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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
10/02/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/03/2031
Actual
Sample size
Target
300
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
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United States of America
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Arizona
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United States of America
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California
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Colorado
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Florida
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Georgia
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Illinois
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Kansas
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Louisiana
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Maryland
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Massachusetts
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Michigan
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Minnesota
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New Jersey
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New York
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North Carolina
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South Dakota
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Tennessee
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Texas
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Utah
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Virginia
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Washington
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Austria
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Innsbruck
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Austria
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Salzburg
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Austria
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St. Poelten
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Austria
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Vienna
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Canada
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Montreal
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Canada
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Ottawa
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Canada
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Toronto
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France
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Bordeaux
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France
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Lille cedex
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France
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Montpellier CEDEX 05
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France
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Paris
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France
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Rennes CEDEX
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Germany
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Berlin
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Germany
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Bonn
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Germany
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Duesseldorf
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Germany
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Erlangen
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Italy
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Bologna
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Italy
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Milano
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Italy
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Rome
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Italy
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Rozzano
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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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Utrecht
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Portugal
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Lisbon
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Portugal
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Porto
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Spain
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Barcelona
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Spain
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Madrid
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Salamanca
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Santander
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Spain
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Valencia
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United Kingdom
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Birmingham
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United Kingdom
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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
[email protected]
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.


Results not provided in https://clinicaltrials.gov/study/NCT05605899