Study of Effectiveness of Axicabtagene Ciloleucel Compared to Standard of Care Therapy in Patients With Relapsed/Refractory Diffuse Large B Cell Lymphoma (ZUMA-7)

A Phase 3, Randomized, Open-Label Study Evaluating the Efficacy of Axicabtagene Ciloleucel Versus Standard of Care Therapy in Subjects With Relapsed/Refractory Diffuse Large B Cell Lymphoma (ZUMA-7)

The goal of this clinical study is to assess whether axicabtagene ciloleucel therapy improves the clinical outcome compared with standard of care second-line therapy in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL).

Study Overview

• Status: Active, not recruiting
• Conditions: Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL)
• Intervention / Treatment: Drug: Cyclophosphamide; Drug: Fludarabine; Biological: Axicabtagene Ciloleucel; Drug: Platinum-containing salvage chemotherapy (eg, R-ICE) followed by high dose therapy (eg, BEAM) and autologous stem cell transplant in responders.

Detailed Description

This is a phase 3 randomized, open-label, multicenter study evaluating the efficacy of axicabtagene ciloleucel versus standard of care therapy in participants with relapsed/refractory DLBCL. Adult participants with relapsed/refractory DLBCL after first-line rituximab and anthracycline-based chemotherapy will be randomized in a 1:1 ratio to receive axicabtagene ciloleucel or standard of care second-line therapy.

Standard of care will consist of a protocol-defined, platinum-based salvage combination chemotherapy regimen followed by high-dose therapy and autologous stem cell transplant in those who respond to salvage chemotherapy. After completing the treatment period, all participants will be followed in the post-treatment follow-up period for up to 5 years. Thereafter, participants who received at least one dose of axicabtagene ciloleucel as protocol therapy will transition to a separate long term follow up (LTFU) study and complete the remainder of the 15-year follow-up assessments within KT-US-982-5968 (NCT05041309).

