Study Details

PROTOCOL SUMMARY

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).

Participation Requirements

Age

18 Years +

Sex

ALL

Healthy Volunteers

Medical Condition

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

Gender

N/A

Date

November 2022 - January 2025

Study Type

INTERVENTIONAL

Study Phase

PHASE2

Product

Brexucabtagene Autoleucel, Cyclophosphamide, Fludarabine

Eligibility Information

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.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Locations

Locations (26)

City of Hope (City of Hope National Medical Center)

Duarte, California, United States, 91010

Stanford Cancer Institute

Stanford, California, United States, 94305

Colorado Blood Cancer Institute

Denver, Colorado, United States, 80218

Georgetown University Medical Centre

Washington, District of Columbia, United States, 20037

University of Iowa

Iowa City, Iowa, United States, 52242

Washington University School of Medicine

Saint Louis, Missouri, United States, 63110

Hackensack University Medical Center

Hackensack, New Jersey, United States, 07601

The Ohio State University Wexner Medical Center - James Cancer HospitalS

Columbus, Ohio, United States, 43210

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, United States, 15232

Tennessee Oncology, PLLC

Nashville, Tennessee, United States, 37203

Vanderbilt University

Nashville, Tennessee, United States, 37232

MD Anderson Cancer Center

Houston, Texas, United States, 77030

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

Vienna, Austria, 01090

Hopital de la Pitie Salpetriere

Paris, France, 75013

Centre hospitalier de Toulouse - Hematology department

Toulouse Cedex 09, France, 31059

Universitatsklinikum Heidelberg

Heidelberg, Germany, 69120

Universitatsklinikum Koln

Koln, Germany, 50937

Universitatsklinikum Ulm

Ulm, Germany, 89081

IRCCS Azienda Ospedaliero - Universitaria di Bologna

Bologna, Italy, 40138

ASST Grande Ospedale Metropolitano Niguarda

Milano, Italy, 20162

Azienda Ospedale di Perugia - Ospedale S. Maria della Misericordia

Perugia, Italy, 06132

Radboud University Nijmegen Medical Centre

Nijmegen, Netherlands, 6525 GA

Hospital Clinic de Barcelona

Barcelona, Spain, 08036

Hospital Universitario de Salamanca

Salamanca, Spain, 37007

Hospital Universitario Virgen del Rocio

Sevilla, Spain, 41013

Istituto Oncologico Della Svizzera Italiana (IOSI)

Bellinzona, Switzerland, 6500

Study of Brexucabtagene Autoleucel in Adults With Rare B-cell Malignancies (ZUMA-25)

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