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Zanubrutinib (BGB-3111) in Participants With Previously Treated B-Cell Lymphoma Intolerant of Prior Bruton Tyrosine Kinase Inhibitor (BTKi) Treatment

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. Identifier: NCT04116437
Recruitment Status : Recruiting
First Posted : October 4, 2019
Last Update Posted : December 7, 2020
Information provided by (Responsible Party):

Brief Summary:
The primary objective of this study is to evaluate the safety of zanubrutinib (also known as BGB-3111) in participants with previously treated chronic lymphocytic leukemia/small lymphocytic lymphoma, Waldenström macroglobulinemia, mantle cell lymphoma, or marginal zone lymphoma intolerant of prior ibrutinib and/or acalabrutinib treatment, compared with their ibrutinib and/or acalabrutinib intolerance adverse event profile as assessed by the recurrence and the change in severity of adverse events.

Condition or disease Intervention/treatment Phase
Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Mantle Cell Lymphoma Marginal Zone Lymphoma Waldenstrom Macroglobulinemia Drug: Zanubrutinib Phase 2

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2, Multicenter, Single-arm Study of Zanubrutinib (BGB-3111) in Patients With Previously Treated B-Cell Lymphoma Intolerant of Prior Treatment With Ibrutinib and/or Acalabrutinib
Actual Study Start Date : October 15, 2019
Estimated Primary Completion Date : September 2022
Estimated Study Completion Date : October 2022

Arm Intervention/treatment
Experimental: Zanubrutinib
Chronic lymphocytic leukemia (CLL)/ Small Lymphocytic Lymphoma (SLL), Waldenstrom Macroglobulinemia (WM), Mantle Cell Lymphoma (MCL), or Marginal Zone Lymphoma (MZL) previously treated with ibrutinib and/acalbrutinib
Drug: Zanubrutinib
Zanubrutinib (BGB-3111) will be orally administered at a dose of 160 mg twice daily or 320mg once daily until disease progression, unacceptable toxicity, treatment consent withdrawal, or study termination.
Other Names:
  • BGB-3111

Primary Outcome Measures :
  1. Recurrence and change in severity of treatment-emergent Adverse Events (AEs) of interest. [ Time Frame: 24 months ]

Secondary Outcome Measures :
  1. Overall response as determined by investigator [ Time Frame: 24 months ]
  2. Progression free survival (PFS) as determined by investigator [ Time Frame: 24 months ]
  3. Patient reported outcomes as measured by EuroQol five dimension scale (EQ-5D) [ Time Frame: 24 months ]
  4. Patient reported outcomes as measured by European Organisation for Research and Treatment of Cancer (EORTC) [ Time Frame: 24 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Key Inclusion Criteria:

  1. Participants must meet protocol defined disease criteria requiring treatment for their respective disease prior to initiation of ibrutinib or acalabrutinib
  2. Ibrutininb and/or acalabrutinib intolerance defined as an unacceptable toxicity where, in the opinion of the investigator, treatment should be discontinued in spite of optimal supportive care as a result of one of the following:

    1. 1 or more Grade ≥2 non-hematological toxicities for >7 days (with or without treatment)
    2. 1 or more Grade ≥3 non-hematological toxicity of any duration
    3. 1 or more Grade 3 neutropenia with infection or fever or
    4. Grade 4 heme toxicity which persists to the point that the investigator chose to stop therapy due to toxicity NOT progression.
  3. Ibrutinib and/or acalabrutinib-related toxicities must have resolved to Grade ≤ 1 or baseline prior to initiating treatment with zanubrutinib.
  4. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
  5. Absolute neutrophil count (ANC) ≥ 1000/mm3 with or without growth factor support and platelet count ≥ 50,000/mm^3 (may be post-transfusion), on or prior to C1D1 of zanubrutinib

Key Exclusion Criteria:

  1. Clinically significant cardiovascular disease including the following:

    1. Myocardial infarction within 6 months before the Screening
    2. Unstable angina within 3 months before the Screening
    3. New York Heart Association class III or IV congestive heart failure
    4. History of sustained ventricular tachycardia, ventricular fibrillation, and/or Torsades de Pointes
    5. QT interval corrected by Fridericia's formula > 480 milliseconds
    6. History of Mobitz II second-degree or third-degree heart block without a permanent pacemaker in place
  2. History of central nervous system (CNS) hemorrhage
  3. Documented progressive disease (PD) during ibrutinib and/or acalabrutinib treatment.
  4. Have received any anticancer therapy (other than immunotherapy) for CLL/SLL, WM, MCL, and MZL < 7 days before any Screening assessments are performed or any immunotherapy treatment, taken alone or as part of a chemoimmunotherapy regimen, < 4 weeks before any Screening assessments are performed
  5. Requires ongoing need for corticosteroid treatment > 10 mg daily of prednisone or equivalent corticosteroid. Note: Systemic corticosteroids must be fully tapered off/discontinued ≥ 5 days before the first dose of study drug is administered.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

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 identifier (NCT number): NCT04116437

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Contact: BeiGene 1-877-828-5568

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Sponsors and Collaborators
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Study Director: Dih-Yih Chen, MD BeiGene
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Responsible Party: BeiGene Identifier: NCT04116437    
Other Study ID Numbers: BGB-3111-215
First Posted: October 4, 2019    Key Record Dates
Last Update Posted: December 7, 2020
Last Verified: December 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by BeiGene:
Ibrutinib Intolerance
BTK Inhibitor
Acalabrutinib Intolerance
Additional relevant MeSH terms:
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Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Mantle-Cell
Waldenstrom Macroglobulinemia
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, Lymphoid
Leukemia, B-Cell
Lymphoma, Non-Hodgkin
Neoplasms, Plasma Cell
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action