Study to Compare Axicabtagene Ciloleucel With Standard of Care Therapy as First-line Treatment in Participants With High-risk Large B-cell Lymphoma
- Conditions
- High-risk Large B-cell Lymphoma (LBCL)
- Interventions
- Registration Number
- NCT05605899
- Lead Sponsor
- Kite, A Gilead Company
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 300
-
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
-
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.
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Presence of CNS disorder. History of stroke, transient ischemic attack, or posterior reversible encephalopathy syndrome (PRES) within 12 months prior to enrollment.
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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.
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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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Axicabtagene Ciloleucel Cyclophosphamide 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. Standard of Care Therapy Rituximab 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 Axicabtagene Ciloleucel Fludarabine 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. Axicabtagene Ciloleucel 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. Standard of Care Therapy Cyclophosphamide 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 Standard of Care Therapy Etoposide 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 Standard of Care Therapy Doxorubicin 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 Standard of Care Therapy Prednisone 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 Standard of Care Therapy Vincristine 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
- Primary Outcome Measures
Name Time Method Event-free Survival (EFS) by Blinded Central Assessment Up to 5 years EFS, is defined as the time from randomization to the earliest occurrence of death due to any cause, disease progression/relapse, initiation of any non-protocol specified subsequent new lymphoma therapy for the treatment of residual disease or Biopsy-proven residual disease at the Month 6 disease assessment or later, regardless of whether subsequent new lymphoma therapy is initiated or not.
- Secondary Outcome Measures
Name Time Method PFS by Investigator Assessment Up to 5 years PFS is defined as the time from randomization to disease progression or death due to any cause.
Overall Survival Up to 5 years OS is defined as the time from randomization to death due to any cause.
Progression-free Survival (PFS) by Blinded Central Assessment Up to 5 years PFS is defined as the time from randomization to disease progression or death due to any cause.
Complete Response (CR) Rate by Blinded Central Assessment Up to 5 years CR rate is defined as the proportion of participants who have achieved CR per Lugano classification after treatment completion and prior to subsequent new off protocol anti-lymphoma therapy.
Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths First dose date up to 5 years plus 30 days Percentage of Participants Experiencing Clinically Significant Changes in Safety Laboratory Values First dose date up to 5 years plus 30 days Change From Baseline in the European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire-30 (EORTC QLQ-C30) Score Baseline, Month 18 The EORTC-QLQ-C30 is a multi-item questionnaire measuring the following content: five (5) multi-item functional scales, three (3) multi-item symptom scales, six (6) symptom single-item scales, one (1) global health status scale, and one (1) global health-related quality of life (HRQoL). Each scale is measured from 0 to 100 after a linear transformation. Higher scores for functioning scales and for the Global Health Status or Global HRQoL scales indicate a higher level of functioning and a better HRQoL respectively, whereas higher scores in symptom scales represent a higher level of symptoms.
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 Baseline, Month 18 The EORTC QLQ-NHL-HG29 is a 29-item patient-reported assessment measuring patients' high-grade NHL-specific symptoms and functioning. The 29 items assess symptom burden due to disease and/or treatment, fatigue/physical condition, neuropathy, emotional impacts, and worries/fears health and functioning. Each scale is measured from 0 to 100 after a linear transformation. Higher scores for functional scales indicate a higher level of functioning and a better HRQoL, whereas higher scores in symptom scales represent a higher level of symptoms.
Change From Baseline in the European Quality of Life Five Dimensions Five Levels Questionnaire (EQ-5D-5L) Score Baseline, Month 18 The EQ-5D-5L questionnaire is a generic measure of health status that provides a simple descriptive profile and a single index value. The EQ-5D-5L comprises 2 components: a questionnaire covering 5 dimensions and a tariff of values based upon direct valuations of health states using a visual analog scale (VAS). Rating gets recorded on a vertical VAS in which the endpoints are labeled best imaginable health state is 100 (on the top) and worst imaginable health state is 0 (on the bottom). Higher scores of EQ VAS indicate better health.
