Study to Evaluate the Efficacy and Safety of Axicabtagene... | NCT03761056

ID	Type	Description	Link
2019-002291-13	EudraCT Number

Label	Type	Description	Intervention Names
Axicabtagene Ciloleucel	Experimental	Participants will receive cyclophosphamide 500 mg/m^2/day intravenously (IV) and fludarabine 30 mg/m^2/day IV conditioning chemotherapy for 3 days followed by axicabtagene ciloleucel administered as a single IV infusion at a target dose of 2 x 10^6 anti-cluster of differentiation (CD)19 chimeric antigen receptor (CAR) transduced autologous T cells/kg on Day 0. For participants weighing ≥ 100 kg, a maximum flat dose of axicabtagene ciloleucel at 2 x 10^8 anti-CD19 CAR T cells will be administered. Participants who achieve partial response or complete response and subsequently experience disease progression will have an option to receive second course of conditioning chemotherapy therapy and axicabtagene ciloleucel. Participants will receive the same axicabtagene ciloleucel regimen as the original target dose anytime during the study.	Biological: Axicabtagene Ciloleucel Drug: Fludarabine Drug: Cyclophosphamide

Name	Type	Description	Arm Group Labels	Other Names
Axicabtagene Ciloleucel	Biological	A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells	Axicabtagene Ciloleucel

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Complete Response (CR) Rate Per the Lugano Classification as Determined by Study Investigators	CR Rate is the percentage of participants with CR (complete metabolic response (CMR); complete radiological response (CRR)). CMR: positron emission tomography (PET) 5-point scale (5-PS) scores of 1 (no uptake above background), 2 (uptake ≤ mediastinum), 3 (uptake > mediastinum but ≤ liver) with/without a residual mass); no new lesions; and no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow (BM). CRR: target nodes/nodal masses regressed to ≤ 1.5 cm in longest transverse diameter of lesion (LDi); no extralymphatic sites of disease; absent non-measured lesion (NMLs); organ enlargement regress to normal; no new sites; and bone marrow normal by morphology.	Up to 4 years

Secondary Outcomes

Measure	Description	Time Frame
Objective Response Rate (ORR) Per the Lugano Classification as Determined by Study Investigators	ORR: percentage of participants with CR (CMR;CRR) or PR (partial metabolic response (PMR); partial radiologic response (PRR)). CMR: PET 5PS scores of 1 (no uptake above background, 2 (uptake ≤mediastinum), 3 (uptake >mediastinum but ≤liver) with/without a residual mass; no new lesions; no evidence of FDG-avid disease in BM. CRR: target nodes/nodal masses regressed to ≤1.5 cm in LDi; no extralymphatic sites of disease; absent NMLs; organ enlargement regress to normal; no new sites; bone marrow morphology normal. PMR: scores 4 (uptake moderately >liver),5 (uptake markedly >liver, new lesions) with reduced uptake compared with baseline and residual mass; no new lesions; responding disease at interim/residual disease at end of treatment (EOT). PRR: ≥50% decrease in sum of the product of perpendicular diameters (SPD) of up to 6 target measurable nodes and extra-nodal sites; absent/normal, regressed, but no increase of NMLs; spleen regressed by >50% in length beyond normal; no new sites.

Eligibility Module

Eligibility Criteria

Key Inclusion Criteria:

Histologically confirmed large B-cell lymphoma
High-grade large B-cell lymphoma
Individuals must have a positive interim positron emission tomography (PET) (Deauville PET score of 4 or 5) after 2 cycles (PET2+) of chemoimmunotherapy
No evidence, suspicion and/or history of central nervous system (CNS) involvement of lymphoma
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Absolute neutrophil count ≥ 1000/μL
Platelet count ≥ 75,000/μL
Absolute lymphocyte count ≥ 100/μL
Adequate renal, hepatic, pulmonary, and cardiac function defined as:
- Creatinine clearance (as estimated by Cockcroft Gault) ≥ 60 mL/min
- Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 upper limit of normal (ULN)
- Total bilirubin ≤1.5 mg/dL, except in individuals with Gilbert's syndrome
Cardiac ejection fraction ≥ 50%, no evidence of pericardial effusion as determined by an echocardiogram (ECHO), and no clinically significant electrocardiogram (ECG) findings
No clinically significant pleural effusion
Baseline oxygen saturation > 92% on room air

Key Exclusion Criteria:

History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (eg cervix, bladder, breast) unless disease free for at least 3 years
History of Richter's transformation of chronic lymphocytic leukemia or primary mediastinal B-cell lymphoma
History of autologous or allogeneic stem cell transplant
Prior CD19-targeted therapy
Prior chimeric antigen receptor therapy or other genetically modified T-cell therapy
Presence or suspicion of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management
History of human immunodeficiency virus (HIV) infection or acute or chronic active hepatitis B or C infection
Presence of any indwelling line or drain dedicated central venous access catheters, such as a Port-a-Cath or Hickman catheter, are permitted
Individuals with detectable cerebrospinal fluid malignant cells, brain metastases, or active CNS lymphoma
History or presence of CNS disorder, such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement
History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment
History of autoimmune disease resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years
History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months of enrollment

