Back to resultsStudy of Brexucabtagene Autoleucel (KTE-X19) in Participants With Relapsed/Refractory Mantle Cell Lymphoma (Cohort 3) (ZUMA-2)
Primary Purpose
Relapsed/Refractory Mantle Cell Lymphoma
Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Fludarabine
Cyclophosphamide
Brexucabtagene autoleucel
Sponsored by
About this trial
This is an interventional treatment trial for Relapsed/Refractory Mantle Cell Lymphoma
Eligibility Criteria
Key Inclusion Criteria:
- Up to 5 prior regimens for MCL. Prior therapy must have included anthracycline- or bendamustine-containing chemotherapy and anti-CD20 monoclonal antibody therapy. Individuals must not have received prior therapy with a BTKi.
- At least 1 measurable lesion
- Platelet count ≥ 75,000/uL
- Creatinine clearance (as estimated by Cockcroft Gault) ≥ to 60 cc/min
- Cardiac ejection fraction ≥ 50%, no evidence of pericardial effusion as determined by an echocardiogram (ECHO) or multigated acquisition (MUGA), and no clinically significant electrocardiogram (ECG) findings
- Baseline oxygen saturation > 92% on room air
Key Exclusion Criteria:
- Known history of infection with human immunodeficiency virus (HIV) or hepatitis B (HBsAG positive) or hepatitis C virus (anti-HCV positive). Individuals with a history of hepatitis infection must have cleared their infection as determined by standard serological and genetic testing
- History of a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, cerebral edema, posterior reversible encephalopathy syndrome, or any autoimmune disease with central nervous system (CNS) involvement
- Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Sites / Locations
- Banner MD Anderson Cancer Center
- Stanford University
- University California Los Angeles (UCLA)
- Sarah Cannon- Denver
- University of Miami
- Moffitt Cancer Center
- Emory University
- University of Chicago
- Loyola University Medical Center
- Advocate Aurora Health - Advocate Lutheran General Hospital
- Dana Farber Cancer Institute
- Karmanos Cancer Institute
- Hackensack University Medical Center
- University of Rochester
- Duke University
- Cleveland Clinic - Taussig Cancer Institute
- Ohio State University
- Fox Chase Cancer Center
- Sarah Cannon - Tenessee
- Vanderbilt University
- Baylor Cancer Hospital
- MD Anderson Cancer Center
- Swedish Cancer Institute
- CHU de Montpellier
- Hospital Saint Louis
- Hopital Haut-Leveque
- Centre Hospitalier Lyon Sud
- CHU de Rennes
- Johannes Gutenberg University Hospital-University Mainz
- Munich University of Technology-Medical Faculty- Ethics Committee
- Universitaetsklinikum Wuerzburg
- Academisch Medisch Centrum
- University Medical Center Groningen
- Erasmus MC
- Hospital Universitari Vall D'Hebron
- Hospital Clinic Barcelona
- Hospital Universitario de Salamanca
- Queen Elizabeth University Hospital
- Kings College Hospital
- Manchester Royal Infirmary
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Brexucabtagene autoleucel (KTE-X19)
Arm Description
Participants with relapsed/refractory mantle cell lymphoma will receive conditioning chemotherapy consisting of fludarabine 30 mg/m^2/day and cyclophosphamide 500 mg/m^2/day intravenous (IV) infusion for 3 days followed by a single infusion of brexucabtagene autoleucel (KTE-X19) at a targeted dose of 2 x 10^6 anti-CD19 chimeric antigen receptor (CAR) T cells/kg, with a maximum flat dose of 2 x 10^8 anti-CD19 CAR T cells for participants ≥ 100 kg on Day 0 in Cohort 3.
Outcomes
Primary Outcome Measures
Objective Response Rate (ORR) Per Lugano Classification as Determined by the Independent Radiology Review Committee (IRRC)
ORR is defined as the incidence of either a complete response (CR) or partial response (PR) per the Lugano Classification as determined by IRRC.
Secondary Outcome Measures
Duration of Response (DOR)
DOR is defined as the time from their first objective response to disease progression or death.
Percentage of Participants With Best Objective Response (BOR)
Best objective response is defined as the incidence of complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), or unevaluable as best response to treatment.