• Study Type: Interventional
• Enrollment (Actual): 359
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Peter MacCallum Cancer Center
• Austria
  • Graz, Austria, 6020
    • Universitatsklinikum Graz, Division of Hematology
  • Innsbruck, Austria, 6020
    • Medizinische Universitat Innsbruck, Innere Medizin V - Hamatologie und Onkologie
• Belgium
  • Brussels, Belgium
    • Cliniques Universiaires Saint-Luc
  • Leuven, Belgium
    • UZ Gasthuisberg
• Canada
  • Halifax, Canada, B3H 2Y9
    • QEII Health Sciences Centre
  • Montréal, Canada, H1T 2M4
    • Centre Integre Universitaire de Sante et Services Sociaux de l'Est-de-l'lle-de-Montreal / Hopital Maisonneuve-Rosemont
  • Ottawa, Canada, K1H 8L6
    • The Ottawa Hospital - General Campus
  • Québec, Canada, G1J 1Z4
    • CHU de Quebec-Universite Laval, Hopital de L'Enfante-Jesus
  • British Columbia
    • Vancouver, British Columbia, Canada
      • Vancouver General Hospital
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • CancerCare Manitoba
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Uninversity Health Network - Princess Margaret Cancer Center
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • McGill University Health Center
• France
  • Lille cedex, France, 59037
    • CHRU de Lille - Hopital Claude Huriez
  • Paris, France, 75010
    • Hopital Saint-Louis
  • Pierre Benite, France, 69495
    • Centre Hospitalier Lyon-Sud - Service d'Hematologie clinique
  • Rennes, France, 35033
    • Centre Hospitalier Universitaire de Rennes - Hopital Pontchaillou
• Germany
  • Dresden, Germany, 01307
    • Universitäts-klinikum Dresden
  • Göttingen, Germany, 37075
    • Universitätsmedizin Göttingen
  • Hamburg, Germany, 20246
    • Universitätsklinikum Hamburg-Eppendorf
  • Heidelberg, Germany, 69120
    • Universitätsklinikum Heidelberg
  • Würzburg, Germany, 97080
    • Universitäts-klinikum Würzburg
• Israel
  • Tel Aviv, Israel, 6423906
    • Tel Aviv Sourasky Medical Center
• Italy
  • Bologna, Italy, 40138
    • Instituto di Ematologia "L. e A. Seragnoli" - Dipartimento di Medicina Specialistica Diagnostica e Sperimentale
  • Milano, Italy, 20132
    • IRCCS Ospedale San Raffaele di Milano
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Academic Medical Center
  • Groningen, Netherlands, 9700 RB
    • University Medical Center Groningen
  • Rotterdam, Netherlands, 3011PL
    • Erasmus Medical Center
  • Utrecht, Netherlands
    • University Medical Center Utrecht
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic De Barcelona
  • Barcelona, Spain, 08908
    • Institut Català d'Oncologia
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Pamplona, Spain, 31008
    • Clinica Universidad de Navarra
  • Salamanca, Spain, 37007
    • Hospital Universitario de Salamanca
• Sweden
  • Uppsala, Sweden, 75185
    • Uppsala Akademiska Sjukhus
• Switzerland
  • Bellinzona, Switzerland, 6500
    • IOSI, OSpedale Regionale Bellinzona e Valli
  • Zürich, Switzerland, 8091
    • University Hospital Zurich
• United Kingdom
  • Birmingham, United Kingdom, B15 2GW
    • University Hospitals Birmingham NHS Foundation Trust
  • London, United Kingdom, EC1A 7BE
    • Barts Health NHS Trust
  • London, United Kingdom, NW3 2QG
    • University College London Hospitals NHS Foundation Trust
  • Manchester, United Kingdom, M20 4BX
    • The Christie NHS Foundation Trust
  • Sutton, United Kingdom, SM2 5PT
    • The Royal Marsden NHS Foundation Trust
• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Banner MD Anderson Cancer Center
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Hospital
  • California
    • La Jolla, California, United States, 92093
      • UC San Diego Moores Cancer Center
    • Santa Monica, California, United States, 90404
      • UCLA
    • Stanford, California, United States, 94305
      • Stanford Cancer Institute
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Hospital and Clinics/Sylvester Comprehensive Cancer Center
    • Tampa, Florida, United States, 12902
      • Moffitt Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
    • Chicago, Illinois, United States, 60612
      • Northwestern University
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinincs
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • The University of Kansas Cancer Center
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland, Greenbaum Comprehensive Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Barbara Ann Karmanos Cancer Institute
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic, Patient Location
  • Missouri
    • Saint Louis, Missouri, United States, 63130
      • Washington University School of Medicine
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • John Theurer Cancer Center at Hackensack University Medical Center
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
    • New York, New York, United States, 10021
      • Memorial Sloan Kettering Cancer Center
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Columbus, Ohio, United States, 43210
      • James Cancer Hospital and Solove Research Institute at The Ohio State University Comprehensive Cancer Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC Hillman Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
    • Nashville, Tennessee, United States, 37232
      • Henry-Joyce Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas, MD Anderson Cancer Center
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • University of Utah, Huntsman Cancer Institute
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Health System
  • Washington
    • Seattle, Washington, United States, 98104
      • Swedish Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Histologically proven large B-cell lymphoma including the following types defined by World Health Organization (WHO) 2016.

  • Diffuse large B-cell lymphoma (DLBCL) not otherwise specified activated B-cell/ germinal center B-cell (ABC/GCB).
  • High-grade B-cell lymphoma (HGBL) with or without myelocytomatosis oncogene (MYC) and B-cell lymphoma (BCL) 2 and/or BCL6 rearrangement.
  • DLBCL arising from follicular lymphoma (FL).
  • T-cell/histiocyte rich large B-cell lymphoma.
  • DLBCL associated with chronic inflammation.
  • Primary cutaneous DLBCL, leg type.
  • Epstein-Barr virus (EBV) + DLBCL.

• Relapsed or refractory disease after first-line chemoimmunotherapy.

  • Refractory disease defined as no complete remission to first-line therapy; individuals who are intolerant to first-line therapy are excluded.

    • Progressive disease (PD) as best response to first-line therapy.
    • Stable disease (SD) as best response after at least 4 cycles of first-line therapy (eg, 4 cycles of R-CHOP).
    • Partial response (PR) as best response after at least 6 cycles and biopsy-proven residual disease or disease progression ≤ 12 months of therapy.
  • Relapsed disease defined as complete remission to first-line therapy followed by biopsy-proven relapse ≤ 12 months of first-line therapy.

• Individuals must have received adequate first-line therapy including at a minimum:

  • Anti-Cluster of Differentiation antigen (CD) 20 monoclonal antibody unless investigator determines that tumor is CD20 negative, and
  • An anthracycline containing chemotherapy regimen.
• No known history or suspicion of central nervous system involvement by lymphoma.
• Eastern cooperative oncology group (ECOG) performance status of 0 or 1.

• Adequate bone marrow function as evidenced by:

  • Absolute neutrophil count (ANC) ≥ 1000/uL
  • Platelet ≥ 75,000/uL
  • Absolute lymphocyte count ≥ 100/uL

• Adequate renal, hepatic, cardiac, and pulmonary function as evidenced by:

  • Creatinine clearance (Cockcroft Gault) ≥ 60 mL/min.
  • Serum Alanine aminotransferase/Aspartate aminotransferase (ALT/AST) ≤ 2.5 Upper limit of normal (ULN).
  • Total bilirubin ≤ 1.5 mg/dl
  • 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.
• Received more than one line of therapy for DLBCL.
• History of autologous or allogeneic stem cell transplant.
• Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring intravenous antimicrobials for management.
• Known history of infection with human immunodeficiency virus (HIV) or hepatitis B (HBsAg positive) or hepatitis C virus (anti-HCV positive). If there is a positive history of treated hepatitis B or hepatitis C, the viral load must be undetectable per quantitative polymerase chain reaction (PCR) and/or nucleic acid testing.
• Individuals with detectable cerebrospinal fluid malignant cells or known brain metastases, or with a history of cerebrospinal fluid malignant cells or brain metastases.
• History or presence of non-malignant central nervous system (CNS) disorder such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement.
• Presence of any indwelling line or drain. Dedicated central venous access catheter such as a Port-a-Cath or Hickman catheter are permitted.
• History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, New York Heart Association Class II or greater congestive heart failure, or other clinically significant cardiac diseases within 12 months of enrollment.
• History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months of enrollment.
• History of autoimmune disease, requiring systemic immunosuppression and/or systemic disease modifying agents within the last 2 years.
• History of anti-CD19 or CAR-T therapy or history of prior randomization in ZUMA-7.

