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.

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CAR T-cell Therapy

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

Q: What is the mechanism of action of this treatment?

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.

Phase 2

Waitlist Available

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

Must not have

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

Diagnosis of RT not of DLBCL subtype, 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

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

No Placebo-Only Group

Summary

This trial tests a new treatment called brexucabtagene autoleucel for patients with difficult-to-treat B-cell cancers. The treatment involves enhancing the patient's own immune cells to better fight the cancer. It aims to help those whose cancers have returned or resisted other treatments. Brexucabtagene autoleucel was approved as the first anti-CD19 CAR T-cell therapy for relapsed/refractory mantle cell lymphoma.

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.

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.

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.

Eligibility Criteria

Inclusion Criteria

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

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

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

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

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

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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You have certain types of lymphoma, had a stem cell transplant in the past 3 months, have active graft-versus-host disease, or your cancer has spread to your central nervous system.

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I have a type of lymphoma that is not DLBCL, had a stem cell transplant less than 3 months ago, and I don't have active graft-versus-host disease.

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I have not had CAR therapy or anti-CD19 treatment.

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My cancer has spread to my brain or spinal fluid.

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I have an autoimmune disease like Crohn's, rheumatoid arthritis, or lupus.

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

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

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 study objectives

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

+16 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

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 4

~1860

Cyclophosphamide

2010

Completed Phase 4

~2310

0 / 9Eligibility 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

3,961 Total Patients Enrolled

Kite Study DirectorStudy DirectorKite, A Gilead Company

29 Previous Clinical Trials

3,344 Total Patients Enrolled

Media Library

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

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