NCT02348216: ZUMA-1

Study Evaluating the Safety and Efficacy of KTE-C19 in Adult Participants With Refractory Aggressive Non-Hodgkin Lymphoma

Completed Phase 1, PHASE2 Results posted Last updated 4 June 2024

What this trial tests

Phase 1, PHASE2 trial testing Axicabtagene Ciloleucel in Refractory Diffuse Large B Cell Lymphoma (DLBCL) in 307 participants. Completed in 27 July 2023.

Timeline

21 April 2015

Primary endpoint
27 July 2023

27 July 2023

Quick facts

Lead sponsor	Kite, A Gilead Company
Phase	Phase 1, PHASE2
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	sequential
Masking	none
Primary purpose	treatment
Enrollment	307
Start date	21 April 2015
Primary completion	27 July 2023
Estimated completion	27 July 2023
Sites	36 locations across France, Netherlands, Israel, Germany, Canada, United States

Drugs / interventions tested

• Axicabtagene Ciloleucel
• Fludarabine
• Cyclophosphamide
• Levetiracetam
• Tocilizumab
• Dexamethasone (dexamethasone) — full drug profile →
• High-dose methylprednisolone
• Bendamustine (BENDAMUSTINE) — full drug profile →
• Rituximab
• Doxorubicin
• Prednisone
• Vincristine
• Ifosfamide
• Carboplatin
• Etoposide
• Gemcitabine
• Oxaliplatin (Oxaliplatin) — full drug profile →
• Cisplatin (cisplatin) — full drug profile →
• Methylprednisolone (methylprednisolone) — full drug profile →

Conditions studied

• Refractory Diffuse Large B Cell Lymphoma (DLBCL) — all drugs for Refractory Diffuse Large B Cell Lymphoma (DLBCL) →
• Relapsed Diffuse Large B-Cell Lymphoma — all drugs for Relapsed Diffuse Large B-Cell Lymphoma →
• Transformed Follicular Lymphoma (TFL) — all drugs for Transformed Follicular Lymphoma (TFL) →
• Primary Mediastinal B-cell Lymphoma (PMBCL) — all drugs for Primary Mediastinal B-cell Lymphoma (PMBCL) →

Sponsor

Kite, A Gilead Company — full company profile →

Who can join

18 and older, any sex, with Refractory Diffuse Large B Cell Lymphoma (DLBCL) or Relapsed Diffuse Large B-Cell Lymphoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Phase 1 Study: Number of Participants Experiencing Adverse Events (AEs) Defined as Dose Limiting Toxicities (DLTs) Primary · First infusion date of axicabtagene ciloleucel up to 30 days

DLT was defined as axicabtagene ciloleucel-related events with onset within first 30 days following infusion: * Grade (GR) 4 neutropenia lasting \> 21 days and GR 4 thrombocytopenia lasting \> 35 days from day of cell transfer; * Any axicabtagene ciloleucel-related AE requiring intubation; * All other GR 3 toxicities lasting \> 3 days and all GR 4 toxicities, with exception of following conditions which were not considered DLTs: aphasia/dysphasia or confusion/cognitive disturbance which resolved to GR ≤ 1 within 2 weeks and to baseline within 4 weeks; fever GR 3; myelosuppression defined as l

Group	Value	95% CI
Phase 1 Study: Axicabtagene Ciloleucel and Conditioning Chemotherapy	1

Phase 2 Pivotal Study (Cohorts 1 and 2): Overall Response Rate (ORR) as Assessed by Investigator Per Revised International Working Group (IWG) Response Criteria for Malignant Lymphoma Primary · First infusion date of axicabtagene ciloleucel up to last follow-up visit (maximum duration: 7.7 years)

