Efficacy and Safety of Axicabtagene Ciloleucel as First-Line Therapy in Participants With High-Risk Large B-Cell Lymphoma (ZUMA-12)
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT03761056 |
Recruitment Status :
Active, not recruiting
First Posted : December 3, 2018
Last Update Posted : February 28, 2022
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Condition or disease | Intervention/treatment | Phase |
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B-cell Lymphoma | Biological: Axicabtagene Ciloleucel Drug: Fludarabine Drug: Cyclophosphamide | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 40 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Phase 2 Multicenter Study Evaluating the Efficacy and Safety of Axicabtagene Ciloleucel as First-Line Therapy in Subjects With High-Risk Large B-Cell Lymphoma (ZUMA-12) |
Actual Study Start Date : | January 29, 2019 |
Actual Primary Completion Date : | May 18, 2021 |
Estimated Study Completion Date : | November 2035 |

Arm | Intervention/treatment |
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Experimental: Axicabtagene Ciloleucel
Participants will receive cyclophosphamide and fludarabine conditioning chemotherapy followed by the investigational treatment, axicabtagene ciloleucel
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Biological: Axicabtagene Ciloleucel
A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells administered intravenously
Other Name: Yescarta® Drug: Fludarabine Administered according to package insert Drug: Cyclophosphamide Administered according to package insert |
- Complete Response (CR) Rate [ Time Frame: Up to 2 years ]Complete Response rate is defined as the incidence of a CR per the Lugano Classification (Cheson et al, 2014), as determined by study investigators.
- Objective Response Rate (ORR) [ Time Frame: Up to 2 years ]ORR is defined as the incidence of either a CR or a partial response (PR) per the Lugano Classification as determined by study investigators.
- Duration of Response (DOR) [ Time Frame: Up to 2 years ]DOR is defined only for participants who experience an objective response after axicabtagene ciloleucel infusion and is the time from the first objective response to disease progression or death from any cause.
- Event-Free Survival (EFS) [ Time Frame: Up to 5 years ]EFS is defined as the time from the axicabtagene ciloleucel infusion date to the earliest date of disease progression, commencement of subsequent new anti-lymphoma therapy including stem cell transplant (SCT), or death from any cause.
- Progression-Free Survival (PFS) [ Time Frame: Up to 2 years ]PFS is defined as the time from the axicabtagene ciloleucel infusion date to the date of disease progression or death from any cause.
- Overall Survival (OS) [ Time Frame: Up to 5 years ]OS is defined as the time from axicabtagene ciloleucel infusion to the date of death from any cause.
- Percentage of participants experiencing adverse events and Clinical Significant Changes in Safety Lab Values [ Time Frame: Up to 2 years ]
- Relapse with Central Nervous Disease (CNS) Disease [ Time Frame: Up to 5 years ]Relapse with CNS disease is defined as the time from the axicabtagene ciloleucel infusion date to the earliest date of CNS involvement with lymphoma as determined by typical symptoms, CSF evaluation, and/or diagnostic imaging.
- Levels of anti-CD19 CAR T cells in blood [ Time Frame: Up to 1 year ]
- Levels of cytokines in serum [ Time Frame: Up to 1 year ]

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Key Inclusion Criteria:
- Histologically confirmed large B-cell lymphoma
- High-grade large B-cell lymphoma
- Individuals must have a positive interim positron emission tomography (PET) per Cheson, 2014 (Deauville PET score of 4 or 5) after 2 cycles (PET2+) of chemoimmunotherapy
- No evidence, suspicion and/or history of 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
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Adequate renal, hepatic, pulmonary, and cardiac function defined as:
- Creatinine clearance (as estimated by Cockcroft Gault) ≥ 60 mL/min
- Serum alanine aminotransferase (ALT/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 ECHO, and no clinically significant ECG findings
- No clinically significant pleural effusion
- Baseline oxygen saturation > 92% on room air
Key Exclusion Criteria:
- History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (eg cervix, bladder, breast) unless disease free for at least 3 years
- 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 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
Note: Other protocol defined Inclusion/Exclusion criteria may apply.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03761056
United States, Arizona | |
Banner Health MD Anderson Cancer Center | |
Gilbert, Arizona, United States, 85234 | |
United States, California | |
City of Hope | |
Duarte, California, United States, 91010-3012 | |
UCLA | |
Los Angeles, California, United States, 90095 | |
United States, Florida | |
H. Lee Moffitt Cancer Center and Research Institute | |
Tampa, Florida, United States, 33612 | |
United States, Illinois | |
University of Chicago | |
Chicago, Illinois, United States, 606337 | |
United States, Minnesota | |
Mayo Clinic | |
Rochester, Minnesota, United States, 55905 | |
United States, Tennessee | |
Vanderbilt University Medical Center | |
Nashville, Tennessee, United States, 37232 | |
United States, Texas | |
The University of Texas MD Anderson Cancer Center | |
Houston, Texas, United States, 77030 | |
United States, Washington | |
Fred Hutchinson Cancer Research Center | |
Seattle, Washington, United States, 98109 | |
Australia, Victoria | |
Peter MacCallum Cancer Centre | |
Melbourne, Victoria, Australia, 3000 | |
Canada | |
Ottawa Hospital | |
Ottawa, Canada, K1H 8L6 | |
France | |
Hopital Saint Louis | |
Paris, France, 75475 |
Study Director: | Kite Study Director | Kite, A Gilead Company |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | Kite, A Gilead Company |
ClinicalTrials.gov Identifier: | NCT03761056 |
Other Study ID Numbers: |
KTE-C19-112 2019-002291-13 ( EudraCT Number ) |
First Posted: | December 3, 2018 Key Record Dates |
Last Update Posted: | February 28, 2022 |
Last Verified: | February 2022 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Lymphoma Lymphoma, B-Cell Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Lymphoma, Non-Hodgkin Cyclophosphamide |
Fludarabine Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists |