Brexucabtagene Autoleucel for Mantle Cell Lymphoma

(ZUMA-2 Trial)

No longer recruiting at 43 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of a new treatment, brexucabtagene autoleucel, for individuals with relapsed or refractory mantle cell lymphoma (MCL). Participants will first receive the chemotherapy drugs cyclophosphamide and fludarabine, followed by an infusion of the study treatment. It suits those who have undergone up to five previous treatments for MCL, including specific chemotherapy and antibody therapies, and who have at least one measurable tumor. The trial aims to determine if the new treatment can manage the cancer better than current options. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research shows that brexucabtagene autoleucel, also known as KTE-X19, is generally well-tolerated by patients with relapsed or refractory mantle cell lymphoma. Studies have found that it offers long-lasting benefits with a manageable safety profile. Most patients experience side effects, but these are usually manageable and similar to those observed in earlier research.

The chemotherapy drugs used in this trial, cyclophosphamide and fludarabine, are well-known cancer treatments with a long history of use. While they can cause side effects, these are well-documented and often predictable.

Overall, earlier studies have shown promise for the treatment combination in this trial, with known and manageable side effects. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for mantle cell lymphoma?

Unlike the standard treatments for mantle cell lymphoma, which often include chemotherapy, targeted therapy, and immunotherapy, brexucabtagene autoleucel is a form of CAR T-cell therapy. This innovative treatment harnesses the patient's own immune cells, which are genetically modified to target and destroy cancer cells. Its mechanism is distinctive because it specifically targets the CD19 protein on cancer cells, potentially leading to more effective and direct cancer cell elimination. Researchers are excited about brexucabtagene autoleucel because it offers a personalized approach and has shown promise in treating cases that are resistant to other therapies.

What evidence suggests that this trial's treatments could be effective for mantle cell lymphoma?

Research has shown that brexucabtagene autoleucel (KTE-X19), which participants in this trial will receive, may be a promising treatment for mantle cell lymphoma (MCL) that has returned or not responded to other treatments. In a major study, 92% of patients with this condition responded well to the treatment. About 67% of these patients had a complete response, meaning their cancer was no longer detectable. Other studies support these results, indicating that KTE-X19 can lead to long-lasting improvements with manageable side effects. This suggests that brexucabtagene autoleucel could be an effective option for people with relapsed or refractory MCL. ^{1 2 6 7 8}

Who Is on the Research Team?

Kite Study Director

Principal Investigator

Kite, A Gilead Company

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9430665/

P1117: THREE-YEAR FOLLOW-UP OF OUTCOMES WITH ... KTE-X19 induces durable long-term responses with manageable safety and low late relapse potential in R/R MCL.

2. ashpublications.org ashpublications.org/bloodadvances/article/doi/10.1182/bloodadvances.2024015014/546349/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 ...

3. pubmed.ncbi.nlm.nih.gov pubmed.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 ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02601313

NCT02601313 | Study of Brexucabtagene Autoleucel (KTE ... 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) ...

5. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/106/502399/Outcomes-of-Patients-with-Relapsed-Refractory

Outcomes of Patients with Relapsed/Refractory Mantle Cell ... After a median of 35.6-months follow-up in the pivotal Phase 2, multicenter ZUMA-2 study, brexu-cel demonstrated an objective response rate (ORR) ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35658525/

Three-Year Follow-Up of KTE-X19 in Patients With Relapsed ... KTE-X19 induced durable long-term responses with manageable safety in patients with relapsed/refractory MCL and may also benefit those with high-risk ...

7. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/4388/533705/Five-Year-Outcomes-of-Patients-Pts-with-Relapsed

Five-Year Outcomes of Patients (Pts) with Relapsed ... After ~4 years (y) of median follow-up, Brexu-cel demonstrated a median overall survival (OS) of 46.4 months (mo) in 68 pts with R/R MCL in ...

8. asco.org asco.org/abstracts-presentations/ABSTRACT361758

Three-year follow-up of outcomes with KTE-X19 in patients ... Conclusions: These data represent the longest follow-up of CAR T-cell therapy in pts with MCL to date and suggest that KTE-X19 induces durable long-term ...