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Study of Effectiveness of Axicabtagene Ciloleucel Compared to Standard of Care Therapy in Patients With Relapsed/Refractory Diffuse Large B Cell Lymphoma (ZUMA-7)

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: NCT03391466
Recruitment Status : Active, not recruiting
First Posted : January 5, 2018
Last Update Posted : July 6, 2023
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences ( Kite, A Gilead Company )

Tracking Information
First Submitted Date  ICMJE December 21, 2017
First Posted Date  ICMJE January 5, 2018
Last Update Posted Date July 6, 2023
Actual Study Start Date  ICMJE January 25, 2018
Actual Primary Completion Date January 25, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 3, 2023)
Event Free Survival (EFS) [ Time Frame: Up to 5 years ]
Event free survival is defined as the time from randomization to the earliest date of disease progression per Lugano Classification, commencement of new lymphoma therapy, or death from any cause as determined by blinded central review.
Original Primary Outcome Measures  ICMJE
 (submitted: December 29, 2017)
Event Free Survival [ Time Frame: 3 years ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 3, 2023)
  • Objective Response Rate (ORR) [ Time Frame: Up to 5 years ]
    Objective response rate is defined as the incidence of either a complete response or a partial response by the Lugano Classification, as determined by blinded central review.
  • Overall Survival (OS) [ Time Frame: Up to 5 years ]
    Overall survival is defined as the time from randomization to death from any cause
  • Modified Event Free Survival (mEFS) [ Time Frame: Up to 5 years ]
    Modified event free survival is defined the same way as EFS, except that failure to attain CR or PR by Day 150 assessment is not considered an event. mEFS will be analyzed per blinded central review and per investigator disease assessments.
  • Progression-Free Survival (PFS) [ Time Frame: Up to 5 years ]
    Progression Free Survival is defined as the time from randomization to disease progression per Lugano Classification or death from any cause.
  • Duration of Response (DOR) [ Time Frame: Up to 5 years ]
    Duration of response is derived only among subjects who experience an objective response per Lugano Classification, as determined by blinded central review and is defined as the time from first response to disease progression per the Lugano Classification or death from any cause.
  • Duration of Complete Response [ Time Frame: Up to 5 years ]
    Duration of complete response is derived only among subjects who experience a complete response per Lugano Classification as determined by blinded central review and is defined as the time from first response to disease progression per the Lugano Classification or death from any cause.
  • Event Free Survival (EFS) Per Investigator Disease Assessments [ Time Frame: Up to 5 years ]
    Event free survival is defined as the time from randomization to the earliest date of disease progression per Lugano Classification, commencement of new lymphoma therapy, or death from any cause as determined by investigator disease assessments.
  • Changes in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Cancer-30 (EORTC QLQ-C30) Domains [ Time Frame: Up to 5 years ]
    The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Cancer-30 (EORTC QLQ-C30) is a multi-item questionnaire measuring the following content five (5) multi-item functional scales, three (3) multi-item symptom scales, one (1) global health status scale, and one (1) global health-related quality of life (HRQoL) each scale is measured from 0 to 100 after a linear transformation. Higher scores for functioning scales and for the Global Health Status or Global HRQoL scales indicate a higher level of functioning and a better HRQoL respectively, whereas higher scores in symptom scales represent a higher level of symptoms.
  • Percentage of Participants Experiencing Adverse Events and Clinical Significant Changes in Safety Lab Values, Including Antibodies to Axicabtagene Ciloleucel. [ Time Frame: Up to 5 years ]
  • Changes Over Time in the European Quality of Life Five Dimensions Five Levels Scale (EQ-5D-5L) [ Time Frame: Up to 5 years ]
    The Euro-QOL, Five Dimensions, Five Levels (EQ-5D-5L) questionnaire is a generic measure of health status that provides a simple descriptive profile and a single index value. The EQ-5D-5L comprises 2 components: a questionnaire covering 5 dimensions and a tariff of values based upon direct valuations of health states using a visual analog scale (VAS).
  • Changes Over Time in the Visual Analog Scale (VAS) Scores [ Time Frame: Up to 5 years ]
    The EQ-5D-5L VAS is a 20-cm VAS for recording self-rated current HRQoL state and is used to describe the subjects' health status on the day of the assessment. The EQ-5D-5L VAS score is recorded by each subject for his or her current HRQoL state and scored 0 ("the worst health you can imagine") to 100 ("the best health you can imagine").
Original Secondary Outcome Measures  ICMJE
 (submitted: December 29, 2017)
  • Objective Response Rate [ Time Frame: 3 years ]
  • Overall Survival Rate [ Time Frame: 4 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Effectiveness of Axicabtagene Ciloleucel Compared to Standard of Care Therapy in Patients With Relapsed/Refractory Diffuse Large B Cell Lymphoma
Official Title  ICMJE A Phase 3, Randomized, Open-Label Study Evaluating the Efficacy of Axicabtagene Ciloleucel Versus Standard of Care Therapy in Subjects With Relapsed/Refractory Diffuse Large B Cell Lymphoma
Brief Summary The goal of this clinical study is to assess whether axicabtagene ciloleucel therapy improves the clinical outcome compared with standard of care second-line therapy in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL).
Detailed Description

This is a phase 3 randomized, open-label, multicenter study evaluating the efficacy of axicabtagene ciloleucel versus standard of care therapy in subjects with relapsed/refractory DLBCL. Adult subjects with relapsed/refractory DLBCL after first-line rituximab and anthracycline-based chemotherapy will be randomized in a 1:1 ratio to receive axicabtagene ciloleucel or standard of care second-line therapy.

