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

Mantle Cell Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04116437
• Other study ID #: BGB-3111-215
• Status: Recruiting
• Phase: Phase 2
• Start date: October 15, 2019
• Est. completion date: October 2025

Study information

• Verified date: April 2024
• Source: BeiGene
• Contact: BeiGene
• Phone: 1-877-828-5568
• Email: clinicaltrials[@]beigene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: October 2025
• Est. primary completion date: October 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
• Leukemia, Lymphocytic, Chronic, B-Cell
• Lymphoma
• Lymphoma, Mantle-Cell
• Mantle Cell Lymphoma
• Marginal Zone Lymphoma
• Waldenstrom Macroglobulinemia

Intervention

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.

Locations

Country	Name	City	State
United States	Texas Oncology Amarillo	Amarillo	Texas
United States	Rocky Mountain Cancer Centers (Williams) Usor	Aurora	Colorado
United States	St Lukes University Health Network	Bethlehem	Pennsylvania
United States	Minnesota Oncology Burnsville Clinic	Burnsville	Minnesota
United States	Baylor Research Institute	Dallas	Texas
United States	Oncology Associates of Oregon Willamette Valley Cancer Center	Eugene	Oregon
United States	Us Oncology Virginia Cancer Specialists, Pc	Fairfax	Virginia
United States	Summit Medical Group	Florham Park	New Jersey
United States	Scri Florida Cancer Specialists South	Fort Myers	Florida
United States	Abington Hematology Oncology Associates	Horsham	Pennsylvania
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Ssm Health Cancer Care Dean Medical Center	Madison	Wisconsin
United States	Texas Oncology McAllen South Second Street	McAllen	Texas
United States	Morristown Medical Center	Morristown	New Jersey
United States	Tennessee Oncology, Pllc Nashville	Nashville	Tennessee
United States	Christiana Care	Newark	Delaware
United States	Scri Florida Cancer Specialists North	Saint Petersburg	Florida
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Medical Oncology Associates	Spokane	Washington
United States	Healthcare Research Network Iii, Llc	Tinley Park	Illinois
United States	Arizona Oncology Associates, Pc Hope	Tucson	Arizona
United States	Texas Oncology Tyler Longview	Tyler	Texas
United States	Virginia Oncology Associates Hampton	Virginia Beach	Virginia
United States	Clinical Research Alliance, Inc	Westbury	New York

Sponsors (1)

Lead Sponsor	Collaborator
BeiGene

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recurrence and change in severity of treatment-emergent Adverse Events (AEs) of interest.		24 months
Secondary	Overall response as determined by investigator		24 months
Secondary	Progression free survival (PFS) as determined by investigator		24 months
Secondary	Patient reported outcomes as measured by EuroQol five dimension scale (EQ-5D)		24 months
Secondary	Patient reported outcomes as measured by European Organisation for Research and Treatment of Cancer (EORTC)		24 months
Secondary	Disease control rate as determined by investigator		24 months