BRAZAN Treatment for Mantle Cell Lymphoma

(BRAZAN Trial)

Recruiting at 1 trial location

Overseen By Clare Phinney

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Christine Ryan

Must not be taking: Warfarin, Strong CYP3A inducers

Disqualifiers: CNS involvement, Active infection, Cardiac conditions, 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: 2

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of drugs to treat mantle cell lymphoma, a type of blood cancer. The study aims to evaluate the effectiveness and safety of combining bendamustine, rituximab, cytarabine, and zanubrutinib (a targeted therapy) in combating this cancer. After initial treatment, participants might receive additional drugs, such as sonrotoclax, to prevent recurrence. Individuals with a confirmed diagnosis of mantle cell lymphoma who have not received significant prior treatment may be suitable candidates. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it does mention that participants cannot take certain medications like warfarin or strong CYP3A inducers. You will be counseled on potential drug interactions during the enrollment process.

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

In a previous study, the combination of zanubrutinib and rituximab showed promising results for treating mantle cell lymphoma. It achieved an overall response rate of 83.7% and a complete response rate of 77.9%, with no new safety concerns, indicating that the combination is generally well-tolerated.

Research on the combination of zanubrutinib, rituximab, and sonrotoclax also shows it is safe and manageable. One study reported a 79% overall response rate without severe side effects, indicating patients could handle the treatment well.

These findings suggest that the treatments used in the trial have a history of being manageable for patients with mantle cell lymphoma. However, as with any treatment, risks may still exist, so discussing concerns with the trial team is always advisable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for Mantle Cell Lymphoma because they offer a new combination approach that could enhance effectiveness. Zanubrutinib, a key component, is a Bruton's tyrosine kinase (BTK) inhibitor, which works by targeting and disrupting signals that help cancer cells survive, potentially offering more precise action compared to standard therapies like chemotherapy. Additionally, the inclusion of Sonrotoclax, especially with its ramp-up initiation for incomplete responders, introduces a different mechanism that may boost the overall response by targeting cancer cell survival pathways. This multi-pronged strategy aims to improve outcomes and provide new hope for patients with this challenging form of lymphoma.

What evidence suggests that this trial's treatments could be effective for Mantle Cell Lymphoma?

This trial will evaluate different maintenance therapies for mantle cell lymphoma (MCL) following induction therapy. Studies have shown that combining zanubrutinib and rituximab effectively treats MCL. In some studies, this combination led to a complete response in 94.1% of patients and a two-year period without disease progression in 96.6% of patients. In this trial, participants in Maintenance Arm A will receive this combination. Meanwhile, Maintenance Arm B will test adding sonrotoclax to zanubrutinib and rituximab. Research suggests that this combination can be effective, resulting in a 66% complete response rate in patients whose MCL had returned or did not respond to previous treatments. These results suggest that the treatments tested in this trial may work well for MCL. ^{3 5 6 7 8}

Who Is on the Research Team?

Christine Ryan, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

The BRAZAN trial is for individuals with Mantle Cell Lymphoma (MCL). Participants should be suitable for an induction regimen, which may include maintenance therapy. Specific eligibility criteria are not provided, but typically participants must meet certain health standards and have no conflicting conditions.

Inclusion Criteria

Willingness to provide a pre-treatment tumor sample.

Willingness to use effective contraception methods.

Ability to understand and sign an informed consent document.

Exclusion Criteria

Severe or uncontrolled medical conditions that may affect study participation.

I have uncontrolled autoimmune blood disorders.

Baseline EKG criteria.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Induction

Participants receive Bendamustine/Rituximab + Zanubrutinib for 3 cycles, followed by Rituximab/Cytarabine for 3 cycles

5 months

In-clinic treatment visits

Maintenance

Participants receive maintenance therapy with either Zanubrutinib + Rituximab or Zanubrutinib + Rituximab + Sonrotoclax

2 years

Cycles 1-24 (28-day cycles), PET/CT on Cycles 7, 12, 19, and at end of treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment

Every 6 months, PET/CT every 12 months

What Are the Treatments Tested in This Trial?

Interventions

• Bendamustine
• Rituximab
• Sonrotoclax
• Zanubrutinib

Trial Overview This study tests the effectiveness and safety of a combination treatment (BRAZAN) using Bendamustine, Rituximab, Cytarabine, Zanubrutinib followed by maintenance therapy with Zanubrutinib and Rituximab with or without Sonrotoclax in treating MCL.

How Is the Trial Designed?

Group I: Maintenance Arm B: Zanubrutinib + Rituximab + Sonrotoclax Experimental Treatment 3 Interventions

Following randomization participants with a complete response to induction therapy will complete: * Cycles 1 - 24 (28-day cycles): * Days 1 through 28: Predetermined dose of Zanubrutinib 2x daily * Days 1 through 28: Predetermined dose of Sonrotoclax 1x daily * Day 1 every other cycle: Predetermined dose of Rituximab 1x daily * PET/CT on Cycles 7, 12, 19, and at end of treatment * Post-treatment follow up: every 6 months. PET/CT every 12 months

Group II: Maintenance Arm B with Sonrotoclax Ramp-Up: Zanubrutinib + Rituximab + Sonrotoclax Experimental Treatment 3 Interventions

