000/μL or ANC is < 1000/μL. Disease progression is defined as increase of at least 25% in the absolute number of circulating or bone marrow blasts or development of extramedullary disease. Disease assessments recorded on or after start of a new anticancer therapy, including HSCT, will not be considered, nor will disease assessments reported after a PD or relapse has been observed.

Posted

Number

95% Confidence Interval

percentage of participants

Up to Day 56

ID	Title	Description
OG000	0.05 x 10^6 CAR+ T Cells/kg	Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.05 x 10^6 CAR+ T cells per kilogram (kg) post leukapheresis.

Secondary

Number of Participants Who Achieved a Response After JCAR017 Infusion and Then Proceeded to Hematopoietic Stem Cell Transplant

Number of participants who undergo HSCT after receiving a JCAR017 infusion and achieving a response are presented. The time of proceeding to HSCT is defined as the time of commencing the conditioning regimen as required for HSCT. CR is defined as absence of circulating blasts, extramedullary disease, lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement, Trilineage hematopoiesis (TLH) and < 5%, Absolute neutrophil count (ANC) > 1000 per microliter, Platelets > 100,000 per microliter and no recurrence for 4 weeks. CRi is defined as meeting all criteria for CR except platelets < 100,000/μL or ANC is < 1000/μL. Disease progression is defined as increase of at least 25% in the absolute number of circulating or bone marrow blasts or development of extramedullary disease.

Safety Analysis Set included all participants who received conforming JCAR017 infusion with baseline and post-baseline measurements.

Posted

Count of Participants

Participants

Up to approximately 24 months

ID	Title	Description
OG000	0.05 x 10^6 CAR+ T Cells/kg	Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.05 x 10^6 CAR+ T cells per kilogram (kg) post leukapheresis.
OG001	0.15 x 10^6 CAR+ T Cells/kg	Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.15 x 106 CAR+ T cells/kg post leukapheresis.

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	26.0	Systematic Assessment	EG0005 affected7 at risk EG0015 affected6 at risk EG0021 affected1 at risk EG0030 at risk
Coagulopathy	Blood and lymphatic system disorders	26.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected6 at risk EG0021 affected1 at risk EG003
Febrile neutropenia	Blood and lymphatic system disorders	26.0	Systematic Assessment	EG0001 affected7 at risk EG0010 affected6 at risk EG0020 affected1 at risk EG003
Leukopenia	Blood and lymphatic system disorders	26.0	Systematic Assessment	EG0004 affected7 at risk EG0011 affected6 at risk EG0021 affected1 at risk EG003
Neutropenia	Blood and lymphatic system disorders	26.0	Systematic Assessment	EG0003 affected7 at risk EG0012 affected6 at risk EG0021 affected1 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	26.0	Systematic Assessment	EG0004 affected7 at risk EG0013 affected6 at risk EG0021 affected1 at risk EG003
Bradycardia	Cardiac disorders	26.0	Systematic Assessment	EG0000 affected7 at risk EG0011 affected6 at risk EG0021 affected1 at risk EG003
Tachycardia	Cardiac disorders	26.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected6 at risk EG0021 affected1 at risk EG003
Ear pain	Ear and labyrinth disorders	26.0	Systematic Assessment	EG0001 affected7 at risk EG0010 affected6 at risk EG0020 affected1 at risk EG003
Abdominal pain	Gastrointestinal disorders	26.0	Systematic Assessment	EG0001 affected7 at risk EG0011 affected6 at risk EG0020 affected1 at risk EG003
Anaesthesia oral	Gastrointestinal disorders	26.0	Systematic Assessment	EG0000 affected7 at risk EG0011 affected6 at risk EG0020 affected1 at risk EG003
Anal fissure	Gastrointestinal disorders	26.0	Systematic Assessment	EG0001 affected7 at risk EG0011 affected6 at risk EG0020 affected1 at risk EG003
Colitis	Gastrointestinal disorders	26.0	Systematic Assessment	EG0001 affected7 at risk EG0010 affected6 at risk EG0020 affected1 at risk EG003
Constipation	Gastrointestinal disorders	26.0	Systematic Assessment	EG0000 affected7 at risk EG0011 affected6 at risk EG0020 affected1 at risk EG003
Diarrhoea	Gastrointestinal disorders	26.0	Systematic Assessment	EG0000 affected7 at risk EG0011 affected6 at risk EG0021 affected1 at risk EG003
Intestinal haemorrhage	Gastrointestinal disorders	26.0	Systematic Assessment	EG0001 affected7 at risk EG0010 affected6 at risk EG0020 affected1 at risk EG003
Lip dry	Gastrointestinal disorders	26.0	Systematic Assessment	EG0000 affected7 at risk EG0011 affected6 at risk EG0020 affected1 at risk EG003
Nausea	Gastrointestinal disorders	26.0	Systematic Assessment	EG0002 affected7 at risk EG0011 affected6 at risk EG0020 affected1 at risk EG003
Oral mucosal erythema	Gastrointestinal disorders	26.0	Systematic Assessment	EG0000 affected7 at risk EG0011 affected6 at risk EG0020 affected1 at risk EG003
Vomiting	Gastrointestinal disorders	26.0	Systematic Assessment	EG0001 affected7 at risk EG0013 affected6 at risk EG0020 affected1 at risk EG003
Pyrexia	General disorders	26.0	Systematic Assessment	EG0001 affected7 at risk EG0010 affected6 at risk EG0020 affected1 at risk EG003
Cholecystitis	Hepatobiliary disorders	26.0	Systematic Assessment	EG0001 affected7 at risk EG0010 affected6 at risk EG0020 affected1 at risk EG003
Hyperbilirubinaemia	Hepatobiliary disorders	26.0	Systematic Assessment	EG0001 affected7 at risk EG0010 affected6 at risk EG0020 affected1 at risk EG003
Cytokine release syndrome	Immune system disorders	26.0	Systematic Assessment	EG0004 affected7 at risk EG0011 affected6 at risk EG0021 affected1 at risk EG003
Haemophagocytic lymphohistiocytosis	Immune system disorders	26.0	Systematic Assessment	EG0000 affected7 at risk EG0011 affected6 at risk EG0020 affected1 at risk EG003
Hypogammaglobulinaemia	Immune system disorders	26.0	Systematic Assessment	EG0001 affected7 at risk EG0011 affected6 at risk EG0021 affected1 at risk EG003
Bacteraemia	Infections and infestations	26.0	Systematic Assessment	EG0001 affected7 at risk EG0011 affected6 at risk EG0020 affected1 at risk EG003
Clostridium difficile infection	Infections and infestations	26.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected6 at risk EG0021 affected1 at risk EG003
Cytomegalovirus infection	Infections and infestations	26.0	Systematic Assessment	EG0001 affected7 at risk EG0010 affected6 at risk EG0020 affected1 at risk EG003
Paronychia	Infections and infestations	26.0	Systematic Assessment	EG0001 affected7 at risk EG0010 affected6 at risk EG0020 affected1 at risk EG003
Pneumonia fungal	Infections and infestations	26.0	Systematic Assessment	EG0001 affected7 at risk EG0010 affected6 at risk EG0020 affected1 at risk EG003
Staphylococcal bacteraemia	Infections and infestations	26.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected6 at risk EG0021 affected1 at risk EG003
Upper respiratory tract infection	Infections and infestations	26.0	Systematic Assessment	EG0001 affected7 at risk EG0010 affected6 at risk EG0020 affected1 at risk EG003
Refractoriness to platelet transfusion	Injury, poisoning and procedural complications	26.0	Systematic Assessment	EG0000 affected7 at risk EG0011 affected6 at risk EG0020 affected1 at risk EG003
Alanine aminotransferase increased	Investigations	26.0	Systematic Assessment	EG0004 affected7 at risk EG0010 affected6 at risk EG0021 affected1 at risk EG003
Aspartate aminotransferase increased	Investigations	26.0	Systematic Assessment	EG0004 affected7 at risk EG0010 affected6 at risk EG0020 affected1 at risk EG003
Bilirubin conjugated increased	Investigations	26.0	Systematic Assessment	EG0001 affected7 at risk EG0010 affected6 at risk EG0020 affected1 at risk EG003
Blood bilirubin increased	Investigations	26.0	Systematic Assessment	EG0001 affected7 at risk EG0010 affected6 at risk EG0020 affected1 at risk EG003
Blood creatinine increased	Investigations	26.0	Systematic Assessment	EG0001 affected7 at risk EG0010 affected6 at risk EG0020 affected1 at risk EG003
