Study of Zanubrutinib (BGB-3111) in Participants With Marginal Zone Lymphoma

NCT ID: NCT03846427

Last Updated: 2024-10-26

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

68 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-02-19

Study Completion Date

2022-05-04

Brief Summary

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This is a single arm study to evaluate the efficacy, safety and tolerability of zanubrutinib (BGB-3111) in participants with relapsed/refractory marginal zone lymphoma (R/R MZL).

Detailed Description

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Conditions

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Marginal Zone Lymphoma MZL

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Zanubrutinib

Zanubrutinib 160 mg (two 80-mg capsules) orally twice daily with or without food until progressive disease, intolerable toxicity, or withdrawal of consent

Group Type EXPERIMENTAL

Zanubrutinib

Intervention Type DRUG

Zanubrutinib at a dose of 160 mg orally twice a day (BID)

Interventions

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Zanubrutinib

Zanubrutinib at a dose of 160 mg orally twice a day (BID)

Intervention Type DRUG

Other Intervention Names

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BGB-3111 Brukinsa

Eligibility Criteria

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Inclusion Criteria

1. Age 18 years or older
2. Histologically confirmed diagnosis of MZL including splenic, nodal, and extranodal subtypes
3. Previously received one or more lines of therapy including at least one CD20-directed regimen (either as monotherapy or as chemoimmunotherapy) with documented failure to achieve at least partial response or documented progressive disease (PD) after, the most recent systemic treatment
4. Current need for systemic therapy for MZL
5. Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI)
6. Eastern Cooperative Oncology Group (ECOG) of 0-2
7. Life expectancy ≥ 6 months
8. Adequate bone marrow function
9. Adequate organ function
10. Male and female participants must use highly effective methods of contraception

Exclusion Criteria

1. Known transformation to aggressive lymphoma, eg, large cell lymphoma
2. Clinically significant cardiovascular disease
3. Prior malignancy within the past 2 years, except for curatively treated basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast, or localized Gleason score 6 prostate cancer
4. History of severe bleeding disorder such as hemophilia A, hemophilia B, von Willebrand disease, or history of spontaneous bleeding requiring blood transfusion or other medical intervention
5. History of stroke or intracranial hemorrhage
6. Severe or debilitating pulmonary disease
7. Active fungal, bacterial and/or viral infection requiring systemic therapy
8. Known central nervous system involvement by lymphoma
9. Known infection with HIV, or serologic status reflecting active viral hepatitis B (HBV) or viral hepatitis C (HCV) infection
10. Major surgery within 4 weeks of the first dose of study drug
11. Prior treatment with a Bruton's tyrosine kinase (BTK) inhibitor
12. Pregnant or lactating women
13. Requires ongoing treatment with a strong Cytochrome P4503A (CYP3A) inhibitor or inducer
14. Concurrent participation in another therapeutic clinical trial
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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BeiGene

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Study Director

Role: PRINCIPAL_INVESTIGATOR

BeiGene

Locations

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Clinical Research Alliance, Inc