Note: Other protocol defined Inclusion/Exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Axicabtagene Ciloleucel Treatment; 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 antigen (CD) 19 CAR transduced autologous T cells/kg on Day 0.	Drug: Cyclophosphamide; Administered intravenously; Drug: Fludarabine; Administered intravenously; Biological: Axicabtagene Ciloleucel; A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells administered intravenously following a conditioning chemotherapy regimen of fludarabine and cyclophosphamide; Other Names: KTE-C19; axi-cel; Yescarta ®
Active Comparator: Standard of Care Therapy; Participants will receive 2 or 3 21-day cycles of second-line chemotherapy regimen; R-ICE: rituximab 375 mg/m^2 before chemotherapy,ifosfamide 5 g/m^2 24hour(hr) infusion on Day 2+mesna,carboplatin area under the curve (AUC) 5 on Day 2, maximum dose 800 mg,etoposide 100 mg/ m^2/day on Days 1-3; R-ESHAP: rituximab 375 mg/m^2 Day 1,etoposide 40 mg/m^2/day IV on Days 1-4,methylprednisolone 500 mg/day IV on Days 1-4 or 5,cisplatin at 25 mg/m^2/day Days 1-4,cytarabine 2 g/m^2 on Day 5; R-GDP: rituximab 375 mg/m^2 Day 1(or Day 8),gemcitabine 1g/m^2 on Days 1 and 8,dexamethasone 40 mg on Days 1-4,cisplatin 75mg/m^2 on Day 1 or carboplatin AUC=5; or R-DHAP: Rituximab 375 mg/ m^2 before chemotherapy,dexamethasone 40 mg/day on Days 1-4,highdose cytarabine 2 g/m^2 every 12 hours for 2 doses on Day 2 following/platinum,cisplatin 100 mg/m^2 24hr infusion on Day 1 or oxaliplatin 100 mg/m^2. Participants who will respond will get high dose therapy and autologous stem cell transplant.	Drug: Platinum-containing salvage chemotherapy (eg, R-ICE) followed by high dose therapy (eg, BEAM) and autologous stem cell transplant in responders.; Platinum-containing salvage chemotherapy (R-ICE, R-DHAP, R-ESHAP, or R-GDP as selected by treating investigator) followed by high dose therapy (eg, BEAM) and autologous stem cell transplant in responders.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event Free Survival (EFS) Per Blinded Central Assessment	EFS:Time from randomization to disease progression (PD), best response of SD up to and including Day 150, commencement of subsequent new anti-lymphoma therapy including stem cell transplant, or death from any cause. PD=score 4 (uptake moderately>liver)/5 (uptake markedly >liver and/or new lesions) with an increase in intensity of uptake from baseline;new fluorodeoxyglucose (FDG)-avid foci consistent with lymphoma at interim/EOT assessment, rather than another etiology or in bone marrow;an individual node/lesion must be abnormal with LDi >1.5 cm, increase by ≥50% from cross-product of LDi and perpendicular diameter nadir, increase in LDi or shortest axis perpendicular to LDi from nadir, splenic length must increase by >50% of extent of its prior increase beyond Baseline. If no prior splenomegaly, increase must be ≥2 cm from baseline;new/recurrent splenomegaly;new/clear progression of pre-existing NMLs;new lesion;new/recurrent bone marrow involvement. KM estimates was used for analysis.	From randomization date up to a median follow-up: 24.9 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) Per Blinded Central Assessment	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 non-measured lesions (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.	From randomization date up to a median follow-up: 24.9 months
Overall Survival (OS)	Overall survival is defined as the time from randomization to death from any cause. Kaplan-Meier (KM) estimates was used for analysis.	From randomization date up to a median follow-up: 47.2 months
Duration of Response (DOR) Per Blinded Central Assessments	DOR is defined only for participants who experience an objective response after axicabtagene ciloleucel infusion and is the time from the first objective response per Lugano classification to disease progression or death from any cause. Objective response is defined in outcome measure 2 and disease progression is defined in outcome measure 1. KM estimates were used for analysis.	From the date of first confirmed objective response (CR or PR) to disease progression or death regardless of cause (Up to 37.8 months)
Modified Event Free Survival (mEFS) Per Blinded Central Assessment	Modified event free survival is defined the same way as EFS, except that a best response of SD up to and including Day 150 assessment post randomization was not considered an event. KM estimates were used for analysis.	From randomization date up to a median follow-up: 24.9 months
