A Study Comparing BGB-3111 and Ibrutinib in Participants With Waldenström's Macroglobulinemia (WM)
Condition: Waldenström's Macroglobulinemia
MeSH terms: Waldenstrom Macroglobulinemia
Intervention: BGB-3111; Ibrutinib
Intervention description: 160 mg PO BID until progressive disease, unacceptable toxicity, death, withdrawal of consent, or study termination by sponsor; 420 mg PO QD until progressive disease, unacceptable toxicity, death, withdrawal of consent, or study termination by sponsor
Intervention MeSH terms: Zanubrutinib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 201.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This study evaluated the safety, efficacy and clinical benefit of BGB-3111 (zanubrutinib) vs
      ibrutinib in participants with MYD88 Mutation Waldenström's Macroglobulinemia.
    

Eligibility criteria:

        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

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

          -  Adequate bone marrow function

          -  Adequate renal and hepatic function

          -  Electrocardiogram/multigated acquisition scan (ECHO/MUGA) demonstrating left
             ventricular ejection fraction (LVEF)≥ the lower limit of institutional normal

          -  Participants 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 > 480 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.