Standard of care will consist of a protocol-defined, platinum-based salvage combination chemotherapy regimen followed by high-dose therapy and autologous stem cell transplant in those who respond to salvage chemotherapy. After completing the treatment period, all subjects will be followed in the post-treatment follow-up period for up to 5 years. Thereafter, subjects who received at least one dose of axicabtagene ciloleucel as protocol therapy will transition to a separate long term follow up (LTFU) study and complete the remainder of the 15-year follow-up assessments within KT-US-982-5968.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Two arms, SOC and experimental treatment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL)
Intervention  ICMJE
  • Biological: Axicabtagene Ciloleucel
    A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells administered intravenously following a conditioning chemotherapy regimen of fludarabine and cyclophosphamide
    Other Names:
    • KTE-C19
    • axi-cel
    • Yescarta ®
  • Drug: Platinum-containing salvage chemotherapy (eg, R-ICE) followed by high dose therapy (eg, BEAM) and autologous stem cell transplant in responders.
    Platinum-containing salvage chemotherapy (R-ICE, R-DHAP, R-ESHAP, or R-GDP as selected by treating investigator) followed by high dose therapy (eg, BEAM) and autologous stem cell transplant in responders.
  • Drug: Cyclophosphamide
    Administered intravenously
  • Drug: Fludarabine
    Administered intravenously
Study Arms  ICMJE
  • Experimental: Axicabtagene Ciloleucel Treatment
    Interventions:
    • Biological: Axicabtagene Ciloleucel
    • Drug: Cyclophosphamide
    • Drug: Fludarabine
  • Active Comparator: Standard of Care Therapy
    Intervention: Drug: Platinum-containing salvage chemotherapy (eg, R-ICE) followed by high dose therapy (eg, BEAM) and autologous stem cell transplant in responders.
Publications *

*   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 1, 2019)
359
Original Estimated Enrollment  ICMJE
 (submitted: December 29, 2017)
350
Estimated Study Completion Date  ICMJE January 2035
Actual Primary Completion Date January 25, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  • Histologically proven large B-cell lymphoma including the following types defined by WHO 2016 (Swerdlow et al, 2016)

    • DLBCL not otherwise specified (ABC/GCB)
    • HGBL with or without MYC and BCL2 and/or BCL6 rearrangement
    • DLBCL arising from FL
    • T-cell/histiocyte rich large B-cell lymphoma
    • DLBCL associated with chronic inflammation
    • Primary cutaneous DLBCL, leg type
    • Epstein-Barr virus (EBV) + DLBCL
  • Relapsed or refractory disease after first-line chemoimmunotherapy

    • Refractory disease defined as no complete remission to first-line therapy; individuals who are intolerant to first-line therapy are excluded.

      • Progressive disease (PD) as best response to first-line therapy
      • Stable disease (SD) as best response after at least 4 cycles of first-line therapy (eg, 4 cycles of R-CHOP)
      • Partial response (PR) as best response after at least 6 cycles and biopsy-proven residual disease or disease progression ≤ 12 months of therapy
    • Relapsed disease defined as complete remission to first-line therapy followed by biopsy-proven relapse ≤ 12 months of first-line therapy
  • Individuals must have received adequate first-line therapy including at a minimum:

    • Anti-CD20 monoclonal antibody unless investigator determines that tumor is CD20 negative, and
    • An anthracycline containing chemotherapy regimen
  • No known history or suspicion of central nervous system involvement by lymphoma
  • Eastern cooperative oncology group (ECOG) performance status of 0 or 1
  • Adequate bone marrow function as evidenced by:

    • Absolute neutrophil count (ANC) ≥ 1000/uL
    • Platelet ≥ 75,000/uL
    • Absolute lymphocyte count ≥ 100/uL
  • Adequate renal, hepatic, cardiac, and pulmonary function as evidenced by:

    • Creatinine clearance (Cockcroft Gault) ≥ 60 mL/min
    • Serum Alanine aminotransferase/Aspartate aminotransferase (ALT/AST) ≤ 2.5 Upper limit of normal (ULN)
    • Total bilirubin ≤ 1.5 mg/dl
    • 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

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
  • Received more than one line of therapy for DLBCL
  • History of autologous or allogeneic stem cell transplant
  • Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring intravenous antimicrobials for management.
  • Known history of infection with human immunodeficiency virus (HIV) or hepatitis B (HBsAg positive) or hepatitis C virus (anti-HCV positive). If there is a positive history of treated hepatitis B or hepatitis C, the viral load must be undetectable per quantitative polymerase chain reaction (PCR) and/or nucleic acid testing.
  • Individuals with detectable cerebrospinal fluid malignant cells or known brain metastases, or with a history of cerebrospinal fluid malignant cells or brain metastases.
  • History or presence of non-malignant central nervous system (CNS) disorder such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement
  • Presence of any indwelling line or drain. Dedicated central venous access catheter such as a Port-a-Cath or Hickman catheter are permitted.
  • History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, New York Heart Association Class II or greater congestive heart failure, or other clinically significant cardiac diseases within 12 months of enrollment
  • History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months of enrollment
  • History of autoimmune disease, requiring systemic immunosuppression and/or systemic disease modifying agents within the last 2 years
  • History of anti-CD19 or CAR-T therapy or history of prior randomization in ZUMA-7

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 Australia,   Austria,   Belgium,   Canada,   France,   Germany,   Israel,   Italy,   Netherlands,   Spain,   Sweden,   Switzerland,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03391466
Other Study ID Numbers  ICMJE KTE-C19-107
2017-002261-22 ( 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
Current Responsible Party Gilead Sciences ( Kite, A Gilead Company )
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Kite, A Gilead Company
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Kite Study Director Kite, A Gilead Company
PRS Account Gilead Sciences
Verification Date July 2023

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