Zanubrutinib for Lymphoma

Not currently recruiting at 67 trial locations

Overseen By BeiGene

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: BeiGene

Must not be taking: Anticoagulants, Acid-reducing agents

Disqualifiers: Cardiovascular disease, CNS hemorrhage, 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

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: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called zanubrutinib (also known as Brukinsa) for individuals with certain types of lymphoma who cannot tolerate their current medications, ibrutinib or acalabrutinib, due to side effects. The goal is to determine if zanubrutinib is safer and causes fewer adverse effects. It is suitable for those who have experienced significant side effects from ibrutinib or acalabrutinib and whose conditions have stabilized after stopping these drugs. As a Phase 2 trial, this research measures how well zanubrutinib works in an initial, smaller group of participants, offering a chance to benefit from a potentially safer treatment.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop all current medications. However, you must stop taking corticosteroids over 10 mg daily at least 5 days before starting the study drug. Also, you cannot have received anticancer therapy less than 7 days before screening or immunotherapy less than 4 weeks before screening.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you must stop taking corticosteroids above a certain dose at least 5 days before starting the study drug. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that zanubrutinib is likely to be safe for humans?

Research has shown that zanubrutinib is generally well-tolerated by patients with certain types of lymphoma. In one study of patients who couldn't handle previous treatments like ibrutinib or acalabrutinib, only 40% of the side effects from ibrutinib and 28% from acalabrutinib reappeared when they switched to zanubrutinib. This finding suggests that zanubrutinib may cause fewer or milder side effects for some patients.

Additionally, zanubrutinib has already received approval for treating mantle cell lymphoma in patients who have tried other treatments. This approval indicates that doctors have a good understanding of its side effects. Overall, the evidence suggests that zanubrutinib might be a safer option for those who have had issues with other treatments. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for lymphoma?

Zanubrutinib is unique because it specifically targets the Bruton's tyrosine kinase (BTK) pathway, which is crucial for the growth and survival of certain lymphoma cells. Unlike the standard treatments like ibrutinib or acalabrutinib, zanubrutinib is designed to minimize off-target effects, potentially leading to fewer side effects. Researchers are excited about this treatment because it offers hope for patients who have already been treated with other BTK inhibitors, potentially providing a more effective and safer alternative.

What evidence suggests that zanubrutinib might be an effective treatment for lymphoma?

Studies have shown that zanubrutinib effectively treats certain blood cancers, such as mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL). In this trial, participants will receive zanubrutinib, which research indicates works well for patients who have already tried other medications, such as ibrutinib or acalabrutinib. Patients have achieved good results with zanubrutinib, even if their cancer returned or didn't respond to other treatments. Most patients tolerate it well, experiencing few severe side effects. The FDA has approved zanubrutinib for CLL/SLL and MCL, supporting its effectiveness for these conditions. ^{1 2 4 6 7}

Who Is on the Research Team?

Dih-Yih Chen, MD

Principal Investigator

BeiGene

Are You a Good Fit for This Trial?

This trial is for people with certain B-cell lymphomas or leukemia who had bad reactions to previous treatments with ibrutinib or acalabrutinib. They should be relatively active (ECOG status of 0-2), have a minimum number of neutrophils and platelets, and not have severe heart problems, recent heart attacks, CNS hemorrhage, or need high doses of steroids.

Inclusion Criteria

My condition requires treatment before starting ibrutinib or acalabrutinib.

My blood tests show enough neutrophils and platelets for treatment.

I can take care of myself and am up and about more than half of my waking hours.

Exclusion Criteria

I need more than 10 mg of prednisone or similar medication daily.

My condition worsened while on ibrutinib or acalabrutinib treatment.

I have serious heart issues, including recent heart attacks or unstable angina.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive zanubrutinib to evaluate safety and adverse event profile

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Zanubrutinib

Trial Overview The study tests Zanubrutinib's safety in patients intolerant to prior BTKi treatments. It looks at whether the side effects are less severe or occur less often than before. Patients previously treated with other cancer therapies must wait specific periods before joining.