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Name	Affiliation	Role
Kite Study Director	Kite, A Gilead Company	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Banner Health MD Anderson Cancer Center		Gilbert	Arizona	85234	United States
City of Hope

PubMed Identifier	Type	Citation
	Background	Neelapu SS, Dickinson M, Munoz J, Ulrickson ML, Thieblemont C, Oluwole OO, et al. 739 Primary Analysis of ZUMA-12: A Phase 2 Study of Axicabtagene Ciloleucel (Axi-Cel) As First-Line Therapy in Patients with High-Risk Large B-Cell Lymphoma (LBCL) [Abstract]. 63rd American Society of Hematology (ASH) Annual Meeting and Exposition; 2021 11-14 December.
	Background	Neelapu SS, Dickinson M, Ulrickson ML, Oluwole OO, Herrera AF, Thieblemont C, et al. 405 Interim Analysis of ZUMA-12: A Phase 2 Study of Axicabtagene Ciloleucel (Axi-Cel) as First-Line Therapy in Patients (Pts) With High-Risk Large B-Cell Lymphoma (LBCL) [Abstract]. 62nd American Society of Hematology (ASH) Annual Meeting and Exposition Virtual; 2020 05-08 December.
	Background	Neelapu SS, Chavez JC, Lin Y, Munoz J, Ujjani CS, Riedell P, et al. ZUMA-12: A Phase 2 Multicenter Study of Axicabtagene Ciloleucel (Axi-Cel) as a First-Line Therapy in Patients (Pts) with High-Risk Large B-Cell Lymphoma (LBCL) [Abstract]. J Clin Oncol 2019;37 (15).
35314842

Label	URL
Gilead Clinical Trials Website	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Axicabtagene Ciloleucel	Participants received cyclophosphamide 500 mg/m^2/day intravenously (IV) and fludarabine 30 mg/m^2/day IV conditioning chemotherapy for 3 days followed by axicabtagene ciloleucel administered as a single IV infusion at a target dose of 2 x 10^6 anti-cluster of differentiation (CD)19 chimeric antigen receptor (CAR) transduced autologous T cells/kg on Day 0. For participants weighing ≥ 100 kg, a maximum flat dose of axicabtagene ciloleucel at 2 x 10^8 anti-CD19 CAR T cells was administered. Participants who achieved partial response or complete response and subsequently experienced disease progression had an option to receive second course of conditioning chemotherapy therapy and axicabtagene ciloleucel. Participants received the same axicabtagene ciloleucel regimen as the original target dose anytime during the study (Up to 4 years).

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol: Study Protocol Amendment 2	Mar 25, 2022

ID	Title	Description
BG000	Axicabtagene Ciloleucel	Participants received cyclophosphamide 500 mg/m^2/day IV and fludarabine 30 mg/m^2/day IV conditioning chemotherapy for 3 days followed by axicabtagene ciloleucel administered as a single IV infusion at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg on Day 0. For participants weighing ≥ 100 kg, a maximum flat dose of axicabtagene ciloleucel at 2 x 10^8 anti-CD19 CAR T cells was administered. Participants who achieved partial response or complete response and subsequently experienced disease progression had an option to receive second course of conditioning chemotherapy therapy and axicabtagene ciloleucel. Participants received the same axicabtagene ciloleucel regimen as the original target dose anytime during the study (Up to 4 years).

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

Complete Response (CR) Rate Per the Lugano Classification as Determined by Study Investigators

CR Rate is the percentage of participants with CR (complete metabolic response (CMR); complete radiological response (CRR)). CMR: positron emission tomography (PET) 5-point scale (5-PS) scores of 1 (no uptake above background), 2 (uptake ≤ mediastinum), 3 (uptake > mediastinum but ≤ liver) with/without a residual mass); no new lesions; and no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow (BM). CRR: target nodes/nodal masses regressed to ≤ 1.5 cm in longest transverse diameter of lesion (LDi); no extralymphatic sites of disease; absent non-measured lesion (NMLs); organ enlargement regress to normal; no new sites; and bone marrow normal by morphology.

The Response Evaluable Analysis set included participants who were enrolled and treated with axicabtagene ciloleucel at a dose of at least 1 x 10^6 anti-CD19 CAR T cells/kg, and centrally confirmed disease type (double-/triple- hit lymphomas) or International Prognostic Index (IPI) score ≥ 3.

Posted

Number

95% Confidence Interval

percentage of participants

Up to 4 years

ID	Title	Description
OG000	Axicabtagene Ciloleucel	Participants received cyclophosphamide 500 mg/m^2/day IV and fludarabine 30 mg/m^2/day IV conditioning chemotherapy for 3 days followed by axicabtagene ciloleucel administered as a single IV infusion at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg on Day 0. For participants weighing ≥ 100 kg, a maximum flat dose of axicabtagene ciloleucel at 2 x 10^8 anti-CD19 CAR T cells was administered. Participants who achieved partial response or complete response and subsequently experienced disease progression had an option to receive second course of conditioning chemotherapy therapy and axicabtagene ciloleucel. Participants received the same axicabtagene ciloleucel regimen as the original target dose anytime during the study (Up to 4 years).

