Clinical trial NCT05605899: Study to Compare Axicabtagene Ciloleucel With Standard of Care Therapy as First-line Treatment in Participants With High-risk Large B-cell Lymphoma
Official 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: High-risk Large B-cell Lymphoma (LBCL)
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2022-11-04
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this clinical study is to compare the study drug, axicabtagene ciloleucel, versus standard of care (SOC) in first-line therapy in participants with high-risk large B-cell lymphoma.

Detailed description: Five years after randomization, participants who have received axicabtagene ciloleucel will transition to a separate long-term follow-up study (study KT-US-982-5968) to complete the remainder of the 15-year follow-up assessments.

Eligibility criteria: Key Inclusion Criteria:

* 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 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.

Primary outcomes:
measure: Event-free Survival (EFS) by Blinded Central Assessment
timeFrame: Up to 5 years
Secondary outcomes:
measure: Progression-free Survival (PFS) by Blinded Central Assessment
timeFrame: Up to 5 years
measure: Overall Survival
timeFrame: Up to 5 years
measure: PFS by Investigator Assessment
timeFrame: Up to 5 years
measure: Complete Response (CR) Rate by Blinded Central Assessment
timeFrame: Up to 5 years
measure: Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths
timeFrame: First dose date up to 5 years plus 30 days
measure: Percentage of Participants Experiencing Clinically Significant Changes in Safety Laboratory Values
timeFrame: First dose date up to 5 years plus 30 days
measure: Change From Baseline in the European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire-30 (EORTC QLQ-C30) Score
timeFrame: Baseline, Month 18
measure: 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
timeFrame: Baseline, Month 18
measure: Change From Baseline in the European Quality of Life Five Dimensions Five Levels Questionnaire (EQ-5D-5L) Score
timeFrame: Baseline, Month 18
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Hospital
state: Alabama
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: Phoenix
country: United States
facility: Mayo Clinic
state: Arizona
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: University of California Los Angeles (UCLA)
state: California
city: Palo Alto
country: United States
facility: Stanford Cancer Institute
state: California
city: Denver
country: United States
facility: Colorado Blood Cancer Institute
state: Colorado
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Augusta
country: United States
facility: Georgia Cancer Center at Augusta University
state: Georgia
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Westwood
country: United States
facility: The University of Kansas Hospital
state: Kansas
city: Shelbyville
country: United States
facility: Norton Cancer Institute, St. Matthews Campus
state: Kentucky
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Baltimore
country: United States
facility: University of MD Greenebaum Comprehensive Cancer Center
state: Maryland
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center Outpatient Pharmacy
state: Minnesota
city: Hackensack
country: United States
facility: John Theurer Cancer Center at Hackensack University Medical Center
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College - NewYork Presbyterian Hospital
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Charlotte
country: United States
facility: Novant Health Cancer Institute- Hematology
state: North Carolina
city: Cincinnati
country: United States
facility: Oncology Hematology Care Clinical Trials, LLC
state: Ohio
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center
state: Pennsylvania
city: Greenville
country: United States
facility: Prisma Health Cancer Institute
state: South Carolina
city: Sioux Falls
country: United States
facility: Avera Cancer Institute
state: South Dakota
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Nashville
country: United States
facility: Henry-Joyce Cancer Center
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: The University of Texas, MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: Intermountain LDS Hospital/Blood and Marrow Transplant/ Acute Leukemia Program
state: Utah
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center
state: Washington
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: South Brisbane
country: Australia
facility: Royal Brisbane and Women's Hospital
state: Queensland
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Center
state: Victoria
city: Innsbruck
country: Austria
facility: Medizinische Universität Innsbruck
city: Salzburg
country: Austria
facility: Zuniklinikum Salzburg, Landeskrankenhaus, Universitatsklinik fur Innere Medizin III der PMU
city: St. Poelten
country: Austria
facility: Universitätsklinikum St. Pölten
city: Vienna
country: Austria
facility: Medizinische Universität Wien (AKH Wien, Medical University Vienna and General Hospital Vienna)
city: Montreal
country: Canada
facility: Jewish General Hospital
city: Ottawa
country: Canada
facility: The Ottowa Hospital- General Campus
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
city: Bordeaux
country: France
facility: CHU Bordeaux-Hopital Haut-Leveque
city: Cedex Lyon 08
country: France
facility: Centre Leon Berard
city: Dijon
country: France
facility: CHU Dijon
city: Lille cedex
country: France
facility: Hopital Claude Huriez CHU Lille, Service Maladies du sang
city: Montpellier CEDEX 05
country: France
facility: Hopital Saint Eloi
city: Nice
country: France
facility: Centre Hospitalier Universitaire de Nice
city: Paris
country: France
facility: Hopital Henri MONDOR, APHP
city: Rennes CEDEX
country: France
facility: CHU Pontchaillou
city: Toulouse
country: France
facility: Centre Hospitalier Universitaire(CHU) de Toulouse
city: Berlin
country: Germany
facility: Helios Klinikum Berlin-Buch
city: Berlin
country: Germany
facility: Charite Universitaetsmedizin Berlin
city: Bonn
country: Germany
facility: Universitätsklinikum bonn, medizinische klinik III
city: Duesseldorf
country: Germany
facility: Uniklinikum Duesseldorf, Klinik fuer Haematologie, Onkologie und klinische Immunologie
city: Erlangen
country: Germany
facility: Universitätsklinik Erlangen
city: Bologna
country: Italy
facility: IRCCS Azienda Ospedaliero-Universitaria di Bologna
city: Brescia
country: Italy
facility: ASST Degli Spedali Civili di Brescia
city: Milano
country: Italy
facility: Ospedale San Raffaele
city: Perugia
country: Italy
facility: Azienda Ospedaliera di Perugia - Ospedale S. Maria della Misericordia
city: Reggio Calabria
country: Italy
facility: Grande Ospedale Metropolitano Bianchi Melacrino Morelli
city: Rome
country: Italy
facility: Universita Cattolica del Sacro Cuore
city: Rozzano
country: Italy
facility: IRCCS Istituto Clinico Humanitas
city: Kyoto
country: Japan
facility: University Hospital, Kyoto Prefectural University of Medicine
city: Miyagi
country: Japan
facility: Tohoku University Hospital
city: Osaka
country: Japan
facility: Osaka University Hospital
city: Tokyo
country: Japan
facility: Juntendo University Hospital
city: Tokyo
country: Japan
facility: Tokyo Metropolitan Komagome Hospital
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Maastricht
country: Netherlands
facility: Maastricht Universitair Medisch Centrum
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht
city: Lisbon
country: Portugal
facility: Centro Hospitalar Universitario Lisboa Norte, E.P.E. - Hospital de Santa Maria
city: Lisbon
country: Portugal
facility: Instituto Portugues de Oncologia de Lisboa Francisco Gentil - E.P.E.
city: Porto
country: Portugal
facility: Instituto Portugues de Oncologia do Porto Francisco Gentil, E.P.E.
city: Barcelona
country: Spain
facility: Institut Catala d'Oncologia
city: Barcelona
country: Spain
facility: Hospital Universitari Vall D'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: Santander
country: Spain
facility: Hospital Universitario Marqués de Valdecilla
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
city: Birmingham
country: United Kingdom
facility: Addenbrookes Hospital (Cambridge University Hospitals NHS Foundation Trust)
city: Southampton
country: United Kingdom
facility: University Hospitals Southampton
Study officials:
affiliation: Kite, A Gilead Company
name: Kite Study Director
role: STUDY_DIRECTOR
References: