What side effects are associated with this type of intervention?

Common treatments for Hairy Cell Leukemia include 2-chlorodeoxyadenosine (2-CdA), interferon alpha, and deoxycoformycin. The side effects of 2-CdA can include myelosuppression, increased risk of infections, and potential long-term immunosuppression. Interferon alpha may cause flu-like symptoms, fatigue, and depression. Deoxycoformycin can lead to myelosuppression and gastrointestinal disturbances. For CAR-T cell therapy, such as Brexucabtagene Autoleucel, side effects often include cytokine release syndrome (CRS), neurotoxicity, and increased risk of infections due to immunosuppression.

What prior FDA approvals exist?

The FDA has approved several treatments for Hairy Cell Leukemia (HCL), primarily focusing on purine analogs such as cladribine and pentostatin, which have been the mainstay of therapy. Additionally, rituximab, a monoclonal antibody targeting CD20, has been used in combination with these agents. For patients with resistant or relapsed HCL, options include vemurafenib (a BRAF inhibitor) and moxetumomab pasudotox (an anti-CD22 immunotoxin). While CAR-T cell therapies like Brexucabtagene Autoleucel, which target CD19, are being studied in other B-cell malignancies, they represent a novel approach that has not yet been widely applied to HCL.

What other types of research exist?

Promising novel alternatives to Brexucabtagene Autoleucel for Hairy Cell Leukemia patients include other CAR-T cell therapies such as Ciltacabtagene Autoleucel, which targets B-cell maturation antigen (BCMA) and has shown efficacy in multiple myeloma. Additionally, exploring Janus kinase inhibitors like Ruxolitinib, which has shown effectiveness in alopecia areata, might offer new therapeutic avenues. These alternatives should be discussed with a healthcare provider to determine their suitability for HCL treatment.

← Back to Search

CAR T-cell Therapy

Gene Therapy for Rare B-Cell Cancers (ZUMA-25 Trial)

Phase 2

Recruiting

Research Sponsored by Kite, A Gilead Company

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

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

Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years for substudies b and c; up to 5 years for substudies a and d

Awards & highlights

ZUMA-25 Trial Summary

This trial studies a new gene therapy to treat 4 rare B-cell malignancies, such as Waldenstrom macroglobulinemia, Richter transformation, Burkitt lymphoma, and hairy cell leukemia.

Who is the study for?

Adults with certain rare B-cell malignancies like Richter Transformation, Burkitt Lymphoma, and Waldenstrom Macroglobulinemia can join if they've recovered from previous treatments to a mild level, have good physical function, and proper organ function. They must use contraception if applicable. Those who've had recent CAR therapy or stem cell transplants, CNS involvement, autoimmune diseases or HIV not well-controlled are excluded.Check my eligibility

What is being tested?

The trial is testing brexucabtagene autoleucel's effectiveness on various subtypes of B-cell malignancies. Participants will also receive fludarabine and cyclophosphamide as part of the treatment regimen. The study includes different substudies for each condition but some are no longer recruiting.See study design

What are the potential side effects?

Potential side effects may include reactions related to immune system activation such as fever and fatigue, blood count abnormalities that could lead to infections or bleeding problems, and possible damage to organs due to the body's response against cancer cells.

ZUMA-25 Trial Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I have chronic lymphocytic leukemia that has transformed into a more aggressive type.

Select...

I am fully active or restricted in physically strenuous activity but can do light work.

Select...

Any side effects from my previous treatments are mild or gone.

Select...

My condition worsened or didn't improve after one treatment, and I have at least one measurable tumor.

ZUMA-25 Trial Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years for substudies b and c; up to 5 years for substudies a and d

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years for substudies b and c; up to 5 years for substudies a and d

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 years for substudies b and c; up to 5 years for substudies a and d for reporting.

Treatment Details

Study Objectives

Outcome measures can provide a clearer picture of what you can expect from a treatment.

Primary outcome measures

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)

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

Substudy C: ORR Determined by Central Assessment per the Lugano Classification

+1 more

Secondary outcome measures

All Substudies (Substudies A, B, C and D): Change From Baseline in the European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire-30 (EORTC QLQ-C30) Score

All Substudies (Substudies A, B, C and D): Changes From Baseline in the European Quality of Life Five Dimensions Five Levels Questionnaire (EQ-5D-5L) Score

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

+20 more

ZUMA-25 Trial Design

4Treatment groups

Experimental Treatment

Group I: Substudy D (Relapsed/Refractory hairy cell leukemia): Brexucabtagene AutoleucelExperimental Treatment3 Interventions

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 II: Substudy C (Relapsed/Refractory Burkitt Lymphoma): Brexucabtagene AutoleucelExperimental Treatment3 Interventions

Group III: Substudy B (Relapsed/Refractory Richter Transformation): Brexucabtagene AutoleucelExperimental Treatment3 Interventions

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 IV: Substudy A (Relapsed/Refractory Waldenstrom Macroglobulinemia): Brexucabtagene AutoleucelExperimental Treatment3 Interventions

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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Fludarabine

2012

Completed Phase 3

~1080

Cyclophosphamide

1995

Completed Phase 3

~3770

0 / 4Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Hairy Cell Leukemia (HCL) include purine analogs like cladribine and pentostatin, which work by inhibiting DNA synthesis, leading to cell death. Additionally, monoclonal antibodies such as rituximab target CD20 on B-cells, marking them for destruction by the immune system. CAR-T Cell Therapy, like brexucabtagene autoleucel, involves modifying a patient's T-cells to express a chimeric antigen receptor (CAR) that specifically targets CD19 on B-cells, leading to their elimination. This is particularly significant for HCL patients as it offers a targeted approach that can potentially lead to long-term remission, especially in cases where the disease is refractory to conventional treatments.

Axicabtagene ciloleucel for the treatment of relapsed/refractory B-cell non-Hodgkin's lymphomas.

Find a Location

Who is running the clinical trial?

Kite, A Gilead CompanyLead Sponsor

44 Previous Clinical Trials

4,011 Total Patients Enrolled

Kite Study DirectorStudy DirectorKite, A Gilead Company

29 Previous Clinical Trials

3,369 Total Patients Enrolled

Media Library

Brexucabtagene Autoleucel (CAR T-cell Therapy) Clinical Trial Eligibility Overview. Trial Name: NCT05537766 — Phase 2

$Hairy Cell Leukemia Research Study Groups: Substudy D (Relapsed/Refractory hairy cell leukemia): Brexucabtagene Autoleucel, Substudy C (Relapsed/Refractory Burkitt Lymphoma): Brexucabtagene Autoleucel, Substudy B (Relapsed/Refractory Richter Transformation): Brexucabtagene Autoleucel, Substudy A (Relapsed/Refractory Waldenstrom Macroglobulinemia): Brexucabtagene Autoleucel$