Units	Counts
Participants	OG00037

Title

Denominators

Categories

Title	Measurements
	OG00086(71 to 95)

Secondary

Objective Response Rate (ORR) Per the Lugano Classification as Determined by Study Investigators

ORR: percentage of participants with CR (CMR;CRR) or PR (partial metabolic response (PMR); partial radiologic response (PRR)). CMR: PET 5PS scores of 1 (no uptake above background, 2 (uptake ≤mediastinum), 3 (uptake >mediastinum but ≤liver) with/without a residual mass; no new lesions; no evidence of FDG-avid disease in BM. CRR: target nodes/nodal masses regressed to ≤1.5 cm in LDi; no extralymphatic sites of disease; absent NMLs; organ enlargement regress to normal; no new sites; bone marrow morphology normal. PMR: scores 4 (uptake moderately >liver),5 (uptake markedly >liver, new lesions) with reduced uptake compared with baseline and residual mass; no new lesions; responding disease at interim/residual disease at end of treatment (EOT). PRR: ≥50% decrease in sum of the product of perpendicular diameters (SPD) of up to 6 target measurable nodes and extra-nodal sites; absent/normal, regressed, but no increase of NMLs; spleen regressed by >50% in length beyond normal; no new sites.

Participants in the Response Evaluable Analysis Set were analyzed.

Posted

Number

95% Confidence Interval

percentage of participants

Up to 4 years

ID	Title	Description
OG000	Axicabtagene Ciloleucel	Participants received cyclophosphamide 500 mg/m^2/day IV and fludarabine 30 mg/m^2/day IV conditioning chemotherapy for 3 days followed by axicabtagene ciloleucel administered as a single IV infusion at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg on Day 0. For participants weighing ≥ 100 kg, a maximum flat dose of axicabtagene ciloleucel at 2 x 10^8 anti-CD19 CAR T cells was administered. Participants who achieved partial response or complete response and subsequently experienced disease progression had an option to receive second course of conditioning chemotherapy therapy and axicabtagene ciloleucel. Participants received the same axicabtagene ciloleucel regimen as the original target dose anytime during the study (Up to 4 years).

Secondary

Duration of Response (DOR) Per the Lugano Classification

DOR is defined only for participants who experience an objective response after axicabtagene ciloleucel infusion and is the time from the first objective response to disease progression (PD) (Lugano classification) or death from any cause. Objective response is defined in outcome measure (OM) 2. PD is defined as a score 4 (uptake moderately > liver) or 5 (uptake markedly >liver and/or new lesions) with an increase in intensity of uptake from baseline; new FDG-avid foci consistent with lymphoma at interim or end of treatment assessment; new FDG-avid foci consistent with lymphoma rather than another etiology (eg, infection, inflammation); new or recurrent FDG-avid foci in bone marrow. Kaplan-Meier (KM) estimates were used for analysis.

Participants in the Response Evaluable Analysis Set who achieved ORR were analyzed. Participants not meeting the criteria by analysis data cutoff date were censored at their last evaluable disease assessment date prior to the data cutoff date or new anti-lymphoma therapy start (including stem cell transplant or retreatment of axicabtagene ciloleucel), whichever is earlier.

Posted

Median

Full Range

months

Up to 4 years

ID	Title	Description
OG000	Axicabtagene Ciloleucel	Participants received cyclophosphamide 500 mg/m^2/day IV and fludarabine 30 mg/m^2/day IV conditioning chemotherapy for 3 days followed by axicabtagene ciloleucel administered as a single IV infusion at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg on Day 0. For participants weighing ≥ 100 kg, a maximum flat dose of axicabtagene ciloleucel at 2 x 10^8 anti-CD19 CAR T cells was administered. Participants who achieved partial response or complete response and subsequently experienced disease progression had an option to receive second course of conditioning chemotherapy therapy and axicabtagene ciloleucel. Participants received the same axicabtagene ciloleucel regimen as the original target dose anytime during the study (Up to 4 years).

Secondary

Event-Free Survival (EFS)

EFS was defined as the time from axicabtagene ciloleucel infusion date to earliest date of disease progression (Lugano classification), commencement of subsequent new anti-lymphoma therapy including stem cell transplant, or death from any cause. PD is defined in OM 3. KM estimates were used for analysis.

Posted

Median

Full Range

months

Up to 4 years

ID	Title	Description
OG000	Axicabtagene Ciloleucel	Participants received cyclophosphamide 500 mg/m^2/day IV and fludarabine 30 mg/m^2/day IV conditioning chemotherapy for 3 days followed by axicabtagene ciloleucel administered as a single IV infusion at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg on Day 0. For participants weighing ≥ 100 kg, a maximum flat dose of axicabtagene ciloleucel at 2 x 10^8 anti-CD19 CAR T cells was administered. Participants who achieved partial response or complete response and subsequently experienced disease progression had an option to receive second course of conditioning chemotherapy therapy and axicabtagene ciloleucel. Participants received the same axicabtagene ciloleucel regimen as the original target dose anytime during the study (Up to 4 years).