ORR was defined as the percentage of participants achieving either a complete response (CR) or a partial response (PR), as assessed by the study investigators using revised IWG Response Criteria for Malignant Lymphoma (Cheson et al, 2007). CR: complete disappearance of all detectable clinical evidence of disease and disease-related symptoms; all lymph nodes and nodal masses must have regressed to normal size; spleen and/or liver must be normal size, not be palpable, and no nodules; bone marrow aspirate and biopsy must show no evidence of disease. PR: a ≥ 50% decrease in sum of the product of t

Group	Value	95% CI
Phase 2 (Pivotal Study): Cohort 1	83	73 – 91
Phase 2 (Pivotal Study): Cohort 2	83	63 – 95

Phase 2 Safety Management Study (Cohort 3): Percentage of Participants With Treatment-Emergent Cytokine Release Syndrome (CRS) and Neurologic Toxicities by Severity Grades Primary · First infusion date of axicabtagene ciloleucel up to last follow-up visit (maximum duration: 6.8 years)

TEAE was defined as any AE with onset on or after the start of treatment. CRS events were graded by Lee et al 2014. Grade 1 : No life threatening symptoms and require symptomatic treatment only; Grade 2: Symptoms require and respond to moderate intervention; Grade 3: Symptoms require and respond to aggressive intervention; Grade 4: Life-threatening symptoms and requirements for ventilator support or continuous venovenous hemodialysis (CVVHD), and Grade 5: Death. Neurologic toxicities were graded by Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Grade 1: Mild, asymptomatic

Worst Grade 1 CRS

Group	Value	95% CI
Phase 2 (Safety Management Study): Cohort 3	34

Worst Grade 2 CRS

Group	Value	95% CI
Phase 2 (Safety Management Study): Cohort 3	55

Worst Grade 3 CRS

Group	Value	95% CI
Phase 2 (Safety Management Study): Cohort 3	0

Worst Grade 4 CRS

Group	Value	95% CI
Phase 2 (Safety Management Study): Cohort 3	3

Worst Grade 5 CRS

Group	Value	95% CI
Phase 2 (Safety Management Study): Cohort 3	0

Worst Grade ≥ 3 CRS

Group	Value	95% CI
Phase 2 (Safety Management Study): Cohort 3	3

Worst Grade 1 Neurologic Toxicities

Group	Value	95% CI
Phase 2 (Safety Management Study): Cohort 3	24

Worst Grade 2 Neurologic Toxicities

Group	Value	95% CI
Phase 2 (Safety Management Study): Cohort 3	21

Phase 2 Safety Management Study (Cohort 4): Percentage of Participants With Treatment-Emergent CRS and Neurologic Toxicities by Severity Grades Primary · First infusion date of axicabtagene ciloleucel up to last follow-up visit (maximum duration: 5.4 years)

TEAE was defined as any AE with onset on or after the start of treatment. CRS events were graded by Lee et al 2014. Grade 1 : No life threatening symptoms and require symptomatic treatment only; Grade 2: Symptoms require and respond to moderate intervention; Grade 3: Symptoms require and respond to aggressive intervention; Grade 4: Life-threatening symptoms and requirements for ventilator support or CVVHD, and Grade 5: Death. Neurologic toxicities were graded by CTCAE version 4.03. Grade 1: Mild, asymptomatic or mild symptoms and intervention not indicated; Grade 2: Moderate and minimal, local

Worst Grade 1 CRS

Group	Value	95% CI
Phase 2 (Safety Management Study): Cohort 4	32

Worst Grade 2 CRS

Group	Value	95% CI
Phase 2 (Safety Management Study): Cohort 4	59

Worst Grade 3 CRS

Group	Value	95% CI
Phase 2 (Safety Management Study): Cohort 4	2

Worst Grade 4 CRS

Group	Value	95% CI
Phase 2 (Safety Management Study): Cohort 4	0

Worst Grade 5 CRS

Group	Value	95% CI
Phase 2 (Safety Management Study): Cohort 4	0

Worst Grade ≥ 3 CRS

Group	Value	95% CI
Phase 2 (Safety Management Study): Cohort 4	2

Worst Grade 1 Neurologic Toxicities

Group	Value	95% CI
Phase 2 (Safety Management Study): Cohort 4	34

Worst Grade 2 Neurologic Toxicities

Group	Value	95% CI
Phase 2 (Safety Management Study): Cohort 4	10

Phase 2 Safety Management Study (Cohort 5): Percentage of Participants With Treatment-Emergent CRS and Neurologic Toxicities by Severity Grades Primary · First infusion date of axicabtagene ciloleucel up to last follow-up visit (maximum duration: 4.4 years)

