A Study to Investigate Zanubrutinib in Chinese Participants With B-cell Lymphoma

NCT ID: NCT03189524

Last Updated: 2024-12-27

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

44 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-07-05

Study Completion Date

2020-08-26

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

This phase I clinical study was to investigate the safety, tolerability, and pharmacokinetics/pharmacodynamics of Bruton tyrosine kinase (BTK) inhibitor zanubrutinib (BGB-3111) in Chinese participants with B-cell lymphoma by conducting in two stages, the first stage being the safety assessment of dose and the second stage being the dose expansion.

Part I: Safety evaluation - according to the results of preclinical toxicological trials and the results of the phase I clinical study conducted in Australia and New Zealand, two regimens of zanubrutinib 320 milligrams (mg) daily (160 mg twice daily \[BID\]), administered in the morning and at night, or 320 mg once daily \[QD\]) and "3+3" design was adopted for the assessment. The recommended dose and method of administration of the phase II clinical study was determined according to the Part I results.

Part II: Dose expansion - this stage was to further evaluate the preliminary anti-tumor effects of zanubrutinib in Chinese participants with follicular lymphoma (FL) or marginal zone lymphoma (MZL), approximately 20 participants with relapsed or refractory FL or MZL were to be enrolled. The recommended Phase 2 dose (RP2D) was used in Part II.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

B-cell Lymphoma

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Part I: 160 mg BID

Safety Evaluation: Two regimens of zanubrutinib 320 milligrams (mg) daily (160 mg twice daily \[BID\]) administered in the morning and at night, or 320 mg (once daily \[QD\]), and a "3+3" design was adopted for Part I of the study to determine recommended Phase 2 dose (RP2D).

Group Type EXPERIMENTAL

Zanubrutinib

Intervention Type DRUG

Zanubrutinib is a white to off-white solid that is slightly hygroscopic. The drug product was formulated as 20-mg (blue, size 3) and 80-mg (white, size 0) hard gelatin, opaque oral capsules. Zanubrutinib is classified as a Biopharmaceutics Classification System Class II compound.

Part I: 320 mg QD

Safety Evaluation: Two regimens of zanubrutinib 320 mg daily (160 mg BID, administered in the morning and at night, or 320 mg QD) and a "3+3" design was adopted for Part I of the study to determine RP2D.

Group Type EXPERIMENTAL

Zanubrutinib

Intervention Type DRUG

Zanubrutinib is a white to off-white solid that is slightly hygroscopic. The drug product was formulated as 20-mg (blue, size 3) and 80-mg (white, size 0) hard gelatin, opaque oral capsules. Zanubrutinib is classified as a Biopharmaceutics Classification System Class II compound.

Part II: 160 mg BID

Dose Expansion: The RP2D determined in Part I was used in Part II to further evaluate the preliminary anti-tumor effects of zanubrutinib in Chinese participants with follicular lymphoma (FL) or marginal zone lymphoma (MZL).

Group Type EXPERIMENTAL

Zanubrutinib

Intervention Type DRUG

Zanubrutinib is a white to off-white solid that is slightly hygroscopic. The drug product was formulated as 20-mg (blue, size 3) and 80-mg (white, size 0) hard gelatin, opaque oral capsules. Zanubrutinib is classified as a Biopharmaceutics Classification System Class II compound.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Zanubrutinib

Zanubrutinib is a white to off-white solid that is slightly hygroscopic. The drug product was formulated as 20-mg (blue, size 3) and 80-mg (white, size 0) hard gelatin, opaque oral capsules. Zanubrutinib is classified as a Biopharmaceutics Classification System Class II compound.

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

BGB-3111

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Men and women between the age of 18-75 years.
* Participants with B-cell lymphoma (defined by World Health Organization classification) refractory or relapsed following at least one line of therapy.
* Judged by the investigator as requiring treatment.
* Eastern Cooperative Oncology Group performance status of 0-1.
* Life expectancy of at least 4 months.
* Adequate hematological function.
* Adequate renal function.
* Adequate liver function.
* Adequate coagulation function.
* Female participants of childbearing potential and non-sterile males must have practiced at least one of the following methods of birth control with partner(s) throughout the study and for 90 days after discontinuing study drug: total abstinence from sexual intercourse, double-barrier contraception, intrauterine device or hormonal contraceptive initiated at least 3 months prior to first dose of study drug.
* Male participants must not have donated sperm from start of study drug administration, until 90 days after discontinuation of treatment.

