Clinical trial · Interventional
Zanubrutinib (BGB-3111) in Participants With Previously Treated B-Cell Lymphoma Intolerant of Prior Bruton Tyrosine Kinase Inhibitor (BTKi) Treatment
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
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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
Conditions (4)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma | Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma | ONTOLOGY_EXACT | 0.90 |
| Mantle Cell Lymphoma | Mantle Cell Lymphoma | ONTOLOGY_EXACT | 0.98 |
| Marginal Zone Lymphoma | Marginal Zone Lymphoma | ONTOLOGY_EXACT | 0.98 |
| Waldenstrom Macroglobulinemia | Waldenstrom Macroglobulinemia | ONTOLOGY_EXACT | 0.98 |
Interventions
Interventions (1)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Zanubrutinib | Drug | Zanubrutinib | ALIAS |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- Zanubrutinib
- description
- 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
- interventionNames
- Drug: Zanubrutinib
Primary outcomes (1)
- measure
- Recurrence and change in severity of treatment-emergent Adverse Events (AEs) of interest.
- timeFrame
- 24 months
Secondary outcomes (5)
- measure
- Overall response as determined by investigator
- timeFrame
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
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.References
Publications (2)
- DERIVEDShadman 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
- DERIVEDShadman 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