Units	Counts

Secondary

Progression-Free Survival (PFS)

PFS was defined as the time from axicabtagene ciloleucel infusion date to the date of disease progression per Lugano classification or death from any cause. PD is defined in OM 3. KM estimates were used for analysis.

Participants in the Response Evaluable Analysis Set were analyzed. Participants not meeting the criteria by analysis data cutoff date were censored at their last evaluable disease assessment date prior to the data cutoff date or new antilymphoma therapy start date (including stem cell transplant or retreatment of axicabtagene ciloleucel) whichever was earlier.

Posted

Median

Full Range

months

Up to 4 years

ID	Title	Description
OG000	Axicabtagene Ciloleucel	Participants received cyclophosphamide 500 mg/m^2 IV and fludarabine 30 mg/m^2/day IV conditioning chemotherapy for 3 days followed by axicabtagene ciloleucel administered as a single IV infusion at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg on Day 0. For participants weighing ≥ 100 kg, a maximum flat dose of axicabtagene ciloleucel at 2 x 10^8 anti-CD19 CAR T cells was administered. Participants who achieved partial response or complete response and subsequently experienced disease progression had an option to receive second course of conditioning chemotherapy therapy and axicabtagene ciloleucel. Participants received the same axicabtagene ciloleucel regimen as the original target dose anytime during the study (Up to 4 years).

Secondary

Overall Survival (OS)

OS is defined as the time from axicabtagene ciloleucel infusion to the date of death from any cause. KM estimates were used for analysis.

Participants in the Response Evaluable Analysis Set were analyzed.

Posted

Median

Full Range

months

Up to 4 years

ID	Title	Description
OG000	Axicabtagene Ciloleucel	Participants received cyclophosphamide 500 mg/m^2/day IV and fludarabine 30 mg/m^2/day IV conditioning chemotherapy for 3 days followed by axicabtagene ciloleucel administered as a single IV infusion at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg on Day 0. For participants weighing ≥ 100 kg, a maximum flat dose of axicabtagene ciloleucel at 2 x 10^8 anti-CD19 CAR T cells was administered.

Units	Counts
Participants	OG000

Secondary

Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (SAE)

An AE was any untoward medical occurrence in a participant in a clinical trial participant, which did not necessarily have a causal relationship with the treatment. Treatment-emergent adverse events were defined as any adverse event with onset on or after the axicabtagene ciloleucel infusion. Serious adverse event was defined as an event that resulted in the following: death; life-threatening situation; in-patient hospitalization or prolongation of existing hospitalization; persistent or significant disability or incapacity; congenital anomaly or birth defect; and medically important event or reaction.

Safety Analysis Set included all participants treated with any dose of study drug.

Posted

Number

percentage of participants

Up to 2 years

ID	Title	Description
OG000	Axicabtagene Ciloleucel	Participants received cyclophosphamide 500 mg/m^2/day IV and fludarabine 30 mg/m^2/day IV conditioning chemotherapy for 3 days followed by axicabtagene ciloleucel administered as a single IV infusion at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg on Day 0. For participants weighing ≥ 100 kg, a maximum flat dose of axicabtagene ciloleucel at 2 x 10^8 anti-CD19 CAR T cells was administered. Participants who achieved partial response or complete response and subsequently experienced disease progression had an option to receive second course of conditioning chemotherapy therapy and axicabtagene ciloleucel. Participants received the same axicabtagene ciloleucel regimen as the original target dose anytime during the study (Up to 4 years).

Secondary

Percentage of Participants Experiencing Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value

Grading categories were determined by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

Participants in the Safety Analysis Set were analyzed.

Posted

Number

percentage of participants

Up to 2 years

ID	Title	Description
OG000	Axicabtagene Ciloleucel	Participants received cyclophosphamide 500 mg/m^2/day IV and fludarabine 30 mg/m^2/day IV conditioning chemotherapy for 3 days followed by axicabtagene ciloleucel administered as a single IV infusion at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg on Day 0. For participants weighing ≥ 100 kg, a maximum flat dose of axicabtagene ciloleucel at 2 x 10^8 anti-CD19 CAR T cells was administered. Participants who achieved partial response or complete response and subsequently experienced disease progression had an option to receive second course of conditioning chemotherapy therapy and axicabtagene ciloleucel. Participants received the same axicabtagene ciloleucel regimen as the original target dose anytime during the study (Up to 4 years).

Units	Counts
Participants

Secondary

Percentage of Participants Experiencing Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Value

Grading categories were determined by CTCAE version 5.0.

Participants in the Safety Analysis Set were analyzed.

