Study to Evaluate the Efficacy and Safety of Axicabtagene Ciloleucel as First-Line Therapy in Participants With High-Risk Large B-Cell Lymphoma
NCT ID: NCT03761056
Last Updated: 2024-12-04
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE2
42 participants
INTERVENTIONAL
2019-01-29
2023-10-12
Brief Summary
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After the end of KTE-C19-112 (ZUMA-12), participants who received an infusion of axicabtagene ciloleucel will complete the remainder of the 15-year follow-up assessments in a separate long-term follow-up study, KT-US-982-5968.
Detailed Description
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Conditions
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Axicabtagene Ciloleucel
Participants will receive cyclophosphamide 500 mg/m\^2/day intravenously (IV) and fludarabine 30 mg/m\^2/day IV conditioning 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. For participants weighing ≥ 100 kg, a maximum flat dose of axicabtagene ciloleucel at 2 x 10\^8 anti-CD19 CAR T cells will be administered.
Participants who achieve partial response or complete response and subsequently experience disease progression will have an option to receive second course of conditioning chemotherapy therapy and axicabtagene ciloleucel. Participants will receive the same axicabtagene ciloleucel regimen as the original target dose anytime during the study.
Axicabtagene Ciloleucel
A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells
Fludarabine
Administered according to package insert
Cyclophosphamide
Administered according to package insert
Interventions
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Axicabtagene Ciloleucel
A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells
Fludarabine
Administered according to package insert
Cyclophosphamide
Administered according to package insert
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* High-grade large B-cell lymphoma
* Individuals must have a positive interim positron emission tomography (PET) (Deauville PET score of 4 or 5) after 2 cycles (PET2+) of chemoimmunotherapy
* No evidence, suspicion and/or history of central nervous system (CNS) involvement of lymphoma
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Absolute neutrophil count ≥ 1000/μL
* Platelet count ≥ 75,000/μL
* Absolute lymphocyte count ≥ 100/μL
* Adequate renal, hepatic, pulmonary, and cardiac function defined as:
* Creatinine clearance (as estimated by Cockcroft Gault) ≥ 60 mL/min
* Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 upper limit of normal (ULN)
* Total bilirubin ≤1.5 mg/dL, except in individuals with Gilbert's syndrome
* Cardiac ejection fraction ≥ 50%, no evidence of pericardial effusion as determined by an echocardiogram (ECHO), and no clinically significant electrocardiogram (ECG) findings
* No clinically significant pleural effusion
* Baseline oxygen saturation \> 92% on room air
Exclusion Criteria
* History of Richter's transformation of chronic lymphocytic leukemia or primary mediastinal B-cell lymphoma
* History of autologous or allogeneic stem cell transplant
* Prior CD19-targeted therapy
* Prior chimeric antigen receptor therapy or other genetically modified T-cell therapy
* Presence or suspicion of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management
* History of human immunodeficiency virus (HIV) infection or acute or chronic active hepatitis B or C infection
* Presence of any indwelling line or drain dedicated central venous access catheters, such as a Port-a-Cath or Hickman catheter, are permitted
* Individuals with detectable cerebrospinal fluid malignant cells, brain metastases, or active CNS lymphoma
* History or presence of CNS disorder, such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement
* History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment
* History of autoimmune disease resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years
* History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months of enrollment
18 Years
ALL
No
Sponsors
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Kite, A Gilead Company
INDUSTRY
Responsible Party
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Principal Investigators
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Kite Study Director
Role: STUDY_DIRECTOR
Kite, A Gilead Company
Locations
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Banner Health MD Anderson Cancer Center
Gilbert, Arizona, United States
City of Hope
Duarte, California, United States
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, United States
Vanderbilt University Medical Center
Nashville, Tennessee, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States
Peter MacCallum Cancer Centre
Melbourne, Victoria, Australia
Hopital Saint Louis
Paris, , France
Countries
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References
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Neelapu SS, Dickinson M, Munoz J, Ulrickson ML, Thieblemont C, Oluwole OO, et al. 739 Primary Analysis of ZUMA-12: A Phase 2 Study of Axicabtagene Ciloleucel (Axi-Cel) As First-Line Therapy in Patients with High-Risk Large B-Cell Lymphoma (LBCL) [Abstract]. 63rd American Society of Hematology (ASH) Annual Meeting and Exposition; 2021 11-14 December.
Neelapu SS, Dickinson M, Ulrickson ML, Oluwole OO, Herrera AF, Thieblemont C, et al. 405 Interim Analysis of ZUMA-12: A Phase 2 Study of Axicabtagene Ciloleucel (Axi-Cel) as First-Line Therapy in Patients (Pts) With High-Risk Large B-Cell Lymphoma (LBCL) [Abstract]. 62nd American Society of Hematology (ASH) Annual Meeting and Exposition Virtual; 2020 05-08 December.
Neelapu SS, Chavez JC, Lin Y, Munoz J, Ujjani CS, Riedell P, et al. ZUMA-12: A Phase 2 Multicenter Study of Axicabtagene Ciloleucel (Axi-Cel) as a First-Line Therapy in Patients (Pts) with High-Risk Large B-Cell Lymphoma (LBCL) [Abstract]. J Clin Oncol 2019;37 (15).
Neelapu SS, Dickinson M, Munoz J, Ulrickson ML, Thieblemont C, Oluwole OO, Herrera AF, Ujjani CS, Lin Y, Riedell PA, Kekre N, de Vos S, Lui C, Milletti F, Dong J, Xu H, Chavez JC. Axicabtagene ciloleucel as first-line therapy in high-risk large B-cell lymphoma: the phase 2 ZUMA-12 trial. Nat Med. 2022 Apr;28(4):735-742. doi: 10.1038/s41591-022-01731-4. Epub 2022 Mar 21.
Chavez JC, Dickinson M, Munoz JL, Ulrickson ML, Thieblemont C, Oluwole OO, et al. 3-Year Analysis of ZUMA-12: A Phase 2 Study of Axicabtagene Ciloleucel (Axi-Cel) As First-Line Therapy in Patients with High-Risk Large B-Cell Lymphoma (LBCL). Blood 2023;142 (Supplement 1):894-7
Chavez JC, Dickinson M, Munoz J, Ulrickson ML, Thieblemont C, Oluwole OO, Herrera AF, Ujjani CS, Lin Y, Riedell PA, Kekre N, de Vos S, Wulff J, Williams CM, Winters J, Kloos I, Xu H, Neelapu SS. Three-year follow-up analysis of first-line axicabtagene ciloleucel for high-risk large B-cell lymphoma: the ZUMA-12 study. Blood. 2025 May 15;145(20):2303-2311. doi: 10.1182/blood.2024027347.
Provided Documents
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Document Type: Study Protocol: Study Protocol Amendment 2
Document Type: Study Protocol: Study Protocol Amendment 3
Document Type: Statistical Analysis Plan: Statistical analysis plan
Document Type: Statistical Analysis Plan: Translational Statistical analysis plan
Related Links
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Gilead Clinical Trials Website
Other Identifiers
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2019-002291-13
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
KTE-C19-112
Identifier Type: -
Identifier Source: org_study_id