Gene Therapy for Rare B-Cell Cancers

(ZUMA-25 Trial)

No longer recruiting at 31 trial locations
MI
Overseen ByMedical Information
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial
Approved in 2 JurisdictionsThis treatment is already approved in other countries

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called brexucabtagene autoleucel, a gene therapy, for individuals with certain rare B-cell cancers that have returned or resist existing treatments. It targets specific conditions, such as Burkitt lymphoma, an aggressive type of non-Hodgkin lymphoma. The trial aims to evaluate how effectively this new therapy shrinks or controls these cancers. Individuals whose cancer has returned after initial treatment or who did not respond to the first round of treatment might be suitable candidates for this trial. As a Phase 2 trial, it measures the treatment's effectiveness in an initial, smaller group of participants.

Do I have to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that brexucabtagene autoleucel, a type of CAR T-cell therapy, is generally safe. The FDA approved this treatment for relapsed or hard-to-treat mantle cell lymphoma, supporting its safety profile. Like other CAR T-cell therapies, it can cause side effects such as fever, tiredness, and low blood cell counts, but serious side effects occur less frequently.

In studies for rare B-cell cancers, participants received one infusion of brexucabtagene autoleucel after a brief round of chemotherapy. The treatment's safety is consistent across different B-cell cancers. This trial is in Phase 2, indicating that earlier studies have already demonstrated some safety. Researchers now aim to confirm this in larger groups and assess its effectiveness.12345

Why are researchers excited about this trial?

Researchers are excited about brexucabtagene autoleucel for treating rare B-cell cancers because it introduces a new approach using CAR T-cell therapy. Unlike traditional treatments like chemotherapy and monoclonal antibodies, this therapy involves modifying a patient's own T cells to specifically target cancer cells by recognizing the CD19 protein on their surface. This personalized and targeted approach has the potential to be more effective and long-lasting, as it harnesses the body's immune system to fight cancer more precisely.

What evidence suggests that this trial's treatments could be effective for rare B-cell cancers?

Research shows that brexucabtagene autoleucel, a type of CAR T-cell therapy, holds promise for treating rare B-cell cancers. Participants in this trial will receive brexucabtagene autoleucel after lymphodepletion chemotherapy with fludarabine and cyclophosphamide. Studies have demonstrated this treatment's effectiveness for patients whose B-cell cancers have returned or resisted other treatments. Specifically, in conditions like mantle cell lymphoma, real-world results have shown it to be both effective and safe. The treatment uses specially modified immune cells to locate and attack cancer cells, leading to positive outcomes in difficult cases. Overall, evidence supports brexucabtagene autoleucel as a potentially effective option for these rare and challenging cancers.12367

Who Is on the Research Team?

KS

Kite Study Director

Principal Investigator

Kite, A Gilead Company

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

Individuals of childbearing potential who engage in heterosexual intercourse must agree to use specified method(s) of contraception
My blood and organs are functioning well.
I have chronic lymphocytic leukemia that has transformed into a more aggressive type.
See 3 more

Exclusion Criteria

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.
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.
I have not had CAR therapy or anti-CD19 treatment.
See 3 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive fludarabine and cyclophosphamide lymphodepletion chemotherapy for 3 days followed by a single infusion of brexucabtagene autoleucel

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years for substudies B and C; Up to 5 years for substudies A and D

Long-term follow-up

Participants transition to a separate long-term follow-up study to continue follow-up out to 15 years

Up to 15 years

What Are the Treatments Tested in This Trial?

Interventions

  • Brexucabtagene Autoleucel
  • Cyclophosphamide
  • Fludarabine
Trial Overview 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.
How Is the Trial Designed?
4Treatment groups
Experimental Treatment
Group I: Substudy D (Relapsed/Refractory hairy cell leukemia): Brexucabtagene AutoleucelExperimental Treatment3 Interventions
Group II: Substudy C (Relapsed/Refractory Burkitt Lymphoma): Brexucabtagene AutoleucelExperimental Treatment3 Interventions
Group III: Substudy B (Relapsed/Refractory Richter Transformation): Brexucabtagene AutoleucelExperimental Treatment3 Interventions
Group IV: Substudy A (Relapsed/Refractory Waldenstrom Macroglobulinemia): Brexucabtagene AutoleucelExperimental Treatment3 Interventions

Brexucabtagene Autoleucel is already approved in European Union, United States for the following indications:

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Approved in European Union as Tecartus for:
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Approved in United States as Tecartus for:

Find a Clinic Near You

Who Is Running the Clinical Trial?

Kite, A Gilead Company

Lead Sponsor

Trials
45
Recruited
4,300+

Citations

Study of Brexucabtagene Autoleucel in Adults With Rare B- ...Master protocol: The goal of this master clinical study is to test how well the study drug, brexucabtagene autoleucel, works in participants with rare ...
Study of Brexucabtagene Autoleucel in Adults With Rare B- ...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.
A Phase 2, Open-Label, Multicenter, Basket Study ...A Phase 2, Open-Label, Multicenter, Basket Study Evaluating the Safety and Efficacy of Brexucabtagene Autoleucel in Adults with Rare B-cell Malignancies.
Study of Brexucabtagene Autoleucel in Adults With Rare B- ...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- ...
5.pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov/40706035/
Real-world outcomes of brexucabtagene autoleucel for ...Here, we report real-world effectiveness and safety outcomes of brexu-cel in a prospective study of patients with r/r MCL, including subgroups ...
6.pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov/36753699/
Results From the US Lymphoma CAR T Consortium - PubMedBrexucabtagene autoleucel (brexu-cel) is an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory mantle ...
Study of Brexucabtagene Autoleucel in Adults With Rare B ...Substudy D (Relapsed/Refractory hairy cell leukemia): Brexucabtagene Autoleucel, Participants will receive fludarabine 30 mg/m^2/day and ...
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