Zanubrutinib for Mantle Cell Lymphoma

Recruiting at 249 trial locations

Overseen By Anne Beaven, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Alliance for Clinical Trials in Oncology

Must not be taking: Strong CYP3A4 inhibitors, inducers

Disqualifiers: Cardiovascular disease, Hepatitis, Stroke, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

421 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether patients with previously untreated mantle cell lymphoma (a type of blood cancer) can safely switch from continuous to intermittent zanubrutinib (also known as Brukinsa, a cancer drug) treatment after achieving complete remission with rituximab. The goal is to determine if taking breaks from the drug can be as effective as continuous use while reducing side effects and costs, particularly for older adults. Participants must have mantle cell lymphoma confirmed by specific tests, have not received prior treatment for it, and should not be candidates for or have declined stem cell transplant. 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.

Will I have to stop taking my current medications?

The trial requires that you stop taking any strong CYP3A4 inhibitors or inducers 14 days before starting the study. If you are on these medications, you will need to discontinue them before participating.

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

Research has shown that zanubrutinib is generally safe for people with mantle cell lymphoma (MCL). In one study involving patients who had tried other treatments for MCL, zanubrutinib proved effective and was mostly well-tolerated over about 35 months. Most side effects were manageable and not serious.

When combined with rituximab, another study compared this combination to a different treatment and found it safe for patients who hadn't been treated before, suggesting the combination does not cause significant harm.

Since this trial is in an advanced phase, zanubrutinib has already undergone human testing, and its safety is well understood. This provides reassurance about its use in this trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Zanubrutinib is unique because it specifically targets and inhibits Bruton’s tyrosine kinase (BTK), a protein that plays a crucial role in the survival and proliferation of malignant B cells in mantle cell lymphoma. Unlike standard treatments that might include chemotherapy or other BTK inhibitors, zanubrutinib is designed to be more selective, potentially offering fewer side effects and improved effectiveness. Researchers are excited about this treatment because it promises to provide a more targeted and potentially safer option for patients, which could lead to better outcomes and improved quality of life.

What evidence suggests that zanubrutinib could be an effective treatment for mantle cell lymphoma?

Research has shown that zanubrutinib effectively treats mantle cell lymphoma (MCL). Studies indicate that about 84% of patients responded to zanubrutinib, with many experiencing benefits lasting over 18 months. In this trial, some participants will receive zanubrutinib alone, while others will receive it in combination with rituximab. When combined with rituximab, zanubrutinib has produced promising results for newly diagnosed MCL patients, indicating a high response rate. These findings suggest that zanubrutinib, whether used alone or with rituximab, can effectively manage MCL by blocking enzymes necessary for cancer cell growth. This promising data highlights the potential for better outcomes in patients with this type of lymphoma. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for older adults with untreated Mantle Cell Lymphoma (MCL). Eligible participants are those aged 70+ or 60-69 with certain health issues, have measurable disease, and haven't had prior MCL treatments like stem cell transplants, radiation for stage I MCL, systemic treatments, BTK inhibitors or anti-CD20 monoclonal antibodies.

Inclusion Criteria

I have never been treated with BTK inhibitors or anti-CD20 drugs.

I am taking steroids for my lymphoma, but not more than 100mg/day of prednisone or its equivalent, and for no longer than 7 days.

My lymphoma is confirmed to be mantle cell type with specific genetic markers.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Therapy

Patients receive zanubrutinib orally and rituximab intravenously. They undergo bone marrow biopsy and imaging studies.

12 weeks

Multiple visits for drug administration and assessments

Maintenance Therapy

Patients achieving a complete remission are randomized to continuous or intermittent zanubrutinib treatment.

Until disease progression

Regular visits for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

10 years

Every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Zanubrutinib

Trial Overview

The study tests continuous versus intermittent Zanubrutinib treatment after complete remission using Rituximab in older patients with MCL. It aims to determine if stopping Zanubrutinib after remission and restarting upon progression is as effective as continuous treatment.

How Is the Trial Designed?

Group I: Induction therapy (Zanubrutinib, rituximab) Experimental Treatment 12 Interventions

Patients receive zanubrutinib PO and rituximab IV on study. Patients undergo bone marrow biopsy and FDG PET/CT or CT throughout the trial. Patients may also undergo EDG and/or colonoscopy on study as clinically indicated. Patients may optionally undergo blood sample collection throughout the trial.

Group II: Arm A (Zanubrutinib) Experimental Treatment 11 Interventions

Patients receive zanubrutinib PO until first disease progression on study. Patients undergo CT or MRI or FDG PET/CT throughout the trial. Patients may optionally undergo blood sample collection throughout the trial.

Group III: ARM B (Observation) Active Control 11 Interventions

Patients undergo observation until first disease progression and then receive zanubrutinib PO until second disease progression on study. Patients undergo CT or MRI or FDG PET/CT throughout the trial. Patients may optionally undergo blood sample collection throughout the trial.

Zanubrutinib is already approved in United States, China for the following indications:

Approved in United States as Brukinsa for:

• Chronic lymphocytic leukemia (CLL)
• Small lymphocytic lymphoma (SLL)

Approved in China as Brukinsa for:

• Chronic lymphocytic leukemia (CLL)
• Small lymphocytic lymphoma (SLL)

Who Is Running the Clinical Trial?

Alliance for Clinical Trials in Oncology

Lead Sponsor

Trials

521

Recruited

224,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Zanubrutinib, an oral Bruton tyrosine kinase (BTK) inhibitor, received accelerated approval in the USA on November 14, 2019, for treating adult patients with mantle cell lymphoma (MCL) who have undergone at least one prior therapy.

