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

This study is currently recruiting participants.
Verified November 2017 by BeiGene
Sponsor:
ClinicalTrials.gov Identifier:
NCT03332173
First Posted: November 6, 2017
Last Update Posted: November 6, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
BeiGene
  Purpose
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.

Condition Intervention Phase
Waldenström's Macroglobulinemia (WM) Drug: BGB-3111 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by BeiGene:

Primary Outcome Measures:
  • 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)


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 40
Actual Study Start Date: August 8, 2017
Estimated Study Completion Date: November 2021
Estimated Primary Completion Date: April 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BGB-3111 Drug: BGB-3111
BGB-3111 160 mg BID (in 80 mg white opaque capsules) administered orally

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Gender Based Eligibility:   Yes
Gender Eligibility Description:   male and female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Clinical and definitive histologic diagnosis of WM, 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.
  3. Previous pathology report, concurrently with newly generated central lab report to be reviewed to confirm WM diagnosis.
  4. Men and women ≥ 18 years of age.
  5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
  6. Received at least one prior treatment for WM, and the most recent therapy resulted in a response or stable disease that has now progressed, or progression without response.
  7. Neutrophils ≥ 0.75 x 109/L independent of growth factor support within 7 days of study entry.
  8. Platelets ≥ 50 x 109/L, independent of growth factor support or transfusion within 7 days of study entry.
  9. 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]).
  10. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x ULN.
  11. Bilirubin ≤ 2 x ULN (unless documented Gilbert's syndrome).
  12. International normalized ratio (INR) ≤ 1.5 and activated partial thromboplastin time (APTT) ≤ 2.0 x ULN. Patients with lupus anticoagulant or acquired von Willebrand disease due to WM may be enrolled after discussion with the medical monitor.
  13. Echocardiogram (ECHO) must demonstrate left ventricular ejection fraction (LVEF) ≥50% (AHA,2016).
  14. Subjects may be enrolled who relapse after autologous stem cell transplant if they are at least 6 months after transplant. To be eligible after transplant, subjects s should be no active related infections.
  15. Female 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.
  16. Life expectancy of > 4 months.
  17. Able to provide written informed consent and can understand and comply with the requirements of the study.

Exclusion Criteria:

  1. Central nervous system (CNS) involvement by WM.
  2. Prior exposure to a BTK inhibitor.
  3. Evidence of disease transformation at the time of study entry.
  4. Prior corticosteroids (>20 mg/day of prednisolone) given with anti neoplastic intent within 7 days, prior chemotherapy, targeted therapy, radiation therapy, or Chinese herbal medication given for anti-cancer treatment within 3 weeks, or antibody-based therapies within 4 weeks of the start of study drug.
  5. Major surgery within 4 weeks of screening.
  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, 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 >450 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. Uncontrolled systemic infection or infection requiring parenteral 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 cytochrome P450, family 3, subfamily A (CYP3A) inhibitors or strong CYP3A inducers.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03332173


Contacts
Contact: Meng Ji +86 10 589580000 clinicaltrials@beigene.com

Locations
China, Beijing
Peking Union Medical College Hospital Recruiting
Beijing, Beijing, China
Peking University Pepole's Hospital Not yet recruiting
Beijing, Beijing, China
China, Guangdong
Guangdong General Hospital Not yet recruiting
Guangzhou, Guangdong, China
China, Henan
Henan Cancer Hospital Not yet recruiting
Zhengzhou, Henan, China
China, Hubei
Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Recruiting
Wuhan, Hubei, China
China, Jiangsu
Jiangsu Province Hospital Not yet recruiting
Nanjing, Jiangsu, China
The first affiliated hospital of Soochow University Not yet recruiting
Suzhou, Jiangsu, China
China, Shanghai
Ruijin Hospital, Shanghai Jiaotong University School of Medicine Not yet recruiting
Shanghai, Shanghai, China
China, Sichuan
West China Hospital, Sichuan University Not yet recruiting
Chengdu, Sichuan, China
China, Tianjin
Institute of Hematology & Blood Diseases Hospital Recruiting
Tianjin, Tianjin, China
China, Zhejiang
The First Affiliated Hospital of Zhejiang University Not yet recruiting
Hangzhou, Zhejiang, China
Sponsors and Collaborators
BeiGene
  More Information

Responsible Party: BeiGene
ClinicalTrials.gov Identifier: NCT03332173     History of Changes
Other Study ID Numbers: BGB-3111-210
First Submitted: November 2, 2017
First Posted: November 6, 2017
Last Update Posted: November 6, 2017
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
URL: http://

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Waldenstrom Macroglobulinemia
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases