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

NCT05537766 | Terminated Phase 2 Results DMC FDA Drug

• 5 other identifiers: KT-US-568-01382022-501259-102022-501260-182022-501261-462022-501262-21
• Study Type: interventional
• Target: 19
• Locations: 8 countries
• Sites: 26

Brief 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).

Conditions

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

Outcome Measures

Primary Outcomes (4)

• Substudy A: Combined Rate of Complete Response (CR) and Very Good Partial Response (VGPR) Determined by Central Assessment Per the Sixth International Workshop in Waldenstrom Macroglobulinemia (WM)

  The combined rate of CR and VGPR was defined as the percentage of participants who achieved a best response of either CR or VGPR per the Sixth International Workshop in WM.

  Up to 2 years

• Substudy B: Objective Response Rate (ORR) Determined by Central Assessment Per the Lugano Classification

  ORR was defined as the percentage of participants who achieved a best response of either CR or PR per the Lugano Classification.

  Up to 2 years

• Substudy C: ORR Determined by Central Assessment Per the Lugano Classification

  ORR was defined as the percentage of participants who achieved a best response of either CR or PR per the Lugano Classification.

  Up to 2 years

• Substudy D: ORR Determined by Central Assessment Per the Response Criteria Described by Grever and Colleagues

  ORR was defined as the percentage of participants who achieved a best response of either CR or PR per Grever and colleagues. CR: Near normalization of peripheral blood counts: hemoglobin \>11 g/dL (without transfusion); platelets \>100 000/μL; absolute neutrophil count \>1500/μL. Regression of splenomegaly on physical examination. Absence of morphologic evidence of HCL on both the peripheral blood smear and the bone marrow examination. PR: PR required near normalization of the peripheral blood count (as in CR) with a minimum of 50% improvement in organomegaly and bone marrow biopsy infiltration with HCL.

  Up to 2 years

Secondary Outcomes (25)

• All Substudies (Substudies A, B, C and D): Complete Response (CR) Rate Determined by Central Assessment

  Up to 2 years

• All Substudies (Substudies A, B, C and D): Duration of Response (DOR)

  Up to 2 years

• All Substudies (Substudies A, B, C and D): Overall Survival (OS)

  Up to 2 years

• All Substudies (Substudies A, B, C and D): Progression Free Survival (PFS)

  Up to 2 years

• All Substudies (Substudies A, B, C and D): Time to Next Treatment (TTNT)

  Up to 2 years

Study Arms (4)

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

EXPERIMENTAL

Participants with Relapsed/Refractory Waldenstrom Macroglobulinemia will receive the following treatment during the study:Lymphodepletion chemotherapy regimen of fludarabine 30 mg/m\^2/day intravenously (IV) and cyclophosphamide 500 mg/m\^2/day IV for 3 days (Day -5 to Day -3). A single IV infusion of brexucabtagene autoleucel at target dose of 2 × 10\^6 anti-cluster of differentiation 19 (CD19) chimeric antigen receptor (CAR) T cells/kg on Day 0.

Biological: Brexucabtagene Autoleucel; Drug: Cyclophosphamide; Drug: Fludarabine

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

EXPERIMENTAL

Participants with Relapsed/Refractory Richter Transformation will receive the following treatment during the study: Lymphodepletion chemotherapy regimen of fludarabine 30 mg/m\^2/day IV and cyclophosphamide 500 mg/m\^2/day IV for 3 days (Day -5 to Day -3).A single IV infusion of brexucabtagene autoleucel at target dose of 2 × 10\^6 anti-CD19 CAR T cells/kg on Day 0.

Biological: Brexucabtagene Autoleucel; Drug: Cyclophosphamide; Drug: Fludarabine

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

EXPERIMENTAL

Participants with Relapsed/Refractory Burkitt Lymphoma will receive the following treatment during the study:Lymphodepletion chemotherapy regimen of fludarabine 30 mg/m\^2/day IV and cyclophosphamide 500 mg/m\^2/day IV for 3 days (Day -5 to Day -3).A single IV infusion of brexucabtagene autoleucel at target dose of 2 × 10\^6 anti-CD19 CAR T cells/kg on Day 0.

