Brexucabtagene Autoleucel for B-Cell Leukemia

Overseen By Elias Jabbour, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Anti-CD19 CAR T

Disqualifiers: Philadelphia positive, Pregnant, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called brexucabtagene autoleucel (also known as Tecartus or KTE-X19) for individuals with B-cell acute lymphoblastic leukemia (B-cell ALL). The researchers aim to determine if the treatment is safe and effective for those whose cancer has returned or hasn't responded well to other treatments. Participants must have tried specific therapies and possess certain cancer characteristics that make their condition high-risk or difficult to treat. This trial may suit someone with B-cell ALL that hasn't responded to previous treatments and who meets the specific medical criteria. As a Phase 1/Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you have chronic viral infections like Hepatitis B, C, or HIV, you can participate if your infections are under control with therapy.

Is there any evidence suggesting that brexucabtagene autoleucel is likely to be safe for humans?

Research has shown that brexucabtagene autoleucel is generally well-tolerated in patients with certain B-cell cancers that have returned or are not responding to treatment. One study found that patients with B-cell acute lymphoblastic leukemia (B-ALL) had positive safety results. Most side effects were manageable, though some patients experienced serious reactions like cytokine release syndrome, a strong immune response.

Another study examined patients aged 60 and older and reported similar safety results. While side effects occurred, they were typical for treatments of this kind. The treatment shows promise, but participants should prepare for possible side effects. It is important to consult a healthcare provider to understand the potential risks and benefits before joining a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Brexucabtagene autoleucel is unique because it harnesses the power of CAR T-cell therapy specifically tailored for B-cell leukemia. Unlike most treatments that rely on chemotherapy and radiation, brexucabtagene autoleucel works by genetically modifying a patient's own T-cells to better target and destroy cancer cells. This personalized approach not only aims to improve effectiveness but also offers the potential for more durable remissions. Researchers are excited about this treatment because it represents a significant shift from traditional therapies by aiming to directly enhance the immune system's ability to fight leukemia.

What evidence suggests that brexucabtagene autoleucel might be an effective treatment for B-cell leukemia?

Research has shown that brexucabtagene autoleucel, which participants in this trial will receive, holds promise for treating relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-cell ALL), an aggressive form of leukemia. Studies have found that many patients achieved complete remission, with cancer symptoms disappearing and no cancer cells detected after treatment. This includes patients whose cancer had spread to the brain and spinal cord, who also responded well to the therapy. Overall, brexucabtagene autoleucel has demonstrated strong potential in controlling this challenging form of leukemia. ^{1 3 6 7 8}

Who Is on the Research Team?

Elias Jabbour, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with B-cell Acute Lymphocytic Leukemia (ALL) who have either not responded to previous treatments or are newly diagnosed and at high risk. Participants must have completed treatment with inotuzumab ozogamicin, blinatumomab, and hyper-CVAD or mini-hyper-CVD.

Inclusion Criteria

My kidney and liver functions are within the required limits.

I am 18 or older with B-cell ALL that has come back or didn't respond to treatment.

My cancer cells are mostly CD19 positive.

Exclusion Criteria

I have previously received CAR T cell therapy targeting CD-19.

I cannot or do not want to sign the consent form.

My doctor thinks I have an active and uncontrolled disease or infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Cytoreduction

Participants receive cytoreductive therapy with inotuzumab ozogamicin, blinatumomab, and either hyper-CVAD or mini-hyper-CVD

4-6 weeks

Lymphodepletion and CAR-T Infusion

Participants undergo lymphodepletion chemotherapy followed by 1 dose of brexucabtagene autoleucel

1-2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including CAR-T-cell expansion and B-cell aplasia assessments

24 months

Monthly up to 3 months, then every 3 months up to 24 months

What Are the Treatments Tested in This Trial?

Interventions

• Brexucabtagene Autoleucel

Trial Overview The study is testing the safety and effectiveness of brexucabtagene autoleucel as a follow-up therapy in controlling B-cell ALL after initial treatment with inotuzumab ozogamicin, blinatumomab, and hyper-CVAD/mini-hyper-CVD regimens.

How Is the Trial Designed?

Group I: Phase 1B + Phase 2 Experimental Treatment 4 Interventions

Participants found to be eligible to take part in this study, you will be assigned to a study phase (Phase 1B or Phase 2). Up to 10 participants will be enrolled in Phase 1B, and up to 30 will be enrolled in Phase 2. All participants will first receive cytoreductive therapy (inotuzumab ozogamicin, blinatumomab, and either hyper-CVAD or mini-hyper-CVD), followed by lymphodepletion chemotherapy and 1 dose of brexucabtagene autoleucel.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

Brexucabtagene autoleucel (KTE-X19) CAR T-cell therapy showed a remarkable 91% objective response rate and 68% complete response rate in 68 patients with relapsed/refractory mantle cell lymphoma after a median follow-up of 35.6 months, indicating its efficacy in this challenging patient population.