TEAE was defined as any AE with onset on or after the start of treatment. CRS events were graded by Lee et al 2014. Grade 1 : No life threatening symptoms and require symptomatic treatment only; Grade 2: Symptoms require and respond to moderate intervention; Grade 3: Symptoms require and respond to aggressive intervention; Grade 4: Life-threatening symptoms and requirements for ventilator support or CVVHD, and Grade 5: Death. Neurologic toxicities were graded by CTCAE version 4.03. Grade 1: Mild, asymptomatic or mild symptoms and intervention not indicated; Grade 2: Moderate and minimal, local

Worst Grade 1 CRS

Group	Value	95% CI
Phase 2 (Safety Management Study): Cohort 5	38

Worst Grade 2 CRS

Group	Value	95% CI
Phase 2 (Safety Management Study): Cohort 5	46

Worst Grade 3 CRS

Group	Value	95% CI
Phase 2 (Safety Management Study): Cohort 5	0

Worst Grade 4 CRS

Group	Value	95% CI
Phase 2 (Safety Management Study): Cohort 5	2

Worst Grade 5 CRS

Group	Value	95% CI
Phase 2 (Safety Management Study): Cohort 5	0

Worst Grade ≥ 3 CRS

Group	Value	95% CI
Phase 2 (Safety Management Study): Cohort 5	2

Worst Grade 1 Neurologic Toxicities

Group	Value	95% CI
Phase 2 (Safety Management Study): Cohort 5	26

Worst Grade 2 Neurologic Toxicities

Group	Value	95% CI
Phase 2 (Safety Management Study): Cohort 5	18

Phase 2 Safety Management Study (Cohort 6): Percentage of Participants With Treatment-Emergent CRS and Neurologic Toxicities by Severity Grades Primary · First infusion date of axicabtagene ciloleucel up to last follow-up visit (maximum duration: 4.1 years)

TEAE was defined as any AE with onset on or after the start of treatment. CRS events were graded by Lee et al 2014. Grade 1 : No life threatening symptoms and require symptomatic treatment only; Grade 2: Symptoms require and respond to moderate intervention; Grade 3: Symptoms require and respond to aggressive intervention; Grade 4: Life-threatening symptoms and requirements for ventilator support or CVVHD, and Grade 5: Death. Neurologic toxicities were graded by CTCAE version 4.03. Grade 1: Mild, asymptomatic or mild symptoms and intervention not indicated; Grade 2: Moderate and minimal, local

Worst Grade 1 CRS

Group	Value	95% CI
Phase 2 (Safety Management Study): Cohort 6	35

Worst Grade 2 CRS

Group	Value	95% CI
Phase 2 (Safety Management Study): Cohort 6	45

Worst Grade 3 CRS

Group	Value	95% CI
Phase 2 (Safety Management Study): Cohort 6	0

Worst Grade 4 CRS

Group	Value	95% CI
Phase 2 (Safety Management Study): Cohort 6	0

Worst Grade 5 CRS

Group	Value	95% CI
Phase 2 (Safety Management Study): Cohort 6	0

Worst Grade ≥ 3 CRS

Group	Value	95% CI
Phase 2 (Safety Management Study): Cohort 6	0

Worst Grade 1 Neurologic Toxicities

Group	Value	95% CI
Phase 2 (Safety Management Study): Cohort 6	23

Worst Grade 2 Neurologic Toxicities

Group	Value	95% CI
Phase 2 (Safety Management Study): Cohort 6	18

Phase 2: Duration of Response (DOR) as Assessed by Investigator Per Revised IWG Response Criteria for Malignant Lymphoma Secondary · First OR to last follow-up visit (maximum duration: 7.7, 6.8, 5.4, 4.4, 4.1 years for Cohorts 1, 2, 3, 4, 5, and 6 respectively)