How Is the Trial Designed?

Group I: Zanubrutinib Experimental Treatment 1 Intervention

Cohort 1: Chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL), Waldenström macroglobulinemia (WM), mantle cell lymphoma (MCL), or marginal zone lymphoma (MZL) previously treated with ibrutinib Cohort 2: Chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL), Waldenström macroglobulinemia (WM), mantle cell lymphoma (MCL), or marginal zone lymphoma (MZL) previously treated with acalabrutinib alone/with ibrutinib

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?

BeiGene

Lead Sponsor

Trials

216

Recruited

32,500+

Published Research Related to This Trial

Zanubrutinib demonstrated a high overall response rate of 95.4% in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma, with treatment-naïve patients showing even better outcomes (100% response) compared to those with relapsed/refractory disease (91.0%).

The long-term follow-up indicated that earlier treatment with zanubrutinib leads to significantly longer progression-free and overall survival, while maintaining a favorable safety profile, with serious adverse events primarily being infections and neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zanubrutinib Monotherapy for Naïve and Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: A Pooled Analysis of Three Studies. Xu, W., Yang, S., Tam, CS., et al.[2022]

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]

In a phase 3 study involving 590 patients with untreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), zanubrutinib significantly improved progression-free survival compared to bendamustine-rituximab, with a hazard ratio of 0.42, indicating a strong efficacy advantage.

Zanubrutinib demonstrated an acceptable safety profile, with fewer severe adverse events like neutropenia compared to bendamustine-rituximab, suggesting it could be a promising new treatment option for patients with CLL and SLL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zanubrutinib versus bendamustine and rituximab in untreated chronic lymphocytic leukaemia and small lymphocytic lymphoma (SEQUOIA): a randomised, controlled, phase 3 trial. Tam, CS., Brown, JR., Kahl, BS., et al.[2023]

Zanubrutinib, a selective Bruton tyrosine kinase inhibitor, was found to be generally well tolerated when combined with obinutuzumab in a phase 1 study involving 81 patients with chronic lymphocytic leukemia (CLL) and follicular lymphoma (FL).

The combination therapy showed high efficacy, achieving a 100% overall response rate in treatment-naïve CLL patients and a 92% response rate in relapsed/refractory CLL patients, with a 72% response rate in relapsed/refractory FL patients over a median follow-up of 20 to 29 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zanubrutinib (BGB-3111) plus obinutuzumab in patients with chronic lymphocytic leukemia and follicular lymphoma. Tam, CS., Quach, H., Nicol, A., et al.[2021]

Zanubrutinib is a next-generation BTK inhibitor that shows improved selectivity and reduced off-target toxicities compared to ibrutinib, making it a safer option for treating B-cell malignancies.

In recent clinical trials, zanubrutinib demonstrated significant efficacy in improving progression-free survival in patients with chronic lymphocytic leukemia (CLL) and showed better safety profiles, including a lower risk of serious side effects like atrial fibrillation and major bleeding compared to ibrutinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zanubrutinib for the treatment of lymphoid malignancies: Current status and future directions. Wolska-Washer, A., Robak, T.[2023]

In a study of 27 patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL), the combination of zanubrutinib and salvage chemotherapy resulted in a high overall response rate of 74.1% and a complete remission rate of 33.3%, indicating significant efficacy.

The most common severe side effects were neutropenia and thrombocytopenia, but the treatment was generally manageable, suggesting that zanubrutinib plus chemotherapy could be a viable option for R/R DLBCL patients, especially those with poor responses to initial treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zanubrutinib plus salvage chemotherapy for relapsed or refractory diffuse large B-cell lymphoma. Yuan, X., Li, X., Huang, Y., et al.[2022]

Zanubrutinib, a selective Bruton tyrosine kinase inhibitor, showed a high overall response rate of 94.5% in treatment-naïve patients with chronic lymphocytic leukemia or small lymphocytic lymphoma carrying the del(17p) mutation, indicating its efficacy in a challenging patient population.

