Brief Title
A Study Comparing BGB-3111 and Ibrutinib in Participants With Waldenström's Macroglobulinemia (WM)
Official Title
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)
Brief Summary
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.
Detailed Description
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.
Study Phase
Phase 3
Study Type
Interventional
Primary Outcome
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.
Secondary Outcome
Efficacy measured by major response rate (MRR) in Cohort 1
Condition
Waldenström's Macroglobulinemia
Intervention
BGB-3111
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]
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
229
Start Date
January 25, 2017
Completion Date
June 21, 2022
Primary Completion Date
June 21, 2022
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
- (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.
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Aileen Cohen, MD, ,
Location Countries
Australia
Location Countries
Australia
Administrative Informations
NCT ID
NCT03053440
Organization ID
BGB-3111-302
Secondary IDs
2016-002980-33
Responsible Party
Sponsor
Study Sponsor
BeiGene
Study Sponsor
Aileen Cohen, MD, Study Director, BeiGene
Verification Date
July 2022