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Completed

NCT Number: NCT03846427

Study of Zanubrutinib (BGB-3111) in Participants With Marginal Zone Lymphoma

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).

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Canberra Hospital, Garran, Australian Capital Territory, Australia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Key Inclusion Criteria:

  • Age 18 years or older
  • Histologically confirmed diagnosis of MZL including splenic, nodal, and extranodal subtypes
  • 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
  • Current need for systemic therapy for MZL
  • Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI)
  • Eastern Cooperative Oncology Group (ECOG) of 0-2
  • Life expectancy ≥ 6 months
  • Adequate bone marrow function
  • Adequate organ function
  • Male and female participants must use highly effective methods of contraception

Key Exclusion Criteria:

  • Known transformation to aggressive lymphoma, eg, large cell lymphoma
  • Clinically significant cardiovascular disease
  • 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
  • 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
  • History of stroke or intracranial hemorrhage
  • Severe or debilitating pulmonary disease
  • Active fungal, bacterial and/or viral infection requiring systemic therapy
  • Known central nervous system involvement by lymphoma
  • Known infection with HIV, or serologic status reflecting active viral hepatitis B (HBV) or viral hepatitis C (HCV) infection
  • Major surgery within 4 weeks of the first dose of study drug
  • Prior treatment with a Bruton's tyrosine kinase (BTK) inhibitor
  • Pregnant or lactating women
  • Requires ongoing treatment with a strong Cytochrome P4503A (CYP3A) inhibitor or inducer
  • Concurrent participation in another therapeutic clinical trial

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Treatment and study plan

Zanubrutinib

Drug

Zanubrutinib at a dose of 160 mg orally twice a day (BID)

Other names: BGB-3111, Brukinsa

Primary outcomes

  1. Overall Response Rate (ORR) by Independent Review Committee (IRC) Assessment

    Time frame: Up to approximately 3 years and 2.5 months

    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

Secondary outcomes

  1. ORR by Investigator Assessment

    Time frame: Up to approximately 3 years and 2.5 months

    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.

  2. ORR by IRC Assessment Using Positron Emission Tomography-Computed Tomography (PET-CT)

    Time frame: Up to approximately 3 years and 2.5 months

    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

  3. Progression-free Survival (PFS) by Investigator Assessment

    Time frame: Up to approximately 3 years and 2.5 months

    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

  4. PFS Event-Free Rate by Investigator Assessment

    Time frame: Up to 3 years and 2.5 months after first participant enrolled; Month 24 reported

    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.

  5. PFS by IRC Assessment

    Time frame: Up to approximately 3 years and 2.5 months

    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

  6. PFS Event-Free Rate by IRC Assessment

    Time frame: Up to 3 years and 2.5 months after first participant enrolled; Month 24 reported

    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.

  7. Overall Survival (OS)

    Time frame: Up to approximately 3 years and 2.5 months

    OS is defined as the time from first study drug administration to the date of death due to any cause

  8. OS Event-Free Rate

    Time frame: Up to 3 years and 2.5 months after first participant enrolled; Month 24 reported

    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.

  9. Duration of Response (DOR) by Investigator Assessment

    Time frame: Up to approximately 3 years and 2.5 months

    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.

  10. DOR Event-Free Rate by Investigator Assessment

    Time frame: Up to 3 years and 2.5 months after first participant enrolled; Month 24 reported

    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.

  11. DOR by IRC Assessment

    Time frame: Up to approximately 3 years and 2.5 months

    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.

  12. DOR Event-Free Rate by IRC Assessment

    Time frame: Up to 3 years and 2.5 months after first participant enrolled; Month 24 reported

    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.

  13. Time to Treatment Failure (TTF)

    Time frame: Up to approximately 3 years and 2.5 months

    TTF is defined as the time from study treatment start to the date of discontinuation of study drug due to any reason.

  14. TTF Event-Free Rate

    Time frame: Up to 3 years and 2.5 months after first participant enrolled; Month 24 reported

    TTF is defined as the time from study treatment start to the date of discontinuation of study drug due to any reason. The Kaplan-Meier method was used to estimate the percentage of participants who were event-free for TTF at 24 months with 95% confidence intervals estimated using Greenwood's formula.

  15. Time to Next Line of Therapy

    Time frame: Up to approximately 3 years and 2.5 months

    Time to next line of therapy is defined as the time from study treatment start to the start of the first subsequent therapy for MZL

  16. Time to Next Line of Therapy Event-Free Rate

    Time frame: Up to 3 years and 2.5 months after first participant enrolled; Month 24 reported

    Time to next line of therapy is defined as the time from study treatment start to the start of the first subsequent therapy for MZL. The Kaplan-Meier method was used to estimate the percentage of participants who were event-free for time to next line of therapy at 24 months with 95% confidence intervals estimated using Greenwood's formula.

  17. Time to Response (TTR) by Investigator Assessment

    Time frame: Up to approximately 3 years and 2.5 months

    TTR is defined as the time from study treatment start to date of the earliest qualifying response (partial response or better) as assessed by the investigator using Lugano Classification

  18. TTR by IRC Assessment

    Time frame: Up to approximately 3 years and 2.5 months

    TTR is defined as the time from study treatment start to date of the earliest qualifying response (partial response or better), as assessed by the IRC using Lugano Classification.

  19. Change From Baseline in EuroQol 5-dimension 5-level (EQ-5D-5L) Visual Analogue Score (VAS)

    Time frame: Baseline to Cycle 30 (28 days per cycle)

    Mean change from baseline in EQ-5D-5L VAS. The EQ-5D-5L measures health outcomes using a VAS to record a participant's self-rated health on a scale from 0 to 100, where 100 is 'the best health you can imagine' and 0 is 'the worst health you can imagine.' Positive change from baseline indicates improved health.

  20. Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Global Health Status

    Time frame: Baseline to Cycle 30 (28 days per cycle)

    Mean change from baseline in EORTC QLQ-C30 Global Health Status/Quality of Life score. The EORTC QLQ-C30 v3.0 is a questionnaire that assesses quality of life of cancer patients and includes global health status and quality of life questions related to their overall health in which participants respond based on a 7-point scale, where 1 is very poor and 7 is excellent. Answers are converted to a score of 0 to 100, with a positive score from baseline indicating improved health.

  21. Number of Participants With Adverse Events

    Time frame: From first dose to 30 days after last dose of study drug (Up to approximately 3 years and 2.5 months)

    Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), including laboratory tests, physical exams, and vital signs

  22. Area Under the Curve From Time 0 to 6 Hours (AUC0-6)

    Time frame: Predose (within 30 min prior to dose) and 0.5, 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 (28 days per cycle)

  23. Apparent Oral Clearance (CL/F) of Zanubrutinib

    Time frame: Predose (within 30 min prior to dose) and 0.5, 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 (28 days per cycle)

  24. Maximum Observed Concentration (Cmax)

    Time frame: Predose (within 30 min prior to dose) and 0.5, 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 (28 days per cycle)

  25. Elimination Half Life (t1/2)

    Time frame: Predose (within 30 min prior to dose) and 0.5, 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 (28 days per cycle)

Sponsors and collaborators

Lead sponsor

BeiGene

Industry

Registry information

Official study title

A Phase 2, Open-label Study of Zanubrutinib (BGB-3111) in Patients With Relapsed or Refractory Marginal Zone Lymphoma

Acronym: MAGNOLIA

Important dates

Study start
2019
Primary completion
2022
Study completion
2022
First posted
Feb 19, 2019
Registry last updated
Oct 26, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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