The approval was based on the overall response rate (ORR) observed in phase II and I/II clinical trials, highlighting its efficacy in managing B-cell malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zanubrutinib: First Approval. Syed, YY.[2020]

In a phase 1/2 study involving 32 patients with relapsed/refractory mantle cell lymphoma, zanubrutinib showed a high overall response rate of 84%, with 25% of patients achieving a complete response and a median duration of response of 18.5 months.

Zanubrutinib was generally well tolerated, with the most common adverse events being diarrhea (43.8%) and infections (18.8% experiencing grade ≥3 infections), indicating that while there are side effects, the treatment is effective for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zanubrutinib for the treatment of relapsed or refractory mantle cell lymphoma. Tam, CS., Opat, S., Simpson, D., et al.[2021]

This case report presents the first documented instance of severe liver injury associated with zanubrutinib, a Bruton's tyrosine kinase inhibitor used in treating B cell malignancies, after 30 months of treatment.

The patient's liver function improved significantly after discontinuing zanubrutinib, highlighting the need for clinical vigilance regarding potential liver toxicity and the importance of stopping the drug if liver injury occurs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zanubrutinib-induced liver injury: a case report and literature review. Atallah, E., Wijayasiri, P., Cianci, N., et al.[2021]

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]

In a phase II study involving 86 patients with relapsed mantle-cell lymphoma, zanubrutinib demonstrated a high overall response rate of 84%, with 68.6% achieving a complete response after a median follow-up of 18.4 months.

Zanubrutinib was generally well tolerated, with most adverse events being manageable; serious side effects like major bleeding were rare, indicating a favorable safety profile for this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Patients with Relapsed or Refractory Mantle-Cell Lymphoma with Zanubrutinib, a Selective Inhibitor of Bruton's Tyrosine Kinase. Song, Y., Zhou, K., Zou, D., et al.[2021]

Zanubrutinib, a second-generation BTK inhibitor, has shown an impressive overall response rate of 84% in treating relapsed/refractory mantle cell lymphoma (MCL) based on data from 118 patients in two clinical trials, with a duration of response lasting 14-18 months.

Despite 57% of patients experiencing significant side effects, only 8% discontinued treatment, indicating that zanubrutinib is generally well tolerated and may offer advantages over first-generation BTK inhibitors like ibrutinib due to its higher selectivity and potential for combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zanubrutinib: a new BTK inhibitor for treatment of relapsed/refractory mantle cell lymphoma. Weaver, AN., Jimeno, A.[2020]

A 75-year-old patient developed a severe disseminated cryptococcal infection, leading to pneumonia and meningitis, four months after starting zanubrutinib for Waldenström's macroglobulinemia, highlighting a potential risk of serious infections associated with BTK inhibitors.

Despite initial treatment, the patient's condition worsened, resulting in septic shock and multiorgan failure, suggesting that while zanubrutinib can be effective for certain cancers, it may also compromise immune function, increasing vulnerability to invasive fungal infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A fatal disseminated cryptococcal infection in a patient treated with zanubrutinib for Waldenström's macroglobulinemia. Patel, D., Sidana, M., Mdluli, X., et al.[2022]

Citations

1.

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. At 36 months, this translates to an ...

2.

brukinsahcp.com

brukinsahcp.com/mcl/efficacy/

BRUKINSA® (zanubrutinib) Efficacy in MCL | HCPs

84% OF PATIENTS RESPONDED TO BRUKINSA · 84% OF PATIENTS RESPONDED TO BRUKINSA · MOST PATIENTS RESPONDED FOR MORE THAN 18 MONTHS · MOST PATIENTS EXPERIENCED ...

3.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e23270

Real-world zanubrutinib treatment patterns in mantle cell ...

Real-world data from across the US have demonstrated the effectiveness of zanu in MCL after treatment with another BTKi. Reasons for ...

4.

clinical-lymphoma-myeloma-leukemia.com

clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(24)01602-1/fulltext

MCL-509 Indirect Comparison of Efficacy of Zanubrutinib ...

This STC demonstrated that zanubrutinib had significantly better PFS and OS vs acalabrutinib in the treatment of patients with R/R MCL after adjusting for a ...

5.

tandfonline.com

tandfonline.com/doi/full/10.2147/BLCTT.S426588

Zanubrutinib in Mantle Cell Lymphoma Management

The results showed that overall response rate (ORR) was 84%, with 25% achieving complete response (CR). The median response (DOR) was 18.5 months. The median ...

6.

ashpublications.org

ashpublications.org/blood/article/139/21/3148/484435/Zanubrutinib-in-relapsed-refractory-mantle-cell

Zanubrutinib in relapsed/refractory mantle cell lymphoma

Zanubrutinib demonstrated deep and durable responses and a favorable safety profile in R/R MCL at median 35.3 months follow-up.

7.

onclive.com

onclive.com/view/first-line-zanubrutinib-obinutuzumab-shows-efficacy-safety-in-older-mcl

First-Line Zanubrutinib/Obinutuzumab Shows Efficacy, ...

The frontline combination of obinutuzumab and zanubrutinib demonstrated efficacy and safety in older patients with mantle cell lymphoma.

8.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0006497124091237

Preliminary Investigation of the Efficacy and Safety ...

This ongoing phase II clinical trial (ChiCTR2200055483) aims to assess the efficacy and safety of zanubrutinib in combination with R-Chemo as a first-line ...