Study of Brexucabtagene Autoleucel (KTE-X19) in Participants With Relapsed/Refractory Mantle Cell Lymphoma (Cohort 3)
- Conditions
- Relapsed/Refractory Mantle Cell Lymphoma
- Interventions
- Registration Number
- NCT04880434
- Lead Sponsor
- Kite, A Gilead Company
- 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
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 90
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Brexucabtagene autoleucel (KTE-X19) Brexucabtagene autoleucel 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. Brexucabtagene autoleucel (KTE-X19) Cyclophosphamide 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. Brexucabtagene autoleucel (KTE-X19) Fludarabine 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.
- Primary Outcome Measures
Name Time Method Objective Response Rate (ORR) Per Lugano Classification as Determined by the Independent Radiology Review Committee (IRRC) Up to 2 years 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
Name Time Method Progression Free Survival (PFS) Up to 7 years Levels of Anti-CD19 CAR T Cells in Blood Up to 7 years Percentage of Participants With Best Objective Response (BOR) Up to 7 years 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.
Levels of Cytokines in Serum Up to 7 years Change Over Time in European Quality of Life-5 Dimensions(EQ-5D) Visual Analogue Scale (VAS) Score Baseline and up to 24 months 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.
Percentage of Participants Who Develop Anti-CD19 CAR Antibodies Up to 7 years Change Over Time in European Quality of Life-5 Dimensions(EQ-5D) Scale Score Baseline and up to 24 months 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.
Changes in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30) Score from Baseline Over Time Baseline and up to 6 months 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.
Duration of Response (DOR) Up to 7 years DOR is defined as the time from their first objective response to disease progression or death.
Objective Response Rate (ORR) per Lugano Classification as Determined by Investigators Up to 7 years ORR, as determined by investigators, is defined as the incidence of either a complete response (CR) or partial response (PR) per the Lugano Classification.
Overall Survival Up to 7 years Percentage of Participants Experiencing Treatment-Emergent Adverse Events Up to 7 years Percentage of Participants With Clinically Significant Changes in Laboratory Values Up to 7 years
Trial Locations
- Locations (40)
University of Chicago
🇺🇸Chicago, Illinois, United States
Loyola University Medical Center
🇺🇸Maywood, Illinois, United States
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Swedish Cancer Institute
🇺🇸Seattle, Washington, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Cleveland Clinic - Taussig Cancer Institute
🇺🇸Cleveland, Ohio, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Hospital Universitario de Salamanca
🇪🇸Salamanca, Spain
Hospital Universitari Vall D'Hebron
🇪🇸Barcelona, Spain
Kings College Hospital
🇬🇧London, United Kingdom
Hopital Haut-Leveque
🇫🇷Pessac, France
University California Los Angeles (UCLA)
🇺🇸Santa Monica, California, United States
Advocate Aurora Health - Advocate Lutheran General Hospital
🇺🇸Park Ridge, Illinois, United States
University of Rochester
🇺🇸Rochester, New York, United States
Ohio State University
🇺🇸Columbus, Ohio, United States
Baylor Cancer Hospital
🇺🇸Dallas, Texas, United States
CHU de Montpellier
🇫🇷Montpellier CEDEX 05, France
Banner MD Anderson Cancer Center
🇺🇸Gilbert, Arizona, United States
Universitaetsklinikum Wuerzburg
🇩🇪Wuerzburg, Germany
Hospital Saint Louis
🇫🇷Paris, France
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Centre Hospitalier Lyon Sud
🇫🇷Pierre Benite, France
Johannes Gutenberg University Hospital-University Mainz
🇩🇪Mainz, Germany
Academisch Medisch Centrum
🇳🇱Amsterdam, Netherlands
Munich University of Technology-Medical Faculty- Ethics Committee
🇩🇪München, Germany
University Medical Center Groningen
🇳🇱Groningen, Netherlands
Erasmus MC
🇳🇱Rotterdam, Netherlands
Sarah Cannon- Denver
🇺🇸Denver, Colorado, United States
University of Miami
🇺🇸Miami, Florida, United States
Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Duke University
🇺🇸Durham, North Carolina, United States
Sarah Cannon - Tenessee
🇺🇸Nashville, Tennessee, United States
Vanderbilt University
🇺🇸Nashville, Tennessee, United States
Queen Elizabeth University Hospital
🇬🇧Glasgow, United Kingdom
Manchester Royal Infirmary
🇬🇧Manchester, United Kingdom
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Stanford University
🇺🇸Palo Alto, California, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Hospital Clinic Barcelona
🇪🇸Barcelona, Spain
CHU de Rennes
🇫🇷Rennes, France