A Phase 2, Open-Label, Multicenter, Basket Study Evaluating the Efficacy of Brexucabtagene Autoleucel in Adults With Rare B-cell Malignancies (ZUMA-25) (ZUMA-25)

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), r/r Richter transformation (RT) (Substudy B), r/r Burkitt lymphoma (BL) (Substudy C) and r/r hairy cell leukemia (HCL) (Substudy D).

Participation requirements

Age

18 years +

Sex

All

Healthy Volunteers

Study details

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

Phase 2

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 chimeric antigen receptor (CAR) therapy or treatment with any anti-Cluster of Differentiation 19 (CD19) therapy.
human immunodeficiency virus (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/μL.
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 central nervous system (CNS) involvement. Individuals with a prior history of CNS involvement are eligible if they show a negative cerebrospinal fluid (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

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

For more information, please contact the

For more information, please contact the

OVERVIEW

PROTOCOL SUMMARY

Participation requirements

Study details

Eligibility information

Inclusion criteria

Exclusion criteria

Locations

Locations (26)

City of Hope (City of Hope National Medical Center)

Stanford Cancer Institute

Colorado Blood Cancer Institute

Georgetown University Medical Centre

University of Iowa

Washington University School of Medicine

Hackensack University Medical Center

The Ohio State University Wexner Medical Center - James Cancer HospitalS

UPMC Hillman Cancer Center

Tennessee Oncology, PLLC

Vanderbilt University

MD Anderson Cancer Center

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

Hopital de la Pitie Salpetriere

Centre hospitalier de Toulouse - Hematology department

Universitatsklinikum Koln

Universitatsklinikum Heidelberg

Universitatsklinikum Ulm

IRCCS Azienda Ospedaliero - Universitaria di Bologna

ASST Grande Ospedale Metropolitano Niguarda

Azienda Ospedale di Perugia - Ospedale S. Maria della Misericordia

Radboud University Nijmegen Medical Centre

Hospital Clinic de Barcelona

Hospital Universitario de Salamanca

Hospital Universitario Virgen del Rocio

Istituto Oncologico Della Svizzera Italiana (IOSI)