Posted

Number

percentage of participants

Up to 2 years

ID	Title	Description
OG000	Axicabtagene Ciloleucel	Participants received cyclophosphamide 500 mg/m^2/day IV and fludarabine 30 mg/m^2/day IV conditioning chemotherapy for 3 days followed by axicabtagene ciloleucel administered as a single IV infusion at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg on Day 0. For participants weighing ≥ 100 kg, a maximum flat dose of axicabtagene ciloleucel at 2 x 10^8 anti-CD19 CAR T cells was administered. Participants who achieved partial response or complete response and subsequently experienced disease progression had an option to receive second course of conditioning chemotherapy therapy and axicabtagene ciloleucel. Participants received the same axicabtagene ciloleucel regimen as the original target dose anytime during the study (Up to 4 years).

Units	Counts
Participants	OG000

Secondary

Relapse With Central Nervous System (CNS) Disease

Relapse with CNS disease was defined as the time from the axicabtagene ciloleucel infusion date to the earliest date of CNS involvement with lymphoma as determined by typical symptoms, cerebrospinal fluid (CSF) evaluation, and/or diagnostic imaging.

Participants in the Response Evaluable Analysis Set with available data were analyzed.

Posted

Median

Full Range

months

Up to 4 years

ID	Title	Description
OG000	Axicabtagene Ciloleucel	Participants received cyclophosphamide 500 mg/m^2 IV and fludarabine 30 mg/m^2/day IV conditioning chemotherapy for 3 days followed by axicabtagene ciloleucel administered as a single IV infusion at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg on Day 0. For participants weighing ≥ 100 kg, a maximum flat dose of axicabtagene ciloleucel at 2 x 10^8 anti-CD19 CAR T cells was administered. Participants who achieved partial response or complete response and subsequently experienced disease progression had an option to receive second course of conditioning chemotherapy therapy and axicabtagene ciloleucel. Participants received the same axicabtagene ciloleucel regimen as the original target dose anytime during the study (Up to 4 years).

Units	Counts
Participants

Secondary

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

Peak was defined as the maximum number of CAR T cells in blood measured after infusion.

Participants in the Safety Analysis Set were analyzed.

Posted

Median

Inter-Quartile Range

cells/µL

Up to Month 24

ID	Title	Description
OG000	Axicabtagene Ciloleucel	Participants received cyclophosphamide 500 mg/m^2 IV and fludarabine 30 mg/m^2/day IV conditioning chemotherapy for 3 days followed by axicabtagene ciloleucel administered as a single IV infusion at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg on Day 0. For participants weighing ≥ 100 kg, a maximum flat dose of axicabtagene ciloleucel at 2 x 10^8 anti-CD19 CAR T cells was administered. Participants who achieved partial response or complete response and subsequently experienced disease progression had an option to receive second course of conditioning chemotherapy therapy and axicabtagene ciloleucel. Participants received the same axicabtagene ciloleucel regimen as the original target dose anytime during the study (Up to 4 years).

Units	Counts
Participants	OG000

Secondary

Peak Serum Level of Granzyme B, Interferon-gamma (IFNg), Interleukin (IL)-2, IL-5, IL-6, IL-8

Peak is defined as the maximum post-baseline level of cytokine from baseline to Week 4.

Participants in the Safety Analysis Set with data available were analyzed.

Posted

Median

Inter-Quartile Range

pg/mL

Up to Week 4

ID	Title	Description
OG000	Axicabtagene Ciloleucel	Participants received cyclophosphamide 500 mg/m^2/day IV and fludarabine 30 mg/m^2/day IV conditioning chemotherapy for 3 days followed by axicabtagene ciloleucel administered as a single IV infusion at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg on Day 0. For participants weighing ≥ 100 kg, a maximum flat dose of axicabtagene ciloleucel at 2 x 10^8 anti-CD19 CAR T cells was administered. Participants who achieved partial response or complete response and subsequently experienced disease progression had an option to receive second course of conditioning chemotherapy therapy and axicabtagene ciloleucel. Participants received the same axicabtagene ciloleucel regimen as the original target dose anytime during the study (Up to 4 years).

Units	Counts
Participants	OG000

Secondary

Peak Serum Level of C-Reactive Protein (CRP)

Peak is defined as the maximum post-baseline level of cytokine from baseline to Week 4.

Participants in the Safety Analysis Set with data available were analyzed.

Posted

Median

Inter-Quartile Range

mg/L

Up to Week 4

ID	Title	Description
OG000	Axicabtagene Ciloleucel	Participants received cyclophosphamide 500 mg/m^2/day IV and fludarabine 30 mg/m^2/day IV conditioning chemotherapy for 3 days followed by axicabtagene ciloleucel administered as a single IV infusion at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg on Day 0. For participants weighing ≥ 100 kg, a maximum flat dose of axicabtagene ciloleucel at 2 x 10^8 anti-CD19 CAR T cells was administered. Participants who achieved partial response or complete response and subsequently experienced disease progression had an option to receive second course of conditioning chemotherapy therapy and axicabtagene ciloleucel. Participants received the same axicabtagene ciloleucel regimen as the original target dose anytime during the study (Up to 4 years).

