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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03391466




Registration number
NCT03391466
Ethics application status
Date submitted
21/12/2017
Date registered
5/01/2018
Date last updated
7/03/2024

Titles & IDs
Public title
Study of Effectiveness of Axicabtagene Ciloleucel Compared to Standard of Care Therapy in Patients With Relapsed/Refractory Diffuse Large B Cell Lymphoma
Scientific title
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)
Secondary ID [1] 0 0
2017-002261-22
Secondary ID [2] 0 0
KTE-C19-107
Universal Trial Number (UTN)
Trial acronym
ZUMA-7
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL) 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Axicabtagene Ciloleucel
Treatment: Drugs - Platinum-containing salvage chemotherapy (eg, R-ICE) followed by high dose therapy (eg, BEAM) and autologous stem cell transplant in responders.
Treatment: Drugs - Cyclophosphamide
Treatment: Drugs - Fludarabine

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.

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.


Other interventions: 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

Treatment: Drugs: 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.

Treatment: Drugs: Cyclophosphamide
Administered intravenously

Treatment: Drugs: Fludarabine
Administered intravenously
Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Event Free Survival (EFS) Per Blinded Central Assessment
Timepoint [1] 0 0
From randomization date up to a median follow-up: 24.9 months
Secondary outcome [1] 0 0
Objective Response Rate (ORR) Per Blinded Central Assessment
Timepoint [1] 0 0
From randomization date up to a median follow-up: 24.9 months
Secondary outcome [2] 0 0
Overall Survival (OS)
Timepoint [2] 0 0
From randomization date up to a median follow-up: 47.2 months
Secondary outcome [3] 0 0
Duration of Response (DOR) Per Blinded Central Assessments
Timepoint [3] 0 0
From the date of first confirmed objective response (CR or PR) to disease progression or death regardless of cause (Up to 37.8 months)
Secondary outcome [4] 0 0
Modified Event Free Survival (mEFS) Per Blinded Central Assessment
Timepoint [4] 0 0
From randomization date up to a median follow-up: 24.9 months
Secondary outcome [5] 0 0
Event Free Survival Per Investigator Disease Assessments
Timepoint [5] 0 0
From randomization date up to a median follow-up: 47.2 months
Secondary outcome [6] 0 0
Progression-Free Survival (PFS) Per Investigator Disease Assessments
Timepoint [6] 0 0
From randomization date up to a median follow-up: 47.2 months
Secondary outcome [7] 0 0
Modified Event Free Survival (mEFS) Per Investigator Assessment
Timepoint [7] 0 0
From randomization date up to a median follow-up: 47.2 months
Secondary outcome [8] 0 0
Change From Baseline in Global Health Status Scores
Timepoint [8] 0 0
Baseline, Days 50, 100, and 150; Months 9, 12, 15, 18, 21 and 24
Secondary outcome [9] 0 0
Change From Baseline in EORTC QLQ-C30 Physical Functioning Score
Timepoint [9] 0 0
Baseline, Days 50, 100, 150, Months 9, 12, 15, 18, 21 and 24
Secondary outcome [10] 0 0
Changes From Baseline in the European Quality of Life Five Dimensions Five Levels Scale (EQ-5D-5L) Index Score
Timepoint [10] 0 0
Baseline, Days 50, 100, 150; Months 9, 12, 15, 18, 21 and 24
Secondary outcome [11] 0 0
Change From Baseline in EQ-5D-5L VAS Scale Score
Timepoint [11] 0 0
Baseline, Days 50, 100, 150; Months 9, 12, 18, 21 and 24
Secondary outcome [12] 0 0
Number of Participants With Anti-Axicabtagene Ciloleucel Antibodies
Timepoint [12] 0 0
From first dose of axicabtagene up to a median follow-up: 24 months
Secondary outcome [13] 0 0
Percentage of Participants Experiencing Treatment-emergent Adverse Events
Timepoint [13] 0 0
Up to 5 years
Secondary outcome [14] 0 0
Percentage of Participants With Clinically Significant Changes in Laboratory Values Reported as Grade 3 or Higher TEAEs
Timepoint [14] 0 0
Up to 5 years

