TriangleNCT03846427 · CITED IN SOURCE DOCUMENTS
Study of Zanubrutinib (BGB-3111) in Participants With Marginal Zone Lymphoma
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE2
- Status at capture
- COMPLETED
- Registry last update
- 2024-10-26
This is a single arm study to evaluate the efficacy, safety and tolerability of zanubrutinib (BGB-3111) in participants with relapsed/refractory marginal zone lymphoma (R/R MZL).
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Overall Response Rate (ORR) by Independent Review Committee (IRC) Assessment
ORR by Investigator Assessment
ORR by IRC Assessment Using Positron Emission Tomography-Computed Tomography (PET-CT)
Progression-free Survival (PFS) by Investigator Assessment
PFS Event-Free Rate by Investigator Assessment
PFS by IRC Assessment
PFS Event-Free Rate by IRC Assessment
Overall Survival (OS)
OS Event-Free Rate
Duration of Response (DOR) by Investigator Assessment
DOR Event-Free Rate by Investigator Assessment
DOR by IRC Assessment
DOR Event-Free Rate by IRC Assessment
Time to Treatment Failure (TTF)
TTF Event-Free Rate
Time to Next Line of Therapy
Time to Next Line of Therapy Event-Free Rate
Time to Response (TTR) by Investigator Assessment
TTR by IRC Assessment
Change From Baseline in EuroQol 5-dimension 5-level (EQ-5D-5L) Visual Analogue Score (VAS)
Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Global Health Status
Number of Participants With Adverse Events
Area Under the Curve From Time 0 to 6 Hours (AUC0-6)
Apparent Oral Clearance (CL/F) of Zanubrutinib
Maximum Observed Concentration (Cmax)
Elimination Half Life (t1/2)
Adverse events
Limitations, agreements, and source contact
Who could take part
- eligibility Criteria
- Key Inclusion Criteria: 1. Age 18 years or older 2. Histologically confirmed diagnosis of MZL including splenic, nodal, and extranodal subtypes 3. Previously received one or more lines of therapy including at least one CD20-directed regimen (either as monotherapy or as chemoimmunotherapy) with documented failure to achieve at least partial response or documented progressive disease (PD) after, the most recent systemic treatment 4. Current need for systemic therapy for MZL 5. Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) 6. Eastern Cooperative Oncology Group (ECOG) of 0-2 7. Life expectancy ≥ 6 months 8. Adequate bone marrow function 9. Adequate organ function 10. Male and female participants must use highly effective methods of contraception Key Exclusion Criteria: 1. Known transformation to aggressive lymphoma, eg, large cell lymphoma 2. Clinically significant cardiovascular disease 3. Prior malignancy within the past 2 years, except for curatively treated basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast, or localized Gleason score 6 prostate cancer 4. History of severe bleeding disorder such as hemophilia A, hemophilia B, von Willebrand disease, or history of spontaneous bleeding requiring blood transfusion or other medical intervention 5. History of stroke or intracranial hemorrhage 6. Severe or debilitating pulmonary disease 7. Active fungal, bacterial and/or viral infection requiring systemic therapy 8. Known central nervous system involvement by lymphoma 9. Known infection with HIV, or serologic status reflecting active viral hepatitis B (HBV) or viral hepatitis C (HCV) infection 10. Major surgery within 4 weeks of the first dose of study drug 11. Prior treatment with a Bruton's tyrosine kinase (BTK) inhibitor 12. Pregnant or lactating women 13. Requires ongoing treatment with a strong Cytochrome P4503A (CYP3A) inhibitor or inducer 14. Concurrent participation in another therapeutic clinical trial NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- Zanubrutinib 160 mg (two 80-mg capsules) orally twice daily with or without food until progressive disease, intolerable toxicity, or withdrawal of consent
- intervention Names
- Drug: Zanubrutinib
- label
- Zanubrutinib
- type
- EXPERIMENTAL
- interventions
- arm Group Labels
- Zanubrutinib
- description
- Zanubrutinib at a dose of 160 mg orally twice a day (BID)
- name
- Zanubrutinib
- other Names
- BGB-3111
- Brukinsa
- type
- DRUG
Study design
- allocation
- NA
- intervention Model
- SINGLE_GROUP
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 68
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- ORR is defined as the percentage of participants with complete or partial response as the best overall response, as determined by an IRC using the Lugano Classification
- measure
- Overall Response Rate (ORR) by Independent Review Committee (IRC) Assessment
- time Frame
- Up to approximately 3 years and 2.5 months
- secondary Outcomes
- description
- ORR is defined as the percentage of participants with complete or partial response as the best overall response, as determined by the investigator using the Lugano Classification.