Units	Counts
Participants	OG000

Secondary

Peak Serum Level of Ferritin

Peak is defined as the maximum post-baseline level of cytokine from baseline to Week 4.

Participants in the Safety Analysis Set with data available were analyzed.

Posted

Median

Inter-Quartile Range

ng/mL

Up to Week 4

ID	Title	Description
OG000	Axicabtagene Ciloleucel	Participants received cyclophosphamide 500 mg/m^2 IV and fludarabine 30 mg/m^2/day IV conditioning chemotherapy for 3 days followed by axicabtagene ciloleucel administered as a single IV infusion at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg on Day 0. For participants weighing ≥ 100 kg, a maximum flat dose of axicabtagene ciloleucel at 2 x 10^8 anti-CD19 CAR T cells was administered. Participants who achieved partial response or complete response and subsequently experienced disease progression had an option to receive second course of conditioning chemotherapy therapy and axicabtagene ciloleucel. Participants received the same axicabtagene ciloleucel regimen as the original target dose anytime during the study (Up to 4 years).

Units	Counts
Participants	OG000

Secondary

Time to Peak Serum Level of Granzyme B, Interferon-gamma (IFNg), Interleukin (IL)-2, IL-5, IL-6, IL-8, CRP, and Ferritin

Time to peak is defined as the number of days from axicabtagene ciloleucel infusion to the date when the cytokine first reached the maximum post-baseline level.

Participants in the Safety Analysis Set with data available were analyzed.

Posted

Median

Inter-Quartile Range

days

Up to Week 4

ID	Title	Description
OG000	Axicabtagene Ciloleucel	Participants received cyclophosphamide 500 mg/m^2/day IV and fludarabine 30 mg/m^2/day IV conditioning chemotherapy for 3 days followed by axicabtagene ciloleucel administered as a single IV infusion at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg on Day 0. For participants weighing ≥ 100 kg, a maximum flat dose of axicabtagene ciloleucel at 2 x 10^8 anti-CD19 CAR T cells was administered. Participants who achieved partial response or complete response and subsequently experienced disease progression had an option to receive second course of conditioning chemotherapy therapy and axicabtagene ciloleucel. Participants received the same axicabtagene ciloleucel regimen as the original target dose anytime during the study (Up to 4 years).