Blood fibrinogen decreased	Investigations	26.0	Systematic Assessment	EG0001 affected7 at risk EG0010 affected6 at risk EG0020 affected1 at risk EG003
Blood triglycerides increased	Investigations	26.0	Systematic Assessment	EG0001 affected7 at risk EG0010 affected6 at risk EG0020 affected1 at risk EG003
Blood uric acid increased	Investigations	26.0	Systematic Assessment	EG0001 affected7 at risk EG0010 affected6 at risk EG0020 affected1 at risk EG003
Gamma-glutamyltransferase increased	Investigations	26.0	Systematic Assessment	EG0004 affected7 at risk EG0010 affected6 at risk EG0020 affected1 at risk EG003
Interleukin level increased	Investigations	26.0	Systematic Assessment	EG0000 affected7 at risk EG0011 affected6 at risk EG0020 affected1 at risk EG003
International normalised ratio increased	Investigations	26.0	Systematic Assessment	EG0001 affected7 at risk EG0010 affected6 at risk EG0020 affected1 at risk EG003
Oxygen saturation decreased	Investigations	26.0	Systematic Assessment	EG0000 affected7 at risk EG0012 affected6 at risk EG0020 affected1 at risk EG003
Serum ferritin increased	Investigations	26.0	Systematic Assessment	EG0000 affected7 at risk EG0011 affected6 at risk EG0020 affected1 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	26.0	Systematic Assessment	EG0001 affected7 at risk EG0011 affected6 at risk EG0020 affected1 at risk EG003
Fluid retention	Metabolism and nutrition disorders	26.0	Systematic Assessment	EG0001 affected7 at risk EG0010 affected6 at risk EG0020 affected1 at risk EG003
Hyperamylasaemia	Metabolism and nutrition disorders	26.0	Systematic Assessment	EG0001 affected7 at risk EG0010 affected6 at risk EG0020 affected1 at risk EG003
Hyperlipidaemia	Metabolism and nutrition disorders	26.0	Systematic Assessment	EG0001 affected7 at risk EG0010 affected6 at risk EG0020 affected1 at risk EG003
Hypermagnesaemia	Metabolism and nutrition disorders	26.0	Systematic Assessment	EG0001 affected7 at risk EG0010 affected6 at risk EG0020 affected1 at risk EG003
Hypernatraemia	Metabolism and nutrition disorders	26.0	Systematic Assessment	EG0001 affected7 at risk EG0010 affected6 at risk EG0020 affected1 at risk EG003
Hyperphosphataemia	Metabolism and nutrition disorders	26.0	Systematic Assessment	EG0001 affected7 at risk EG0010 affected6 at risk EG0021 affected1 at risk EG003
Hypertriglyceridaemia	Metabolism and nutrition disorders	26.0	Systematic Assessment	EG0003 affected7 at risk EG0010 affected6 at risk EG0020 affected1 at risk EG003
Hypoalbuminaemia	Metabolism and nutrition disorders	26.0	Systematic Assessment	EG0002 affected7 at risk EG0010 affected6 at risk EG0020 affected1 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	26.0	Systematic Assessment	EG0000 affected7 at risk EG0011 affected6 at risk EG0020 affected1 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	26.0	Systematic Assessment	EG0001 affected7 at risk EG0010 affected6 at risk EG0020 affected1 at risk EG003
Hypomagnesaemia	Metabolism and nutrition disorders	26.0	Systematic Assessment	EG0001 affected7 at risk EG0010 affected6 at risk EG0020 affected1 at risk EG003
Hypophosphataemia	Metabolism and nutrition disorders	26.0	Systematic Assessment	EG0001 affected7 at risk EG0010 affected6 at risk EG0021 affected1 at risk EG003
Tumour lysis syndrome	Metabolism and nutrition disorders	26.0	Systematic Assessment	EG0000 affected7 at risk EG0011 affected6 at risk EG0020 affected1 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	26.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected6 at risk EG0021 affected1 at risk EG003
Dizziness	Nervous system disorders	26.0	Systematic Assessment	EG0000 affected7 at risk EG0011 affected6 at risk EG0020 affected1 at risk EG003
Hemiplegia	Nervous system disorders	26.0	Systematic Assessment	EG0001 affected7 at risk EG0010 affected6 at risk EG0020 affected1 at risk EG003
Neurotoxicity	Nervous system disorders	26.0	Systematic Assessment	EG0000 affected7 at risk EG0011 affected6 at risk EG0021 affected1 at risk EG003
Insomnia	Psychiatric disorders	26.0	Systematic Assessment	EG0001 affected7 at risk EG0010 affected6 at risk EG0020 affected1 at risk EG003
Haematuria	Renal and urinary disorders	26.0	Systematic Assessment	EG0000 affected7 at risk EG0011 affected6 at risk EG0020 affected1 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	26.0	Systematic Assessment	EG0001 affected7 at risk EG0010 affected6 at risk EG0020 affected1 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	26.0	Systematic Assessment	EG0001 affected7 at risk EG0010 affected6 at risk EG0020 affected1 at risk EG003
Dermatitis atopic	Skin and subcutaneous tissue disorders	26.0	Systematic Assessment	EG0000 affected7 at risk EG0011 affected6 at risk EG0020 affected1 at risk EG003
Erythema	Skin and subcutaneous tissue disorders	26.0	Systematic Assessment	EG0000 affected7 at risk EG0011 affected6 at risk EG0020 affected1 at risk EG003
Night sweats	Skin and subcutaneous tissue disorders	26.0	Systematic Assessment	EG0000 affected7 at risk EG0010 affected6 at risk EG0021 affected1 at risk EG003
Rash	Skin and subcutaneous tissue disorders	26.0	Systematic Assessment	EG0001 affected7 at risk EG0010 affected6 at risk EG0020 affected1 at risk EG003
Rash maculo-papular	Skin and subcutaneous tissue disorders	26.0	Systematic Assessment	EG0000 affected7 at risk EG0011 affected6 at risk EG0020 affected1 at risk EG003
Skin erosion	Skin and subcutaneous tissue disorders	26.0	Systematic Assessment	EG0000 affected7 at risk EG0011 affected6 at risk EG0020 affected1 at risk EG003
Skin exfoliation	Skin and subcutaneous tissue disorders	26.0	Systematic Assessment	EG0000 affected7 at risk EG0011 affected6 at risk EG0020 affected1 at risk EG003
Cyanosis	Vascular disorders	26.0	Systematic Assessment	EG0000 affected7 at risk EG0011 affected6 at risk EG0020 affected1 at risk EG003
Hypertension	Vascular disorders	26.0	Systematic Assessment	EG0001 affected7 at risk EG0010 affected6 at risk EG0021 affected1 at risk EG003