Event Free Survival Per Investigator Disease Assessments	EFS was defined as the time from randomization to the earliest date of disease progression per the IWG Lugano Classification, best response of stable disease (SD) up to and including Day 150, commencement of new lymphoma therapy, or death from any cause. Disease progression is defined in outcome measure 1.	From randomization date up to a median follow-up: 47.2 months
Progression-Free Survival (PFS) Per Investigator Disease Assessments	PFS is defined as the time from the randomization date to the date of disease progression per Lugano classification or death from any cause. Disease progression is defined in outcome measure 1. KM estimates was used for analysis.	From randomization date up to a median follow-up: 47.2 months
Modified Event Free Survival (mEFS) Per Investigator Assessment	Modified event free survival is defined the same way as EFS, except that a best response of SD up to and including Day 150 assessment post randomization was not considered an event. KM estimates were used for analysis.	From randomization date up to a median follow-up: 47.2 months
Change From Baseline in Global Health Status Scores	Global health status was measured using European Organization for Research and Treatment of Cancer (EORTC) Quality Life Questionnaire (QLQ) C-30. This health related quality of life (HRQoL) questionnaire was comprised of 15 questions on functional scales, 13 questions on symptom scales and 2 on global health status scale. Global Health Status used a 7 point Likert-type scale of 1 (Very poor) to 7 (Excellent). All scores were transformed to 0-100. Higher scores for Global Health Status indicated better HRQoL.	Baseline, Days 50, 100, and 150; Months 9, 12, 15, 18, 21 and 24
Change From Baseline in EORTC QLQ-C30 Physical Functioning Score	The EORTC QLQ-C30 is composed of global health status/QoL scale; five functional domains (physical, role, emotional, cognitive, and social); three symptom domains (fatigue, nausea and vomiting, and pain); and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The Physical Functioning domain includes 5 questions in which participants were asked to rate their overall health and overall quality of life as it relates to physical functioning during the past week on a scale from 1 (very poor) to 7 (excellent). The 5 scores were transformed to a scale from 0 to 100, where a high score indicated better QoL. A positive change from baseline indicates better QoL.	Baseline, Days 50, 100, 150, Months 9, 12, 15, 18, 21 and 24
Changes From Baseline in the European Quality of Life Five Dimensions Five Levels Scale (EQ-5D-5L) Index Score	The Euro-QOL, Five Dimensions, Five Levels (EQ-5D-5L) questionnaire is a generic measure of health status that provides a simple descriptive profile and a single index value. The EQ-5D-5L comprises 2 components: a questionnaire covering 5 dimensions and a tariff of values based upon direct valuations of health states using a visual analog scale (VAS). The total score for EQ-5D-5L index- is presented on a range from 0 to 1 where higher scores indicate better outcome. A positive change from Baseline indicates improvement.	Baseline, Days 50, 100, 150; Months 9, 12, 15, 18, 21 and 24
Change From Baseline in EQ-5D-5L VAS Scale Score	The EQ-5D-5L VAS is a 20-cm VAS for recording self-rated current HRQoL state and is used to describe the participants' health status on the day of the assessment. The EQ-5D-5L VAS score is recorded by each participant for his or her current HRQoL state and scored 0 ("the worst health you can imagine") to 100 ("the best health you can imagine"). The value 100 indicates improvement.	Baseline, Days 50, 100, 150; Months 9, 12, 18, 21 and 24
Number of Participants With Anti-Axicabtagene Ciloleucel Antibodies		From first dose of axicabtagene up to a median follow-up: 24 months
Percentage of Participants Experiencing Treatment-emergent Adverse Events	A TEAE is defined as any AE that begins on or after the first dose of study treatment (axicabtagene ciloleucel infusion or SOC), excluding bridging therapy. Participant incidence rates of TEAEs, including all, serious, fatal, CTCAE Grade 3 or higher, and treatment related AEs reported will be tabulated by preferred term and system organ class coded with the Medical Dictionary for Regulatory Activities (MedDRA).	Up to 5 years
Percentage of Participants With Clinically Significant Changes in Laboratory Values Reported as Grade 3 or Higher TEAEs	Grading categories were determined by Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Grade 1: mild, Grade 2: moderate, Grade 3: severe or medically significant, Grade 4: life-threatening.	Up to 5 years

