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

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ClinicalTrials.gov Identifier: NCT03332173
Recruitment Status : Active, not recruiting
First Posted : November 6, 2017
Last Update Posted : September 30, 2020
Sponsor:
Information provided by (Responsible Party):
BeiGene

Tracking Information
First Submitted Date  ICMJE November 2, 2017
First Posted Date  ICMJE November 6, 2017
Last Update Posted Date September 30, 2020
Actual Study Start Date  ICMJE August 31, 2017
Actual Primary Completion Date May 8, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 20, 2017)
Major response rate(MRR) [ Time Frame: up to 3 years ]
defined as complete response(CR) + very good partial response(VGPR) + partial response(PR), to be assessed by an independent review committee (IRC) according to an adaptation of the response criteria updated at the 6th Workshop on Waldenström's Macroglobulinemia (IWWM, Owen et al 2013 and NCCN Guidelines, Lymphoplasmacytic Lymphoma/Waldenström's Macroglobulinemia 2015: v2)
Original Primary Outcome Measures  ICMJE
 (submitted: November 2, 2017)
MMR [ Time Frame: up to 3 years ]
defined as CR + VGPR + PR, to be assessed by an IRC according to an adaptation of the response criteria updated at the 6th Workshop on Waldenström's Macroglobulinemia (IWWM, Owen et al 2013 and NCCN Guidelines, Lymphoplasmacytic Lymphoma/Waldenström's Macroglobulinemia 2015: v2)
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 2, 2017)
  • Progression free survival (PFS) [ Time Frame: up to 3 years ]
    defined as time from first dose of BGB-3111 until first documentation of progression (by IWWM criteria) or death, whichever comes first.
  • Overall response rate (ORR) [ Time Frame: up to 3 years ]
    ORR is the proportion of subjects with a minor, partial, very good partial, and complete response
  • Duration of major response (DOMR) [ Time Frame: up to 3 years ]
    defined as the time from the date that the major response criteria are first met to the date that progressive disease (PD) is objectively documented or death, whichever occurs first.
  • Resolution of treatment precipitating symptoms [ Time Frame: up to 3 years ]
    defined as absence of symptoms at any point during study treatment, which triggered the initiation of study treatment as per the IWWM treatment guidelines.
  • Anti-lymphoma effect [ Time Frame: up to 3 years ]
    defined as any reduction during the course of study treatment in bone marrow involvement by lymphoplasmacytoid lymphocytes and/or size of lymphadenopathy and/or hepatosplenomegaly by CT scan. Lymphadenopathy is defined as any node with longest diameter (LDi) > 1.5 cm and splenomegaly is defined as vertical spleen length > 13 cm.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of BTK Inhibitor BGB-3111 in Chinese Participants With Relapsed/Refractory Waldenström's Macroglobulinemia (WM)
Official Title  ICMJE A Phase 2, Single-Arm, Open-Label, Multicenter Study of Bruton's Tyrosine Kinase (BTK) Inhibitor BGB-3111 in Chinese Subjects With Relapsed/Refractory Waldenström's Macroglobulinemia (WM)
Brief 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Waldenström's Macroglobulinemia (WM)
Intervention  ICMJE Drug: BGB-3111
BGB-3111 160 mg twice daily(BID) (in 80 mg white opaque capsules) administered orally
Study Arms  ICMJE Experimental: BGB-3111
Intervention: Drug: BGB-3111
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: September 28, 2020)
44
Original Estimated Enrollment  ICMJE
 (submitted: November 2, 2017)
40
Estimated Study Completion Date  ICMJE November 2020
Actual Primary Completion Date May 8, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Gender Based Eligibility: Yes
Gender Eligibility Description: male and female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03332173
Other Study ID Numbers  ICMJE BGB-3111-210
CTR20170208 ( Registry Identifier: Center for drug evaluation, CFDA )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Responsible Party BeiGene
Study Sponsor  ICMJE BeiGene
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Lugui Qiu, MD Institute of Hematology & Blood Diseases Hospital
PRS Account BeiGene
Verification Date September 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP