Zanubrutinib + Rituximab vs Bendamustine + Rituximab for Mantle Cell Lymphoma

(MANGROVE Trial)

Not currently recruiting at 349 trial locations

Overseen By BeiGene

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: BeiGene

Must not be taking: Strong CYP3A inhibitors

Disqualifiers: CNS involvement, Cardiovascular disease, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to approximately 7 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatment combinations for individuals with mantle cell lymphoma (MCL) who haven't received prior treatments and can't undergo stem cell transplantation. One group receives zanubrutinib (a targeted therapy) and rituximab, while the other receives bendamustine (a chemotherapy drug) and rituximab. The trial aims to determine which combination is more effective and safer for treating MCL. Individuals with a confirmed MCL diagnosis who haven't started systemic treatments may be suitable for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop your current medications, but you cannot participate if you need ongoing treatment with a strong CYP3A inhibitor or inducer (types of drugs that affect how your body processes other medications).

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

Research has shown that using zanubrutinib with rituximab is generally safe and well-tolerated for treating mantle cell lymphoma (MCL). Early results suggest this treatment has a good safety record, with patients often managing this non-chemotherapy approach well and experiencing manageable side effects.

The combination of bendamustine and rituximab is already known to be effective for MCL. It is widely used and generally considered safe, though some people might experience more side effects, such as low blood counts or nausea.

Overall, previous studies have shown both treatments to be safe, with zanubrutinib and rituximab noted for being easier to tolerate. As always, individual experiences may vary. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using zanubrutinib plus rituximab for mantle cell lymphoma because it offers a novel approach to treatment. Unlike the standard options like bendamustine combined with rituximab, zanubrutinib is a Bruton’s tyrosine kinase (BTK) inhibitor, which specifically targets and blocks a key protein involved in the growth of cancer cells. This targeted action could potentially lead to more effective and precise treatment outcomes. Additionally, after the initial combination with rituximab, zanubrutinib can be continued as a monotherapy, which might help sustain remission and provide an ongoing defense against the disease.

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

In this trial, participants will receive either zanubrutinib plus rituximab or bendamustine plus rituximab. Research has shown that combining zanubrutinib with rituximab is promising for treating mantle cell lymphoma (MCL). Studies have found that this combination can lead to strong response rates in patients newly diagnosed with MCL. Zanubrutinib targets a specific part of cancer cells, helping to stop their growth. Patients who received this treatment experienced positive results and manageable side effects, making it a potential alternative to traditional chemotherapy. Conversely, bendamustine with rituximab has been a standard treatment, known for its effectiveness in managing MCL. This trial closely compares both treatment options to determine which offers the best results for patients. ^{1 2 3 6 7}

Who Is on the Research Team?

Study Director

Principal Investigator

BeiGene

Are You a Good Fit for This Trial?

This trial is for people aged 70 or older, or those 60-69 with health issues preventing stem cell transplant. They must have untreated mantle cell lymphoma confirmed by tests, be able to perform daily activities (ECOG 0-2), and not have infections needing systemic treatment, CNS lymphoma involvement, plans for tumor debulking before a transplant, severe heart disease, bleeding disorders, or gastrointestinal problems affecting drug absorption.

Inclusion Criteria

I have not received any systemic treatments for my MCL.

I am 70 or older, or I am between 60 and 70 with health issues preventing a specific stem cell treatment.

My diagnosis of mantle cell lymphoma is confirmed by tissue analysis.

Exclusion Criteria

I am currently being treated for a serious infection.

I cannot swallow pills or have major digestive issues.

My treatment goal is to reduce my tumor size before a stem cell transplant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either zanubrutinib plus rituximab or bendamustine plus rituximab. Zanubrutinib monotherapy continues until disease progression for Arm A, while Arm B is followed by observation.

Up to approximately 7 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 7 years

What Are the Treatments Tested in This Trial?

Interventions

• Bendamustine
• Rituximab
• Zanubrutinib

Trial Overview The study compares two treatments: Zanubrutinib plus Rituximab versus Bendamustine plus Rituximab in patients who haven't been treated for mantle cell lymphoma and can't undergo stem cell transplantation. It's randomized so participants are put into groups by chance to see which treatment works better and is safer.

How Is the Trial Designed?

Group I: Arm A: zanubrutinib plus rituximab Experimental Treatment 2 Interventions

Participants will receive zanubrutinib plus rituximab, followed by zanubrutinib monotherapy until Independent Review Committee (IRC)-confirmed disease progression.

Group II: Arm B: bendamustine plus rituximab Active Control 2 Interventions

Participants will receive bendamustine plus rituximab, followed by observation.

Bendamustine is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Treanda for:

• Chronic lymphocytic leukemia
• Non-Hodgkin lymphoma

Approved in European Union as Ribomustin for:

• Chronic lymphocytic leukemia
• Non-Hodgkin lymphoma
• Multiple myeloma

Approved in Canada as Levact for:

• Chronic lymphocytic leukemia
• Non-Hodgkin lymphoma

Approved in Japan as Bendamustine hydrochloride for:

• Chronic lymphocytic leukemia
• Non-Hodgkin lymphoma

Who Is Running the Clinical Trial?

BeiGene

Lead Sponsor

Trials

216

Recruited

32,500+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04002297

NCT04002297 | A Study to Investigate the Efficacy of ... This is a randomized study to compare the efficacy and safety of zanubrutinib plus rituximab versus bendamustine plus rituximab in previously untreated ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32985902/

A Phase III study of zanubrutinib plus rituximab versus ... An ongoing Phase III study comparing the efficacy and safety of zanubrutinib plus rituximab followed by zanubrutinib monotherapy versus bendamustine plus ...

3. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/6307/527874/A-Prospective-Study-of-Rituximab-Bendamustine-and

Zanubrutinib Induction Therapy with or without ASCT in Young ... This prospective study demonstrated a favorable efficacy and tolerable safety of alternating BR and R-DHAP +/- zanubrutinib in young newly diagnosed MCL ...

4. 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 ... The chemotherapy-free induction regimen of zanubrutinib plus rituxumab produced response rates in patients with newly diagnosed mantle cell lymphoma.

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

A Phase III Study of Zanubrutinib Plus Rituximab Versus ... Updated safety and efficacy data in the phase 1 trial of patients with mantle cell lymphoma (MCL) treated with Bruton tyrosine kinase (BTK) inhibitor ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO-25-00690

Acalabrutinib Plus Bendamustine-Rituximab in Untreated ... The combination of the Bruton tyrosine kinase inhibitor ibrutinib with bendamustine-rituximab for first-line treatment of mantle cell lymphoma (MCL) prolonged ...

7. clinicaltrial.be clinicaltrial.be/en/details/62865?per_page=100&only_recruiting=0&only_eligible=0&source=14&only_active=0

Study Comparing Zanubrutinib + Rituximab Versus ... This is a randomized study to compare the efficacy and safety of zanubrutinib plus rituximab versus bendamustine plus rituximab in previously ...