Study of Brexucabtagene Autoleucel (KTE-X19) in Participants With Relapsed/Refractory Mantle Cell Lymphoma (Cohort 3) (ZUMA-2)

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

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Relapsed/Refractory Mantle Cell Lymphoma
• Intervention / Treatment: Drug: Cyclophosphamide; Drug: Fludarabine; Biological: Brexucabtagene autoleucel

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

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Montpellier CEDEX 05, France, 34295
    • CHU de Montpellier
  • Paris, France, 75010
    • Hospital Saint Louis
  • Pessac, France, 44035
    • Hôpital Haut-Lévêque
  • Pierre Benite, France, 69495
    • Centre Hospitalier Lyon Sud
  • Rennes, France, 35033
    • CHU de Rennes
• Germany
  • Mainz, Germany, 55101
    • Johannes Gutenberg University Hospital-University Mainz
  • München, Germany, 81377
    • Munich University of Technology-Medical Faculty- Ethics Committee
  • Wuerzburg, Germany, 97080
    • Universitaetsklinikum Wuerzburg
• Netherlands
  • Amsterdam, Netherlands, 1100
    • Academisch Medisch Centrum
  • Groningen, Netherlands, 9700 RB
    • University Medical Center Groningen
  • Rotterdam, Netherlands, 3015 CE
    • Erasmus MC
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain
    • Hospital Clinic Barcelona
  • Salamanca, Spain, 37007
    • Hospital Universitario de Salamanca
• United Kingdom
  • Glasgow, United Kingdom, G51 4TF
    • Queen Elizabeth University Hospital
  • London, United Kingdom, SE5 9RS
    • Kings College Hospital
  • Manchester, United Kingdom, M13 9WL
    • Manchester Royal Infirmary
• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Banner MD Anderson Cancer Center
  • California
    • Palo Alto, California, United States, 94305
      • Stanford University
    • Santa Monica, California, United States, 90404
      • University California Los Angeles (UCLA)
  • Colorado
    • Denver, Colorado, United States, 80218
      • Sarah Cannon- Denver
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
    • Park Ridge, Illinois, United States, 60068
      • Advocate Aurora Health - Advocate Lutheran General Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
  • New York
    • Rochester, New York, United States, 14642
      • University of Rochester
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic - Taussig Cancer Institute
    • Columbus, Ohio, United States, 43220
      • Ohio State University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon - Tenessee
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor Cancer Hospital
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
  • Washington
    • Seattle, Washington, United States, 98104
      • Swedish Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Brexucabtagene autoleucel (KTE-X19); 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.

Drug: Cyclophosphamide; Administered intravenously; Drug: Fludarabine; Administered intravenously; Biological: Brexucabtagene autoleucel; A single infusion of brexucabtagene autoleucel (KTE-X19) anti-CD 19 CAR T cells; Other Names: KTE-X19; TECARTUS™

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response (DOR)	DOR is defined as the time from their first objective response to disease progression or death.	Up to 7 years
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
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
Progression Free Survival (PFS)		Up to 7 years
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
Percentage of Participants Who Develop Anti-CD19 CAR Antibodies		Up to 7 years
Levels of Anti-CD19 CAR T Cells in Blood		Up to 7 years
Levels of Cytokines in Serum		Up to 7 years
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
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
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

Collaborators and Investigators

• Sponsor: Kite, A Gilead Company
• Investigators: Study Director: Kite Study Director, Kite, A Gilead Company

Publications and helpful links

Helpful Links

• Gilead Clinical Trials Website

Study record dates

Study Major Dates

• Study Start (Actual): April 27, 2021
• Primary Completion (Actual): November 26, 2023
• Study Completion (Estimated): October 1, 2038

Study Registration Dates

• First Submitted: April 30, 2021
• First Submitted That Met QC Criteria: May 5, 2021
• First Posted (Actual): May 10, 2021

Study Record Updates

• Last Update Posted (Actual): December 14, 2023
• Last Update Submitted That Met QC Criteria: December 12, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, Mantle-Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Immunological; Cyclophosphamide; Fludarabine; Brexucabtagene autoleucel
• Other Study ID Numbers: KTE-C19-102 (Cohort 3); 2015-005008-27 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No