Exclusion Criteria

* With central nervous system involvement of the disease.
* The pathological type of the disease had disease transformation.
* Had underdone allogeneic hematopoietic stem cell transplantation.
* Had received corticosteroid anti-neoplastic treatment within 7 days before the first dose, has received radiotherapy and chemotherapy within 4 weeks before the first dose or has received treatment with monoclonal antibody within 4 weeks before the first dose.
* Had received BTK inhibitor treatment prior to enrollment.
* Had received chemotherapy and has not yet recovered from toxicity
* Had received Chinese herbal medicine as anti-neoplastic therapy within 4 weeks before starting study treatment.
* History of other malignancies within 2 years before study.
* With uncontrolled systemic infection.
* Major surgery in the past 4 weeks.
* With known HIV, or active hepatitis B or hepatitis C virus infection.
* With cardiovascular disease of New York Heart Association Classification ≥ 3.
* Significant electrocardiogram abnormalities.
* Significant active renal, neurologic, psychiatric, hepatic or endocrinologic disease that in the investigator's opinion would adversely impact on his/her participation in the study.
* Inability to comply with study procedures.
* Was currently taking anticoagulant drugs.
* Was currently taking potent cytochrome P450 3A inhibitor or inducer.
* Had stroke or cerebral hemorrhage within 6 months before enrollment.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

BeiGene

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Study Director

Role: PRINCIPAL_INVESTIGATOR

BeiGene

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Beijing Cancer Hospital

Beijing, Beijing Municipality, China

Site Status

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

Wuhan, Hubei, China

Site Status

Jiangsu Province Hospital

Nanjing, Jiangsu, China

Site Status

Institute of Hematology and Hospital of Blood Disease

Tianjin, Tianjin Municipality, China

Site Status

Countries

Review the countries where the study has at least one active or historical site.

China

References

Explore related publications, articles, or registry entries linked to this study.

Jun Zhu, BS, Jianyong Li, MD, Jianfeng Zhou, Yuqin Song, MD, Junyuan Qi, Wei Xu, Dengju Li, MD, Mingyuan Sun, Ling Xue, PhD, Liudi Yang, Yinwei Zhang, Lai Wang, PhD, Jane Huang, MD, Shibao Feng, PhD, Lugui Qiu, MD. BGB-3111, a Highly Specific BTK Inhibitor, Is Well Tolerated and Highly Active in Chinese Patients with Relapsed/Refractory B-Cell Malignancies: Initial Report of a Phase 1 Trial in China. Blood. 2017; 130(1): 5347. https://doi.org/10.1182/blood.V130.Suppl_1.5347.5347

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)

Xu W, Yang S, Tam CS, Seymour JF, Zhou K, Opat S, Qiu L, Sun M, Wang T, Trotman J, Pan L, Gao S, Zhou J, Zhou D, Zhu J, Song Y, Hu J, Feng R, Huang H, Su D, Shi M, Li J. Zanubrutinib Monotherapy for Naive and Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: A Pooled Analysis of Three Studies. Adv Ther. 2022 Sep;39(9):4250-4265. doi: 10.1007/s12325-022-02238-7. Epub 2022 Jul 28.

Reference Type DERIVED
PMID: 35900694 (View on PubMed)

Song Y, Sun M, Qi J, Xu W, Zhou J, Li D, Li J, Qiu L, Du C, Guo H, Huang J, Tang Z, Ou Y, Wu B, Yu Y, Zhu J. A two-part, single-arm, multicentre, phase I study of zanubrutinib, a selective Bruton tyrosine kinase inhibitor, in Chinese patients with relapsed/refractory B-cell malignancies. Br J Haematol. 2022 Jul;198(1):62-72. doi: 10.1111/bjh.18162. Epub 2022 Apr 5.

Reference Type DERIVED
PMID: 35383885 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

CTR20160204

Identifier Type: REGISTRY

Identifier Source: secondary_id

BGB-3111-1002

Identifier Type: -

Identifier Source: org_study_id