Among participants who experience an objective response (OR), DOR was defined as the date of their first objective response (CR or PR which was subsequently confirmed) to disease progression per the revised IWG Response Criteria for Malignant Lymphoma or death regardless of cause. CR and PR as defined in outcome measure 2. Disease progression (PD) was defined by at least one of the following: ≥ 50% increase from nadir in the sum of the products of at least 2 lymph nodes, or at least a 50% increase in the product of the diameters of a single lymph node; appearance of a new lesion \> 1.5 cm in a

Group	Value	95% CI
Phase 2 (Pivotal Study): Cohort 1	5.0	2.1 – 34.7
Phase 2 (Pivotal Study): Cohort 2	75.4	11.1 – NA
Phase 2 (Safety Management Study): Cohort 3	NA	5.0 – NA
Phase 2 (Safety Management Study): Cohort 4	NA	NA – NA
Phase 2 (Safety Management Study): Cohort 5	27.5	2.2 – NA
Phase 2 (Safety Management Study): Cohort 6	NA	7.8 – NA

Phase 1 Study: ORR as Assessed by Investigator Per Revised IWG Response Criteria for Malignant Lymphoma Secondary · First infusion date of axicabtagene ciloleucel to the data cutoff date of 27 January 2017 (maximum: 20 months)

ORR was defined as the percentage of participants achieving either a CR or a PR, as assessed by the study investigators using revised IWG Response Criteria for Malignant Lymphoma (Cheson et al, 2007). CR: complete disappearance of all detectable clinical evidence of disease and disease-related symptoms; all lymph nodes and nodal masses must have regressed to normal size; spleen and/or liver must be normal size, not be palpable, and no nodules; bone marrow aspirate and biopsy must show no evidence of disease. PR: a ≥ 50% decrease in SPD of up to 6 of the largest dominant nodes or nodal masses;

Group	Value	95% CI
Phase 1 Study: Axicabtagene Ciloleucel and Conditioning Chemotherapy	71

Phase 2 Pivotal Study (Cohorts 1 and 2): ORR Per Independent Radiological Review Committee (IRRC) Secondary · First infusion date of axicabtagene ciloleucel to the data cutoff date of 11 August 2018 (maximum: 2.7 years)

ORR was defined as the percentage of participants achieving either a CR or a PR, as assessed by the IRRC using revised IWG Response Criteria for Malignant Lymphoma. CR: complete disappearance of all detectable clinical evidence of disease and disease-related symptoms; all lymph nodes and nodal masses must have regressed to normal size; spleen and/or liver must be normal size, not be palpable, and no nodules; bone marrow aspirate and biopsy must show no evidence of disease. PR: a ≥ 50% decrease in SPD of up to 6 of the largest dominant nodes or nodal masses; no increase in size of nodes, liver

Group	Value	95% CI
Phase 2 (Pivotal Study): Cohort 1	70	59 – 80
Phase 2 (Pivotal Study): Cohort 2	88	68 – 97

Phase 2 Safety Management Study (Cohorts 3, 4, 5, and 6): ORR as Assessed by Investigator Per the Revised IWG Response Criteria for Malignant Lymphoma Secondary · First infusion date of axicabtagene ciloleucel to last follow-up visit (maximum duration: 6.8, 5.4, 4.4, 4.1 years for Cohorts 3, 4, 5, and 6 respectively)