- measure
- ORR by Investigator Assessment
- time Frame
- Up to approximately 3 years and 2.5 months
- description
- ORR is defined as the percentage of participants with complete and partial response as the best overall response, as determined by an IRC using PET-CT assessment data for participants with fluorodeoxyglucose (FDG)-avid disease
- measure
- ORR by IRC Assessment Using Positron Emission Tomography-Computed Tomography (PET-CT)
- time Frame
- Up to approximately 3 years and 2.5 months
- description
- PFS is defined as the time from first dose until first documentation of progression or death, whichever comes first, as assessed by the investigator using Lugano Classification
- measure
- Progression-free Survival (PFS) by Investigator Assessment
- time Frame
- Up to approximately 3 years and 2.5 months
- description
- PFS is defined as the time from first dose until first documentation of progression or death, whichever comes first, as assessed by the investigator using Lugano Classification. The Kaplan-Meier method was used to estimate the percentage of participants who were event-free for PFS at 24 months with 95% confidence intervals estimated using Greenwood's formula.
- measure
- PFS Event-Free Rate by Investigator Assessment
- time Frame
- Up to 3 years and 2.5 months after first participant enrolled; Month 24 reported
- description
- PFS is defined as the time from first dose until first documentation of progression or death, whichever comes first, as assessed by an IRC using Lugano Classification
- measure
- PFS by IRC Assessment
- time Frame
- Up to approximately 3 years and 2.5 months
- description
- PFS is defined as the time from first dose until first documentation of progression or death, whichever comes first, as assessed by the IRC using Lugano Classification. The Kaplan-Meier method was used to estimate the percentage of participants who were event-free for PFS at 24 months with 95% confidence intervals estimated using Greenwood's formula.
- measure
- PFS Event-Free Rate by IRC Assessment
- time Frame
- Up to 3 years and 2.5 months after first participant enrolled; Month 24 reported
- description
- OS is defined as the time from first study drug administration to the date of death due to any cause
- measure
- Overall Survival (OS)
- time Frame
- Up to approximately 3 years and 2.5 months
- description
- OS is defined as the time from first study drug administration to the date of death due to any cause. The Kaplan-Meier method was used to estimate the percentage of participants who were event-free for OS at 24 months with 95% confidence intervals estimated using Greenwood's formula.
- measure
- OS Event-Free Rate
- time Frame
- Up to 3 years and 2.5 months after first participant enrolled; Month 24 reported
- description
- DOR is defined as the time from the date that response criteria are first met to the date that progressive disease is objectively documented or death, whichever comes first, as assessed by the investigator using Lugano Classification.
- measure
- Duration of Response (DOR) by Investigator Assessment
- time Frame
- Up to approximately 3 years and 2.5 months
- description
- DOR is defined as the time from the date that response criteria are first met to the date that progressive disease is objectively documented or death, whichever comes first, as assessed by the investigator using Lugano Classification. The Kaplan-Meier method was used to estimate the percentage of participants who were event-free for progression or death at 24 months with 95% confidence intervals estimated using Greenwood's formula.
- measure
- DOR Event-Free Rate by Investigator Assessment
- time Frame
- Up to 3 years and 2.5 months after first participant enrolled; Month 24 reported
- description
- DOR is defined as the time from the date that response criteria are first met to the date that progressive disease is objectively documented or death, whichever comes first, as assessed by the IRC using Lugano Classification.
- measure
- DOR by IRC Assessment
- time Frame
- Up to approximately 3 years and 2.5 months
- description
- DOR is defined as the time from the date that response criteria are first met to the date that progressive disease is objectively documented or death, whichever comes first, as assessed by the IRC using Lugano Classification. The Kaplan-Meier method was used to estimate the percentage of participants who were event-free for progression or death at 24 months with 95% confidence intervals estimated using Greenwood's formula.
- measure
- DOR Event-Free Rate by IRC Assessment
- time Frame
- Up to 3 years and 2.5 months after first participant enrolled; Month 24 reported
Full study description
- brief Summary
- This is a single arm study to evaluate the efficacy, safety and tolerability of zanubrutinib (BGB-3111) in participants with relapsed/refractory marginal zone lymphoma (R/R MZL).
Source references
- references
- citation
- Stephen Opat, Robert Marcus, MA, FRCP, FRCPath, Craig A. Portell, MD, William Reed, MD, Chris Tankersley, Jane Huang, MD, Judith Trotman, MBChB, FRACP, FRCPA. Phase 2 Study of Zanubrutinib (BGB-3111) in Patients with Relapsed/Refractory Marginal Zone Lymphoma. Blood. 2019; 134(1):5256. https://doi.org/10.1182/blood-2019-122629
- type
- BACKGROUND
- citation
- Stephen Opat, et al. Efficacy and Safety of Zanubrutinib in Patients with Relapsed/Refractory Marginal Zone Lymphoma: Initial Results of the MAGNOLIA (BGB-3111-214) Trial. Presented at the 62nd American Society of Hematology (ASH) Annual Meeting, December 5-8, 2020. Abstract 339.
- type
- BACKGROUND
- citation
- Opat S, Tedeschi A, Linton K, McKay P, Hu B, Chan H, Jin J, Sobieraj-Teague M, Zinzani PL, Coleman M, Thieblemont C, Browett P, Ke X, Sun M, Marcus R, Portell CA, Ardeshna K, Bijou F, Walker P, Hawkes EA, Mapp S, Ho SJ, Talaulikar D, Zhou KS, Co M, Li X, Zhou W, Cappellini M, Tankersley C, Huang J, Trotman J. The MAGNOLIA Trial: Zanubrutinib, a Next-Generation Bruton Tyrosine Kinase Inhibitor, Demonstrates Safety and Efficacy in Relapsed/Refractory Marginal Zone Lymphoma. Clin Cancer Res. 2021 Dec 1;27(23):6323-6332. doi: 10.1158/1078-0432.CCR-21-1704. Epub 2021 Sep 15.
- pmid
- 34526366
- type
- BACKGROUND
- citation
- Opat S, Tedeschi A, Hu B, et al: Long-term efficacy and safety of zanubrutinib in patients with relapsed/refractory marginal zone lymphoma. 2022 ASH Annual Meeting and Exposition. Abstract 234. Presented December 10, 2022.
- type
- BACKGROUND
- citation
- Moslehi JJ, Furman RR, Tam CS, Salem JE, Flowers CR, Cohen A, Zhang M, Zhang J, Chen L, Ma H, Brown JR. Cardiovascular events reported in patients with B-cell malignancies treated with zanubrutinib. Blood Adv. 2024 May 28;8(10):2478-2490. doi: 10.1182/bloodadvances.2023011641.
- pmid
- 38502198
- type
- DERIVED
- citation
- Opat S, Tedeschi A, Hu B, Linton KM, McKay P, Leitch S, Coleman M, Zinzani PL, Jin J, Sun M, Sobieraj-Teague M, Browett P, Ke X, Thieblemont C, Ardeshna K, Bijou F, Walker P, Hawkes EA, Ho SJ, Zhou K, Liang Z, Xu J, Tankersley C, Delarue R, Co M, Trotman J. Safety and efficacy of zanubrutinib in relapsed/refractory marginal zone lymphoma: final analysis of the MAGNOLIA study. Blood Adv. 2023 Nov 28;7(22):6801-6811. doi: 10.1182/bloodadvances.2023010668.
- pmid
- 37682792
- type
- DERIVED
Source notices and limitations
Discovery and provenance
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- in 50% (13 out of 26 response evaluable patients; 95% CI: 29.9, 70.1). 14.3 Marginal Zone Lymphoma The efficacy of BRUKINSA was assessed in Study BGB-3111-214 [NCT03846427], an open-label, multicenter, single-arm trial that evaluated 66 patients with MZL who received at least one prior anti–CD20-based therapy. BRUKINSA was given
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Preserved source evidence · Not medical advice