---
title: Study of Brexucabtagene Autoleucel in Adults With Rare B-cell Malignancies
nct_id: NCT05537766
overall_status: TERMINATED
phase: PHASE2
sponsor: Kite, A Gilead Company
study_type: INTERVENTIONAL
primary_condition: Relapsed/Refractory Waldenstrom Macroglobulinemia
countries: United States, Austria, France, Germany, Italy, Netherlands, Spain, Switzerland
canonical_url: "https://parkinsonspathways.com/agent/trials/NCT05537766.md"
clinicaltrials_gov: "https://clinicaltrials.gov/study/NCT05537766"
ct_last_update_post_date: 2026-03-10
last_seen_at: "2026-05-12T07:08:12.328Z"
source: ClinicalTrials.gov (mirrored, no enrichment)
---
# Study of Brexucabtagene Autoleucel in Adults With Rare B-cell Malignancies

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

**NCT ID:** [NCT05537766](https://clinicaltrials.gov/study/NCT05537766)

## Key Facts

- **Status:** TERMINATED
- **Why Stopped:** Sponsor decision to terminate study.
- **Phase:** PHASE2
- **Study Type:** INTERVENTIONAL
- **Target Enrollment:** 19
- **Lead Sponsor:** Kite, A Gilead Company
- **Conditions:** Relapsed/Refractory Waldenstrom Macroglobulinemia, Relapsed/Refractory Richter Transformation, Relapsed/Refractory Burkitt Lymphoma, Relapsed/Refractory Hairy Cell Leukemia
- **Start Date:** 2022-11-01
- **Completion Date:** 2025-01-27
- **CT.gov Last Update:** 2026-03-10

## 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).

## Detailed Description

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.

All substudies have been early terminated by the sponsor. Below is summary of enrollment in each Substudy:

* Substudy-A This substudy was withdrawn. Therefore no participants were enrolled.
* Substudy-B enrollment closed, actual enrollment is 6.
* Substudy-C enrollment closed, actual enrollment is 12.
* Substudy-D enrollment closed, actual enrollment is 1.

## Eligibility

- **Minimum age:** 18 Years
- **Sex:** ALL
- **Healthy Volunteers:** No

```
Key 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.

Key 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.
```

## Arms

- **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.
- **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.
- **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.
- **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.

## Interventions

- **Brexucabtagene Autoleucel** (BIOLOGICAL) — Administered intravenously
- **Cyclophosphamide** (DRUG) — Administered intravenously
- **Fludarabine** (DRUG) — Administered intravenously

## Primary Outcomes

- **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)** _(time frame: Up to 2 years)_ — 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.
- **Substudy B: Objective Response Rate (ORR) Determined by Central Assessment Per the Lugano Classification** _(time frame: Up to 2 years)_ — ORR was defined as the percentage of participants who achieved a best response of either CR or PR per the Lugano Classification.
- **Substudy C: ORR Determined by Central Assessment Per the Lugano Classification** _(time frame: Up to 2 years)_ — ORR was defined as the percentage of participants who achieved a best response of either CR or PR per the Lugano Classification.
- **Substudy D: ORR Determined by Central Assessment Per the Response Criteria Described by Grever and Colleagues** _(time frame: Up to 2 years)_ — 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.

