Study of Brexucabtagene Autoleucel in Adults With Rare B-cell Malignancies

NCT ID: NCT05537766

Last Updated: 2025-03-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

19 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-11-01

Study Completion Date

2025-01-27

Brief Summary

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Master protocol: The goal of this master clinical study is to test how well the study drug, brexucabtagene autoleucel, works in participants with rare B-cell malignancies: relapsed/refractory Waldenstrom macroglobulinemia (r/r WM) (Substudy A - no longer recruiting), relapsed/refractory Richter transformation (r/r RT) (Substudy B), relapsed/refractory Burkitt lymphoma (r/r BL) (Substudy C and relapsed/refractory hairy cell leukemia (r/r HCL) (Substudy D - no longer recruiting).

Detailed Description

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Master protocol: The primary objective of this study is to evaluate the efficacy of brexucabtagene autoleucel in two rare B-cell malignancies. This study will use a basket study design with separate, indication-specific substudies, to investigate r/r RT and r/r BL.

After completing the treatment period, all participants will be followed in the post-treatment follow-up period. Thereafter, participants will transition to a separate long-term follow-up study (KT-US-982-5968) to continue follow-up out to 15 years.

Substudies A and D have been early terminated by the sponsor.

Conditions

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Relapsed/Refractory Waldenstrom Macroglobulinemia Relapsed/Refractory Richter Transformation Relapsed/Refractory Burkitt Lymphoma Relapsed/Refractory Hairy Cell Leukemia

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Substudy A (Relapsed/Refractory Waldenstrom Macroglobulinemia): Brexucabtagene Autoleucel

Participants will receive fludarabine 30 mg/m\^2/day and cyclophosphamide 500 mg/m\^2/day lymphodepletion chemotherapy for 3 days followed by a single infusion of brexucabtagene autoleucel at target dose of 2 × 10\^6 anti-CD19 chimeric antigen receptor (CAR) T cells/kg.

This arm is no longer recruiting.

Group Type EXPERIMENTAL

Brexucabtagene Autoleucel

Intervention Type BIOLOGICAL

Administered intravenously

Cyclophosphamide

Intervention Type DRUG

Administered intravenously

Fludarabine

Intervention Type DRUG

Administered intravenously

Substudy B (Relapsed/Refractory Richter Transformation): Brexucabtagene Autoleucel

Participants will receive fludarabine 30 mg/m\^2/day and cyclophosphamide 500 mg/m\^2/day lymphodepletion chemotherapy for 3 days followed by a single infusion of brexucabtagene autoleucel at target dose of 2×10\^6 anti-CD19 CAR T cells/kg.

This arm is no longer recruiting.

Group Type EXPERIMENTAL

Brexucabtagene Autoleucel

Intervention Type BIOLOGICAL

Administered intravenously

Cyclophosphamide

Intervention Type DRUG

Administered intravenously

Fludarabine

Intervention Type DRUG

Administered intravenously

Substudy C (Relapsed/Refractory Burkitt Lymphoma): Brexucabtagene Autoleucel

Participants will receive fludarabine 30 mg/m\^2/day and cyclophosphamide 500 mg/m\^2/day lymphodepletion chemotherapy for 3 days followed by a single infusion of brexucabtagene autoleucel at a target dose of 2x10\^6 anti-CD19 CAR T cells/kg.

Group Type EXPERIMENTAL

Brexucabtagene Autoleucel

Intervention Type BIOLOGICAL

Administered intravenously

Cyclophosphamide

Intervention Type DRUG

Administered intravenously

Fludarabine

Intervention Type DRUG

Administered intravenously

Substudy D (Relapsed/Refractory hairy cell leukemia): Brexucabtagene Autoleucel

Participants will receive fludarabine 30 mg/m\^2/day and cyclophosphamide 500 mg/m\^2/day lymphodepletion chemotherapy for 3 days followed by a single infusion of brexucabtagene autoleucel at a target dose of 2 × 10\^6 anti-CD19 CAR T cells/kg.

This arm is no longer recruiting.

Group Type EXPERIMENTAL

Brexucabtagene Autoleucel

Intervention Type BIOLOGICAL

Administered intravenously

Cyclophosphamide

Intervention Type DRUG

Administered intravenously

Fludarabine

Intervention Type DRUG

Administered intravenously

Interventions

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Brexucabtagene Autoleucel

Administered intravenously

Intervention Type BIOLOGICAL

Cyclophosphamide

Administered intravenously

Intervention Type DRUG

Fludarabine

Administered intravenously

Intervention Type DRUG

Other Intervention Names

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KTE-X19

Eligibility Criteria

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Inclusion Criteria

All Substudies:

* Presence of toxicities due to prior therapy must be stable and recovered to Grade 1 or lower.
* Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
* Adequate hematologic and end-organ function.
* Individuals of childbearing potential who engage in heterosexual intercourse must agree to use specified method(s) of contraception.

