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Waldenström's Macroglobulinemia (WM)Phase 2NCT03332173

Study of BTK Inhibitor BGB-3111 in Chinese Subjects With Relapsed/Refractory Waldenström's Macroglobulinemia (WM)

A Phase 2 study testing Zanubrutinib in people with Waldenström's Macroglobulinemia (WM), run by BeiGene at 10 sites in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This was a single-arm, multicenter Phase 2 study in Chinese participants with relapsed or refractory Waldenström's macroglobulinemia who exhibited one or more of the criteria for requiring treatment based on consensus guidelines from the Seventh International Workshop on Waldenström's Macroglobulinemia (IWWM). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Waldenström's Macroglobulinemia (WM)
What is being tested?
Zanubrutinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
44 participants
Where
10 sitesChina
Study dates
31 Aug 2017to 11 Jan 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Clinical and definitive histologic diagnosis of WM, meeting at least one criterion for treatment according to consensus panel criteria from the Seventh IWWM.
  • WM pathology confirmation by central lab prior to study enrollment. Previous pathology report, concurrently with newly generated central lab report to be reviewed to support WM diagnosis.
  • Men and women ≥ 18 years of age.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
  • Previously treated with a minimum of 1 prior line of standard chemotherapy-containing regimen (with completion of ≥ 2 continuous treatment cycles).
  • Documented failure to achieve at least minor response or documented disease progression after response to the most recent treatment regimen.
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  • Neutrophils ≥ 0.75 x 10^9/L independent of growth factor support within 7 days of first dose.
  • Platelets ≥ 50 x 10^9/L, independent of growth factor support or transfusion within 7 days of first dose.
  • Hemoglobin ≥80 g/L, independent of erythropoietin (EPO) support or transfusion within 7 days of first dose of study drug.
  • Creatinine clearance of ≥ 30 mL/min (as estimated by the Cockcroft-Gault equation or estimated glomerular filtration rate [eGFR] from the Modification of Diet in Renal Disease [MDRD]).
  • Aspartate transaminase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x upper limit of normal (ULN).
  • Bilirubin ≤ 2 x ULN (unless documented Gilbert's syndrome).
  • International normalized ratio ≤ 1.5 and activated partial thromboplastin time ≤ 1.5 x ULN. Participants with lupus anticoagulant or acquired von Willebrand disease due to WM may be enrolled after discussion with the medical monitor.
  • ECHO must demonstrate left ventricular ejection fraction (LVEF) ≥50%.
  • Participants who relapse after autologous stem cell transplant may be enrolled if they are at least 6 months after transplant at screening. To be eligible after transplant, participants should have no active related infections.
  • Females of childbearing potential must agree to use highly effective forms of birth control throughout the course of the study and at least up to 90 days after last dose of study drug. Highly effective forms of birth control can be defined as abstinence, hysterectomy, bilateral oophorectomy with no menstrual bleeding for up to 6 months, intrauterine contraception, hormonal methods such as contraceptive injection, oral contraceptive, etc. Males must have undergone sterilization-vasectomy, or use a barrier method where the female partner uses the effective forms of birth control noted above and must not donate sperm for at least 90 days after last dose of study drug.
  • Life expectancy of > 4 months.
  • Able to provide written informed consent and can understand and comply with the requirements of the study.

