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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 : November 7, 2019
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences ( Kite, A Gilead Company )

Tracking Information
First Submitted Date  ICMJE November 29, 2018
First Posted Date  ICMJE December 3, 2018
Last Update Posted Date November 7, 2019
Actual Study Start Date  ICMJE January 29, 2019
Estimated Primary Completion Date February 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 4, 2019)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: November 29, 2018)
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 as determined by study investigators.
Change History Complete list of historical versions of study NCT03761056 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 1, 2019)
  • 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: November 29, 2018)
  • Objective Response Rate (ORR) [ Time Frame: Up to 15 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 15 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy and Safety of Axicabtagene Ciloleucel as First-Line Therapy in Participants With High-Risk Large B-Cell Lymphoma
Official Title  ICMJE 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)
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE B-cell Lymphoma
Intervention  ICMJE
  • 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
Study Arms  ICMJE Experimental: Axicabtagene Ciloleucel
Participants will receive cyclophosphamide and fludarabine conditioning chemotherapy followed by the investigational treatment, axicabtagene ciloleucel
Interventions:
  • Biological: Axicabtagene Ciloleucel
  • Drug: Fludarabine
  • Drug: Cyclophosphamide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 29, 2018)
40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 2036
Estimated Primary Completion Date February 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Medical Information 1-844-454-5483(1-844-454-KITE) medinfo@kitepharma.com
Listed Location Countries  ICMJE Australia,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03761056
Other Study ID Numbers  ICMJE KTE-C19-112
2019-002291-13 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Gilead Sciences ( Kite, A Gilead Company )
Study Sponsor  ICMJE Kite, A Gilead Company
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Kite Study Director Kite, A Gilead Company
PRS Account Gilead Sciences
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP