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

Trial Summary

What is the purpose of this trial?

To learn about the safety of giving the drug brexucabtagene autoleucel to participants with relapsed/refractory B-cell ALL after treatment with inotuzumab ozogamicin, blinatumomab, and either hyper-CVAD or mini-hyper-CVD. Also, to learn if giving brexucabtagene autoleucel to patients with relapsed/refractory or high-risk, newly diagnosed B-cell ALL after treatment with inotuzumab ozogamicin, blinatumomab, and either hyper-CVAD or mini-hyper-CVD can help to control the disease.

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.

What data supports the effectiveness of the treatment Brexucabtagene Autoleucel for B-cell leukemia?

Brexucabtagene autoleucel has shown effectiveness in treating relapsed or refractory B-cell acute lymphoblastic leukemia, with a complete remission rate of 73% and a median overall survival of 25.4 months in a study with 78 patients. It has also been effective in treating mantle cell lymphoma, with a complete response rate of 68% in a clinical trial. ^{1 2 3 4 5}

Is Brexucabtagene Autoleucel safe for humans?

Brexucabtagene autoleucel, also known as KTE-X19 or brexu-cel, has been studied for safety in patients with B-cell acute lymphoblastic leukemia and mantle cell lymphoma. In these studies, it was generally well-tolerated, but like many treatments, it can have side effects, so it's important to discuss potential risks with your doctor. ^{1 2 3 4 5}

How is the treatment brexucabtagene autoleucel unique for B-cell leukemia?

Brexucabtagene autoleucel is a unique treatment for B-cell leukemia because it is a CAR T-cell therapy that uses the patient's own modified immune cells to target and destroy cancer cells. This approach is different from traditional chemotherapy or radiation, as it specifically targets the CD19 protein on cancer cells, offering a personalized and potentially more effective treatment option for those with relapsed or refractory B-cell acute lymphoblastic leukemia. ^{1 2 3 4 5}

Research Team

Elias Jabbour, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 (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]

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]

References

1. England 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. [2023]

2. United States 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. [2023]

3. England 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. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Brexucabtagene Autoleucel: A Novel Chimeric Antigen Receptor T-cell Therapy for the Treatment of Mantle Cell Lymphoma. [2022]

5. United States 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. [2023]