Objective Response Rate (ORR) per Lugano Classification as Determined by Investigators
ORR, as determined by investigators, is defined as the incidence of either a complete response (CR) or partial response (PR) per the Lugano Classification.
Progression Free Survival (PFS)
Overall Survival
Percentage of Participants Experiencing Treatment-Emergent Adverse Events
Percentage of Participants With Clinically Significant Changes in Laboratory Values
Percentage of Participants Who Develop Anti-CD19 CAR Antibodies
Levels of Anti-CD19 CAR T Cells in Blood
Levels of Cytokines in Serum
Change Over Time in European Quality of Life-5 Dimensions(EQ-5D) Scale Score
The European Quality of Life-5 Dimensions Health Questionnaire (EQ-5D) is a participant-answered questionnaire scoring 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. For each dimension the participant is asked for a three-level assessment of their health on the current day: "no problems" (1), "some problems" (2), "extreme problems" (3). EQ-5D health states, defined by the EQ-5D descriptive system, are converted into a single summary index by applying a formula that attaches values (also called QOL weights or QOL utilities) to each of the levels in each dimension. EQ-5D Summary Index values range from -0.11 (worst health state) to 1.00 (perfect health state). Positive numbers indicate improvement from baseline.
Change Over Time in European Quality of Life-5 Dimensions(EQ-5D) Visual Analogue Scale (VAS) Score
EQ-5D is a standardized participant completed questionnaire that measures health-related quality of life and translates that score into an index value or utility score. EQ-5D-consists of two components: a health state profile and an optional visual analogue scale (VAS). The EQ5D-VAS records the participant's self-rated health on a vertical visual analogue scale, where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine'. EQ-5D-VAS: range 0 to 100. A higher score indicates better self-reported health status.
Changes in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30) Score from Baseline Over Time
EORTC QLQ-C30 includes functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting), and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most questions use 4 point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale (1 'very poor' to 7 'Excellent'). Scores are averaged, transformed to 0-100 scale; higher score indicate high QoL. A positive change from baseline indicates better quality of life.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04880434
Brief Title
Study of Brexucabtagene Autoleucel (KTE-X19) in Participants With Relapsed/Refractory Mantle Cell Lymphoma (Cohort 3)
Acronym
ZUMA-2
Official Title
A Phase 2 Multicenter Study Evaluating the Efficacy of KTE-X19 in Subjects With Relapsed/Refractory Mantle Cell Lymphoma
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 27, 2021 (Actual)
Primary Completion Date
July 2024 (Anticipated)
Study Completion Date
October 2038 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Kite, A Gilead Company
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The goal of this clinical study is to test how well the study drug, brexucabtagene autoleucel (KTE-X19), works in participants with relapsed/refractory (r/r) mantle cell lymphoma (MCL).
Detailed Description
Study KTE-C19-102 (NCT02601313) enrolled participants with r/r MCL who have been treated with up to 5 prior regimens including a Bruton's tyrosine kinase inhibitor (BTKi) in Cohort 1 and Cohort 2. However, to fulfill FDA Postmarketing Requirement Cohort 3 is added to the study. It will include participants with r/r MCL who have been treated with up to 5 prior regimens but have not received prior therapy with a BTKi.
The primary analysis in Cohort 1 and Cohort 2 is already completed. Data for Cohort 3 will be analyzed separately. Therefore, this separate registration is only for Cohort 3.
After the end of KTE-C19-102, subjects who received an infusion of anti-CD19 CAR T cells will complete the remainder of the 15-year follow-up assessments in a separate long-term follow-up study, KT-US-982-5968
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapsed/Refractory Mantle Cell Lymphoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
90 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Brexucabtagene autoleucel (KTE-X19)
Arm Type
Experimental
Arm Description
Participants with relapsed/refractory mantle cell lymphoma will receive conditioning chemotherapy consisting of fludarabine 30 mg/m^2/day and cyclophosphamide 500 mg/m^2/day intravenous (IV) infusion for 3 days followed by a single infusion of brexucabtagene autoleucel (KTE-X19) at a targeted dose of 2 x 10^6 anti-CD19 chimeric antigen receptor (CAR) T cells/kg, with a maximum flat dose of 2 x 10^8 anti-CD19 CAR T cells for participants ≥ 100 kg on Day 0 in Cohort 3.