ID	Term
D054198	Precursor Cell Lymphoblastic Leukemia-Lymphoma
D008228	Lymphoma, Non-Hodgkin
D008232	Lymphoproliferative Disorders
D007154	Immune System Diseases
D007938	Leukemia
D008223	Lymphoma
D008206	Lymphatic Diseases

ID	Term
D007945	Leukemia, Lymphoid
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D007160	Immunoproliferative Disorders

ID	Term
D010752	Phosphoramide Mustards
D009588	Nitrogen Mustard Compounds
D009150	Mustard Compounds
D006846	Hydrocarbons, Halogenated
D006838	Hydrocarbons
D009930	Organic Chemicals
D063088	Phosphoramides
D009943	Organophosphorus Compounds

ID	Title	Description
BG000	0.05 x 10^6 CAR+ T Cells/kg	Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.05 x 10^6 CAR+ T cells per kilogram (kg) post leukapheresis.
BG001	0.15 x 10^6 CAR+ T Cells/kg	Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.15 x 106 CAR+ T cells/kg post leukapheresis.
BG002	0.50 x 106 CAR+T Cells/kg	Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.50 x 106 CAR+T cells/kg post leukapheresis.
BG003	Not Assigned	Participants only underwent leukapheresis.
BG004	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	0.05 x 10^6 CAR+ T Cells/kg	Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.05 x 10^6 CAR+ T cells per kilogram (kg) post leukapheresis.	6	9	5	7	7	7
EG001	0.15 x 10^6 CAR+ T Cells/kg	Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.15 x 106 CAR+ T cells/kg post leukapheresis.	4	8	3	6	6	6
EG002	0.50 x 106 CAR+T Cells/kg	Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.50 x 106 CAR+T cells/kg post leukapheresis.	1	3	1	1	1	1
EG003	Not Assigned	Participants only underwent leukapheresis.	1	1	0	0	0	0