Westbury, New York, United States

Site Status

The Charlotte Mecklenburg Hospital Authority

Charlotte, North Carolina, United States

Site Status

Canberra Hospital

Garran, Australian Capital Territory, Australia

Site Status

Concord Repatriation General Hospital

Concord, New South Wales, Australia

Site Status

The Saint George Hospital Kogarah

Kogarah, New South Wales, Australia

Site Status

Princess Alexandra Hospital

Brisbane, Queensland, Australia

Site Status

Flinders Medical Centre

Bedford PK, South Australia, Australia

Site Status

Box Hill Hospital

Box Hill, Victoria, Australia

Site Status

Monash Health

Clayton, Victoria, Australia

Site Status

Peninsula Private Hospital

Frankston, Victoria, Australia

Site Status

Peking University Third Hospital

Beijing, Beijing Municipality, China

Site Status

Henan Cancer Hospital

Zhengzhou, Henan, China

Site Status

Institute of Hematology and Hospital of Blood Disease

Tianjin, Tianjin Municipality, China

Site Status

The First Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

Site Status

University Hospital Vinohrady Hematology Department

Prague, , Czechia

Site Status

Centre de Lutte Contre Le Cancer Institut Bergonie

Bordeaux, , France

Site Status

Hopital de La Conception Aphm

Marseille, , France

Site Status

Hopital Saint Louis

Paris, , France

Site Status

Chu Hopital Lyon Sud

PierreBenite, , France

Site Status

Policlinico Sorsola Malpighi, Aou Di Bologna

Bologna, , Italy

Site Status

Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda

Milan, , Italy

Site Status

Universita Degli Studi Di Modena Azienda Ospedaliere Policlinco

Modena, , Italy

Site Status

Azienda Ospedaliera S Maria Di Terni

Terni, , Italy

Site Status

Ao Citta Della Salute E Della Scienza Di Torino Presidio O

Torino, , Italy

Site Status

Auckland City Hospital

Auckland, , New Zealand

Site Status

North Shore Hospital

Takapuna, , New Zealand

Site Status

Severance Hospital Yonsei University Health System

Seoul, Seoul Teugbyeolsi, South Korea

Site Status

Beatson West of Scotland Cancer Centre

Glasgow, , United Kingdom

Site Status

The Christie Hospital

Greater Manchester, , United Kingdom

Site Status

University College Hospital

London, , United Kingdom

Site Status

Royal Marsden Hospital

London, , United Kingdom

Site Status

Countries

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United States Australia China Czechia France Italy New Zealand South Korea United Kingdom

References

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Stephen Opat, Robert Marcus, MA, FRCP, FRCPath, Craig A. Portell, MD, William Reed, MD, Chris Tankersley, Jane Huang, MD, Judith Trotman, MBChB, FRACP, FRCPA. Phase 2 Study of Zanubrutinib (BGB-3111) in Patients with Relapsed/Refractory Marginal Zone Lymphoma. Blood. 2019; 134(1):5256. https://doi.org/10.1182/blood-2019-122629

Reference Type BACKGROUND

Stephen Opat, et al. Efficacy and Safety of Zanubrutinib in Patients with Relapsed/Refractory Marginal Zone Lymphoma: Initial Results of the MAGNOLIA (BGB-3111-214) Trial. Presented at the 62nd American Society of Hematology (ASH) Annual Meeting, December 5-8, 2020. Abstract 339.

Reference Type BACKGROUND

Opat S, Tedeschi A, Linton K, McKay P, Hu B, Chan H, Jin J, Sobieraj-Teague M, Zinzani PL, Coleman M, Thieblemont C, Browett P, Ke X, Sun M, Marcus R, Portell CA, Ardeshna K, Bijou F, Walker P, Hawkes EA, Mapp S, Ho SJ, Talaulikar D, Zhou KS, Co M, Li X, Zhou W, Cappellini M, Tankersley C, Huang J, Trotman J. The MAGNOLIA Trial: Zanubrutinib, a Next-Generation Bruton Tyrosine Kinase Inhibitor, Demonstrates Safety and Efficacy in Relapsed/Refractory Marginal Zone Lymphoma. Clin Cancer Res. 2021 Dec 1;27(23):6323-6332. doi: 10.1158/1078-0432.CCR-21-1704. Epub 2021 Sep 15.

Reference Type BACKGROUND
PMID: 34526366 (View on PubMed)

Opat S, Tedeschi A, Hu B, et al: Long-term efficacy and safety of zanubrutinib in patients with relapsed/refractory marginal zone lymphoma. 2022 ASH Annual Meeting and Exposition. Abstract 234. Presented December 10, 2022.

Reference Type BACKGROUND

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.

Reference Type DERIVED
PMID: 38502198 (View on PubMed)

Opat S, Tedeschi A, Hu B, Linton KM, McKay P, Leitch S, Coleman M, Zinzani PL, Jin J, Sun M, Sobieraj-Teague M, Browett P, Ke X, Thieblemont C, Ardeshna K, Bijou F, Walker P, Hawkes EA, Ho SJ, Zhou K, Liang Z, Xu J, Tankersley C, Delarue R, Co M, Trotman J. Safety and efficacy of zanubrutinib in relapsed/refractory marginal zone lymphoma: final analysis of the MAGNOLIA study. Blood Adv. 2023 Nov 28;7(22):6801-6811. doi: 10.1182/bloodadvances.2023010668.

Reference Type DERIVED
PMID: 37682792 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2018-001284-24

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CTR20180823

Identifier Type: REGISTRY

Identifier Source: secondary_id

BGB-3111-214

Identifier Type: -

Identifier Source: org_study_id

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