A Study Comparing BGB-3111 and Ibrutinib in Participants With Waldenström's Macroglobulinemia (WM)
A Phase 3, Randomized, Open-Label, Multicenter Study Comparing the Efficacy and Safety of the Bruton's Tyrosine Kinase (BTK) Inhibitors BGB-3111 and Ibrutinib in Subjects With Waldenström's Macroglobulinemia (WM)
This study is to evaluate the safety, efficacy and clinical benefit of BGB-3111 (Zanubrutinib) vs ibrutinib in participants with MYD88 Mutation Waldenström's Macroglobulinemia.
This open-label, randomized study will compare the efficacy and safety of the Bruton's Tyrosine Kinase (BTK) inhibitors BGB-3111 and ibrutinib in participants with Waldenström's Macroglobulinemia who require therapy. Participants will have baseline bone marrow samples assayed for sequencing of the MYD88 gene. Approximately 188 participants with the MYD88 mutation will be enrolled onto Cohort 1 and randomized to receive 160 mg BGB-3111 PO BID (treatment Arm A) or to receive 420mg ibrutinib QD (treatment Arm B) until disease progression or unacceptable toxicity. Participants with MYD88 wild type will be enrolled to Cohort 2 and will receive 160 mg BGB-3111 PO BID (treatment Arm C) until disease progressive disease (PD) or unacceptable toxicity, withdrawal of consent, loss to follow-up, or study termination by Sponsor.
Proportion of participants achieving either a complete response (CR) or very good partial response (VGPR) in Cohort 1 using an adaptation of the response criteria updated at the Sixth IWWM as assessed by an independent review committee.
Efficacy measured by major response rate (MRR) in Cohort 1
Study Arms / Comparison Groups
Arm A (Experimental Arm-BGB-3111)
Description: Approximately 94 participants with the MYD88 mutation will be enrolled in Cohort 1 and receive BGB-3111 in treatment [Arm A]
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
January 25, 2017
June 21, 2022
Primary Completion Date
June 21, 2022
Key Inclusion Criteria: - Clinical and definitive histologic diagnosis of WM - Measurable disease, requiring treatment - Participants with no prior therapy for WM, must be considered inappropriate candidates for treatment with a standard chemoimmunotherapy regimen - Age ≥ 18 years old - (ECOG) performance status of 0-2 - Adequate bone marrow function - Adequate renal and hepatic function - ECHO/MUGA demonstrating left ventricular ejection fraction (LVEF)≥ the lower limit of institutional normal - Subjects may be enrolled who relapse after autologous stem cell transplant if they are at least 3 months after transplant, and after allogeneic transplant if they are at least 6 months post transplant. - 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. Males must have undergone sterilization- vasectomy, or utilize a barrier method - Life expectancy of > 4 months Key Exclusion Criteria: - Prior exposure to a BTK inhibitor - Evidence of disease transformation at the time of study entry - Corticosteroids given with antineoplastic intent within 7 days, or chemotherapy given with antineoplastic intent, targeted therapy, or radiation therapy within 3 weeks, or antibody-based therapy within 4 weeks of the start of study drug - Major surgery within 4 weeks of study treatment - Toxicity of ≥ Grade 2 from prior anticancer therapy - 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 with curative intent - Currently active, clinically significant cardiovascular disease such as uncontrolled arrhythmia, congestive heart failure, any Class 3 or 4 cardiac disease within 6 months of screening - QTcF prolongation (defined as a QTcF > 450 msec) - Active, clinically significant Electrocardiogram (ECG) abnormalities - 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 - Uncontrolled active systemic infection or recent infection requiring parenteral anti-microbial therapy - Known human immunodeficiency virus (HIV), or active hepatitis B or hepatitis C - Pregnant or lactating women - Any life-threatening illness, medical condition, organ system dysfunction, need for profound anticoagulation, or bleeding disorder, which, in the investigator's opinion, could compromise the subject's safety - Any medications which are strong or moderate cytochrome P450, family 3, subfamily A (CYP3A) inhibitors or strong CYP3A inducers NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
18 Years - N/A
Accepts Healthy Volunteers
Aileen Cohen, MD, ,
Aileen Cohen, MD, Study Director, BeiGene