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出境医 / 临床实验 / Safety and Efficacy of Axicabtagene Ciloleucel in Combination With Rituximab in Participants With Refractory Large B-Cell Lymphoma (ZUMA-14)

Safety and Efficacy of Axicabtagene Ciloleucel in Combination With Rituximab in Participants With Refractory Large B-Cell Lymphoma (ZUMA-14)

Study Description
Brief Summary:
The primary objective of this study is to estimate the efficacy of axicabtagene ciloleucel in combination with rituximab, as measured by assessment of response rates in adult participants with relapsed/refractory large B-cell lymphoma.

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

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 27 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Open-Label, Multicenter Study Evaluating the Safety and Efficacy of Axicabtagene Ciloleucel in Combination With Rituximab in Participants With Refractory Large B-Cell Lymphoma (ZUMA-14)
Actual Study Start Date : November 5, 2019
Estimated Primary Completion Date : June 2021
Estimated Study Completion Date : June 2036
Arms and Interventions
Arm Intervention/treatment
Experimental: Axicabtagene Ciloleucel and Rituximab Combination
Participants will receive rituximab, and fludarabine and cyclophosphamide conditioning chemotherapy, followed by axicabtagene ciloleucel and additional rituximab.
 Biological: Axicabtagene Ciloleucel
A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells administered intravenously
Other Name: Yescarta®

Drug: Rituximab
Administered intravenously
Other Name: RITUXAN®

Drug: Fludarabine
Administered according to package insert

Drug: Cyclophosphamide
Administered according to package insert
Outcome Measures
Primary Outcome Measures :
  1. Complete Response (CR) Rate [ Time Frame: Up to 2 years ]
    CR rate is defined as the incidence of a CR per the Lugano Classification as determined by study investigators.


Secondary Outcome Measures :
  1. Percentage of Participants Experiencing Adverse Events and Clinically Significant Changes in Safety Lab Values [ Time Frame: Up to 15 years ]
  2. Objective Response Rate (ORR) [ Time Frame: 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.

  3. Duration of Response (DOR) [ Time Frame: Up to 2 years ]
    DOR is defined only for participants who experience an objective response and is the time from the first objective response to disease progression per the Lugano Classification as determined by study investigators 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 per Lugano Classification as determined by study investigators or death from any cause.

  5. Overall Survival (OS) [ Time Frame: Up to 15 years ]
    OS is defined as the time from axicabtagene ciloleucel infusion to the date of death.

  6. Levels of Axicabtagene Ciloleucel in Blood [ Time Frame: Up to 2 years ]

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

  • Chemotherapy-refractory disease, defined as one or more of the following:

    • No response to first-line therapy (primary refractory disease)
    • No response to second or greater lines of therapy OR
    • Refractory after autologous stem cell transplant (ASCT)
  • At least 1 measureable lesion according to the Lugano Classification (Cheson 2014).

  • Individuals must have received adequate prior therapy, including at a minimum:

    • Anti-CD20 monoclonal antibody
    • An anthracycline-containing chemotherapy regimen
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Adequate renal, hepatic, pulmonary, and cardiac function

Key Exclusion Criteria:

  • Known CD19 negative or CD20 negative tumor
  • History of Richter's transformation of Chronic Lymphocytic Leukemia (CLL)
  • Prior CAR therapy or other genetically modified T-cell therapy
  • Prior organ transplantation including prior allogeneic stem cell transplant (SCT)
  • Prior CD19 targeted therapy
  • Clinically significant infection or cardiopulmonary disease
  • Presence of any in-dwelling lines or drains (dedicated central venous access catheters allowed)
  • History or presence of central nervous system (CNS) lymphoma or nonmalignant CNS disorder or cerebrospinal fluid (CSF) malignant cells or brain metastases
  • History of autoimmune disease
  • History of deep vein thrombosis (DVT) or pulmonary embolism (PE) within the last 6 months