ORR was defined as the percentage of participants achieving either a CR or a PR, as assessed by the study investigators using revised IWG Response Criteria for Malignant Lymphoma (Cheson et al, 2007). CR: complete disappearance of all detectable clinical evidence of disease and disease-related symptoms; all lymph nodes and nodal masses must have regressed to normal size; spleen and/or liver must be normal size, not be palpable, and no nodules; bone marrow aspirate and biopsy must show no evidence of disease. PR: a ≥ 50% decrease in SPD of up to 6 of the largest dominant nodes or nodal masses;

Group	Value	95% CI
Phase 2 (Safety Management Study): Cohort 3	63	46 – 78
Phase 2 (Safety Management Study): Cohort 4	76	60 – 88
Phase 2 (Safety Management Study): Cohort 5	72	58 – 84
Phase 2 (Safety Management Study): Cohort 6	95	83 – 99

Phase 2: Progression-Free Survival (PFS) as Assessed by Investigator Per Revised IWG Response Criteria for Malignant Lymphoma Secondary · First infusion date of axicabtagene ciloleucel to disease progression or death regardless of cause (maximum duration: 7.7, 6.8, 5.4, 4.4, 4.1 years for Cohorts 1, 2, 3, 4, 5, and 6 respectively)

PFS was defined as the time from the axicabtagene ciloleucel infusion date to the date of disease progression per the revised IWG Response Criteria for Malignant Lymphoma (Cheson et al, 2007) or death from any cause. Participants not meeting the criteria for progression by the analysis data cutoff date were censored at their last evaluable disease assessment date. Disease progression was defined by at least one of the following: ≥ 50% increase from nadir in the sum of the products of at least 2 lymph nodes, or at least a 50% increase in the product of the diameters of a single lymph node; appe

Group	Value	95% CI
Phase 2 (Pivotal Study): Cohort 1	5.1	3.0 – 8.8
Phase 2 (Pivotal Study): Cohort 2	49.1	3.7 – NA
Phase 2 (Safety Management Study): Cohort 3	6.2	2.4 – NA
Phase 2 (Safety Management Study): Cohort 4	NA	3.0 – NA
Phase 2 (Safety Management Study): Cohort 5	3.1	2.9 – 29.1
Phase 2 (Safety Management Study): Cohort 6	NA	8.7 – NA

Phase 2: Overall Survival (OS) Secondary · First infusion date of axicabtagene ciloleucel to the date of death regardless of cause (maximum duration: 7.7, 6.8, 5.4, 4.4, 4.1 years for Cohorts 1, 2, 3, 4, 5, and 6 respectively)

OS was defined as the time from axicabtagene ciloleucel infusion to the date of death. Participants who did not die by the analysis data cutoff date were censored at their last contact date. KM estimates was used for analyses.

Group	Value	95% CI
Phase 2 (Pivotal Study): Cohort 1	15.4	10.4 – 45.7
Phase 2 (Pivotal Study): Cohort 2	NA	15.0 – NA
Phase 2 (Safety Management Study): Cohort 3	34.8	5.4 – NA
Phase 2 (Safety Management Study): Cohort 4	NA	14.6 – NA
Phase 2 (Safety Management Study): Cohort 5	20.6	12.6 – 43.1
Phase 2 (Safety Management Study): Cohort 6	NA	18.9 – NA

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse event: Up to 7.7 years; All-cause mortality: Enrollment up to last follow up visit (maximum duration: 7.7 years; The number of deaths reported in the Participant Flow for Phase 2 Cohort 1 (53) is more than the number of deaths reported in the All-Cause Mortality for Phase 2 Cohort 1 (49) within the table below because the deaths that occurred in the main phase and retreatment phase arms are being reported separately.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Phase 1 Study: Axicabtagene Ciloleucel and Conditioning Chemotherapy

Serious: 5/7 (71%)

Deaths: 5/8

Phase 2 (Pivotal Study): Cohort 1

Serious: 40/77 (52%)

Deaths: 49/81

Phase 2 (Pivotal Study): Cohort 2

Serious: 14/24 (58%)

Deaths: 13/30

Phase 2 (Safety Management Study): Cohort 3

Serious: 26/38 (68%)

Deaths: 23/42

Phase 2 (Safety Management Study): Cohort 4

Serious: 24/41 (59%)

Deaths: 20/46

Phase 2 (Safety Management Study): Cohort 5

Serious: 27/50 (54%)

Deaths: 37/58

Phase 2 (Safety Management Study): Cohort 6

Serious: 25/40 (63%)

Deaths: 20/42

Retreatment Axicabtagene Ciloleucel: Phase 1

Serious: 1/1 (100%)

Deaths: 1/1

Retreatment Axicabtagene Ciloleucel: Phase 2 Cohort 1

Serious: 5/9 (56%)

Deaths: 8/9

Retreatment Axicabtagene Ciloleucel: Phase 2 Cohort 2

Serious: 1/2 (50%)

Deaths: 2/2

Retreatment Axicabtagene Ciloleucel: Phase 2 Cohort 3

Serious: 2/2 (100%)

Deaths: 1/2

Retreatment Axicabtagene Ciloleucel: Phase 2 Cohort 4

Serious: 0/2 (0%)

Deaths: 2/2

Retreatment Axicabtagene Ciloleucel: Phase 2 Cohort 5

Serious: 0/2 (0%)

Deaths: 2/2

Retreatment Axicabtagene Ciloleucel: Phase 2 Cohort 6

Serious: 0

Deaths: 0

Serious adverse events (181 terms)

Reaction	System	Phase 1 Study: Axicabtagen…	Phase 2 (Pivotal Study): C…	Phase 2 (Pivotal Study): C…	Phase 2 (Safety Management…	Phase 2 (Safety Management…	Phase 2 (Safety Management…	Phase 2 (Safety Management…	Retreatment Axicabtagene C…	Retreatment Axicabtagene C…	Retreatment Axicabtagene C…	Retreatment Axicabtagene C…	Retreatment Axicabtagene C…	Retreatment Axicabtagene C…	Retreatment Axicabtagene C…
Encephalopathy	Nervous system disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Pneumonia	Infections and infestations	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Pyrexia	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Confusional state	Psychiatric disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Febrile neutropenia	Blood and lymphatic system disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—
B-cell lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Tremor	Nervous system disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Hypoxia	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Hypotension	Vascular disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Atrial fibrillation	Cardiac disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Covid-19	Infections and infestations	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Septic shock	Infections and infestations	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Ejection fraction decreased	Investigations	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Aphasia	Nervous system disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Seizure	Nervous system disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Somnolence	Nervous system disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Acute kidney injury	Renal and urinary disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Neutropenia	Blood and lymphatic system disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Pancytopenia	Blood and lymphatic system disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Atrial flutter	Cardiac disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Cardiac arrest	Cardiac disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Cellulitis	Infections and infestations	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Escherichia bacteraemia	Infections and infestations	—	—	—	—	—	—	—	—	—	—	—	—	—	—

Other adverse events (210 terms — click to expand)

Reaction	System	Phase 1 Study: Axicabtagen…	Phase 2 (Pivotal Study): C…	Phase 2 (Pivotal Study): C…	Phase 2 (Safety Management…	Phase 2 (Safety Management…	Phase 2 (Safety Management…	Phase 2 (Safety Management…	Retreatment Axicabtagene C…	Retreatment Axicabtagene C…	Retreatment Axicabtagene C…	Retreatment Axicabtagene C…	Retreatment Axicabtagene C…	Retreatment Axicabtagene C…	Retreatment Axicabtagene C…
Pyrexia	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Hypotension	Vascular disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Fatigue	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Headache	Nervous system disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Chills	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Tachycardia	Cardiac disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Neutrophil count decreased	Investigations	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Neutropenia	Blood and lymphatic system disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Platelet count decreased	Investigations	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Hypoxia	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—
White blood cell count decreased	Investigations	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Hypocalcaemia	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Hypokalaemia	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Tremor	Nervous system disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Hypoalbuminaemia	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Febrile neutropenia	Blood and lymphatic system disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Hyponatraemia	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Encephalopathy	Nervous system disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Sinus tachycardia	Cardiac disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Hypophosphataemia	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Confusional state	Psychiatric disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Leukopenia	Blood and lymphatic system disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Alanine aminotransferase increased	Investigations	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Aphasia	Nervous system disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Oedema peripheral	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Lymphocyte count decreased	Investigations	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Hyperglycaemia	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Aspartate aminotransferase increased	Investigations	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Weight decreased	Investigations	—	—	—	—	—	—	—	—	—	—	—	—	—	—