Units	Counts
Participants

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 26.1	Systematic Assessment	EG0001 affected40 at risk EG0010 affected1 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 26.1	Systematic Assessment	EG0001 affected40 at risk EG0010 affected1 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 26.1	Systematic Assessment	EG0001 affected40 at risk EG0010 affected1 at risk
Pericardial effusion	Cardiac disorders	MedDRA 26.1	Systematic Assessment	EG0000 affected40 at risk EG0011 affected1 at risk
Sinus bradycardia	Cardiac disorders	MedDRA 26.1	Systematic Assessment	EG0001 affected40 at risk EG0010 affected1 at risk
Supraventricular tachycardia	Cardiac disorders	MedDRA 26.1	Systematic Assessment	EG0001 affected40 at risk EG0010 affected1 at risk
Hypothyroidism	Endocrine disorders	MedDRA 26.1	Systematic Assessment	EG0001 affected40 at risk EG0010 affected1 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 26.1	Systematic Assessment	EG0001 affected40 at risk EG0010 affected1 at risk
Non-cardiac chest pain	General disorders	MedDRA 26.1	Systematic Assessment	EG0002 affected40 at risk EG0010 affected1 at risk
Pyrexia	General disorders	MedDRA 26.1	Systematic Assessment	EG0003 affected40 at risk EG0010 affected1 at risk
Autoimmune disorder	Immune system disorders	MedDRA 26.1	Systematic Assessment	EG0001 affected40 at risk EG0010 affected1 at risk
Covid-19	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0002 affected40 at risk EG0010 affected1 at risk
Covid-19 pneumonia	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0002 affected40 at risk EG0010 affected1 at risk
Cytomegalovirus infection reactivation	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0001 affected40 at risk EG0010 affected1 at risk
Device related infection	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0001 affected40 at risk EG0010 affected1 at risk
Periorbital infection	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0001 affected40 at risk EG0010 affected1 at risk
Skin infection	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0001 affected40 at risk EG0010 affected1 at risk
Urinary tract infection	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0001 affected40 at risk EG0010 affected1 at risk
Neutrophil count decreased	Investigations	MedDRA 26.1	Systematic Assessment	EG0001 affected40 at risk EG0010 affected1 at risk
Platelet count decreased	Investigations	MedDRA 26.1	Systematic Assessment	EG0001 affected40 at risk EG0010 affected1 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 26.1	Systematic Assessment	EG0002 affected40 at risk EG0010 affected1 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 26.1	Systematic Assessment	EG0001 affected40 at risk EG0010 affected1 at risk
Gastrointestinal stromal tumour	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 26.1	Systematic Assessment	EG0001 affected40 at risk EG0010 affected1 at risk
Leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 26.1	Systematic Assessment	EG0001 affected40 at risk EG0010 affected1 at risk
Oesophageal adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 26.1	Systematic Assessment	EG0001 affected40 at risk EG0010 affected1 at risk
Squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 26.1	Systematic Assessment	EG0001 affected40 at risk EG0010 affected1 at risk
Dysarthria	Nervous system disorders	MedDRA 26.1	Systematic Assessment	EG0001 affected40 at risk EG0010 affected1 at risk
Encephalopathy	Nervous system disorders	MedDRA 26.1	Systematic Assessment	EG0005 affected40 at risk EG0010 affected1 at risk
Haemorrhage intracranial	Nervous system disorders	MedDRA 26.1	Systematic Assessment	EG0001 affected40 at risk EG0010 affected1 at risk
Immune effector cell-associated neurotoxicity syndrome	Nervous system disorders	MedDRA 26.1	Systematic Assessment	EG0001 affected40 at risk EG0010 affected1 at risk
Memory impairment	Nervous system disorders	MedDRA 26.1	Systematic Assessment	EG0001 affected40 at risk EG0010 affected1 at risk
Agitation	Psychiatric disorders	MedDRA 26.1	Systematic Assessment	EG0001 affected40 at risk EG0010 affected1 at risk
Confusional state	Psychiatric disorders	MedDRA 26.1	Systematic Assessment	EG0004 affected40 at risk EG0010 affected1 at risk
Acute pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 26.1	Systematic Assessment	EG0001 affected40 at risk EG0010 affected1 at risk
Hypertension	Vascular disorders	MedDRA 26.1	Systematic Assessment	EG0001 affected40 at risk EG0010 affected1 at risk
Hypotension	Vascular disorders	MedDRA 26.1	Systematic Assessment	EG0001 affected40 at risk EG0010 affected1 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 26.1	Systematic Assessment	EG00013 affected40 at risk EG0010 affected1 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 26.1	Systematic Assessment	EG0005 affected40 at risk EG0010 affected1 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 26.1	Systematic Assessment	EG0002 affected40 at risk EG0010 affected1 at risk
Sinus bradycardia	Cardiac disorders	MedDRA 26.1	Systematic Assessment	EG0003 affected40 at risk EG0010 affected1 at risk
Sinus tachycardia	Cardiac disorders	MedDRA 26.1	Systematic Assessment	EG00010 affected40 at risk EG0010 affected1 at risk
Tachycardia	Cardiac disorders	MedDRA 26.1	Systematic Assessment	EG0002 affected40 at risk EG0010 affected1 at risk
Ventricular arrhythmia	Cardiac disorders	MedDRA 26.1	Systematic Assessment	EG0003 affected40 at risk EG0010 affected1 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 26.1	Systematic Assessment	EG0004 affected40 at risk EG0010 affected1 at risk
Constipation	Gastrointestinal disorders	MedDRA 26.1	Systematic Assessment	EG0008 affected40 at risk EG0011 affected1 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 26.1	Systematic Assessment	EG00020 affected40 at risk EG0011 affected1 at risk
Dry mouth	Gastrointestinal disorders	MedDRA 26.1	Systematic Assessment	EG0003 affected40 at risk EG0010 affected1 at risk
Nausea	Gastrointestinal disorders	MedDRA 26.1	Systematic Assessment	EG00021 affected40 at risk EG0010 affected1 at risk
Vomiting	Gastrointestinal disorders	MedDRA 26.1	Systematic Assessment	EG0008 affected40 at risk EG0010 affected1 at risk
Chills	General disorders	MedDRA 26.1	Systematic Assessment	EG00011 affected40 at risk EG0010 affected1 at risk
Fatigue	General disorders	MedDRA 26.1	Systematic Assessment	EG00020 affected40 at risk EG0010 affected1 at risk
Non-cardiac chest pain	General disorders	MedDRA 26.1	Systematic Assessment	EG0002 affected40 at risk EG0010 affected1 at risk