Biological: Brexucabtagene Autoleucel; Drug: Cyclophosphamide; Drug: Fludarabine

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

EXPERIMENTAL

Participant with Relapsed/Refractory Hairy Cell Leukemia will receive the following treatment during the study: Lymphodepletion chemotherapy regimen of fludarabine 30 mg/m\^2/day IV and cyclophosphamide 500 mg/m\^2/day IV for 3 days (Day -5 to Day -3). A single IV infusion of brexucabtagene autoleucel at target dose of 2 × 10\^6 anti-CD19 CAR T cells/kg on Day 0.

Biological: Brexucabtagene Autoleucel; Drug: Cyclophosphamide; Drug: Fludarabine

Interventions

Brexucabtagene Autoleucel BIOLOGICAL

Administered intravenously

Also known as: KTE-X19

Substudy A (Relapsed/Refractory Waldenstrom Macroglobulinemia): Brexucabtagene Autoleucel; Substudy B (Relapsed/Refractory Richter Transformation): Brexucabtagene Autoleucel; Substudy C (Relapsed/Refractory Burkitt Lymphoma): Brexucabtagene Autoleucel; Substudy D (Relapsed/Refractory hairy cell leukemia): Brexucabtagene Autoleucel

Cyclophosphamide DRUG

Administered intravenously

Substudy A (Relapsed/Refractory Waldenstrom Macroglobulinemia): Brexucabtagene Autoleucel; Substudy B (Relapsed/Refractory Richter Transformation): Brexucabtagene Autoleucel; Substudy C (Relapsed/Refractory Burkitt Lymphoma): Brexucabtagene Autoleucel; Substudy D (Relapsed/Refractory hairy cell leukemia): Brexucabtagene Autoleucel

Fludarabine DRUG

Administered intravenously

Substudy A (Relapsed/Refractory Waldenstrom Macroglobulinemia): Brexucabtagene Autoleucel; Substudy B (Relapsed/Refractory Richter Transformation): Brexucabtagene Autoleucel; Substudy C (Relapsed/Refractory Burkitt Lymphoma): Brexucabtagene Autoleucel; Substudy D (Relapsed/Refractory hairy cell leukemia): Brexucabtagene Autoleucel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Kite, A Gilead Company: lead

Study Sites (26)

City of Hope (City of Hope National Medical Center)

Duarte, California, 91010, United States

Location

Stanford Cancer Institute

Stanford, California, 94305, United States

Location

Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

Location

Georgetown University Medical Centre

Washington D.C., District of Columbia, 20037, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

The Ohio State University Wexner Medical Center - James Cancer HospitalS

Columbus, Ohio, 43210, United States

Location

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Tennessee Oncology, PLLC

Nashville, Tennessee, 37203, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

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

Vienna, 01090, Austria

Location

Hopital de la Pitie Salpetriere

Paris, 75013, France

Location

Centre hospitalier de Toulouse - Hematology department

Toulouse, 31059, France

Location

Universitatsklinikum Koln

Cologne, 50937, Germany

Location

Universitatsklinikum Heidelberg

Heidelberg, 69120, Germany

Location

Universitatsklinikum Ulm

Ulm, 89081, Germany

Location

IRCCS Azienda Ospedaliero - Universitaria di Bologna

Bologna, 40138, Italy

Location

ASST Grande Ospedale Metropolitano Niguarda

Milan, 20162, Italy

Location

Azienda Ospedale di Perugia - Ospedale S. Maria della Misericordia

Perugia, 06132, Italy

Location

Radboud University Nijmegen Medical Centre

Nijmegen, 6525 GA, Netherlands

Location

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

Hospital Universitario de Salamanca

Salamanca, 37007, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Istituto Oncologico Della Svizzera Italiana (IOSI)

Bellinzona, 6500, Switzerland

Location

Related Links

• Gilead Clinical Trials Website

MeSH Terms

Conditions

Waldenstrom Macroglobulinemia; Recurrence; Burkitt Lymphoma; Leukemia, Hairy Cell

Interventions

brexucabtagene autoleucel; Cyclophosphamide; fludarabine

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Leukemia

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: Medical Information
• Organization: Kite, A Gilead Company

medinfo@kitepharma.com

844-454-5483 (1-844-454-KITE)

Study Officials

• Kite Study Director

  Kite, A Gilead Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2022
• First Posted: September 13, 2022
• Study Start: November 1, 2022
• Primary Completion: January 27, 2025
• Study Completion: January 27, 2025
• Last Updated: March 10, 2026
• Results First Posted: March 10, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (12); DE (3); FR (2); NL (1); AU (1); IT (3); ES (3); CH (1)