Back to resultsStudy to Compare Axicabtagene Ciloleucel With Standard of Care Therapy as First-line Treatment in Participants With High-risk Large B-cell Lymphoma (ZUMA-23)
Primary Purpose
High-risk Large B-cell Lymphoma (LBCL)
Status
Recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Axicabtagene Ciloleucel
Cyclophosphamide
Fludarabine
Etoposide
Rituximab
Doxorubicin
Vincristine
Prednisone
Sponsored by
About this trial
This is an interventional treatment trial for High-risk Large B-cell Lymphoma (LBCL)
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 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 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.
Sites / Locations
- University of Alabama HospitalRecruiting
- Banner MD Anderson Cancer CenterRecruiting
- UC San Diego Moores Cancer CenterRecruiting
- University of California Los Angeles (UCLA)Recruiting
- Stanford Cancer InstituteRecruiting
- Colorado Blood Cancer InstituteRecruiting
- The University of Kansas HospitalRecruiting
- University of MD Greenebaum Comprehensive Cancer CenterRecruiting
- Dana-Farber Cancer InstituteRecruiting
- University of MichiganRecruiting
- John Theurer Cancer Center at Hackensack University Medical CenterRecruiting
- Montefiore Medical CenterRecruiting
- Columbia University Medical CenterRecruiting
- Avera Cancer InstituteRecruiting
- Tennessee Oncology, PLLCRecruiting
- The University of Texas, MD Anderson Cancer CenterRecruiting
- Fred Hutchinson Cancer CenterRecruiting
- Royal Prince Alfred HospitalRecruiting
- Royal Brisbane and Women's HospitalRecruiting
- Peter MacCallum Cancer CenterRecruiting
- Zuniklinikum Salzburg, Landeskrankenhaus, Universitatsklinik fur Innere Medizin III der PMURecruiting
- The Ottowa Hospital- General CampusRecruiting
- University Medical Center GroningenRecruiting
- Centro Hospitalar Universitario Lisboa Norte, E.P.E. - Hospital de Santa MariaRecruiting
- Hospital Universitario de SalamancaRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Axicabtagene Ciloleucel
Standard of Care Therapy
Arm Description
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.
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
Outcomes
Primary Outcome Measures
Event-free Survival (EFS) by Central Assessment
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
Progression-free Survival (PFS) by Investigator Assessment
PFS is defined as the time from randomization to disease progression or death due to any cause.
Overall Survival
OS is defined as the time from randomization to death due to any cause.
PFS by Central Assessment
PFS is defined as the time from randomization to disease progression or death due to any cause.
Complete Response (CR) Rate by Central Assessment
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
Percentage of Participants Experiencing Clinically Significant Changes in Safety Laboratory Values
Change From Baseline in the European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire-30 (EORTC QLQ-C30) Score
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
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
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.
Full Information
NCT ID
NCT05605899
First Posted
October 31, 2022
Last Updated
October 18, 2023
Sponsor
Kite, A Gilead Company
1. Study Identification
Unique Protocol Identification Number
NCT05605899
Brief Title
Study to Compare Axicabtagene Ciloleucel With Standard of Care Therapy as First-line Treatment in Participants With High-risk Large B-cell Lymphoma
Acronym
ZUMA-23
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
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 10, 2023 (Actual)
Primary Completion Date
March 2031 (Anticipated)
Study Completion Date
March 2031 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Kite, A Gilead Company
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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 the last study participant is randomized, 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
High-risk Large B-cell Lymphoma (LBCL)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
300 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Axicabtagene Ciloleucel
Arm Type
Experimental
Arm Description
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.
Arm Title
Standard of Care Therapy
Arm Type
Active Comparator
Arm Description
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
Intervention Type
Biological
Intervention Name(s)
Axicabtagene Ciloleucel
Other Intervention Name(s)
Yescarta®, Axi-cel
Intervention Description
A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
Administered intravenously
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Intervention Description
Administered intravenously
Intervention Type
Drug
Intervention Name(s)
Etoposide
Intervention Description
Administered intravenously
Intervention Type
Drug
Intervention Name(s)
Rituximab
Intervention Description
Administered intravenously
Intervention Type
Drug
Intervention Name(s)
Doxorubicin
Intervention Description
Administered intravenously
Intervention Type
Drug
Intervention Name(s)
Vincristine
Intervention Description
Administered intravenously
Intervention Type
Drug
Intervention Name(s)
Prednisone
Intervention Description
Administered orally
Primary Outcome Measure Information:
Title
Event-free Survival (EFS) by Central Assessment
Description
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.
Time Frame
Up to 5 years
Secondary Outcome Measure Information:
Title
Progression-free Survival (PFS) by Investigator Assessment
Description
PFS is defined as the time from randomization to disease progression or death due to any cause.
