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

NCT04116437 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: BGB-3111-215
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 24

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.

Conditions

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma; Mantle Cell Lymphoma; Marginal Zone Lymphoma; Waldenstrom Macroglobulinemia

Keywords

BGB-3111; Zanubrutinib; Ibrutinib Intolerance; BTK Inhibitor; Acalabrutinib Intolerance

Outcome Measures

Primary Outcomes (1)

• Recurrence and change in severity of treatment-emergent Adverse Events (AEs) of interest.

  24 months

Secondary Outcomes (5)

• 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

Study Arms (1)

Zanubrutinib

EXPERIMENTAL

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

Drug: Zanubrutinib

Interventions

Zanubrutinib DRUG

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.

Also known as: BGB-3111, BRUKINSA

Zanubrutinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must meet protocol defined disease criteria requiring treatment for their respective disease prior to initiation of ibrutinib or acalabrutinib
• 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:
• For ibrutinib and acalabrutinib intolerance events:
• or more ≥ Grade 2 nonhematologic toxicities for \>7 days (with or without treatment)
• or more ≥ Grade 3 nonhematologic toxicity of any duration
• 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.
• For acalabrutinib intolerance events only;
• or more ≥ Grade 1 nonhematologic toxicities of any duration with \> 3 recurrent episodes; or
• 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
• 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.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• 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

You may not qualify if:

• Clinically significant cardiovascular disease including the following:
• Myocardial infarction within 6 months before the Screening
• Unstable angina within 3 months before the Screening
• New York Heart Association class III or IV congestive heart failure
• History of sustained ventricular tachycardia, ventricular fibrillation, and/or Torsades de Pointes
• QT interval corrected by Fridericia's formula \> 480 milliseconds
• History of Mobitz II second-degree or third-degree heart block without a permanent pacemaker in place
• History of central nervous system (CNS) hemorrhage
• Documented progressive disease (PD) during ibrutinib and/or acalabrutinib treatment.
• 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
• 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.

Sponsors & Collaborators

• BeiGene: lead

Study Sites (24)

Rocky Mountain Cancer Centers (Williams) Usor

Aurora, Colorado, 80012-5405, United States

Location

Christiana Care

Newark, Delaware, 19713-2055, United States

Location

Scri Florida Cancer Specialists South

Fort Myers, Florida, 33901-8108, United States

Location

St Century Oncology

Jacksonville, Florida, 32204-1128, United States

Location

Scri Florida Cancer Specialists North

St. Petersburg, Florida, 33705-1449, United States

Location

Healthcare Research Network Iii, Llc

Flossmoor, Illinois, 60422-2067, United States

Location

Minnesota Oncology Burnsville Clinic

Burnsville, Minnesota, 55337-6749, United States

Location

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89169-3321, United States

Location

Summit Medical Group

Florham Park, New Jersey, 07932-1049, United States

Location

Morristown Medical Center

Morristown, New Jersey, 07960-6136, United States

Location

Clinical Research Alliance, Inc

Westbury, New York, 11590-5119, United States

Location

Oncology Associates of Oregon Willamette Valley Cancer Center

Eugene, Oregon, 97401, United States

Location

St Lukes University Health Network

Fountain Hill, Pennsylvania, 18015-1153, United States

Location

Abington Hematology Oncology Associates

Horsham, Pennsylvania, 19044-2331, United States

Location

Tennessee Oncology, Pllc Nashville

Nashville, Tennessee, 37203, United States

Location

Texas Oncology Amarillo

Amarillo, Texas, 79106-1781, United States

Location

Texas Oncology Tyler Longview

Austin, Texas, 78705-1163, United States

Location

Baylor Research Institute

Dallas, Texas, 75246-2079, United States

Location

Texas Oncology McAllen South Second Street

McAllen, Texas, 78503, United States

Location

Us Oncology Virginia Cancer Specialists, Pc

Fairfax, Virginia, 22031-4629, United States

Location

Virginia Oncology Associates

Norfolk, Virginia, 23502-2800, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109-4433, United States

Location

Medical Oncology Associates

Spokane, Washington, 99208-1129, United States

Location

Ssm Health Cancer Care Dean Medical Center

Madison, Wisconsin, 53717-1959, United States

Location

Related Publications (2)

• Shadman M, Burke JM, Cultrera J, Yimer HA, Zafar SF, Misleh J, Rao SS, Farber CM, Cohen A, Yao H, Idoine A, An Q, Flinn IW, Sharman JP. Zanubrutinib is well tolerated and effective in patients with CLL/SLL intolerant of ibrutinib/acalabrutinib: updated results. Blood Adv. 2025 Aug 26;9(16):4100-4110. doi: 10.1182/bloodadvances.2024015493.

  PMID: 40334067 DERIVED

• Shadman M, Flinn IW, Levy MY, Porter RF, Burke JM, Zafar SF, Misleh J, Kingsley EC, Yimer HA, Freeman B, Rao SS, Chaudhry A, Tumula PK, Gandhi MD, Manda S, Chen DY, By K, Xu L, Liu Y, Crescenzo R, Idoine A, Zhang X, Cohen A, Huang J, Sharman JP. Zanubrutinib in patients with previously treated B-cell malignancies intolerant of previous Bruton tyrosine kinase inhibitors in the USA: a phase 2, open-label, single-arm study. Lancet Haematol. 2023 Jan;10(1):e35-e45. doi: 10.1016/S2352-3026(22)00320-9. Epub 2022 Nov 16.

  PMID: 36400069 DERIVED

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Mantle-Cell; Lymphoma, B-Cell, Marginal Zone; Waldenstrom Macroglobulinemia

Interventions

zanubrutinib

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: October 1, 2019
• First Posted: October 4, 2019
• Study Start: October 15, 2019
• Primary Completion: January 9, 2026
• Study Completion: January 9, 2026
• Last Updated: January 28, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: See plan description
• Access Criteria: See plan description

Locations

US (24)