Trial Locations
- Locations (90)
Hospital Universitario Marqués de Valdecilla
🇪🇸Santander, Spain
Hospital Universitari Vall D'Hebron
🇪🇸Barcelona, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
University of Alabama Hospital
🇺🇸Birmingham, Alabama, United States
Banner MD Anderson Cancer Center
🇺🇸Gilbert, Arizona, United States
Mayo Clinic
🇺🇸Phoenix, Arizona, United States
UC San Diego Moores Cancer Center
🇺🇸La Jolla, California, United States
University of California Los Angeles (UCLA)
🇺🇸Los Angeles, California, United States
Stanford Cancer Institute
🇺🇸Palo Alto, California, United States
Colorado Blood Cancer Institute
🇺🇸Denver, Colorado, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Georgia Cancer Center at Augusta University
🇺🇸Augusta, Georgia, United States
Northwestern Memorial Hospital
🇺🇸Chicago, Illinois, United States
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
University of Iowa
🇺🇸Iowa City, Iowa, United States
The University of Kansas Hospital
🇺🇸Westwood, Kansas, United States
Norton Cancer Institute, St. Matthews Campus
🇺🇸Shelbyville, Kentucky, United States
Ochsner Clinic Foundation
🇺🇸New Orleans, Louisiana, United States
University of MD Greenebaum Comprehensive Cancer Center
🇺🇸Baltimore, Maryland, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Mayo Clinic Cancer Center Outpatient Pharmacy
🇺🇸Rochester, Minnesota, United States
John Theurer Cancer Center at Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Weill Cornell Medical College - NewYork Presbyterian Hospital
🇺🇸New York, New York, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
University of Rochester Medical Center
🇺🇸Rochester, New York, United States
Novant Health Cancer Institute- Hematology
🇺🇸Charlotte, North Carolina, United States
Oncology Hematology Care Clinical Trials, LLC
🇺🇸Cincinnati, Ohio, United States
UPMC Hillman Cancer Center
🇺🇸Pittsburgh, Pennsylvania, United States
Prisma Health Cancer Institute
🇺🇸Greenville, South Carolina, United States
Avera Cancer Institute
🇺🇸Sioux Falls, South Dakota, United States
Tennessee Oncology, PLLC
🇺🇸Nashville, Tennessee, United States
Henry-Joyce Cancer Center
🇺🇸Nashville, Tennessee, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
The University of Texas, MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Intermountain LDS Hospital/Blood and Marrow Transplant/ Acute Leukemia Program
🇺🇸Salt Lake City, Utah, United States
Virginia Commonwealth University
🇺🇸Richmond, Virginia, United States
Fred Hutchinson Cancer Center
🇺🇸Seattle, Washington, United States
Royal Prince Alfred Hospital
🇦🇺Camperdown, New South Wales, Australia
Royal Brisbane and Women's Hospital
🇦🇺South Brisbane, Queensland, Australia
Peter MacCallum Cancer Center
🇦🇺Melbourne, Victoria, Australia
Medizinische Universität Innsbruck
🇦🇹Innsbruck, Austria
Zuniklinikum Salzburg, Landeskrankenhaus, Universitatsklinik fur Innere Medizin III der PMU
🇦🇹Salzburg, Austria
Universitätsklinikum St. Pölten
🇦🇹St. Poelten, Austria
Medizinische Universität Wien (AKH Wien, Medical University Vienna and General Hospital Vienna)
🇦🇹Vienna, Austria
Jewish General Hospital
🇨🇦Montreal, Canada
The Ottowa Hospital- General Campus
🇨🇦Ottawa, Canada
Princess Margaret Cancer Centre
🇨🇦Toronto, Canada
CHU Bordeaux-Hopital Haut-Leveque
🇫🇷Bordeaux, France
Centre Leon Berard
🇫🇷Cedex Lyon 08, France
CHU Dijon
🇫🇷Dijon, France
Hopital Claude Huriez CHU Lille, Service Maladies du sang
🇫🇷Lille cedex, France
Hopital Saint Eloi
🇫🇷Montpellier CEDEX 05, France
Centre Hospitalier Universitaire de Nice
🇫🇷Nice, France
Hopital Henri MONDOR, APHP
🇫🇷Paris, France
CHU Pontchaillou
🇫🇷Rennes CEDEX, France
Hospital Universitario de Salamanca
🇪🇸Salamanca, Spain
Centre Hospitalier Universitaire(CHU) de Toulouse
🇫🇷Toulouse, France
Helios Klinikum Berlin-Buch
🇩🇪Berlin, Germany
Charite Universitaetsmedizin Berlin
🇩🇪Berlin, Germany
Universitätsklinikum bonn, medizinische klinik III
🇩🇪Bonn, Germany
Uniklinikum Duesseldorf, Klinik fuer Haematologie, Onkologie und klinische Immunologie
🇩🇪Duesseldorf, Germany
Universitätsklinik Erlangen
🇩🇪Erlangen, Germany
IRCCS Azienda Ospedaliero-Universitaria di Bologna
🇮🇹Bologna, Italy
ASST Degli Spedali Civili di Brescia
🇮🇹Brescia, Italy
Ospedale San Raffaele
🇮🇹Milano, Italy
Azienda Ospedaliera di Perugia - Ospedale S. Maria della Misericordia
🇮🇹Perugia, Italy
Grande Ospedale Metropolitano Bianchi Melacrino Morelli
🇮🇹Reggio Calabria, Italy
Universita Cattolica del Sacro Cuore
🇮🇹Rome, Italy
IRCCS Istituto Clinico Humanitas
🇮🇹Rozzano, Italy
University Hospital, Kyoto Prefectural University of Medicine
🇯🇵Kyoto, Japan
Tohoku University Hospital
🇯🇵Miyagi, Japan
Osaka University Hospital
🇯🇵Osaka, Japan
Juntendo University Hospital
🇯🇵Tokyo, Japan
Tokyo Metropolitan Komagome Hospital
🇯🇵Tokyo, Japan
Academisch Medisch Centrum
🇳🇱Amsterdam, Netherlands
University Medical Center Groningen
🇳🇱Groningen, Netherlands
Leiden University Medical Center
🇳🇱Leiden, Netherlands
Maastricht Universitair Medisch Centrum
🇳🇱Maastricht, Netherlands
Universitair Medisch Centrum Utrecht
🇳🇱Utrecht, Netherlands
Centro Hospitalar Universitario Lisboa Norte, E.P.E. - Hospital de Santa Maria
🇵🇹Lisbon, Portugal
Instituto Portugues de Oncologia de Lisboa Francisco Gentil - E.P.E.
🇵🇹Lisbon, Portugal
Instituto Portugues de Oncologia do Porto Francisco Gentil, E.P.E.
🇵🇹Porto, Portugal
Institut Catala d'Oncologia
🇪🇸Barcelona, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
Hospital Clínico Universitario de Valencia
🇪🇸Valencia, Spain
Addenbrookes Hospital (Cambridge University Hospitals NHS Foundation Trust)
🇬🇧Birmingham, United Kingdom
University Hospitals Southampton
🇬🇧Southampton, United Kingdom