Time Frame
Up to 5 years
Title
Overall Survival
Description
OS is defined as the time from randomization to death due to any cause.
Time Frame
Up to 5 years
Title
PFS by Central Assessment
Description
PFS is defined as the time from randomization to disease progression or death due to any cause.
Time Frame
Up to 5 years
Title
Complete Response (CR) Rate by Central Assessment
Description
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.
Time Frame
Up to 5 years
Title
Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths
Time Frame
First dose date up to 5 years plus 30 days
Title
Percentage of Participants Experiencing Clinically Significant Changes in Safety Laboratory Values
Time Frame
First dose date up to 5 years plus 30 days
Title
Change From Baseline in the European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire-30 (EORTC QLQ-C30) Score
Description
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.
Time Frame
Baseline, Month 18
Title
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
Description
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.
Time Frame
Baseline, Month 18
Title
Change From Baseline in the European Quality of Life Five Dimensions Five Levels Questionnaire (EQ-5D-5L) Score
Description
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.
Time Frame
Baseline, Month 18
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
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 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Medical Information
Phone
844-454-5483(1-844-454-KITE)
Email
medinfo@kitepharma.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kite Study Director
Organizational Affiliation
Kite, A Gilead Company
Official's Role
Study Director
Facility Information:
Facility Name
University of Alabama Hospital
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Individual Site Status
Recruiting
Facility Name
Banner MD Anderson Cancer Center
City
Gilbert
State/Province
Arizona
ZIP/Postal Code
85234
Country
United States
Individual Site Status
Recruiting
Facility Name
UC San Diego Moores Cancer Center
City
La Jolla
State/Province
California
ZIP/Postal Code
92093
Country
United States
Individual Site Status
Recruiting
Facility Name
University of California Los Angeles (UCLA)
City
Los Angeles
State/Province
California
ZIP/Postal Code
90025
Country
United States
Individual Site Status
Recruiting
Facility Name
Stanford Cancer Institute
City
Palo Alto
State/Province
California
ZIP/Postal Code
94305
Country
United States
Individual Site Status
Recruiting
Facility Name
Colorado Blood Cancer Institute
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Individual Site Status
Recruiting
Facility Name
The University of Kansas Hospital
City
Westwood
State/Province
Kansas
ZIP/Postal Code
66205
Country
United States
Individual Site Status
Recruiting
Facility Name
University of MD Greenebaum Comprehensive Cancer Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Individual Site Status
Recruiting
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Individual Site Status
Recruiting
Facility Name
John Theurer Cancer Center at Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Individual Site Status
Recruiting
Facility Name
Montefiore Medical Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Individual Site Status
Recruiting
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Individual Site Status
Recruiting
Facility Name
Avera Cancer Institute
City
Sioux Falls
State/Province
South Dakota
ZIP/Postal Code
57105
Country
United States
Individual Site Status
Recruiting
Facility Name
Tennessee Oncology, PLLC
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Individual Site Status
Recruiting
Facility Name
The University of Texas, MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Name
Fred Hutchinson Cancer Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Individual Site Status
Recruiting
Facility Name
Royal Prince Alfred Hospital
City
Camperdown
State/Province
New South Wales
ZIP/Postal Code
2050
Country
Australia
Individual Site Status
Recruiting
Facility Name
Royal Brisbane and Women's Hospital
City
South Brisbane
State/Province
Queensland
ZIP/Postal Code
4101
Country
Australia
Individual Site Status
Recruiting
Facility Name
Peter MacCallum Cancer Center
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3000
Country
Australia
Individual Site Status
Recruiting
Facility Name
Zuniklinikum Salzburg, Landeskrankenhaus, Universitatsklinik fur Innere Medizin III der PMU
City
Salzburg
ZIP/Postal Code
5020
Country
Austria
Individual Site Status
Recruiting
Facility Name
The Ottowa Hospital- General Campus
City
Ottawa
ZIP/Postal Code
K1H 8L6
Country
Canada
Individual Site Status
Recruiting
Facility Name
University Medical Center Groningen
City
Groningen
ZIP/Postal Code
9700 RB
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
Centro Hospitalar Universitario Lisboa Norte, E.P.E. - Hospital de Santa Maria
City
Lisbon
Country
Portugal
Individual Site Status
Recruiting
Facility Name
Hospital Universitario de Salamanca
City
Salamanca
ZIP/Postal Code
37007
Country
Spain
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
No
Links:
URL
http://www.gileadclinicaltrials.com/study/?id=KT-US-484-0136
Description
Gilead Clinical Trials Website
Learn more about this trial
Study to Compare Axicabtagene Ciloleucel With Standard of Care Therapy as First-line Treatment in Participants With High-risk Large B-cell Lymphoma
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