Status:

COMPLETED

Study of BTK Inhibitor BGB-3111 in Chinese Subjects With Relapsed/Refractory Waldenström's Macroglobulinemia (WM)

Lead Sponsor:

BeiGene

Conditions:

Waldenström's Macroglobulinemia (WM)

Eligibility:

All Genders

18+ years

Phase:

PHASE2

Brief Summary

This was a single-arm, multicenter Phase 2 study in Chinese participants with relapsed or refractory Waldenström's macroglobulinemia who exhibited one or more of the criteria for requiring treatment b...

Eligibility Criteria

Inclusion

  • Key
  • Clinical and definitive histologic diagnosis of WM, meeting at least one criterion for treatment according to consensus panel criteria from the Seventh IWWM.
  • 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.
  • Men and women ≥ 18 years of age.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
  • Previously treated with a minimum of 1 prior line of standard chemotherapy-containing regimen (with completion of ≥ 2 continuous treatment cycles).
  • Documented failure to achieve at least minor response or documented disease progression after response to the most recent treatment regimen.
  • Neutrophils ≥ 0.75 x 10\^9/L independent of growth factor support within 7 days of first dose.
  • Platelets ≥ 50 x 10\^9/L, independent of growth factor support or transfusion within 7 days of first dose.
  • Hemoglobin ≥80 g/L, independent of erythropoietin (EPO) support or transfusion within 7 days of first dose of study drug.
  • Creatinine clearance of ≥ 30 mL/min (as estimated by the Cockcroft-Gault equation or estimated glomerular filtration rate \[eGFR\] from the Modification of Diet in Renal Disease \[MDRD\]).
  • Aspartate transaminase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x upper limit of normal (ULN).
  • Bilirubin ≤ 2 x ULN (unless documented Gilbert's syndrome).
  • International normalized ratio ≤ 1.5 and activated partial thromboplastin time ≤ 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.
  • ECHO must demonstrate left ventricular ejection fraction (LVEF) ≥50%.
  • Participants who relapse after autologous stem cell transplant may be enrolled if they are at least 6 months after transplant at screening. To be eligible after transplant, participants should have no active related infections.
  • 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.
  • Life expectancy of \> 4 months.
  • Able to provide written informed consent and can understand and comply with the requirements of the study.
  • Key

Exclusion

  • Central nervous system (CNS) involvement by WM.
  • Prior exposure to a BTK inhibitor.
  • Evidence of disease transformation.
  • 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 therapies within 4 weeks of the start of study drug.
  • Major surgery within 4 weeks of randomization.
  • Toxicity of ≥ Grade 1 from prior anti-cancer therapy (except for absolute neutrophil count \[ANC\], platelets, and hemoglobin. For ANC, platelets, and hemoglobin, please follow inclusion criteria #7 \[neutrophils\], #8 \[platelets\], and #9 \[hemoglobin\]).
  • 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.
  • 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.
  • 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.
  • 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.
  • Active infection including infections requiring oral or intravenous anti-microbial therapy.
  • Known human immunodeficiency virus (HIV), or active hepatitis B or hepatitis C infection (detected positive by polymerase chain reaction \[PCR\]).
  • Pregnant or lactating women.
  • 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.
  • On medications which are strong CYP3A inhibitors or strong CYP3A inducers.
  • History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
  • Has received allogenic hematopoietic stem cell transplantation prior to enrollment.
  • NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Key Trial Info

Start Date :

August 31 2017

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

January 11 2021

Estimated Enrollment :

44 Patients enrolled

Trial Details

Trial ID

NCT03332173

Start Date

August 31 2017

End Date

January 11 2021

Last Update

October 26 2024

Active Locations (10)

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Page 1 of 3 (10 locations)

1

Cancer Hospital Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, China, 100021

2

Peking Union Medical College Hospital

Beijing, Beijing Municipality, China, 100730

3

Guangdong Provincial Peoples Hospital

Guangzhou, Guangdong, China, 510080

4

Henan Cancer Hospital

Zhengzhou, Henan, China, 450000