Study of Brexucabtagene Autoleucel (KTE-X19) in Participants With Relapsed/Refractory Mantle Cell Lymphoma (Cohort 1 and Cohort 2)

NCT ID: NCT02601313

Last Updated: 2025-01-14

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

105 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-11-09

Study Completion Date

2023-09-22

Brief Summary

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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

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Study KTE-C19-102 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, details for Cohort 3 were registered separately (NCT04880434) on ClinicalTrials.gov as this cohort will not be part of the main study analysis.

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

Conditions

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Relapsed/Refractory Mantle Cell Lymphoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Axicabtagene ciloleucel/brexucabtagene autoleucel (KTE-X19)

Participants with relapsed/refractory mantle cell lymphoma (MCL) will receive conditioning chemotherapy (CTE) 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 axicabtagene ciloleucel at a targeted dose of 2 x 10\^6 anti-CD19 chimeric antigen receptor (CAR) T cells/kg on Day 0 or brexucabtagene autoleucel (KTE-X19) at a targeted dose of 2 x 10\^6 CAR T cells/kg, with a maximum dose of 2 x 10\^8 anti-CD19 CAR T cells for participants ≥ 100 kg on Day 0 in Cohort 1 or brexucabtagene autoleucel at a targeted dose of 0.5 x 10\^6 anti-CD19 CAR T cells/kg, with a maximum dose of 0.5 x 10\^8 anti-CD19 CAR T cells for participants ≥ 100 kg on Day 0 in Cohort 2.

Group Type EXPERIMENTAL

brexucabtagene autoleucel

Intervention Type BIOLOGICAL

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

Cyclophosphamide

Intervention Type DRUG

Administered intravenously

Fludarabine

Intervention Type DRUG

Administered intravenously

Axicabtagene Ciloleucel

Intervention Type DRUG

A single infusion of axicabtagene ciloleucel anti-CD 19 CAR T cells

Interventions

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brexucabtagene autoleucel

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

Intervention Type BIOLOGICAL

Cyclophosphamide

Administered intravenously

Intervention Type DRUG

Fludarabine

Administered intravenously

Intervention Type DRUG

Axicabtagene Ciloleucel

A single infusion of axicabtagene ciloleucel anti-CD 19 CAR T cells

Intervention Type DRUG

Other Intervention Names

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KTE-X19, TECARTUS™

Eligibility Criteria

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Inclusion Criteria

Up to 5 prior regimens for Mantle cell lymphoma. Prior therapy must have included:

* Anthracycline or bendamustine-containing chemotherapy and
* Anti-CD20 monoclonal antibody therapy and
* Ibrutinib or acalabrutinib

At least 1 measurable lesion

Platelet count ≥ 75,000/uL

Creatinine clearance (as estimated by Cockcroft Gault) \> or = to 60 mL/min

Cardiac ejection fraction ≥ 50%, no evidence of pericardial effusion as determined by an echocardiogram (ECHO), and no clinically significant electrocardiogram (ECG) findings

Baseline oxygen saturation \>92% on room air.

Exclusion Criteria

* Known history of infection with human immunodeficiency virus (HIV) or hepatitis B (HBsAG positive) or hepatitis C virus (anti-HCV positive). A history of hepatitis B or hepatitis C is permitted if the viral load is undetectable per 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Kite, A Gilead Company

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Kite Study Director

Role: STUDY_DIRECTOR

Kite, A Gilead Company

Locations

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Banner MD Anderson

Gilbert, Arizona, United States

Site Status

City of Hope

Duarte, California, United States

Site Status

University California Los Angeles (UCLA)

Santa Monica, California, United States

Site Status

Stanford University

Stanford, California, United States

Site Status

Sarah Cannon

Denver, Colorado, United States

Site Status

University of Miami

Miami, Florida, United States

Site Status

H Lee Moffitt Cancer Center

Tampa, Florida, United States

Site Status

Winship Cancer Institute of Emory University

Atlanta, Georgia, United States

Site Status

University of Chicago

Chicago, Illinois, United States

Site Status

Loyola University Chicago

Maywood, Illinois, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

University of Rochester Medical Center

Rochester, New York, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Site Status

Ohio State University

Columbus, Ohio, United States

Site Status

Robert W. Franz Cancer Research Center

Portland, Oregon, United States

Site Status

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

Baylor Charles A. Sammons Cancer Center

Dallas, Texas, United States

Site Status

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Swedish Cancer Institute

Seattle, Washington, United States

Site Status

Centre Hospitalier Universitaire (CHU)

Bordeaux, , France

Site Status

Hospital Saint Louis

Paris, , France

Site Status

Hopital Haut-Leveque

Pessac, , France

Site Status

Universitätsklinik Dresden

Dresden, , Germany

Site Status

Universitaetsklinikum Wuerzburg

Würzburg, , Germany

Site Status

Academisch Medisch Centrum

Amsterdam, , Netherlands

Site Status

University Medical Center Groningen

Groningen, , Netherlands

Site Status

Erasmus Medical Center

Rotterdam, , Netherlands

Site Status

Countries

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United States France Germany Netherlands

References

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Michael Wang,1 Javier Munoz,2 Andre Goy,3 Frederick L. Locke,4 Caron A. Jacobson,5 Brian T. Hill,6 John M. Timmerman,7 Houston Holmes,8 Samantha Jaglowski,9 Ian W. Flinn,10 Peter A. McSweeney,11 David B. Miklos,12 John M. Pagel,13 Marie José Kersten,14 Noel Milpied,15 Henry Fung,16 Max S. Topp,17 Roch Houot,18 Amer Beitinjaneh,19 Weimin Peng,20 Lianqing Zheng,20 John M. Rossi,20 Rajul K. Jain,20 Arati V. Rao,20 and Patrick M. Reagan21

Reference Type BACKGROUND

Wang M, Munoz J, Goy A, Locke FL, Jacobson CA, Hill BT, Timmerman JM, Holmes H, Jaglowski S, Flinn IW, McSweeney PA,Miklos DB, Pagel JM, Kersten MJ, Peng W,Zheng L,Rossi JM, Jain RK, Rao AV, Reagan PM

Reference Type BACKGROUND

Wang, Michael L., MD(1); Munoz, Javier, MD(2); Goy, Andre, MD(3); Locke, Frederick L., MD(4); Jacobson, Caron A., MD, MMSc(5); Hill, Brian T., MD(6); Timmerman, John M., MD(7); Holmes, Houston, MD(8); Jaglowski, Samantha, MD, MPH(9); Flinn, Ian W., MD, PhD(10); McSweeney, Peter A., MD(11); Miklos, David B., MD, PhD(12); Pagel, John M., MD, PhD, DSc(13); Jose Kersten, Marie, MD, PhD(14); Peng, Weimin, MS(15); Zheng, Lianqing, PhD(15); Rossi, John M., MS(15); Jain, Rajul K., MD(15); Rao, Arati V., MD(15); Reagan, Patrick M, MD(16)

Reference Type BACKGROUND

Wang, Michael; Lundry Locke, Frederick; Munoz, Javier; Goy, Andre; Eccleston Holmes, Houston; Siddiqi, Tanya; Flinn, Ian; McSweeney, Peter A; Michael Reagan, Patrick; Thomas Hill, Brian; Jacobson, Caron A.; Rizzieri, David A.; Heffner, Leonard T.; Mary Jaglowski, Samantha; Bernard Miklos, David; Shaughnessy, Paul; Unabia, Sherry; Rossi, John M.; Jiang, Yizhou; Jain, Rajul K.

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Wang M, Jain P, Chi TL, Chen SE, Heimberger A, Weathers SP, Zheng L, Rao AV, Rossi JM. Management of a patient with mantle cell lymphoma who developed severe neurotoxicity after chimeric antigen receptor T-cell therapy in ZUMA-2. J Immunother Cancer. 2020 Oct;8(2):e001114. doi: 10.1136/jitc-2020-001114.

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Wang M, Munoz J, Goy A, Locke FL, Jacobson CA, Hill BT, Timmerman JM, Holmes H, Jaglowski S, Flinn IW, McSweeney PA, Miklos DB, Pagel JM, Kersten MJ, Milpied N, Fung H, Topp MS, Houot R, Beitinjaneh A, Peng W, Zheng L, Rossi JM, Jain RK, Rao AV, Reagan PM. KTE-X19 CAR T-Cell Therapy in Relapsed or Refractory Mantle-Cell Lymphoma. N Engl J Med. 2020 Apr 2;382(14):1331-1342. doi: 10.1056/NEJMoa1914347.

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Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol: Study Protocol: Amendment 6

View Document

Document Type: Study Protocol: Study Protocol: Amendment 9

View Document

Document Type: Statistical Analysis Plan: Statistical Analysis Plan- Interim Results

View Document

Document Type: Statistical Analysis Plan: Statistical Analysis Plan- Final Results

View Document

Related Links

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Other Identifiers

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2015-005008-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2023-506641-35

Identifier Type: OTHER

Identifier Source: secondary_id

KTE-C19-102

Identifier Type: -

Identifier Source: org_study_id

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