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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03391466
Ethics application status
Date submitted
21/12/2017
Date registered
5/01/2018

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
Treatment: Other - 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.


Treatment: Other: 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
Treatment: Other
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
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Kansas
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United States of America
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Maryland
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United States of America
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Massachusetts
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United States of America
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Michigan
Country [10] 0 0
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Minnesota
Country [11] 0 0
United States of America
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Missouri
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United States of America
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New Jersey
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United States of America
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New York
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United States of America
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Ohio
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Pennsylvania
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United States of America
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Tennessee
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Texas
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Utah
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Virginia
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United States of America
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Washington
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Austria
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Graz
Country [22] 0 0
Austria
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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
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Manitoba
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Canada
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Ontario
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Canada
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Quebec
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Canada
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Halifax
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Canada
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Montréal
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Canada
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Ottawa
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Canada
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Québec
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France
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Lille cedex
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France
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Paris
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France
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Pierre Benite
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France
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Rennes
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Germany
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Dresden
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Germany
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Göttingen
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Germany
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Hamburg
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Germany
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Heidelberg
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Germany
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Würzburg
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Israel
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Tel Aviv
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Italy
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Bologna
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Italy
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Milano
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Netherlands
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Amsterdam
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Netherlands
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Groningen
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Netherlands
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Rotterdam
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Netherlands
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Utrecht
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Spain
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Barcelona
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Spain
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Madrid
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Spain
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Pamplona
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Spain
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Salamanca
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Sweden
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Uppsala
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Switzerland
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Bellinzona
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Switzerland
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Zürich
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United Kingdom
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Birmingham
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United Kingdom
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London
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United Kingdom
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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
Trial website
Trial related presentations / publications
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT03391466