Brief Title
Zanubrutinib (BGB-3111) in Participants With Previously Treated B-Cell Lymphoma Intolerant of Prior Bruton Tyrosine Kinase Inhibitor (BTKi) 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
Brief Summary
The primary objective of this study is to evaluate the safety of zanubrutinib (also known as
BGB-3111) in chronic lymphocytic leukemia/small lymphocytic lymphoma, Waldenström
macroglobulinemia, mantle cell lymphoma, or marginal zone lymphoma patients who have become
intolerant of prior ibrutinib and/or acalabrutinib treatment, by comparing intolerance to
adverse event profile as assessed by the recurrence and the change in severity of adverse
events.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Recurrence and change in severity of treatment-emergent Adverse Events (AEs) of interest.
Secondary Outcome
Overall response as determined by investigator
Condition
Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Intervention
Zanubrutinib
Study Arms / Comparison Groups
Zanubrutinib
Description: Cohort 1: Chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL), Waldenström macroglobulinemia (WM), mantle cell lymphoma (MCL), or marginal zone lymphoma (MZL) previously treated with ibrutinib Cohort 2: Chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL), Waldenström macroglobulinemia (WM), mantle cell lymphoma (MCL), or marginal zone lymphoma (MZL) previously treated with acalabrutinib alone/with ibrutinib
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
90
Start Date
October 15, 2019
Completion Date
July 2025
Primary Completion Date
June 2025
Eligibility Criteria
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. Ibrutinib and acalabrutinib intolerance is 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. For ibrutinib and acalabrutinib intolerance events:
- 1 or more ≥ Grade 2 nonhematologic toxicities for >7 days (with or without
treatment)
- 1 or more ≥ Grade 3 nonhematologic toxicity of any duration
- 1 or more Grade 3 neutropenia with infection or fever of any duration; or
- Grade 4 heme toxicity which persists to the point that the investigator
chose to stop therapy due to toxicity NOT progression.
2. For acalabrutinib intolerance events only;
- 1 or more ≥ Grade 1 nonhematologic toxicities of any duration with > 3
recurrent episodes; or
- 1 or more ≥ Grade 1 nonhematologic toxicities for > 7 days (with or without
treatment); or
- Inability to use acid-reducing agents or anticoagulants (eg, proton pump
inhibitors, warfarin) due to concurrent acalabrutinib use
3. Ibrutinib and/or acalabrutinib-related ≥ Grade 2 toxicities must have resolved to ≤
Grade 1 or baseline prior to initiating treatment with zanubrutinib. Grade 1
acalabrutinib-related toxicities must have resolved to Grade 0 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/mm^3 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.
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Dih-Yih Chen, MD, 1-877-828-5568, [email protected]
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT04116437
Organization ID
BGB-3111-215
Responsible Party
Sponsor
Study Sponsor
BeiGene
Study Sponsor
Dih-Yih Chen, MD, Study Director, BeiGene
Verification Date
April 2021