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Intervention Description
Administered intravenously
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
Administered intravenously
Intervention Type
Biological
Intervention Name(s)
Brexucabtagene autoleucel
Other Intervention Name(s)
KTE-X19, TECARTUS™
Intervention Description
A single infusion of brexucabtagene autoleucel (KTE-X19) anti-CD 19 CAR T cells
Primary Outcome Measure Information:
Title
Objective Response Rate (ORR) Per Lugano Classification as Determined by the Independent Radiology Review Committee (IRRC)
Description
ORR is defined as the incidence of either a complete response (CR) or partial response (PR) per the Lugano Classification as determined by IRRC.
Time Frame
Up to 2 years
Secondary Outcome Measure Information:
Title
Duration of Response (DOR)
Description
DOR is defined as the time from their first objective response to disease progression or death.
Time Frame
Up to 7 years
Title
Percentage of Participants With Best Objective Response (BOR)
Description
Best objective response is defined as the incidence of complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), or unevaluable as best response to treatment.
Time Frame
Up to 7 years
Title
Objective Response Rate (ORR) per Lugano Classification as Determined by Investigators
Description
ORR, as determined by investigators, is defined as the incidence of either a complete response (CR) or partial response (PR) per the Lugano Classification.
Time Frame
Up to 7 years
Title
Progression Free Survival (PFS)
Time Frame
Up to 7 years
Title
Overall Survival
Time Frame
Up to 7 years
Title
Percentage of Participants Experiencing Treatment-Emergent Adverse Events
Time Frame
Up to 7 years
Title
Percentage of Participants With Clinically Significant Changes in Laboratory Values
Time Frame
Up to 7 years
Title
Percentage of Participants Who Develop Anti-CD19 CAR Antibodies
Time Frame
Up to 7 years
Title
Levels of Anti-CD19 CAR T Cells in Blood
Time Frame
Up to 7 years
Title
Levels of Cytokines in Serum
Time Frame
Up to 7 years
Title
Change Over Time in European Quality of Life-5 Dimensions(EQ-5D) Scale Score
Description
The European Quality of Life-5 Dimensions Health Questionnaire (EQ-5D) is a participant-answered questionnaire scoring 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. For each dimension the participant is asked for a three-level assessment of their health on the current day: "no problems" (1), "some problems" (2), "extreme problems" (3). EQ-5D health states, defined by the EQ-5D descriptive system, are converted into a single summary index by applying a formula that attaches values (also called QOL weights or QOL utilities) to each of the levels in each dimension. EQ-5D Summary Index values range from -0.11 (worst health state) to 1.00 (perfect health state). Positive numbers indicate improvement from baseline.
Time Frame
Baseline and up to 24 months
Title
Change Over Time in European Quality of Life-5 Dimensions(EQ-5D) Visual Analogue Scale (VAS) Score
Description
EQ-5D is a standardized participant completed questionnaire that measures health-related quality of life and translates that score into an index value or utility score. EQ-5D-consists of two components: a health state profile and an optional visual analogue scale (VAS). The EQ5D-VAS records the participant's self-rated health on a vertical visual analogue scale, where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine'. EQ-5D-VAS: range 0 to 100. A higher score indicates better self-reported health status.
Time Frame
Baseline and up to 24 months
Title
Changes in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30) Score from Baseline Over Time
Description
EORTC QLQ-C30 includes functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting), and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most questions use 4 point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale (1 'very poor' to 7 'Excellent'). Scores are averaged, transformed to 0-100 scale; higher score indicate high QoL. A positive change from baseline indicates better quality of life.
Time Frame
Baseline and up to 6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
Up to 5 prior regimens for MCL. Prior therapy must have included anthracycline- or bendamustine-containing chemotherapy and anti-CD20 monoclonal antibody therapy. Individuals must not have received prior therapy with a BTKi.