Following randomization participants with an incomplete response to induction therapy will require a ramp-up initiation of sonrotoclax and will complete: * Cycles 1 - 24 (28-day cycles): * Days 1 through 28: Predetermined dose of Zanubrutinib 2x daily * Days 1 through 28: Predetermined dose of Sonrotoclax 1x daily \*\*Cycles 1 and 2: Predetermined dose of Sonrotoclax 1x daily will be increased weekly. * Day 1 every other cycle: Predetermined dose of Rituximab 1x daily * PET/CT on Cycles 7, 12, 19, and at end of treatment * Post-treatment follow up: every 6 months. PET/CT every 12 months

Group III: Maintenance Arm A: Zanubrutinib + Rituximab Experimental Treatment 2 Interventions

Following randomization participants with a complete response to induction therapy will complete: * Cycles 1 - 24 (28-day cycles): * Days 1 through 28: Predetermined dose of Zanubrutinib 2x daily * Day 1 every other cycle: Predetermined dose of Rituximab 1x daily * PET/CT on Cycles 7, 12, 19, and at end of treatment * Post-treatment follow up: every 6 months. PET/CT every 12 months

Group IV: Induction Therapy (All Patients) Experimental Treatment 4 Interventions

Enrolled participants will complete: * Baseline visit with PET/CT, lymph node biopsy, and bone marrow biopsy * Cycles 1 through 3 (28-day cycles): * Days 1 - 28: Predetermined dose of Zanubrutinib 2x daily * Days 1 and 2: Predetermined dose of Bendamustine 1x daily * Day 1: Predetermined dose of Rituximab 1x daily * PET/CT scan * Cycles 4 through 6 (21-day cycles): * Day 1: Predetermined dose of Rituximab 1x daily * Days 1 and 2: Predetermined dose of Cytarabine 2x daily * PET/CT scan Participants without disease progression will proceed to randomization to either Arm A or Arm B for maintenance therapy.

Who Is Running the Clinical Trial?

Christine Ryan

Lead Sponsor

Trials

2

Recruited

130+

BeiGene

Industry Sponsor

Trials

216

Recruited

32,500+

Published Research Related to This Trial

Zanubrutinib, a next-generation Bruton tyrosine kinase inhibitor, shows promise as a targeted therapy for mantle cell lymphoma, particularly for patients who are elderly or have comorbidities and cannot undergo standard treatments.

An ongoing Phase III study is evaluating the safety and efficacy of zanubrutinib combined with rituximab compared to bendamustine with rituximab in patients with untreated mantle cell lymphoma who are not eligible for stem cell transplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase III study of zanubrutinib plus rituximab versus bendamustine plus rituximab in transplant-ineligible, untreated mantle cell lymphoma. Dreyling, M., Tam, CS., Wang, M., et al.[2021]

The combination of bendamustine and rituximab (BR) showed a high overall response rate of 90% in 63 patients with mantle cell or low-grade lymphomas, with a complete remission rate of 60%.

The median progression-free survival was 24 months, indicating that BR is an effective treatment option for patients in their first to third relapse or refractory to previous treatments, although myelosuppression was noted as a significant side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bendamustine plus rituximab is effective and has a favorable toxicity profile in the treatment of mantle cell and low-grade non-Hodgkin's lymphoma. Rummel, MJ., Al-Batran, SE., Kim, SZ., et al.[2022]

Citations

1. ashpublications.org ashpublications.org/blood/article/140/Supplement%201/9356/491751/Frontline-Treatment-with-Zanubrutinib-Plus

Frontline Treatment with Zanubrutinib Plus Rituximab (ZR ... The best CR rate during ZR was 94.1% (16/17). All the 4 patients over 65 years old achieved CR. At the time of last follow-up (June 2022), only ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10431157/

P1089: ZANUBRUTINIB-RITUXIMAB CHEMO-FREE ... This study demonstrates a favorable efficacy and tolerable safety of chemo-free regimen ZR in patients with newly diagnosed MCL and expands therapeutic options.

3. onclive.com onclive.com/view/zanubrutinib-rituximab-induction-may-be-safe-and-effective-in-newly-diagnosed-mantle-cell-lymphoma

Zanubrutinib/Rituximab Induction May Be Safe and ... At a median follow-up of 13.6 months, the 2-year overall survival (OS) and progression-free survival (PFS) rates were 100% and 96.6%, ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05635162

NCT05635162 | Zanubrutinib Plus Rituximab for Patients ... This is a phase II, multicentre, randomised open label study to assess the safety and efficacy of zanubrutinib in combination with rituximab for previously ...

5. tandfonline.com tandfonline.com/doi/full/10.2217/fon-2020-0794

A Phase III Study of Zanubrutinib Plus Rituximab Versus ... In preclinical studies, zanubrutinib was shown to be at least tenfold weaker than ibrutinib in inhibiting rituximab-induced antibody-dependent cell-mediated ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9136878/

Zanubrutinib in relapsed/refractory mantle cell lymphoma Outcomes were promising, with an overall response of 83.7%, a complete response rate of 77.9%, and no new safety concerns.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05164770

NCT05164770 | Study of Zanubrutinib, Rituximab and ... Zanubrutinib is an oral small molecule BTK inhibitor, and has shown good efficacy and safety in multiple subtypes of B-cell lymphoma. Zanubrutinib received FDA ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.7062

Frontline treatment with zanubrutinib plus rituximab (ZR) ... In this multicenter phase II trial (CHESS - chemo-less), we aimed to investigate the efficacy and toxicity of zanubrutinib plus rituximab (ZR) combination.