Study of Brexucabtagene Autoleucel (KTE-X19) in Participants With Relapsed/Refractory Mantle Cell Lymphoma (Cohort 3)

Relapsed/Refractory Mantle Cell Lymphoma Clinical Trial

— ZUMA-2  

Official title:

A Phase 2 Multicenter Study Evaluating the Efficacy of KTE-X19 in Subjects With Relapsed/Refractory Mantle Cell Lymphoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04880434
• Other study ID #: KTE-C19-102 (Cohort 3)
• Secondary ID: 2015-005008-27
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: April 27, 2021
• Est. completion date: October 2038

Study information

• Verified date: December 2023
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 90
• Est. completion date: October 2038
• Est. primary completion date: November 26, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Mantle-Cell
• Relapsed/Refractory Mantle Cell Lymphoma

Intervention

Drug:
• Fludarabine
Administered intravenously
• Cyclophosphamide
Administered intravenously

Biological:
• Brexucabtagene autoleucel
A single infusion of brexucabtagene autoleucel (KTE-X19) anti-CD 19 CAR T cells

Locations

Country	Name	City	State
France	CHU de Montpellier	Montpellier CEDEX 05
France	Hospital Saint Louis	Paris
France	Hopital Haut-Leveque	Pessac
France	Centre Hospitalier Lyon Sud	Pierre Benite
France	CHU de Rennes	Rennes
Germany	Johannes Gutenberg University Hospital-University Mainz	Mainz
Germany	Munich University of Technology-Medical Faculty- Ethics Committee	München
Germany	Universitaetsklinikum Wuerzburg	Wuerzburg
Netherlands	Academisch Medisch Centrum	Amsterdam
Netherlands	University Medical Center Groningen	Groningen
Netherlands	Erasmus MC	Rotterdam
Spain	Hospital Clinic Barcelona	Barcelona
Spain	Hospital Universitari Vall D'Hebron	Barcelona
Spain	Hospital Universitario de Salamanca	Salamanca
United Kingdom	Queen Elizabeth University Hospital	Glasgow
United Kingdom	Kings College Hospital	London
United Kingdom	Manchester Royal Infirmary	Manchester
United States	Emory University	Atlanta	Georgia
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	University of Chicago	Chicago	Illinois
United States	Cleveland Clinic - Taussig Cancer Institute	Cleveland	Ohio
United States	Ohio State University	Columbus	Ohio
United States	Baylor Cancer Hospital	Dallas	Texas
United States	Sarah Cannon- Denver	Denver	Colorado
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	Duke University	Durham	North Carolina
United States	Banner MD Anderson Cancer Center	Gilbert	Arizona
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	MD Anderson Cancer Center	Houston	Texas
United States	Loyola University Medical Center	Maywood	Illinois
United States	University of Miami	Miami	Florida
United States	Sarah Cannon - Tenessee	Nashville	Tennessee
United States	Vanderbilt University	Nashville	Tennessee
United States	Stanford University	Palo Alto	California
United States	Advocate Aurora Health - Advocate Lutheran General Hospital	Park Ridge	Illinois
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	University of Rochester	Rochester	New York
United States	University California Los Angeles (UCLA)	Santa Monica	California
United States	Swedish Cancer Institute	Seattle	Washington
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Kite, A Gilead Company

Countries where clinical trial is conducted

United States,  France,  Germany,  Netherlands,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Up to 2 years
Secondary	Duration of Response (DOR)	DOR is defined as the time from their first objective response to disease progression or death.	Up to 7 years
Secondary	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.	Up to 7 years
Secondary	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.	Up to 7 years
Secondary	Progression Free Survival (PFS)		Up to 7 years
Secondary	Overall Survival		Up to 7 years
Secondary	Percentage of Participants Experiencing Treatment-Emergent Adverse Events		Up to 7 years
Secondary	Percentage of Participants With Clinically Significant Changes in Laboratory Values		Up to 7 years
Secondary	Percentage of Participants Who Develop Anti-CD19 CAR Antibodies		Up to 7 years
Secondary	Levels of Anti-CD19 CAR T Cells in Blood		Up to 7 years
Secondary	Levels of Cytokines in Serum		Up to 7 years
Secondary	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.	Baseline and up to 24 months
Secondary	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.	Baseline and up to 24 months
Secondary	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.	Baseline and up to 6 months

External Links

•   Gilead Clinical Trials Website