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Chronic Lymphocytic Leukemia/Small Lymphocytic LymphomaPhase 2NCT04116437

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

A Phase 2 study testing Zanubrutinib in people with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma and Mantle Cell Lymphoma, run by BeiGene at 24 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Zanubrutinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
96 participants
Where
24 sitesUnited States
Study dates
15 Oct 2019to 9 Jan 2026
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
  • 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
Show all 14Show fewer
  • 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;
  • 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
  • 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

Who cannot join

  • 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
Show all 12Show fewer
  • 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.
  • NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial locations and contacts

24 sites in 1 country.

24 sites in 1 country

United States24 sites

  • Texas Oncology Amarillo

    Amarillo, Texas, 79106-1781

  • Rocky Mountain Cancer Centers (Williams) Usor

    Aurora, Colorado, 80012-5405

  • Texas Oncology Tyler Longview

    Austin, Texas, 78705-1163

  • Minnesota Oncology Burnsville Clinic

    Burnsville, Minnesota, 55337-6749

  • Baylor Research Institute

    Dallas, Texas, 75246-2079

  • Oncology Associates of Oregon Willamette Valley Cancer Center

    Eugene, Oregon, 97401

  • Us Oncology Virginia Cancer Specialists, Pc

    Fairfax, Virginia, 22031-4629

  • Summit Medical Group

    Florham Park, New Jersey, 07932-1049

  • Healthcare Research Network Iii, Llc

    Flossmoor, Illinois, 60422-2067

  • Scri Florida Cancer Specialists South

    Fort Myers, Florida, 33901-8108

  • St Lukes University Health Network

    Fountain Hill, Pennsylvania, 18015-1153

  • Abington Hematology Oncology Associates

    Horsham, Pennsylvania, 19044-2331

  • St Century Oncology

    Jacksonville, Florida, 32204-1128

  • Comprehensive Cancer Centers of Nevada

    Las Vegas, Nevada, 89169-3321

  • Ssm Health Cancer Care Dean Medical Center

    Madison, Wisconsin, 53717-1959

  • Texas Oncology McAllen South Second Street

    McAllen, Texas, 78503

  • Morristown Medical Center

    Morristown, New Jersey, 07960-6136

  • Tennessee Oncology, Pllc Nashville

    Nashville, Tennessee, 37203

  • Christiana Care

    Newark, Delaware, 19713-2055

  • Virginia Oncology Associates

    Norfolk, Virginia, 23502-2800

  • Fred Hutchinson Cancer Research Center

    Seattle, Washington, 98109-4433

  • Medical Oncology Associates

    Spokane, Washington, 99208-1129

  • Scri Florida Cancer Specialists North

    St. Petersburg, Florida, 33705-1449

  • Clinical Research Alliance, Inc

    Westbury, New York, 11590-5119

Other trials in United States

About this study

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

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.

Being tested
Zanubrutinib
Keywords
BGB-3111, Zanubrutinib, Ibrutinib Intolerance, BTK Inhibitor, Acalabrutinib Intolerance
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Mantle-Cell, Lymphoma, B-Cell, Marginal Zone, Waldenstrom Macroglobulinemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ZanubrutinibDrug

    Also called BGB-3111, BRUKINSA

    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.

Study groups in NCT04116437
Study groupRoleWhat they receive
ZanubrutinibExperimentalCohort 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
Receives: Drug: Zanubrutinib

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: 24 months

Secondary outcomes (5)

  1. Overall response as determined by investigator

    Measured: 24 months

  2. Progression free survival (PFS) as determined by investigator

    Measured: 24 months

  3. Patient reported outcomes as measured by EuroQol five dimension scale (EQ-5D)

    Measured: 24 months

  4. Patient reported outcomes as measured by European Organisation for Research and Treatment of Cancer (EORTC)

    Measured: 24 months

  5. Disease control rate as determined by investigator

    Measured: 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Oct 2019
  2. Study start15 Oct 2019
  3. Primary completion9 Jan 2026
  4. Study completion9 Jan 2026

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
96 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04116437
Sponsor's protocol ID
BGB-3111-215
Status last verified
Jan 2026
First submitted
1 Oct 2019
Last updated
28 Jan 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: BeiGene shares data on completed studies responsibly and provides qualified scientific and medical researchers access to data and supporting documentation for clinical trials in dossiers for medicines and indications after submission and approval in the United States, China, and Europe. Clinical trials supporting subsequent local approvals, new indications, or combination products are eligible for sharing once corresponding regulatory approvals are achieved. BeiGene shares data only when permitted by applicable data privacy and security laws and regulations, when it is feasible to do so without compromising the privacy of study participants, and other considerations. Qualified researchers with appropriate competencies who are engaged in novel scientific research may submit a request for participant-level data with a research proposal for BeiGene review. Research teams must include a biostatistician and sign a Data Sharing Agreement prior to receiving access to clinical trial data.
Expanded access
Available

Publications

  • 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.

    PubMed 40334067

  • 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.

    PubMed 36400069

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Zanubrutinib in people with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma and Mantle Cell Lymphoma, run by BeiGene at 24 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 24 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Recurrence and change in severity of treatment-emergent Adverse Events (AEs) of interest. (time frame: 24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04116437, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jan 2026.

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