Collaborators and Investigators

• Sponsor: Kite, A Gilead Company
• Investigators: Study Director: Kite Study Director, Kite, A Gilead Company

Publications and helpful links

General Publications

• Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, Lister TA; Alliance, Australasian Leukaemia and Lymphoma Group; Eastern Cooperative Oncology Group; European Mantle Cell Lymphoma Consortium; Italian Lymphoma Foundation; European Organisation for Research; Treatment of Cancer/Dutch Hemato-Oncology Group; Grupo Espanol de Medula Osea; German High-Grade Lymphoma Study Group; German Hodgkin's Study Group; Japanese Lymphorra Study Group; Lymphoma Study Association; NCIC Clinical Trials Group; Nordic Lymphoma Study Group; Southwest Oncology Group; United Kingdom National Cancer Research Institute. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014 Sep 20;32(27):3059-68. doi: 10.1200/JCO.2013.54.8800.
• Del Pozo Martin Y. 2021 ASH annual meeting. Lancet Haematol. 2022 Feb;9(2):e92-e93. doi: 10.1016/S2352-3026(21)00384-7. Epub 2021 Dec 16. No abstract available.
• Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.
• Kambhampati S, Hunter B, Varnavski A, Fakhri B, Kaplan L, Ai WZ, Pampaloni M, Huang CY, Martin T 3rd, Damon L, Andreadis CB. Ofatumumab, Etoposide, and Cytarabine Intensive Mobilization Regimen in Patients with High-risk Relapsed/Refractory Diffuse Large B-Cell Lymphoma Undergoing Autologous Stem Cell Transplantation. Clin Lymphoma Myeloma Leuk. 2021 Apr;21(4):246-256.e2. doi: 10.1016/j.clml.2020.11.005. Epub 2020 Nov 11.
• Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, Advani R, Ghielmini M, Salles GA, Zelenetz AD, Jaffe ES. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016 May 19;127(20):2375-90. doi: 10.1182/blood-2016-01-643569. Epub 2016 Mar 15.
• The Lancet Haematology. The role of conferences in tackling inequalities. Lancet Haematol. 2022 Feb;9(2):e81. doi: 10.1016/S2352-3026(22)00008-4. No abstract available.
• Elsawy M, Chavez JC, Avivi I, Larouche JF, Wannesson L, Cwynarski K, Osman K, Davison K, Rudzki JD, Dahiya S, Dorritie K, Jaglowski S, Radford J, Morschhauser F, Cunningham D, Martin Garcia-Sancho A, Tzachanis D, Ulrickson ML, Karmali R, Kekre N, Thieblemont C, Enblad G, Dreger P, Malladi R, Joshi N, Wang WJ, Solem CT, Snider JT, Cheng P, To C, Kersten MJ. Patient-reported outcomes in ZUMA-7, a phase 3 study of axicabtagene ciloleucel in second-line large B-cell lymphoma. Blood. 2022 Nov 24;140(21):2248-2260. doi: 10.1182/blood.2022015478.
• Kersten MJ, Qiao Y, Shah R, Solem C, Snider JT, To C, Cheng P, Spooner C, Perales MA. Quality-Adjusted Time without Symptoms or Toxicity: Analysis of Axicabtagene Ciloleucel versus Standard of Care in Patients with Relapsed/Refractory Large B Cell Lymphoma. Transplant Cell Ther. 2023 May;29(5):335.e1-335.e8. doi: 10.1016/j.jtct.2023.01.008. Epub 2023 Jan 14.