## Secondary Outcomes

- **All Substudies (Substudies A, B, C and D): Complete Response (CR) Rate Determined by Central Assessment** _(time frame: Up to 2 years)_
- **All Substudies (Substudies A, B, C and D): Duration of Response (DOR)** _(time frame: Up to 2 years)_
- **All Substudies (Substudies A, B, C and D): Overall Survival (OS)** _(time frame: Up to 2 years)_
- **All Substudies (Substudies A, B, C and D): Progression Free Survival (PFS)** _(time frame: Up to 2 years)_
- **All Substudies (Substudies A, B, C and D): Time to Next Treatment (TTNT)** _(time frame: Up to 2 years)_
- **All Substudies (Substudies A, B, C and D): Time to First Objective Response** _(time frame: Up to 2 years)_
- **All Substudies (Substudies A, B, C and D): Time to Best Objective Response** _(time frame: Up to 2 years)_
- **All Substudies (Substudies A, B, C and D): Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)** _(time frame: First infusion date of brexucabtagene autoleucel up to 2 years)_
- **All Substudies (Substudies A, B, C and D): Number of Participants With Increase in Laboratory Values Reported as Grade 3 or Higher** _(time frame: First infusion date of brexucabtagene autoleucel up to 2 years)_
- **All Substudies (Substudies A, B, C and D): Number of Participants With Decrease in Laboratory Values Reported as Grade 3 or Higher** _(time frame: First dose date up to 2 years)_
- **All Substudies (Substudies A, B, C and D): Number of Participants Experiencing Adverse Events (AEs) Defined as Dose Limiting Toxicities (DLTs)** _(time frame: First infusion date of brexucabtagene autoleucel up to 28 days)_
- **All Substudies (Substudies A, B, C and D): Number of Participants With Positive Anti-brexucabtagene Autoleucel Antibodies** _(time frame: Up to 2 years)_
- **All Substudies (Substudies A, B, C and D): Number of Participants With Replication-competent Retrovirus (RCR) in Peripheral Blood Mononuclear Cells (PBMCs)** _(time frame: Up to 2 years)_
- **All Substudies (Substudies A, B, C and D): Number of Participants With Deterioration Scores From Screening in the European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire-30 (EORTC QLQ-C30)** _(time frame: Day -5, Day 0, Day 28, Month 3, Month 6, Month 9 and Month 12)_
- **All Substudies (Substudies A, B, C and D): Number of Participants With Deterioration Scores From Screening in the European Quality of Life Five Dimensions Five Levels Questionnaire (EQ-5D-5L)** _(time frame: Day -5, Day 0, Day 28, Month 3, Month 6, Month 9 and Month 12)_
- **All Substudies (Substudies A, B, C and D): Change From Screening in the EQ-ED-5L Visual Analogue Scale (EQ-VAS) Score** _(time frame: Screening, Day -5, Day 0, Day 28, Month 3, Month 6, Month 9 and Month 12)_
- **Substudy A: ORR (CR, VGPR, or PR) Determined by Central Assessment Per the Sixth International Workshop in WM** _(time frame: Up to 2 years)_
- **Substudy A: Percentage of Participants With Combined CR and VGPR Determined by Investigator Assessment Per the Sixth International Workshop in WM** _(time frame: Up to 2 years)_
- **Substudy A: PR Rate Determined by Central Assessment Per the Sixth International Workshop in WM** _(time frame: Up to 2 years)_
- **Substudy A: VGPR Rate Determined by Central Assessment Per the Sixth International Workshop in WM** _(time frame: Up to 2 years)_
- **Substudy B: Number of Participants With OR Determined by Investigator Assessment Per the Lugano Classification** _(time frame: Up to 2 years)_
- **Substudy B: Number of Participants With OR Based on Clonal Relationship to the Underlying CLL by Central Assessment Per the Lugano Classification** _(time frame: Up to 2 years)_
- **Substudy B: Number of Participants With OR (CR, CRi, or PR) Determined by Investigator Per International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2018 Criteria** _(time frame: Up to 2 years)_
- **Substudy C: Number of Participants With OR Determined by Investigator Assessment Per the Lugano Classification** _(time frame: Up to 2 years)_
- **Substudy D: Number of Participants With OR Determined by Investigator Assessment Per Grever and Colleagues** _(time frame: Up to 2 years)_

## Locations (26)

- City of Hope (City of Hope National Medical Center), Duarte, California, United States
- Stanford Cancer Institute, Stanford, California, United States
- Colorado Blood Cancer Institute, Denver, Colorado, United States
- Georgetown University Medical Centre, Washington D.C., District of Columbia, United States
- University of Iowa, Iowa City, Iowa, United States
- Washington University School of Medicine, St Louis, Missouri, United States
- Hackensack University Medical Center, Hackensack, New Jersey, United States
- The Ohio State University Wexner Medical Center - James Cancer HospitalS, Columbus, Ohio, United States
- UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, United States
- Tennessee Oncology, PLLC, Nashville, Tennessee, United States
- Vanderbilt University, Nashville, Tennessee, United States
- MD Anderson Cancer Center, Houston, Texas, United States
- Medical University of Vienna, Department of Internal Medicine I, Div. of Hematology, Vienna, Austria
- Hopital de la Pitie Salpetriere, Paris, France
- Centre hospitalier de Toulouse - Hematology department, Toulouse, France
- Universitatsklinikum Koln, Cologne, Germany
- Universitatsklinikum Heidelberg, Heidelberg, Germany
- Universitatsklinikum Ulm, Ulm, Germany
- IRCCS Azienda Ospedaliero - Universitaria di Bologna, Bologna, Italy
- ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
- Azienda Ospedale di Perugia - Ospedale S. Maria della Misericordia, Perugia, Italy
- Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands
- Hospital Clinic de Barcelona, Barcelona, Spain
- Hospital Universitario de Salamanca, Salamanca, Spain
- Hospital Universitario Virgen del Rocio, Seville, Spain
- Istituto Oncologico Della Svizzera Italiana (IOSI), Bellinzona, Switzerland