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Contacts and Locations

Locations
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United States, Arizona
Banner MD Anderson Cancer Center
Gilbert, Arizona, United States, 85234
United States, California
City of Hope National Medical Center
Duarte, California, United States, 91010-3012
Stanford Cancer Institute
Palo Alto, California, United States, 94305
UCLA Hematology/Oncology
Santa Monica, California, United States, 90404
United States, Florida
Mayo Clinic Florida
Jacksonville, Florida, United States, 32224
United States, Illinois
University of Chicago Medical Center
Chicago, Illinois, United States, 60637
Loyola University Medical Center
Maywood, Illinois, United States, 60153
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, New Jersey
John Theurer Cancer Center at Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
United States, New York
Columbia University Medical Center, New York Presbyterian Hospital
New York, New York, United States, 10032
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
United States, Texas
St. David's South Austin Medical Center
Austin, Texas, United States, 78704
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Washington
Swedish Cancer Institute
Seattle, Washington, United States, 98104
Sponsors and Collaborators
Gilead Sciences
Investigators
Layout table for investigator information
Study Director: Kite Study Director Kite, A Gilead Company
Tracking Information
First Submitted Date  ICMJE June 27, 2019
First Posted Date  ICMJE June 28, 2019
Last Update Posted Date March 25, 2021
Actual Study Start Date  ICMJE November 5, 2019
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 27, 2019) 		Complete Response (CR) Rate [ Time Frame: Up to 2 years ]
CR rate is defined as the incidence of a CR per the Lugano Classification as determined by study investigators.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 27, 2019)
  • Percentage of Participants Experiencing Adverse Events and Clinically Significant Changes in Safety Lab Values [ Time Frame: Up to 15 years ]
  • Objective Response Rate (ORR) [ Time Frame: 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 and is the time from the first objective response to disease progression per the Lugano Classification as determined by study investigators 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 per Lugano Classification as determined by study investigators or death from any cause.
  • Overall Survival (OS) [ Time Frame: Up to 15 years ]
    OS is defined as the time from axicabtagene ciloleucel infusion to the date of death.
  • Levels of Axicabtagene Ciloleucel in Blood [ Time Frame: Up to 2 years ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy of Axicabtagene Ciloleucel in Combination With Rituximab in Participants With Refractory Large B-Cell Lymphoma
Official Title  ICMJE A Phase 2 Open-Label, Multicenter Study Evaluating the Safety and Efficacy of Axicabtagene Ciloleucel in Combination With Rituximab in Participants With Refractory Large B-Cell Lymphoma (ZUMA-14)
Brief Summary The primary objective of this study is to estimate the efficacy of axicabtagene ciloleucel in combination with rituximab, as measured by assessment of response rates in adult participants with relapsed/refractory large B-cell lymphoma.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Refractory Large 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: Rituximab
    Administered intravenously
    Other Name: RITUXAN®
  • Drug: Fludarabine
    Administered according to package insert
  • Drug: Cyclophosphamide
    Administered according to package insert
Study Arms  ICMJE Experimental: Axicabtagene Ciloleucel and Rituximab Combination
Participants will receive rituximab, and fludarabine and cyclophosphamide conditioning chemotherapy, followed by axicabtagene ciloleucel and additional rituximab.
Interventions:
  • Biological: Axicabtagene Ciloleucel
  • Drug: Rituximab
  • 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 Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: November 17, 2020) 		27
Original Estimated Enrollment  ICMJE
 (submitted: June 27, 2019) 		60
Estimated Study Completion Date  ICMJE June 2036
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  • Histologically confirmed large B-cell lymphoma

  • Chemotherapy-refractory disease, defined as one or more of the following:

    • No response to first-line therapy (primary refractory disease)
    • No response to second or greater lines of therapy OR
    • Refractory after autologous stem cell transplant (ASCT)
  • At least 1 measureable lesion according to the Lugano Classification (Cheson 2014).

  • Individuals must have received adequate prior therapy, including at a minimum:

    • Anti-CD20 monoclonal antibody
    • An anthracycline-containing chemotherapy regimen
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Adequate renal, hepatic, pulmonary, and cardiac function

Key Exclusion Criteria:

  • Known CD19 negative or CD20 negative tumor
  • History of Richter's transformation of Chronic Lymphocytic Leukemia (CLL)
  • Prior CAR therapy or other genetically modified T-cell therapy
  • Prior organ transplantation including prior allogeneic stem cell transplant (SCT)
  • Prior CD19 targeted therapy
  • Clinically significant infection or cardiopulmonary disease
  • Presence of any in-dwelling lines or drains (dedicated central venous access catheters allowed)
  • History or presence of central nervous system (CNS) lymphoma or nonmalignant CNS disorder or cerebrospinal fluid (CSF) malignant cells or brain metastases
  • History of autoimmune disease
  • History of deep vein thrombosis (DVT) or pulmonary embolism (PE) within the last 6 months

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 information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04002401
Other Study ID Numbers  ICMJE KT-US-471-0114
2019-004803-11 ( EudraCT Number )
Has Data Monitoring Committee No
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
Study Sponsor  ICMJE Gilead Sciences
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Kite Study Director Kite, A Gilead Company
PRS Account Gilead Sciences
Verification Date March 2021

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

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