Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Mantle Cell Lymphoma, Marginal Zone Lymphoma, Waldenstrom Macroglobulinemia
Conditions
Keywords
BGB-3111, Zanubrutinib, Ibrutinib Intolerance, BTK Inhibitor, Acalabrutinib Intolerance
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.
Interventions
DRUGZanubrutinib
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.
Sponsors
BeiGene
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Recurrence and change in severity of treatment-emergent Adverse Events (AEs) of interest. | 24 months |
Secondary
| Measure | Time frame |
|---|---|
| Overall response as determined by investigator | 24 months |
| Progression free survival (PFS) as determined by investigator | 24 months |
| Patient reported outcomes as measured by EuroQol five dimension scale (EQ-5D) | 24 months |
| Patient reported outcomes as measured by European Organisation for Research and Treatment of Cancer (EORTC) | 24 months |
| Disease control rate as determined by investigator | 24 months |
Countries
United States
Outcome results
None listed