Who cannot join

  • Central nervous system (CNS) involvement by WM.
  • Prior exposure to a BTK inhibitor.
  • Evidence of disease transformation.
  • Prior corticosteroids given in excess of prednisone 10 mg/day or its equivalent with antineoplastic intent within 7 days, prior chemotherapy, targeted therapy, or radiation therapy within 3 weeks, antineoplastic therapy with Chinese herbal medicine or antibody based therapies within 4 weeks of the start of study drug.
  • Major surgery within 4 weeks of randomization.
  • Toxicity of ≥ Grade 1 from prior anti-cancer therapy (except for absolute neutrophil count [ANC], platelets, and hemoglobin. For ANC, platelets, and hemoglobin, please follow inclusion criteria #7 [neutrophils], #8 [platelets], and #9 [hemoglobin]).
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  • History of other active malignancies within 2 years of study entry, with exception of (1) adequately treated in-situ carcinoma of cervix; (2) localized basal cell or squamous cell carcinoma of skin; (3) previous malignancy confined and treated locally (surgery or other modality) with curative intent.
  • Currently active clinically significant cardiovascular disease such as uncontrolled arrhythmia, uncontrolled hypertension, congestive heart failure, any Class 3 or 4 cardiac disease as defined by the New York Heart Association (NYHA) Functional Classification, or history of myocardial infarction within 6 months of screening.
  • QTcF prolongation (defined as a QTc >480 msecs based on Fridericia's formula) or other significant ECG abnormalities including second degree atrioventricular (AV) block Type II, or third degree AV block.
  • Unable to swallow capsules or disease significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction.
  • Active infection including infections requiring oral or intravenous anti-microbial therapy.
  • Known human immunodeficiency virus (HIV), or active hepatitis B or hepatitis C infection (detected positive by polymerase chain reaction [PCR]).
  • Pregnant or lactating women.
  • Any life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, or put the study at risk.
  • On medications which are strong CYP3A inhibitors or strong CYP3A inducers.
  • History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
  • Has received allogenic hematopoietic stem cell transplantation prior to enrollment.
  • NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial locations and contacts

10 sites in 1 country.

10 sites in 1 country

China10 sites

  • Cancer Hospital Chinese Academy of Medical Sciences

    Beijing, Beijing Municipality, 100021

  • Peking Union Medical College Hospital

    Beijing, Beijing Municipality, 100730

  • West China Hospital, Sichuan University

    Chengdu, Sichuan, 610041

  • Guangdong Provincial Peoples Hospital

    Guangzhou, Guangdong, 510080

  • The First Affiliated Hospital, Zhejiang University School of Medicine

    Hangzhou, Zhejiang, 310003

  • Jiangsu Province Hospital

    Nanjing, Jiangsu, 210029

  • Rui Jin Hospital Shanghai Jiao Tong University School of Medicine

    Shanghai, Shanghai Municipality, 200025

  • The First Affiliated Hospital of Soochow University Branch Shizi

    Suzhou, Jiangsu, 215006

  • Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology

    Wuhan, Hubei, 430030

  • Henan Cancer Hospital

    Zhengzhou, Henan, 450000

Other trials in China

About this study

Official title: A Phase 2, Single-Arm, Open-Label, Multicenter Study of Bruton's Tyrosine Kinase (BTK) Inhibitor BGB-3111 in Chinese Subjects With Relapsed/Refractory Waldenström's Macroglobulinemia (WM)

This was a single-arm, multicenter Phase 2 study in Chinese participants with relapsed or refractory Waldenström's macroglobulinemia who exhibited one or more of the criteria for requiring treatment based on consensus guidelines from the Seventh International Workshop on Waldenström's Macroglobulinemia (IWWM). The study comprised an initial screening phase (up to 28 days), a single-arm treatment phase, and a follow-up phase.

Being tested
Zanubrutinib
Medical subject headings
Waldenstrom Macroglobulinemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ZanubrutinibDrug

    Also called BGB-3111, Brukinsa

    Oral administration using 80 mg capsules

Study groups in NCT03332173
Study groupRoleWhat they receive
ZanubrutinibExperimentalZanubrutinib 160 mg orally twice daily with or without food until progressive disease or intolerable toxicity
Receives: Drug: Zanubrutinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Major Response Rate (MRR) as Assessed by the Independent Review Committee

    MRR is defined as the percentage of participants who achieved complete response (CR) + very good partial response (VGPR) + partial response (PR), as assessed by an independent review committee according to modified Owen's criteria

    Measured: Up to approximately 1 year and 9 months

Secondary outcomes (8)

  1. Progression Free Survival (PFS)

    PFS is defined as the time from first dose until first documentation of progression or death, whichever comes first, as assessed by an independent review committee using modified Owen's criteria

    Measured: Up to approximately 1 year and 9 months

  2. PFS: Event-free Rate

    Progression/death event-free rates were estimated by Kaplan-Meier method with 95% confidence intervals (CIs) estimated using Greenwood's formula

    Measured: Up to approximately 1 year and 9 months

  3. Overall Response Rate (ORR)

    ORR is defined as the percentage of participants with a minor, partial, very good partial, and complete response, as assessed by an independent review committee using modified Owen's criteria

    Measured: Up to approximately 1 year and 9 months

  4. Duration of Major Response (DOMR)

    DOMR is defined as the time from the date that the major response criteria are first met to the date that progressive disease (PD) is objectively documented or death, whichever comes first, as assessed by an independent review committee using modified Owen's criteria

    Measured: Up to approximately 1 year and 9 months

  5. DOMR: Event-free Rate

    DOMR event-free rates were estimated by Kaplan-Meier method with 95% CIs estimated using Greenwood's formula

    Measured: Up to approximately 1 year and 9 months

  6. Number of Participants With Resolution of Treatment-precipitating Symptoms

    Number of participants with resolution of treatment-precipitating symptoms, defined as any resolution (from "Yes" at baseline to "No" at any postbaseline point onwards during study) of the indications for initiation of therapy in WM signs and symptoms evaluation.

    Measured: Up to approximately 1 year and 9 months

  7. Number of Participants With an Anti-lymphoma Effect

    Number of participants with an anti-lymphoma effect, defined as any reduction during the course of study in bone marrow involvement by lymphoplasmacytoid lymphocytes and/or size of lymphadenopathy and/or splenomegaly by computed tomography scan as assessed by an independent review committee; lymphadenopathy is defined as any node with longest diameter (LDi) > 1.5 cm and splenomegaly is defined as vertical spleen length > 13 cm

    Measured: Up to approximately 1 year and 9 months

  8. Number of Participants With Adverse Events

    Number of participants with treatment-emergent adverse events (TEAEs), grade 3 or higher TEAEs, serious adverse events (SAEs), treatment-related adverse events (AEs), adverse events of special interest, and TEAEs leading to study drug discontinuation, dose reduction and treatment interruption

    Measured: Up to approximately 3 years and 5 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Nov 2017
  2. Study start31 Aug 2017
  3. Primary completion8 May 2019
  4. Study completion11 Jan 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
44 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03332173
Sponsor's protocol ID
BGB-3111-210
Other IDs
CTR20170208
Status last verified
Oct 2024
First submitted
2 Nov 2017
Last updated
26 Oct 2024
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes

Publications

  • An G, Zhou D, Cheng S, Zhou K, Li J, Zhou J, Xie L, Jin J, Zhong L, Yan L, Guo H, Du C, Zhong J, Yu Y, Wu B, Qiu L. A Phase II Trial of the Bruton Tyrosine-Kinase Inhibitor Zanubrutinib (BGB-3111) in Patients with Relapsed/Refractory Waldenstrom Macroglobulinemia. Clin Cancer Res. 2021 Oct 15;27(20):5492-5501. doi: 10.1158/1078-0432.CCR-21-0539. Epub 2021 Jul 12.

    PubMed 34253577

  • Moslehi JJ, Furman RR, Tam CS, Salem JE, Flowers CR, Cohen A, Zhang M, Zhang J, Chen L, Ma H, Brown JR. Cardiovascular events reported in patients with B-cell malignancies treated with zanubrutinib. Blood Adv. 2024 May 28;8(10):2478-2490. doi: 10.1182/bloodadvances.2023011641.

    PubMed 38502198

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Zanubrutinib in people with Waldenström's Macroglobulinemia (WM), run by BeiGene at 10 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Mar 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Major Response Rate (MRR) as Assessed by the Independent Review Committee (time frame: Up to approximately 1 year and 9 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03332173, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2024.

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