The therapy demonstrated durable long-term responses with manageable safety, as late-onset toxicities were infrequent, occurring in only 3% of patients, suggesting that KTE-X19 is a safe and effective treatment option even for those with high-risk characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Three-Year Follow-Up of KTE-X19 in Patients With Relapsed/Refractory Mantle Cell Lymphoma, Including High-Risk Subgroups, in the ZUMA-2 Study. Wang, M., Munoz, J., Goy, A., et al.[2023]

In the updated ZUMA-3 study with a median follow-up of 26.8 months, brexucabtagene autoleucel (KTE-X19) achieved a 71% complete remission rate in adults with relapsed or refractory B-precursor acute lymphoblastic leukemia, indicating its efficacy as a treatment option.

Patients treated with KTE-X19 had a median overall survival of 25.4 months, significantly longer than the 5.5 months observed in matched historical controls, demonstrating a meaningful survival benefit with manageable safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two-year follow-up of KTE-X19 in patients with relapsed or refractory adult B-cell acute lymphoblastic leukemia in ZUMA-3 and its contextualization with SCHOLAR-3, an external historical control study. Shah, BD., Ghobadi, A., Oluwole, OO., et al.[2023]

Brexucabtagene autoleucel (brexu-cel) demonstrated a high overall complete remission rate of 73% and a median overall survival of 25.4 months in adults with relapsed or refractory B-cell acute lymphoblastic leukemia, based on a study of 78 patients with a median follow-up of 29.7 months.

The therapy was effective across various prior treatment subgroups, with high remission rates regardless of previous therapies, indicating its potential as a robust treatment option for patients with R/R B-ALL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of prior therapies and subsequent transplantation on outcomes in adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia treated with brexucabtagene autoleucel in ZUMA-3. Shah, BD., Cassaday, RD., Park, JH., et al.[2023]

In the pivotal ZUMA-2 trial, brexucabtagene autoleucel (brexu-cel) showed high efficacy in treating relapsed or refractory mantle cell lymphoma, with an objective response rate of 85% and a complete response rate of 59%, even among high-risk patients.

While brexu-cel has a similar toxicity profile to other CAR T-cell therapies, it is associated with significant treatment-related adverse effects, including severe cytopenias (94%) and neurotoxicity (31%), highlighting the need for careful management by a specialized medical team.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brexucabtagene Autoleucel: A Novel Chimeric Antigen Receptor T-cell Therapy for the Treatment of Mantle Cell Lymphoma. Anderson, MK., Torosyan, A., Halford, Z.[2022]

Brexucabtagene autoleucel (brexu-cel) demonstrated high efficacy in treating relapsed/refractory mantle cell lymphoma, with overall and complete response rates of 90% and 82%, respectively, in a real-world setting involving 168 patients.

The safety profile was consistent with earlier trials, showing a 9.1% nonrelapse mortality rate primarily due to infections, and notable rates of cytokine release syndrome (8%) and neurotoxicity (32%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brexucabtagene Autoleucel for Relapsed or Refractory Mantle Cell Lymphoma in Standard-of-Care Practice: Results From the US Lymphoma CAR T Consortium. Wang, Y., Jain, P., Locke, FL., et al.[2023]

Citations

1. ashpublications.org ashpublications.org/bloodadvances/article/9/16/4081/537144/Outcomes-of-brexucabtagene-autoleucel-in-patients

Outcomes of brexucabtagene autoleucel in patients with ... Key PointsHigh CNS response rate was observed in patients with CNS B-ALL receiving brexu-cel.No difference was detected in the rates of ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39418622/

Outcomes After Brexucabtagene Autoleucel Administered as a ... Similar to ZUMA-3, high rates of MRD-negative CR were observed after brexu-cel treatment for R/R B-ALL. The use of HCT as consolidation ...

3. ashpublications.org ashpublications.org/bloodadvances/article/9/20/5382/546349/Real-world-outcomes-of-brexucabtagene-autoleucel

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 ...

4. nature.com nature.com/articles/s41375-025-02532-7

Three-year analysis of adult patients with relapsed or ... Real-World Outcomes of Brexucabtagene Autoleucel (brexu-cel) for Relapsed or Refractory (R/R) Adult B-Cell Acute Lymphoblastic Leukemia (B-cell ...

5. tecartushcp.com tecartushcp.com/car-t-cell-therapy/acute-lymphoblastic-leukemia/response

TECARTUS® Efficacy Response Data for R/R B-cell ALL TECARTUS® (brexucabtagene autoleucel) efficacy response data in patients with R/R B-cell acute lymphoblastic leukemia. See Important Safety Information.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40334068/

Outcomes of brexucabtagene autoleucel in patients with ... Patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) with central nervous system (CNS) involvement (CNS B-ALL) have poor outcomes ...

7. ash.confex.com ash.confex.com/ash/2024/webprogram/Paper210682.html

523 Efficacy and Safety of Brexucabtagene Autoleucel for ... Efficacy and safety of Brexucabtagene Autoleucel for relapsed/refractory B-cell acute lymphoblastic leukemia in patients aged 60 and above.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT02614066

NCT02614066 | A Study Evaluating the Safety and Efficacy ... The primary objectives of this study are to determine the safety and efficacy of brexucabtagene autoleucel (KTE-X19) in adult participants with relapsed/ ...