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

NCT ID: NCT04116437

Last Updated: 2025-12-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

90 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-10-15

Study Completion Date

2025-12-31

Brief Summary

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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.

Detailed Description

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Conditions

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

Keywords

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BGB-3111 Zanubrutinib Ibrutinib Intolerance BTK Inhibitor Acalabrutinib Intolerance

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Zanubrutinib

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

Group Type EXPERIMENTAL

Zanubrutinib

Intervention Type 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.

Interventions

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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.

Intervention Type DRUG

Other Intervention Names

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BGB-3111 BRUKINSA

Eligibility Criteria

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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

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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BeiGene

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Scri Florida Cancer Specialists North

St. Petersburg, Florida, United States

Site Status

Healthcare Research Network Iii, Llc

Flossmoor, Illinois, United States

Site Status

Minnesota Oncology Burnsville Clinic

Burnsville, Minnesota, United States

Site Status

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States

Site Status

Summit Medical Group

Florham Park, New Jersey, United States

Site Status

Morristown Medical Center

Morristown, New Jersey, United States

Site Status

Clinical Research Alliance, Inc

Westbury, New York, United States

Site Status

Oncology Associates of Oregon Willamette Valley Cancer Center

Eugene, Oregon, United States

Site Status

St Lukes University Health Network

Fountain Hill, Pennsylvania, United States

Site Status

Abington Hematology Oncology Associates

Horsham, Pennsylvania, United States

Site Status

Tennessee Oncology, Pllc Nashville

Nashville, Tennessee, United States

Site Status

Texas Oncology Amarillo

Amarillo, Texas, United States

Site Status

Texas Oncology Tyler Longview

Austin, Texas, United States

Site Status

Baylor Research Institute

Dallas, Texas, United States

Site Status

Texas Oncology McAllen South Second Street

McAllen, Texas, United States

Site Status

Us Oncology Virginia Cancer Specialists, Pc

Fairfax, Virginia, United States

Site Status

Virginia Oncology Associates

Norfolk, Virginia, United States

Site Status

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Site Status

Rocky Mountain Cancer Centers (Williams) Usor

Aurora, Colorado, United States

Site Status

Christiana Care

Newark, Delaware, United States

Site Status

Scri Florida Cancer Specialists South

Fort Myers, Florida, United States

Site Status

St Century Oncology

Jacksonville, Florida, United States

Site Status

Medical Oncology Associates

Spokane, Washington, United States

Site Status

Ssm Health Cancer Care Dean Medical Center

Madison, Wisconsin, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 40334067 (View on PubMed)

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.

Reference Type DERIVED
PMID: 36400069 (View on PubMed)

Other Identifiers

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BGB-3111-215

Identifier Type: -

Identifier Source: org_study_id