The treatment was well tolerated, with an estimated 18-month progression-free survival rate of 88.6% and an overall survival rate of 95.1%, although some patients experienced adverse events, including neutropenia and infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zanubrutinib monotherapy for patients with treatment naïve chronic lymphocytic leukemia and 17p deletion. Tam, CS., Robak, T., Ghia, P., et al.[2021]

Zanubrutinib is a highly selective second-generation BTK inhibitor that has shown deep and sustained remissions in patients with relapsed and refractory B-cell lymphoma, indicating its efficacy as a targeted therapy.

The drug has a favorable safety profile, making it a promising option for precision therapy in the treatment of B-cell lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical Application of Zanubrutinib in B-Cell Lymphoma --Review]. Tang, X., Zou, WR., Peng, P., et al.[2022]

Zanubrutinib, a selective BTK inhibitor, was evaluated in a pooled analysis of 779 patients across 6 studies, showing a generally well-tolerated safety profile with manageable and mostly reversible treatment-emergent adverse events (TEAEs).

Common nonhematologic TEAEs included upper respiratory tract infections (39%) and rash (27%), while serious adverse events like pneumonia (11%) and sepsis (2%) were noted, but the rates of atrial fibrillation and major hemorrhage were lower than those historically reported for another BTK inhibitor, ibrutinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pooled safety analysis of zanubrutinib monotherapy in patients with B-cell malignancies. Tam, CS., Dimopoulos, M., Garcia-Sanz, R., et al.[2022]

In the phase 3 SEQUOIA trial involving adult patients with treatment-naïve chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), zanubrutinib significantly improved progression-free survival compared to the standard treatment of bendamustine plus rituximab (BR).

Patients treated with zanubrutinib reported better health-related quality-of-life outcomes at 12 and 24 weeks, including improvements in global health status, physical functioning, and reduced symptoms of diarrhea, fatigue, and nausea/vomiting compared to those receiving BR.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-related quality-of-life in treatment-naive CLL/SLL patients treated with zanubrutinib versus bendamustine plus rituximab. Ghia, P., Barnes, G., Yang, K., et al.[2023]

Citations

1. brukinsahcp.com brukinsahcp.com/mcl/

BRUKINSA® (zanubrutinib) for MCL | HCPs BRUKINSA® (zanubrutinib) is indicated for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.

2. ashpublications.org ashpublications.org/bloodadvances/article/9/16/4100/537143/Zanubrutinib-is-well-tolerated-and-effective-in

Zanubrutinib is well tolerated and effective in patients with ... Bruton tyrosine kinase (BTK) inhibitors such as ibrutinib (ibr) revolutionized chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) treatment, ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06859008

Study Details | NCT06859008 | Zanubrutinib in ... Zanubrutinib and sonrotoclax have been shown to be an effective treatment for B-cell cancers. Giving zanubrutinib in combination with sonrotoclax may be ...

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

Zanubrutinib in relapsed/refractory mantle cell lymphoma Song et al present longer term outcomes of a phase 2 study of zanubrutinib therapy for 86 patients with relapsed/refractory MCL. Outcomes were promising.

5. healthtree.org healthtree.org/cll/community/articles/fda-approves-simpler-zanubrutinib-tablets

FDA Approves Simpler Way to Take Zanubrutinib (Brukinsa) Zanubrutinib is currently approved for use in the treatment of: Chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL); Relapsed or ...

6. mayoclinic.org mayoclinic.org/drugs-supplements/zanubrutinib-oral-route/description/drg-20477009

Zanubrutinib (oral route) - Side effects & dosage Zanubrutinib is used to treat mantle cell lymphoma (MCL) in patients who have received at least one previous treatment for their cancer.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04116437

Study Details | NCT04116437 | Zanubrutinib (BGB-3111) in ... The primary objective of this study is to evaluate the safety of zanubrutinib (also known as BGB-3111) in chronic lymphocytic leukemia/small lymphocytic ...