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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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ClinicalTrials.gov Identifier: NCT03761056
Recruitment Status : Recruiting
First Posted : December 3, 2018
Last Update Posted : August 12, 2019
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences ( Kite, A Gilead Company )

Study Description
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Brief Summary:
The primary objective of this study is to estimate the efficacy of axicabtagene ciloleucel in participants with high-risk large B-cell lymphoma.

Condition or disease Intervention/treatment Phase
B-cell Lymphoma Biological: Axicabtagene Ciloleucel Drug: Fludarabine Drug: Cyclophosphamide Phase 2

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
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
Estimated Primary Completion Date : August 2020
Estimated Study Completion Date : January 2035

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arms and Interventions
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Arm Intervention/treatment
Experimental: Axicabtagene Ciloleucel
Participants will receive cyclophosphamide and fludarabine conditioning chemotherapy followed by the investigational treatment, axicabtagene ciloleucel
 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


Outcome Measures
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Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. Percentage of participants experiencing adverse events and Clinical Significant Changes in Safety Lab Values [ Time Frame: Up to 2 years ]
  7. 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.

  8. Levels of anti-CD19 CAR T cells in blood [ Time Frame: Up to 1 year ]
  9. Levels of cytokines in serum [ Time Frame: Up to 1 year ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

  • 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.

Contacts and Locations
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Information from the National Library of Medicine

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


Contacts
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Contact: Medical Information 1-844-454-5483(1-844-454-KITE) medinfo@kitepharma.com

Locations
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United States, Arizona
Banner Health MD Anderson Cancer Center Recruiting
Gilbert, Arizona, United States, 85234
United States, California
City of Hope Recruiting
Duarte, California, United States, 91010-3012
UCLA Recruiting
Los Angeles, California, United States, 90095
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute Recruiting
Tampa, Florida, United States, 33612
United States, Illinois
University of Chicago Recruiting
Chicago, Illinois, United States, 606337
United States, New York
Mayo Clinic Recruiting
Rochester, New York, United States, 55905
United States, Tennessee
Vanderbilt University Medical Center Active, not recruiting
Nashville, Tennessee, United States, 37232
United States, Texas
The University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Australia, Victoria
Peter MacCallum Cancer Centre Recruiting
Melbourne, Victoria, Australia, 3000
Sponsors and Collaborators
Kite, A Gilead Company
Investigators
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Study Director: Kite Study Director Kite, A Gilead Company
More Information
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Responsible Party: Kite, A Gilead Company
ClinicalTrials.gov Identifier: NCT03761056     History of Changes
Other Study ID Numbers: KTE-C19-112
2019-002291-13 ( EudraCT Number )
First Posted: December 3, 2018    Key Record Dates
Last Update Posted: August 12, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Lymphoma
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Cyclophosphamide
Fludarabine phosphate
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
Antimetabolites, Antineoplastic
Antimetabolites