Substudy B:

* Confirmed diagnosis of chronic lymphocytic leukemia (CLL) based on International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2018 criteria with histologically confirmed Richter transformation (RT) to a diffuse large B-cell lymphoma (DLBCL) subtype.
* Relapsed or refractory disease after 1 line of therapy, defined as at least 1 of the following:

* Refractory disease, defined as progressive disease or stable disease as best response to first-line therapy.
* Relapsed disease, defined as complete remission to first-line therapy followed by biopsy-proven disease relapse.
* At least 1 measurable lesion based on the Lugano Classification. Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy.

Substudy C:

* Histologically confirmed mature B-cell non-Hodgkin lymphoma (NHL) Burkitt lymphoma/leukemia.
* Relapsed or refractory disease after first-line chemoimmunotherapy, defined as 1 of the following:

* Refractory disease, defined as progressive disease or stable disease as best response to first-line therapy; individuals who are intolerant to first-line therapy are excluded.
* Relapsed disease, defined as complete remission to first-line therapy followed by biopsy-proven disease relapse.
* At least 1 measurable lesion based on the Lugano Classification. Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy.

Exclusion Criteria

All Substudies:

* Prior CAR therapy or treatment with any anti-CD19 therapy.
* HIV-positive patients, unless taking appropriate anti-HIV medications, having an undetectable viral load by quantitative polymerase chain reaction (qPCR) and a CD4 count \> 200 cells/uL.
* Presence of detectable cerebrospinal fluid malignant cells or brain metastases.
* History of autoimmune disease (eg, Crohn's disease, rheumatoid arthritis, systemic lupus).

Substudy B:

* Diagnosis of RT not of DLBCL subtype (including, but not limited to, Hodgkin lymphoma (HL) and prolymphocytic leukemia).
* Prior allogeneic or autologous stem cell transplant \< 3 months prior to screening and/or \< 4 months prior to planned infusion of brexucabtagene autoleucel.
* Presence of active graft-versus-host disease following prior stem cell transplant.

Substudy C:

* Burkitt-like lymphoma with 11q aberration, high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangement, or high-grade B-cell lymphoma not otherwise specified.
* Prior allogeneic stem cell transplant \< 3 months prior to screening and/or \< 4 months prior to planned infusion of brexucabtagene autoleucel.
* Presence of active graft-versus-host disease following prior allogeneic stem cell transplant.
* Presence of CNS involvement. Individuals with a prior history of CNS involvement are eligible if they show a negative CSF and no involvement by imaging.

Substudies A and D have been early terminated by the sponsor.
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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City of Hope (City of Hope National Medical Center)

Duarte, California, United States

Site Status

Stanford Cancer Institute

Stanford, California, United States

Site Status

Colorado Blood Cancer Institute

Denver, Colorado, United States

Site Status

Georgetown University Medical Centre

Washington D.C., District of Columbia, United States

Site Status

University of Iowa

Iowa City, Iowa, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

The Ohio State University Wexner Medical Center - James Cancer HospitalS

Columbus, Ohio, United States

Site Status

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Site Status

Tennessee Oncology, PLLC

Nashville, Tennessee, United States

Site Status

Vanderbilt University

Nashville, Tennessee, United States

Site Status

MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Medical University of Vienna, Department of Internal Medicine I, Div. of Hematology

Vienna, , Austria

Site Status

Hopital de la Pitie Salpetriere

Paris, , France

Site Status

Centre hospitalier de Toulouse - Hematology department

Toulouse, , France

Site Status

Universitatsklinikum Koln

Cologne, , Germany

Site Status

Universitatsklinikum Heidelberg

Heidelberg, , Germany

Site Status

Universitatsklinikum Ulm

Ulm, , Germany

Site Status

IRCCS Azienda Ospedaliero - Universitaria di Bologna

Bologna, , Italy

Site Status

ASST Grande Ospedale Metropolitano Niguarda

Milan, , Italy

Site Status

Azienda Ospedale di Perugia - Ospedale S. Maria della Misericordia

Perugia, , Italy

Site Status

Radboud University Nijmegen Medical Centre

Nijmegen, , Netherlands

Site Status

Hospital Clinic de Barcelona

Barcelona, , Spain

Site Status

Hospital Universitario de Salamanca

Salamanca, , Spain

Site Status

Hospital Universitario Virgen del Rocio

Seville, , Spain

Site Status

Istituto Oncologico Della Svizzera Italiana (IOSI)

Bellinzona, , Switzerland

Site Status

Countries

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United States Austria France Germany Italy Netherlands Spain Switzerland

Related Links

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Other Identifiers

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2022-501259-10

Identifier Type: OTHER

Identifier Source: secondary_id

2022-501260-18

Identifier Type: OTHER

Identifier Source: secondary_id

2022-501261-46

Identifier Type: OTHER

Identifier Source: secondary_id

2022-501262-21

Identifier Type: OTHER

Identifier Source: secondary_id

KT-US-568-0138

Identifier Type: -

Identifier Source: org_study_id

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