The ANZCTR website will be unavailable from 1pm until 3pm (AEDT) on Wednesday the 30th of October for website maintenance. Please be sure to log out of the system in order to avoid any loss of data.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05605899




Registration number
NCT05605899
Ethics application status
Date submitted
31/10/2022
Date registered
4/11/2022

Titles & IDs
Public title
Study to Compare Axicabtagene Ciloleucel With Standard of Care Therapy as First-line Treatment in Participants With High-risk Large B-cell Lymphoma
Scientific title
An Adaptive Phase 3, Randomized, Open-Label, Multicenter Study to Compare the Efficacy and Safety of Axicabtagene Ciloleucel Versus Standard of Care Therapy as First-Line Therapy in Subjects With High-Risk Large B-Cell Lymphoma (ZUMA-23)
Secondary ID [1] 0 0
2022-501489-24-00
Secondary ID [2] 0 0
KT-US-484-0136
Universal Trial Number (UTN)
Trial acronym
ZUMA-23
Linked study record

Health condition
Health condition(s) or problem(s) studied:
High-risk Large B-cell Lymphoma (LBCL) 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 - Cyclophosphamide
Treatment: Drugs - Fludarabine
Treatment: Drugs - Etoposide
Treatment: Drugs - Rituximab
Treatment: Drugs - Doxorubicin
Treatment: Drugs - Vincristine
Treatment: Drugs - Prednisone

Experimental: Axicabtagene Ciloleucel - Participants will receive cyclophosphamide 500 mg/m\^2/day intravenously (IV) and fludarabine 30 mg/m\^2/day IV lymphodepletion chemotherapy for 3 days followed by axicabtagene ciloleucel administered as a single IV infusion at a target dose of 2 x 10\^6 anti-cluster of differentiation (CD)19 chimeric antigen receptor (CAR) transduced autologous T cells/kg on Day 0.

Active comparator: Standard of Care Therapy - Participants will receive the investigator's choice of one of the following therapies/dosing schedules:

* Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for a total of 6 cycles (21-day cycle)

* Rituximab 375 mg/m\^2 on Day 1
* Cyclophosphamide 750 mg/m\^2 on Day 1
* Doxorubicin 50 mg/m\^2 on Day 1
* Vincristine 1.4 mg/m\^2 (maximum 2 mg) on Day 1
* Prednisone 40 mg/m\^2 on Day 1 through Day 5
* Dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) for a total of 6 cycles (21-day cycle)

* Rituximab 375 mg/m\^2 on Day 1
* Etoposide 50 mg/m\^2 on Days 1 to 4
* Doxorubicin 10 mg/m\^2 on Days 1 to 4
* Vincristine 0.4 mg/m\^2 on Days 1 to 4
* Cyclophosphamide 750 mg/m\^2 on Day 5
* Prednisone 60 mg/m\^2 twice daily on Days 1 to 5


Treatment: Other: Axicabtagene Ciloleucel
A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells

Treatment: Drugs: Cyclophosphamide
Administered intravenously

Treatment: Drugs: Fludarabine
Administered intravenously

Treatment: Drugs: Etoposide
Administered intravenously

Treatment: Drugs: Rituximab
Administered intravenously

Treatment: Drugs: Doxorubicin
Administered intravenously

Treatment: Drugs: Vincristine
Administered intravenously

Treatment: Drugs: Prednisone
Administered orally

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) by Blinded Central Assessment
Timepoint [1] 0 0
Up to 5 years
Secondary outcome [1] 0 0
Progression-free Survival (PFS) by Blinded Central Assessment
Timepoint [1] 0 0
Up to 5 years
Secondary outcome [2] 0 0
Overall Survival
Timepoint [2] 0 0
Up to 5 years
Secondary outcome [3] 0 0
PFS by Investigator Assessment
Timepoint [3] 0 0
Up to 5 years
Secondary outcome [4] 0 0
Complete Response (CR) Rate by Blinded Central Assessment
Timepoint [4] 0 0
Up to 5 years
Secondary outcome [5] 0 0
Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths
Timepoint [5] 0 0
First dose date up to 5 years plus 30 days
Secondary outcome [6] 0 0
Percentage of Participants Experiencing Clinically Significant Changes in Safety Laboratory Values
Timepoint [6] 0 0
First dose date up to 5 years plus 30 days
Secondary outcome [7] 0 0
Change From Baseline in the European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire-30 (EORTC QLQ-C30) Score
Timepoint [7] 0 0
Baseline, Month 18
Secondary outcome [8] 0 0
Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Non-Hodgkin Lymphoma High Grade Module (EORTC QLQ-NHL-HG29) Score
Timepoint [8] 0 0
Baseline, Month 18
Secondary outcome [9] 0 0
Change From Baseline in the European Quality of Life Five Dimensions Five Levels Questionnaire (EQ-5D-5L) Score
Timepoint [9] 0 0
Baseline, Month 18

Eligibility
Key inclusion criteria
Key

* Histologically confirmed large B cell lymphoma (LBCL) based on 2016 World Health Organization (WHO) classification by local pathology lab assessment, including of the following:

* Diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS)
* High-grade B-cell lymphoma (HGBL)
* Note: Transformed DLBCL from follicular lymphoma or from marginal zone lymphoma is eligible if no prior treatment with anthracycline-containing regimen.
* High-risk disease defined as an International Prognostic Index (IPI) score of 4 or 5 at initial diagnosis.
* Have received only 1 cycle of rituximab plus chemotherapy (R-chemotherapy).
* Adequate bone marrow, renal, hepatic, pulmonary, and cardiac function.
* Females of childbearing potential must have a negative serum or urine pregnancy test.