Eligibility
Key inclusion criteria
Key

- 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
25/01/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/10/2024
Actual
Sample size
Target
Accrual to date
Final
359
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Center - Melbourne
Recruitment postcode(s) [1] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Iowa
Country [6] 0 0
United States of America
State/province [6] 0 0
Kansas
Country [7] 0 0
United States of America
State/province [7] 0 0
Maryland
Country [8] 0 0
United States of America
State/province [8] 0 0
Massachusetts
Country [9] 0 0
United States of America
State/province [9] 0 0
Michigan
Country [10] 0 0
United States of America
State/province [10] 0 0
Minnesota
Country [11] 0 0
United States of America
State/province [11] 0 0
Missouri
Country [12] 0 0
United States of America
State/province [12] 0 0
New Jersey
Country [13] 0 0
United States of America
State/province [13] 0 0
New York
Country [14] 0 0
United States of America
State/province [14] 0 0
Ohio
Country [15] 0 0
United States of America
State/province [15] 0 0
Pennsylvania
Country [16] 0 0
United States of America
State/province [16] 0 0
Tennessee
Country [17] 0 0
United States of America
State/province [17] 0 0
Texas
Country [18] 0 0
United States of America
State/province [18] 0 0
Utah
Country [19] 0 0
United States of America
State/province [19] 0 0
Virginia
Country [20] 0 0
United States of America
State/province [20] 0 0
Washington
Country [21] 0 0
Austria
State/province [21] 0 0
Graz
Country [22] 0 0
Austria
State/province [22] 0 0
Innsbruck
Country [23] 0 0
Belgium
State/province [23] 0 0
Brussels
Country [24] 0 0
Belgium
State/province [24] 0 0
Leuven
Country [25] 0 0
Canada
State/province [25] 0 0
British Columbia
Country [26] 0 0
Canada
State/province [26] 0 0
Manitoba
Country [27] 0 0
Canada
State/province [27] 0 0
Ontario
Country [28] 0 0
Canada
State/province [28] 0 0
Quebec
Country [29] 0 0
Canada
State/province [29] 0 0
Halifax
Country [30] 0 0
Canada
State/province [30] 0 0
Montréal
Country [31] 0 0
Canada
State/province [31] 0 0
Ottawa
Country [32] 0 0
Canada
State/province [32] 0 0
Québec
Country [33] 0 0
France
State/province [33] 0 0
Lille cedex
Country [34] 0 0
France
State/province [34] 0 0
Paris
Country [35] 0 0
France
State/province [35] 0 0
Pierre Benite
Country [36] 0 0
France
State/province [36] 0 0
Rennes
Country [37] 0 0
Germany
State/province [37] 0 0
Dresden
Country [38] 0 0
Germany
State/province [38] 0 0
Göttingen
Country [39] 0 0
Germany
State/province [39] 0 0
Hamburg
Country [40] 0 0
Germany
State/province [40] 0 0
Heidelberg
Country [41] 0 0
Germany
State/province [41] 0 0
Würzburg
Country [42] 0 0
Israel
State/province [42] 0 0
Tel Aviv
Country [43] 0 0
Italy
State/province [43] 0 0
Bologna
Country [44] 0 0
Italy
State/province [44] 0 0
Milano
Country [45] 0 0
Netherlands
State/province [45] 0 0
Amsterdam
Country [46] 0 0
Netherlands
State/province [46] 0 0
Groningen
Country [47] 0 0
Netherlands
State/province [47] 0 0
Rotterdam
Country [48] 0 0
Netherlands
State/province [48] 0 0
Utrecht
Country [49] 0 0
Spain
State/province [49] 0 0
Barcelona
Country [50] 0 0
Spain
State/province [50] 0 0
Madrid
Country [51] 0 0
Spain
State/province [51] 0 0
Pamplona
Country [52] 0 0
Spain
State/province [52] 0 0
Salamanca
Country [53] 0 0
Sweden
State/province [53] 0 0
Uppsala
Country [54] 0 0
Switzerland
State/province [54] 0 0
Bellinzona
Country [55] 0 0
Switzerland
State/province [55] 0 0
Zürich
Country [56] 0 0
United Kingdom
State/province [56] 0 0
Birmingham
Country [57] 0 0
United Kingdom
State/province [57] 0 0
London
Country [58] 0 0
United Kingdom
State/province [58] 0 0
Manchester
Country [59] 0 0
United Kingdom
State/province [59] 0 0
Sutton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Kite, A Gilead Company
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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).
Trial website
https://clinicaltrials.gov/ct2/show/NCT03391466
Trial related presentations / 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.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Kite Study Director
Address 0 0
Kite, A Gilead Company
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03391466