• Locke FL, Miklos DB, Jacobson CA, Perales MA, Kersten MJ, Oluwole OO, Ghobadi A, Rapoport AP, McGuirk J, Pagel JM, Munoz J, Farooq U, van Meerten T, Reagan PM, Sureda A, Flinn IW, Vandenberghe P, Song KW, Dickinson M, Minnema MC, Riedell PA, Leslie LA, Chaganti S, Yang Y, Filosto S, Shah J, Schupp M, To C, Cheng P, Gordon LI, Westin JR; All ZUMA-7 Investigators and Contributing Kite Members. Axicabtagene Ciloleucel as Second-Line Therapy for Large B-Cell Lymphoma. N Engl J Med. 2022 Feb 17;386(7):640-654. doi: 10.1056/NEJMoa2116133. Epub 2021 Dec 11.
• Westin JR, Locke FL, Dickinson M, Ghobadi A, Elsawy M, van Meerten T, Miklos DB, Ulrickson ML, Perales MA, Farooq U, Wannesson L, Leslie L, Kersten MJ, Jacobson CA, Pagel JM, Wulf G, Johnston P, Rapoport AP, Du L, Vardhanabhuti S, Filosto S, Shah J, Snider JT, Cheng P, To C, Oluwole OO, Sureda A. Safety and Efficacy of Axicabtagene Ciloleucel versus Standard of Care in Patients 65 Years of Age or Older with Relapsed/Refractory Large B-Cell Lymphoma. Clin Cancer Res. 2023 May 15;29(10):1894-1905. doi: 10.1158/1078-0432.CCR-22-3136.
• Westin JR, Oluwole OO, Kersten MJ, Miklos DB, Perales MA, Ghobadi A, Rapoport AP, Sureda A, Jacobson CA, Farooq U, van Meerten T, Ulrickson M, Elsawy M, Leslie LA, Chaganti S, Dickinson M, Dorritie K, Reagan PM, McGuirk J, Song KW, Riedell PA, Minnema MC, Yang Y, Vardhanabhuti S, Filosto S, Cheng P, Shahani SA, Schupp M, To C, Locke FL; ZUMA-7 Investigators; Kite Members. Survival with Axicabtagene Ciloleucel in Large B-Cell Lymphoma. N Engl J Med. 2023 Jul 13;389(2):148-157. doi: 10.1056/NEJMoa2301665. Epub 2023 Jun 5.
• Filosto S, Vardhanabhuti S, Canales M, Poiré X, Lekakis LJ, de Vos S, et al. Product attributes of axicabtagene ciloleucel (axi-cel) that associate differentially with efficacy and toxicity in second-line large B-cell lymphoma. Cancer Res. 2022;82(12_Supplement):CT004.
• Ghobadi A, Munoz J, Westin J, Locke FL, Miklos DB, Rapoport AP, et al. Outcomes of Subsequent Anti-Lymphoma Therapies in Patients (Pts) with Large B-Cell Lymphoma (LBCL) Treated with Axicabtagene Ciloleucel (Axi-Cel) or Standard of Care (SOC) in the Second-Line (2L) ZUMA-7 Study. Blood. 2022;140(Supplement 1):1595-1597.
• Locke FL, Oluwole OO, Kuruvilla J, Thieblemont C, Morschhauser F, Salles G, et al. Association of Metabolic Tumor Volume (MTV) and Clinical Outcomes in Second-Line (2L) Relapsed/Refractory (R/R) Large B-Cell Lymphoma (LBCL) Following Axicabtagene Ciloleucel (Axi-Cel) Versus Standard-of-Care (SOC) Therapy in ZUMA-7. Blood. 2022;140(Supplement 1):638-640.

Helpful Links

• Gilead Clinical Trials Website

Study record dates

Study Major Dates

• Study Start (Actual): January 25, 2018
• Primary Completion (Actual): March 18, 2021
• Study Completion (Estimated): October 1, 2024

Study Registration Dates

• First Submitted: December 21, 2017
• First Submitted That Met QC Criteria: December 29, 2017
• First Posted (Actual): January 5, 2018

Study Record Updates

• Last Update Posted (Actual): March 7, 2024
• Last Update Submitted That Met QC Criteria: February 9, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Immunological; Cyclophosphamide; Fludarabine; Axicabtagene ciloleucel
• Other Study ID Numbers: KTE-C19-107; 2017-002261-22 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No