Oedema peripheral	General disorders	MedDRA 26.1	Systematic Assessment	EG0005 affected40 at risk EG0010 affected1 at risk
Pyrexia	General disorders	MedDRA 26.1	Systematic Assessment	EG00039 affected40 at risk EG0010 affected1 at risk
Hypogammaglobulinaemia	Immune system disorders	MedDRA 26.1	Systematic Assessment	EG0004 affected40 at risk EG0010 affected1 at risk
Covid-19	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0002 affected40 at risk EG0010 affected1 at risk
Sinusitis	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0002 affected40 at risk EG0010 affected1 at risk
Urinary tract infection	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0003 affected40 at risk EG0010 affected1 at risk
Alanine aminotransferase increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0007 affected40 at risk EG0010 affected1 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0005 affected40 at risk EG0010 affected1 at risk
Blood bilirubin increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0003 affected40 at risk EG0010 affected1 at risk
Blood fibrinogen decreased	Investigations	MedDRA 26.1	Systematic Assessment	EG0003 affected40 at risk EG0010 affected1 at risk
Lymphocyte count decreased	Investigations	MedDRA 26.1	Systematic Assessment	EG0004 affected40 at risk EG0010 affected1 at risk
Neutrophil count decreased	Investigations	MedDRA 26.1	Systematic Assessment	EG00021 affected40 at risk EG0011 affected1 at risk
Platelet count decreased	Investigations	MedDRA 26.1	Systematic Assessment	EG0007 affected40 at risk EG0010 affected1 at risk
White blood cell count decreased	Investigations	MedDRA 26.1	Systematic Assessment	EG00018 affected40 at risk EG0011 affected1 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 26.1	Systematic Assessment	EG0008 affected40 at risk EG0010 affected1 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 26.1	Systematic Assessment	EG0003 affected40 at risk EG0010 affected1 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 26.1	Systematic Assessment	EG0004 affected40 at risk EG0010 affected1 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 26.1	Systematic Assessment	EG00011 affected40 at risk EG0010 affected1 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 26.1	Systematic Assessment	EG0002 affected40 at risk EG0010 affected1 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 26.1	Systematic Assessment	EG0005 affected40 at risk EG0010 affected1 at risk
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA 26.1	Systematic Assessment	EG0007 affected40 at risk EG0010 affected1 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 26.1	Systematic Assessment	EG0004 affected40 at risk EG0010 affected1 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 26.1	Systematic Assessment	EG0006 affected40 at risk EG0010 affected1 at risk
Dizziness	Nervous system disorders	MedDRA 26.1	Systematic Assessment	EG0002 affected40 at risk EG0010 affected1 at risk
Dysgraphia	Nervous system disorders	MedDRA 26.1	Systematic Assessment	EG0003 affected40 at risk EG0010 affected1 at risk
Encephalopathy	Nervous system disorders	MedDRA 26.1	Systematic Assessment	EG0008 affected40 at risk EG0010 affected1 at risk
Headache	Nervous system disorders	MedDRA 26.1	Systematic Assessment	EG00028 affected40 at risk EG0010 affected1 at risk
Memory impairment	Nervous system disorders	MedDRA 26.1	Systematic Assessment	EG0002 affected40 at risk EG0010 affected1 at risk
Tremor	Nervous system disorders	MedDRA 26.1	Systematic Assessment	EG00010 affected40 at risk EG0010 affected1 at risk
Agitation	Psychiatric disorders	MedDRA 26.1	Systematic Assessment	EG0004 affected40 at risk EG0010 affected1 at risk
Confusional state	Psychiatric disorders	MedDRA 26.1	Systematic Assessment	EG00011 affected40 at risk EG0010 affected1 at risk
Insomnia	Psychiatric disorders	MedDRA 26.1	Systematic Assessment	EG0006 affected40 at risk EG0010 affected1 at risk
Pelvic pain	Reproductive system and breast disorders	MedDRA 26.1	Systematic Assessment	EG0002 affected40 at risk EG0010 affected1 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 26.1	Systematic Assessment	EG0005 affected40 at risk EG0010 affected1 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 26.1	Systematic Assessment	EG0003 affected40 at risk EG0010 affected1 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 26.1	Systematic Assessment	EG00011 affected40 at risk EG0010 affected1 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 26.1	Systematic Assessment	EG0003 affected40 at risk EG0010 affected1 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 26.1	Systematic Assessment	EG0003 affected40 at risk EG0010 affected1 at risk
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 26.1	Systematic Assessment	EG0002 affected40 at risk EG0010 affected1 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 26.1	Systematic Assessment	EG0002 affected40 at risk EG0010 affected1 at risk
Hypertension	Vascular disorders	MedDRA 26.1	Systematic Assessment	EG0002 affected40 at risk EG0010 affected1 at risk
Hypotension	Vascular disorders	MedDRA 26.1	Systematic Assessment	EG00014 affected40 at risk EG0010 affected1 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 26.1	Systematic Assessment	EG0001 affected40 at risk EG0011 affected1 at risk

ID	Term
D008228	Lymphoma, Non-Hodgkin
D008223	Lymphoma
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D008232	Lymphoproliferative Disorders
D008206	Lymphatic Diseases
D006425	Hemic and Lymphatic Diseases
D007160	Immunoproliferative Disorders
D007154	Immune System Diseases

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	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Axicabtagene Ciloleucel	Participants received 500 mg/m^2 cyclophosphamide IV and 30 mg/m^2/day fludarabine IV conditioning chemotherapy for 3 days followed by axicabtagene ciloleucel administered as a single IV infusion at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg on Day 0. For participants weighing ≥ 100 kg, a maximum flat dose of axicabtagene ciloleucel at 2 x 10^8 anti-CD19 CAR T cells was administered.	7	42	22	40	40	40
EG001	Retreatment Axicabtagene Ciloleucel	Participants who achieved partial response or complete response and subsequently experienced disease progression had an option to receive second course of conditioning chemotherapy therapy and axicabtagene ciloleucel. Participants received the same axicabtagene ciloleucel regimen as the original target dose anytime during the study (Up to 4 years).	1	1	1	1	1	1

ID	Term
C000629083	axicabtagene ciloleucel
C024352	fludarabine
D003520	Cyclophosphamide