Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03846427
Recruitment Status : Active, not recruiting
First Posted : February 19, 2019
Results First Posted : March 3, 2022
Last Update Posted : March 3, 2022
Sponsor:
Information provided by (Responsible Party):
BeiGene

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).

Condition or disease Intervention/treatment Phase
Marginal Zone Lymphoma Drug: Zanubrutinib Phase 2

Detailed Description:
This is a Phase 2, open-label study of zanubrutinib in approximately 65 participants with R/R MZL. The study will evaluate efficacy, as measured by overall response rate, safety and tolerability.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 68 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2, Open-label Study of Zanubrutinib (BGB-3111) in Patients With Relapsed or Refractory Marginal Zone Lymphoma
Actual Study Start Date : February 19, 2019
Actual Primary Completion Date : January 18, 2021
Estimated Study Completion Date : April 30, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: Zanubrutinib Drug: Zanubrutinib
Zanubrutinib at a dose of 160 mg orally twice a day (BID)
Other Names:
  • BGB-3111
  • Brukinsa




Primary Outcome Measures :
  1. Overall Response Rate (ORR) by Independent Review Committee [ Time Frame: Up to 21.9 months (as of the primary data cutoff date of 18 January 2021) ]
    ORR is defined as the percentage of participants with complete or partial response as the best overall response, as determined by an independent review committee using the Lugano Classification


Secondary Outcome Measures :
  1. ORR by Investigator Assessment [ Time Frame: Up to approximately 3 years and 2 months ]
    ORR is defined as the percentage of participants with complete or partial response as the best overall response, as determined by investigator assessment using the Lugano Classification

  2. Progression-free Survival (PFS) [ Time Frame: Up to approximately 3 years and 2 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 and an independent review committee using Lugano Classification

  3. Overall Survival (OS) [ Time Frame: Up to approximately 3 years and 2 months ]
    OS is defined as the time from first study drug administration to the date of death due to any cause

  4. Duration of Response (DOR) [ Time Frame: Up to approximately 3 years and 2 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 and an independent review committee using Lugano Classification

  5. Time to Response (TTR) [ Time Frame: Up to approximately 3 years and 2 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 and an independent review committee using Lugano Classification

  6. Time to Treatment Failure (TTF) [ Time Frame: Up to approximately 3 years and 2 months ]
    TTF is defined as the time from study treatment start to the date of discontinuation of study drug due to any reason

  7. Time to Next Line of Therapy [ Time Frame: Up to approximately 3 years and 2 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

  8. Quality of Life Assessment: EQ-5D-5L Visual Analogue Score [ Time Frame: Up to approximately 3 years and 2 months ]
    Mean change from baseline in EuroQol (EQ-5D-5L) visual analogue score (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.' A higher score indicates better health outcomes.

  9. Quality of Life Assessment: EORTC QLQ-C30 Global Health Status [ Time Frame: Up to approximately 3 years and 2 months ]
    Mean change from baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (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. A higher score indicates better health outcomes.

  10. Number of Participants With Adverse Events [ Time Frame: Up to approximately 3 years and 2 months ]
    Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), including laboratory tests, physical exams, and vital signs

  11. Area Under the Curve From Time 0 to 12 Hours (AUC0-12) 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) ]
  12. 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) ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03846427


Locations
Show Show 29 study locations
Sponsors and Collaborators
BeiGene
Investigators
Layout table for investigator information
Principal Investigator: Study Director BeiGene
  Study Documents (Full-Text)

Documents provided by BeiGene:
Study Protocol  [PDF] June 3, 2020
Statistical Analysis Plan  [PDF] June 10, 2020

Publications:
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
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.

Layout table for additonal information
Responsible Party: BeiGene
ClinicalTrials.gov Identifier: NCT03846427    
Other Study ID Numbers: BGB-3111-214
2018-001284-24 ( EudraCT Number )
CTR20180823 ( Registry Identifier: Center for drug evaluation, CFDA )
First Posted: February 19, 2019    Key Record Dates
Results First Posted: March 3, 2022
Last Update Posted: March 3, 2022
Last Verified: February 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by BeiGene:
BGB-3111
Zanubrutinib
Additional relevant MeSH terms:
Layout table for MeSH terms
Lymphoma
Lymphoma, B-Cell, Marginal Zone
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, B-Cell
Lymphoma, Non-Hodgkin
Zanubrutinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action