Most-reported serious reactions: Encephalopathy, Pneumonia, Pyrexia, Confusional state, Febrile neutropenia, B-cell lymphoma, Tremor, Hypoxia.

Data from ClinicalTrials.gov NCT02348216 adverse events section.

Sponsor's own description

This study will be separated into 3 distinct phases designated as the Phase 1 study, Phase 2 pivotal study (Cohort 1 and Cohort 2), and Phase 2 safety management study (Cohort 3 and Cohort 4, Cohort 5 and Cohort 6).

The primary objectives of this study are:

* Phase 1 Study: Evaluate the safety of axicabtagene ciloleucel regimens
* Phase 2 Pivotal Study; Evaluate the efficacy of axicabtagene ciloleucel
* Phase 2 Safety Management Study: Assess the impact of prophylactic regimens or earlier interventions on the rate and severity of cytokine release syndrome (CRS) and neurologic toxicities

Subjects who received an infusion of KTE-C19 will complete the remainder of the 15 year follow-up assessments in a separate long-term follow-up study, KT-US-982-5968.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma.
   Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, et al · · 2017 · cited 4538× · PMID 29226797 · DOI 10.1056/nejmoa1707447
2. Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1-2 trial.
   Locke FL, Ghobadi A, Jacobson CA, Miklos DB, et al · · 2019 · cited 1737× · PMID 30518502 · DOI 10.1016/s1470-2045(18)30864-7
3. Engineered T cells: the promise and challenges of cancer immunotherapy.
   Fesnak AD, June CH, Levine BL. · · 2016 · cited 812× · PMID 27550819 · DOI 10.1038/nrc.2016.97
4. Recent advances and discoveries in the mechanisms and functions of CAR T cells.
   Larson RC, Maus MV. · · 2021 · cited 644× · PMID 33483715 · DOI 10.1038/s41568-020-00323-z
5. Standard-of-Care Axicabtagene Ciloleucel for Relapsed or Refractory Large B-Cell Lymphoma: Results From the US Lymphoma CAR T Consortium.
   Nastoupil LJ, Jain MD, Feng L, Spiegel JY, et al · · 2020 · cited 619× · PMID 32401634 · DOI 10.1200/jco.19.02104
6. Phase 1 Results of ZUMA-1: A Multicenter Study of KTE-C19 Anti-CD19 CAR T Cell Therapy in Refractory Aggressive Lymphoma.
   Locke FL, Neelapu SS, Bartlett NL, Siddiqi T, et al · · 2017 · cited 477× · PMID 28129122 · DOI 10.1016/j.ymthe.2016.10.020
7. Chimeric antigen receptor T-cell therapies for lymphoma.
   Brudno JN, Kochenderfer JN. · · 2018 · cited 390× · PMID 28857075 · DOI 10.1038/nrclinonc.2017.128
8. Tumor burden, inflammation, and product attributes determine outcomes of axicabtagene ciloleucel in large B-cell lymphoma.
   Locke FL, Rossi JM, Neelapu SS, Jacobson CA, et al · · 2020 · cited 366× · PMID 33035333 · DOI 10.1182/bloodadvances.2020002394