BRAZAN Treatment for Mantle Cell Lymphoma

(BRAZAN Trial)

Recruiting at 1 trial location

Overseen By Robert Black

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

Trial Summary

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.

What data supports the effectiveness of the BRAZAN treatment for mantle cell lymphoma?

Research shows that the combination of bendamustine and rituximab is effective for treating mantle cell lymphoma, with studies indicating high response rates. Additionally, zanubrutinib, a component of the BRAZAN treatment, is a targeted therapy that has shown promise in treating this type of lymphoma, especially in patients who cannot undergo more intensive treatments. ^{1 2 3 4 5}

Is the BRAZAN treatment safe for humans?

The combination of bendamustine and rituximab, part of the BRAZAN treatment, has been shown to have a favorable safety profile in treating mantle cell lymphoma and other similar conditions. Common side effects include nausea, fatigue, and mild blood-related issues, but serious side effects are less common. ^{1 4 5 6 7}

How is the BRAZAN drug treatment different for mantle cell lymphoma?

The BRAZAN treatment combines bendamustine, rituximab, and zanubrutinib, a next-generation Bruton tyrosine kinase inhibitor, which offers a targeted approach with minimal off-target effects and is suitable for patients who cannot undergo stem cell transplants. This makes it a unique option for those who are ineligible for more intensive treatments. ^{1 2 3 4 8}

What is the purpose of this trial?

This study aims to evaluate the efficacy and safety of an induction regimen combining Bendamustine, Rituximab, Cytarabine (AraC), and Zanubrutinib (BRAZAN), followed by maintenance therapy with Zanubrutinib and Rituximab with or without Sonrotoclax in participants with Mantle Cell Lymphoma (MCL). The names of the study drugs involved in this study are: * bendamustine (a type of alkylating agent) * rituximab (a type of monoclonal antibody) * cytarabine (a type of antineoplastic) * zanubrutinib (a type of kinase inhibitor) * sonrotoclax (a type of BCL2 inhibitor)

Research Team

Christine Ryan, MD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

References

1. United States 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. [2022]

2. England pubmed.ncbi.nlm.nih.gov

A Phase III study of zanubrutinib plus rituximab versus bendamustine plus rituximab in transplant-ineligible, untreated mantle cell lymphoma. [2021]

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

Bendamustine Plus Rituximab for Mantle Cell Lymphoma: A Korean, Multicenter Retrospective Analysis. [2022]

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

Combination of rituximab, bendamustine, and cytarabine for patients with mantle-cell non-Hodgkin lymphoma ineligible for intensive regimens or autologous transplantation. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Bendamustine plus rituximab versus fludarabine plus rituximab for patients with relapsed indolent and mantle-cell lymphomas: a multicentre, randomised, open-label, non-inferiority phase 3 trial. [2019]

6. Germany pubmed.ncbi.nlm.nih.gov

Bendamustine as first-line treatment in patients with advanced indolent non-Hodgkin lymphoma and mantle cell lymphoma in German routine clinical practice. [2018]

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

The combination of bendamustine, bortezomib, and rituximab for patients with relapsed/refractory indolent and mantle cell non-Hodgkin lymphoma. [2021]

8. Greece pubmed.ncbi.nlm.nih.gov

Synergistic Cytotoxicity of Bendamustine and the BTK Inhibitor in a Mantle Cell Lymphoma Cell Line. [2021]