At least 1 measurable lesion
Platelet count ≥ 75,000/uL
Creatinine clearance (as estimated by Cockcroft Gault) ≥ to 60 cc/min
Cardiac ejection fraction ≥ 50%, no evidence of pericardial effusion as determined by an echocardiogram (ECHO) or multigated acquisition (MUGA), and no clinically significant electrocardiogram (ECG) findings
Baseline oxygen saturation > 92% on room air
Key Exclusion Criteria:
Known history of infection with human immunodeficiency virus (HIV) or hepatitis B (HBsAG positive) or hepatitis C virus (anti-HCV positive). Individuals with a history of hepatitis infection must have cleared their infection as determined by standard serological and genetic testing
History of a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, cerebral edema, posterior reversible encephalopathy syndrome, or any autoimmune disease with central nervous system (CNS) involvement
Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kite Study Director
Organizational Affiliation
Kite, A Gilead Company
Official's Role
Study Director
Facility Information:
Facility Name
Banner MD Anderson Cancer Center
City
Gilbert
State/Province
Arizona
ZIP/Postal Code
85234
Country
United States
Facility Name
Stanford University
City
Palo Alto
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
University California Los Angeles (UCLA)
City
Santa Monica
State/Province
California
ZIP/Postal Code
90404
Country
United States
Facility Name
Sarah Cannon- Denver
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
University of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Moffitt Cancer Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Loyola University Medical Center
City
Maywood
State/Province
Illinois
ZIP/Postal Code
60153
Country
United States
Facility Name
Advocate Aurora Health - Advocate Lutheran General Hospital
City
Park Ridge
State/Province
Illinois
ZIP/Postal Code
60068
Country
United States
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Karmanos Cancer Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
University of Rochester
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Duke University
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Cleveland Clinic - Taussig Cancer Institute
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43220
Country
United States
Facility Name
Fox Chase Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111
Country
United States
Facility Name
Sarah Cannon - Tenessee
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Vanderbilt University
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
Baylor Cancer Hospital
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Swedish Cancer Institute
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Name
CHU de Montpellier
City
Montpellier CEDEX 05
ZIP/Postal Code
34295
Country
France
Facility Name
Hospital Saint Louis
City
Paris
ZIP/Postal Code
75010
Country
France
Facility Name
Hopital Haut-Leveque
City
Pessac
ZIP/Postal Code
44035
Country
France
Facility Name
Centre Hospitalier Lyon Sud
City
Pierre Benite
ZIP/Postal Code
69495
Country
France
Facility Name
CHU de Rennes
City
Rennes
ZIP/Postal Code
35033
Country
France
Facility Name
Johannes Gutenberg University Hospital-University Mainz
City
Mainz
ZIP/Postal Code
55101
Country
Germany
Facility Name
Munich University of Technology-Medical Faculty- Ethics Committee
City
München
ZIP/Postal Code
81377
Country
Germany
Facility Name
Universitaetsklinikum Wuerzburg
City
Wuerzburg
ZIP/Postal Code
97080
Country
Germany
Facility Name
Academisch Medisch Centrum
City
Amsterdam
ZIP/Postal Code
1100
Country
Netherlands
Facility Name
University Medical Center Groningen
City
Groningen
ZIP/Postal Code
9700 RB
Country
Netherlands
Facility Name
Erasmus MC
City
Rotterdam
ZIP/Postal Code
3015 CE
Country
Netherlands
Facility Name
Hospital Universitari Vall D'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Clinic Barcelona
City
Barcelona
Country
Spain
Facility Name
Hospital Universitario de Salamanca
City
Salamanca
ZIP/Postal Code
37007
Country
Spain
Facility Name
Queen Elizabeth University Hospital
City
Glasgow
ZIP/Postal Code
G51 4TF
Country
United Kingdom
Facility Name
Kings College Hospital
City
London
ZIP/Postal Code
SE5 9RS
Country
United Kingdom
Facility Name
Manchester Royal Infirmary
City
Manchester
ZIP/Postal Code
M13 9WL
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
Links:
URL
https://www.gileadclinicaltrials.com/study/?id=KTE-C19-102%20(Cohort%203)
Description
Gilead Clinical Trials Website
Learn more about this trial
Study of Brexucabtagene Autoleucel (KTE-X19) in Participants With Relapsed/Refractory Mantle Cell Lymphoma (Cohort 3)
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