Brexucabtagene Autoleucel for Mantle Cell Lymphoma

(ZUMA-2 Trial)

Recruiting at 40 trial locations

Overseen By Medical Information

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Kite, A Gilead Company

Must not be taking: BTKi

Disqualifiers: HIV, Hepatitis B/C, Seizure disorder, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: 1 day

90 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical study is to test how well the study drug, brexucabtagene autoleucel (KTE-X19), works in participants with relapsed/refractory (r/r) mantle cell lymphoma (MCL).

Will I have to stop taking my current medications?

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.

What data supports the effectiveness of the treatment Brexucabtagene autoleucel for Mantle Cell Lymphoma?

Brexucabtagene autoleucel has shown high rates of response in patients with relapsed or refractory mantle cell lymphoma, with a 91% overall response rate and a 68% complete response rate in the ZUMA-2 trial. Additionally, it has been associated with improved survival compared to standard treatments, offering a substantial survival benefit for patients who have previously been treated with Bruton tyrosine kinase inhibitors. ^{1 2 3 4 5}

What safety information is available for Brexucabtagene Autoleucel in humans?

Brexucabtagene autoleucel has been shown to be effective for treating certain types of lymphoma, but it can cause significant side effects, including cytokine release syndrome (a severe immune reaction) and neurologic toxicities (problems with the nervous system), which may require special medical care. ^{1 2 3 4 6}

How is the treatment Brexucabtagene autoleucel unique for mantle cell lymphoma?

Brexucabtagene autoleucel is a unique treatment for mantle cell lymphoma because it is a CAR T-cell therapy, which means it uses the patient's own modified immune cells to target and destroy cancer cells. This approach is different from traditional chemotherapy and has shown high response rates in patients who have not responded to other treatments. ^{1 2 3 4 7}

Research Team

Kite Study Director

Principal Investigator

Kite, A Gilead Company

Eligibility Criteria

This trial is for people with mantle cell lymphoma that has come back or hasn't responded to treatment. They should have had certain previous treatments, including chemotherapy and anti-CD20 therapy, but not BTK inhibitors. Participants need a measurable lesion, good platelet count, heart function, oxygen levels, and kidney function.

Inclusion Criteria

Your blood has enough platelets (tiny cells that help with clotting) and the count is at least 75,000 per microliter.

My heart functions well, with no fluid around it and normal heart rhythm.

I've had up to 5 treatments for MCL, including specific drugs, but no BTK inhibitors.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning Chemotherapy

Participants receive conditioning chemotherapy consisting of fludarabine and cyclophosphamide for 3 days

1 week

3 visits (in-person)

Treatment

Participants receive a single infusion of brexucabtagene autoleucel (KTE-X19)

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Long-term Follow-up

Participants complete the remainder of the 15-year follow-up assessments in a separate long-term follow-up study

15 years

Treatment Details

Interventions

• Brexucabtagene autoleucel
• Cyclophosphamide
• Fludarabine

Trial Overview The study is testing brexucabtagene autoleucel (KTE-X19) in patients with relapsed/refractory mantle cell lymphoma. It involves pre-treatment with fludarabine and cyclophosphamide followed by the investigational drug KTE-X19 to see how effective it is.

Participant Groups

Group I: Brexucabtagene autoleucel (KTE-X19) Experimental Treatment 3 Interventions

Participants with relapsed/refractory mantle cell lymphoma will receive conditioning chemotherapy consisting of fludarabine 30 mg/m\^2/day and cyclophosphamide 500 mg/m\^2/day intravenous (IV) infusion for 3 days followed by a single infusion of brexucabtagene autoleucel (KTE-X19) at a targeted dose of 2 x 10\^6 anti-CD19 chimeric antigen receptor (CAR) T cells/kg, with a maximum flat dose of 2 x 10\^8 anti-CD19 CAR T cells for participants ≥ 100 kg on Day 0 in Cohort 3.

Who Is Running the Clinical Trial?

Kite, A Gilead Company

Lead Sponsor

Trials

45

Recruited

4,300+

Findings from Research

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 (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]

Axicabtagene ciloleucel and brexucabtagene autoleucel are effective anti-CD19 T-cell therapies that have shown high response rates in patients with relapsed and refractory B-cell malignancies, leading to FDA approvals for specific types of lymphoma.

Despite their effectiveness, these therapies can cause significant toxicities, such as cytokine release syndrome and neurologic issues, which necessitate careful management and monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axicabtagene ciloleucel and brexucabtagene autoleucel in relapsed and refractory diffuse large B-cell and mantle cell lymphomas. Reagan, PM., Friedberg, JW.[2021]

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]

In patients with relapsed/refractory mantle cell lymphoma (MCL) who previously failed a Bruton tyrosine kinase inhibitor, brexucabtagene autoleucel (brexu-cel) showed significantly improved overall survival compared to standard of care treatments, with hazard ratios indicating a strong survival benefit.

The analysis used multiple methods to adjust for differences in patient characteristics, consistently showing that brexu-cel led to better outcomes, highlighting its potential as an effective therapy for this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Indirect treatment comparison of brexucabtagene autoleucel (ZUMA-2) versus standard of care (SCHOLAR-2) in relapsed/refractory mantle cell lymphoma. Hess, G., Dreyling, M., Oberic, L., 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]

References

1. 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]

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

Axicabtagene ciloleucel and brexucabtagene autoleucel in relapsed and refractory diffuse large B-cell and mantle cell lymphomas. [2021]

4. 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]

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

Indirect treatment comparison of brexucabtagene autoleucel (ZUMA-2) versus standard of care (SCHOLAR-2) in relapsed/refractory mantle cell lymphoma. [2023]

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

Cost-Effectiveness of brexucabtagene autoleucel for relapsed/refractory mantle cell lymphoma. [2023]

7. 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]