Overview
Study of BTK Inhibitor BGB-3111 in Chinese Participants With Relapsed/Refractory Waldenström's Macroglobulinemia (WM)
Status:
Completed
Completed
Trial end date:
2021-01-11
2021-01-11
Target enrollment:
0
0
Participant gender:
All
All
Summary
Screening (up to 28 days); daily treatment until disease progression, unacceptable toxicity or death, withdrawal of consent, lost to follow-up, or study termination from sponsor; treatment (up to 3 years), safety follow up (28 days); survival follow-up until data cutoff for final analysis.Phase:
Phase 2Accepts Healthy Volunteers?
NoDetails
Lead Sponsor:
BeiGeneTreatments:
Zanubrutinib
Criteria
Key Inclusion Criteria:1. Clinical and definitive histologic diagnosis of WM (Gertz et al 2017), meeting at
least one criterion for treatment according to consensus panel criteria from the
Seventh IWWM (Dimopoulos et al 2014).
2. WM pathology confirmation by central lab prior to study enrollment. Previous pathology
report, concurrently with newly generated central lab report to be reviewed to support
WM diagnosis.
3. Men and women ≥ 18 years of age.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
5. Previously treated with a minimum of 1 prior line of standard chemotheraphy-containing
regimen(with completion of ≥ 2 continuous treatment cycles
6. Documented failure to achieve at least minor response or documented disease
progression after response to the most recent treatment regimen.
7. Neutrophils ≥ 0.75 x 10^9/L independent of growth factor support within 7 days of
first dose.
8. Platelets ≥ 50 x 10^9/L, independent of growth factor support or transfusion within 7
days of first dose.
9. Hemoglobin≥80g/L, independent of erythropoietin (EPO) support or transfusion within 7
days of first dose of study drug.
10. Creatinine clearance of ≥ 30 mL/min (as estimated by the Cockcroft-Gault equation
(Cockcroft and Gault 1976) or estimated glomerular filtration rate [eGFR] from the
Modification of Diet in Renal Disease [MDRD]).
11. AST and ALT ≤ 3.0 x ULN.
12. Bilirubin ≤ 2 x ULN (unless documented Gilbert's syndrome).
13. INR ≤ 1.5 and APTT ≤ 1.5 x ULN. Participants with lupus anticoagulant or acquired von
Willebrand disease due to WM may be enrolled after discussion with the medical
monitor.
14. ECHO must demonstrate left ventricular ejection fraction (LVEF) ≥50% (AHA,2016).
15. Subjects may be enrolled who relapse after autologous stem cell transplant if they are
at least 6 months after transplant at screening. To be eligible after transplant,
subjects should have no active related infections.
16. 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. Highly effective forms of birth control can be defined as abstinence,
hysterectomy, bilateral oophorectomy with no menstrual bleeding for up to 6 months,
intrauterine contraception, hormonal methods such as contraceptive injection, oral
contraceptive, etc. Males must have undergone sterilization-vasectomy, or use a
barrier method where the female partner uses the effective forms of birth control
noted above and must not donate sperm for at least 90 days after last dose of study
drug.
17. Life expectancy of > 4 months.
18. Able to provide written informed consent and can understand and comply with the
requirements of the study.
Key Exclusion Criteria:
1. Central nervous system (CNS) involvement by WM.
2. Prior exposure to a BTK inhibitor.
3. Evidence of disease transformation.
4. Prior corticosteroids given in excess of prednisone 10 mg/day or its equivalent with
antineoplastic intent within 7 days, prior chemotherapy, targeted therapy, or
radiation therapy within 3 weeks, antineoplastic therapy with Chinese herbal medicine
or antibody based theratpies within 4 weeks of the start of study drug.
5. Major surgery within 4 weeks of randomization.
6. Toxicity of ≥Grade 1 from prior anti-cancer therapy (except for absolute neutrophil
count [ANC] and platelets. For ANC and platelets, please follow inclusion criteria #7
[neutrophils] and #8 [platelets]).
7. 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
(surgery or other modality) with curative intent.
8. Currently active clinically significant cardiovascular disease such as uncontrolled
arrhythmia, uncontrolled hypertension, congestive heart failure, any Class 3 or 4
cardiac disease as defined by the New York Heart Association (NYHA) Functional
Classification, or history of myocardial infarction within 6 months of screening.
9. QTcF prolongation (defined as a QTc >480 msecs based on Fridericia's formula) or other
significant ECG abnormalities including second degree atrioventricular (AV) block Type
II, or third degree AV block.
10. 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.
11. Active infection including infections requiring oral or intravenous anti-microbial
therapy.
12. Known human immunodeficiency virus (HIV), or active hepatitis B or hepatitis C
infection (detected positive by polymerase chain reaction [PCR]).
13. Pregnant or lactating women.
14. Any life-threatening illness, medical condition or organ system dysfunction which, in
the investigator's opinion, could compromise the subject's safety, or put the study at
risk.
15. On medications which are strong CYP3A inhibitors or strong CYP3A inducers.
16. History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
17. Has received allogenic hematopoietic stem cell transplantation prior to enrollment.
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.