## Recent Field Changes (last 30 days)

- `eligibility.sex` — added _(2026-05-12)_
- `status.overallStatus` — added _(2026-05-12)_
- `status.whyStopped` — added _(2026-05-12)_
- `status.primaryCompletionDate` — added _(2026-05-12)_
- `status.completionDate` — added _(2026-05-12)_
- `status.lastUpdatePostDate` — added _(2026-05-12)_
- `design.phases` — added _(2026-05-12)_
- `design.enrollmentCount` — added _(2026-05-12)_
- `eligibility.criteria` — added _(2026-05-12)_
- `eligibility.minAge` — added _(2026-05-12)_
- `outcomes.primary` — added _(2026-05-12)_
- `outcomes.secondary` — added _(2026-05-12)_
- `armsInterventions.arms` — added _(2026-05-12)_
- `armsInterventions.interventions` — added _(2026-05-12)_
- `sponsor.lead` — added _(2026-05-12)_
- `results.hasResults` — added _(2026-05-12)_
- `locations.city of hope (city of hope national medical center)|duarte|california|united states` — added _(2026-05-12)_
- `locations.stanford cancer institute|stanford|california|united states` — added _(2026-05-12)_
- `locations.colorado blood cancer institute|denver|colorado|united states` — added _(2026-05-12)_
- `locations.georgetown university medical centre|washington d.c.|district of columbia|united states` — added _(2026-05-12)_
- `locations.university of iowa|iowa city|iowa|united states` — added _(2026-05-12)_
- `locations.washington university school of medicine|st louis|missouri|united states` — added _(2026-05-12)_
- `locations.hackensack university medical center|hackensack|new jersey|united states` — added _(2026-05-12)_
- `locations.the ohio state university wexner medical center - james cancer hospitals|columbus|ohio|united states` — added _(2026-05-12)_
- `locations.upmc hillman cancer center|pittsburgh|pennsylvania|united states` — added _(2026-05-12)_
- `locations.tennessee oncology, pllc|nashville|tennessee|united states` — added _(2026-05-12)_
- `locations.vanderbilt university|nashville|tennessee|united states` — added _(2026-05-12)_
- `locations.md anderson cancer center|houston|texas|united states` — added _(2026-05-12)_
- `locations.medical university of vienna, department of internal medicine i, div. of hematology|vienna||austria` — added _(2026-05-12)_
- `locations.hopital de la pitie salpetriere|paris||france` — added _(2026-05-12)_
- `locations.centre hospitalier de toulouse - hematology department|toulouse||france` — added _(2026-05-12)_
- `locations.universitatsklinikum koln|cologne||germany` — added _(2026-05-12)_
- `locations.universitatsklinikum heidelberg|heidelberg||germany` — added _(2026-05-12)_
- `locations.universitatsklinikum ulm|ulm||germany` — added _(2026-05-12)_
- `locations.irccs azienda ospedaliero - universitaria di bologna|bologna||italy` — added _(2026-05-12)_
- `locations.asst grande ospedale metropolitano niguarda|milan||italy` — added _(2026-05-12)_
- `locations.azienda ospedale di perugia - ospedale s. maria della misericordia|perugia||italy` — added _(2026-05-12)_
- `locations.radboud university nijmegen medical centre|nijmegen||netherlands` — added _(2026-05-12)_
- `locations.hospital clinic de barcelona|barcelona||spain` — added _(2026-05-12)_
- `locations.hospital universitario de salamanca|salamanca||spain` — added _(2026-05-12)_
- `locations.hospital universitario virgen del rocio|seville||spain` — added _(2026-05-12)_
- `locations.istituto oncologico della svizzera italiana (iosi)|bellinzona||switzerland` — added _(2026-05-12)_

---

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