Key
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* The following WHO 2016 subcategories by local assessment:

* T-cell/histiocyte-rich LBCL
* Primary DLBCL of the central nervous system (CNS)
* Primary mediastinal (thymic) LBCL
* B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classical Hodgkin lymphoma
* Burkitt lymphoma
* History of Richter's transformation of chronic lymphocytic leukemia
* Presence of detectable cerebrospinal fluid (CSF)-malignant cells, brain metastases, or a history of CNS involvement of lymphoma.
* Presence of cardiac lymphoma involvement.
* Any prior treatment for LBCL other than the 1 cycle of R-chemotherapy.
* History of severe immediate hypersensitivity reaction to any of the agents used in this study.
* Presence of CNS disorder. History of stroke, transient ischemic attack, or posterior reversible encephalopathy syndrome (PRES) within 12 months prior to enrollment.
* History of acute or chronic active hepatitis B or C infection.
* Positive for human immunodeficiency virus (HIV) unless taking appropriate anti-HIV medications, with an undetectable viral load by PCR and with a cluster of differentiation 4 (CD4) count > 200 cells/uL.
* Medical conditions or residual toxicities from prior therapies likely to interfere with assessment of safety or efficacy of study treatment. Please refer to protocol for further details.
* History of clinically significant cardiac disease within 12 months before enrollment.
* History of any medical condition requiring maintenance systemic immunosuppression/systemic disease modifying agents within the last 2 years.

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
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 0 0
Royal Brisbane and Women's Hospital - South Brisbane
Recruitment hospital [3] 0 0
Peter MacCallum Cancer Center - Melbourne
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
4101 - South Brisbane
Recruitment postcode(s) [3] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
State/province [7] 0 0
Illinois
Country [8] 0 0
United States of America
State/province [8] 0 0
Kansas
Country [9] 0 0
United States of America
State/province [9] 0 0
Louisiana
Country [10] 0 0
United States of America
State/province [10] 0 0
Maryland
Country [11] 0 0
United States of America
State/province [11] 0 0
Massachusetts
Country [12] 0 0
United States of America
State/province [12] 0 0
Michigan
Country [13] 0 0
United States of America
State/province [13] 0 0
Minnesota
Country [14] 0 0
United States of America
State/province [14] 0 0
New Jersey
Country [15] 0 0
United States of America
State/province [15] 0 0
New York
Country [16] 0 0
United States of America
State/province [16] 0 0
North Carolina
Country [17] 0 0
United States of America
State/province [17] 0 0
South Dakota
Country [18] 0 0
United States of America
State/province [18] 0 0
Tennessee
Country [19] 0 0
United States of America
State/province [19] 0 0
Texas
Country [20] 0 0
United States of America
State/province [20] 0 0
Utah
Country [21] 0 0
United States of America
State/province [21] 0 0
Virginia
Country [22] 0 0
United States of America
State/province [22] 0 0
Washington
Country [23] 0 0
Austria
State/province [23] 0 0
Innsbruck
Country [24] 0 0
Austria
State/province [24] 0 0
Salzburg
Country [25] 0 0
Austria
State/province [25] 0 0
St. Poelten
Country [26] 0 0
Austria
State/province [26] 0 0
Vienna
Country [27] 0 0
Canada
State/province [27] 0 0
Montreal
Country [28] 0 0
Canada
State/province [28] 0 0
Ottawa
Country [29] 0 0
Canada
State/province [29] 0 0
Toronto
Country [30] 0 0
France
State/province [30] 0 0
Bordeaux
Country [31] 0 0
France
State/province [31] 0 0
Lille cedex
Country [32] 0 0
France
State/province [32] 0 0
Montpellier CEDEX 05
Country [33] 0 0
France
State/province [33] 0 0
Paris
Country [34] 0 0
France
State/province [34] 0 0
Rennes CEDEX
Country [35] 0 0
Germany
State/province [35] 0 0
Berlin
Country [36] 0 0
Germany
State/province [36] 0 0
Bonn
Country [37] 0 0
Germany
State/province [37] 0 0
Duesseldorf
Country [38] 0 0
Germany
State/province [38] 0 0
Erlangen
Country [39] 0 0
Italy
State/province [39] 0 0
Bologna
Country [40] 0 0
Italy
State/province [40] 0 0
Milano
Country [41] 0 0
Italy
State/province [41] 0 0
Rome
Country [42] 0 0
Italy
State/province [42] 0 0
Rozzano
Country [43] 0 0
Netherlands
State/province [43] 0 0
Amsterdam
Country [44] 0 0
Netherlands
State/province [44] 0 0
Groningen
Country [45] 0 0
Netherlands
State/province [45] 0 0
Utrecht
Country [46] 0 0
Portugal
State/province [46] 0 0
Lisbon
Country [47] 0 0
Portugal
State/province [47] 0 0
Porto
Country [48] 0 0
Spain
State/province [48] 0 0
Barcelona
Country [49] 0 0
Spain
State/province [49] 0 0
Madrid
Country [50] 0 0
Spain
State/province [50] 0 0
Salamanca
Country [51] 0 0
Spain
State/province [51] 0 0
Santander
Country [52] 0 0
Spain
State/province [52] 0 0
Valencia
Country [53] 0 0
United Kingdom
State/province [53] 0 0
Birmingham
Country [54] 0 0
United Kingdom
State/province [54] 0 0
Southampton

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
Medical Information
Address 0 0
Country 0 0
Phone 0 0
844-454-5483(1-844-454-KITE)
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?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.