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

Marginal Zone Lymphoma Clinical Trial

— MAGNOLIA  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03846427
• Other study ID #: BGB-3111-214
• Secondary ID: 2018-001284-24CT
• Status: Completed
• Phase: Phase 2
• Start date: February 19, 2019
• Est. completion date: May 4, 2022

Study information

• Verified date: June 2023
• Source: BeiGene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 68
• Est. completion date: May 4, 2022
• Est. primary completion date: May 4, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, B-Cell, Marginal Zone
• Marginal Zone Lymphoma
• MZL

Intervention

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

Locations

Country	Name	City	State
Australia	Flinders Medical Centre	Bedford Park	South Australia
Australia	Box Hill Hospital (AUS)	Box Hill	Victoria
Australia	Monash Medical Centre	Clayton	Victoria
Australia	Concord Repatriation General Hospital	Concord	New South Wales
Australia	Peninsula Private Hospital	Frankston	Victoria
Australia	Canberra Hospital	Garran	Australian Capital Territory
Australia	St George Hospital	Kogarah	New South Wales
Australia	Princess Alexandra Hospital (AUS)	Woolloongabba	Queensland
China	Peking University Third Hospital	Beijing
China	The First Affiliated Hospital, College of Medicine, Zhejiang University	Hangzhou	Zhejiang
China	Institute of Hematology and Hospital of Blood Disease	Tianjin	Tianjin
China	Henan Cancer Hospital	Zhengzhou	Henan
Czechia	Fakultni nemocnice Kralovske Vinohrady	Praha 10
France	Centre de Lutte Contre Le Cancer - Institut Bergonie	Bordeaux
France	Hopital de la Conception - APHM	Marseille Cedex 05	Bouches-du-Rhône
France	Hôpital Saint-Louis	Paris
France	Centre Hospitalier Lyon Sud	Pierre-Bénite
Italy	Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi	Bologna
Italy	Azienda Socio Sanitaria Territoriale Niguarda (Grande Ospedale Metropolitano Niguarda)	Milano
Italy	A.O.U. Policlinico di Modena	Modena
Italy	Azienda Ospedaliero - Universitaria Maggiore delle Carità	Novara
Italy	Azienda Ospedaliera S. Maria Di Terni	Terni
Korea, Republic of	Severence Hospital	Seoul
New Zealand	Auckland City Hospital	Auckland
New Zealand	North Shore Hospital (NZ)	Auckland
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow	Strathclyde
United Kingdom	Royal Marsden Hospital- London	London	Greater Longon
United Kingdom	University College London Hospitals	London	Greater London
United Kingdom	The Christie	Manchester	Greater Manchester
United States	The Charlotte-Mecklenburg Hospital Authority	Charlotte	North Carolina
United States	Clinical Research Alliance, Inc.	Westbury	New York

Sponsors (1)

Lead Sponsor	Collaborator
BeiGene

Countries where clinical trial is conducted

United States,  Australia,  China,  Czechia,  France,  Italy,  Korea, Republic of,  New Zealand,  United Kingdom, 

References & Publications (4)

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.

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. — View 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.

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response Rate (ORR) by Independent Review Committee (IRC) Assessment	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	Up to approximately 3 years and 2.5 months
Secondary	ORR by Investigator Assessment	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.	Up to approximately 3 years and 2.5 months
Secondary	ORR by IRC Assessment Using Positron Emission Tomography-Computed Tomography (PET-CT)	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	Up to approximately 3 years and 2.5 months
Secondary	Progression-free Survival (PFS) by Investigator Assessment	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	Up to approximately 3 years and 2.5 months
Secondary	PFS Event-Free Rate by Investigator Assessment	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.	Up to 3 years and 2.5 months after first participant enrolled; Month 24 reported
Secondary	PFS by IRC Assessment	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	Up to approximately 3 years and 2.5 months
Secondary	PFS Event-Free Rate by IRC Assessment	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.	Up to 3 years and 2.5 months after first participant enrolled; Month 24 reported
Secondary	Overall Survival (OS)	OS is defined as the time from first study drug administration to the date of death due to any cause	Up to approximately 3 years and 2.5 months
Secondary	OS Event-Free Rate	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.	Up to 3 years and 2.5 months after first participant enrolled; Month 24 reported
Secondary	Duration of Response (DOR) by Investigator Assessment	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.	Up to approximately 3 years and 2.5 months
Secondary	DOR Event-Free Rate by Investigator Assessment	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.	Up to 3 years and 2.5 months after first participant enrolled; Month 24 reported
Secondary	DOR by IRC Assessment	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.	Up to approximately 3 years and 2.5 months
Secondary	DOR Event-Free Rate by IRC Assessment	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.	Up to 3 years and 2.5 months after first participant enrolled; Month 24 reported
Secondary	Time to Treatment Failure (TTF)	TTF is defined as the time from study treatment start to the date of discontinuation of study drug due to any reason.	Up to approximately 3 years and 2.5 months
Secondary	TTF Event-Free Rate	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.	Up to 3 years and 2.5 months after first participant enrolled; Month 24 reported
Secondary	Time to Next Line of Therapy	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	Up to approximately 3 years and 2.5 months
Secondary	Time to Next Line of Therapy Event-Free Rate	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.	Up to 3 years and 2.5 months after first participant enrolled; Month 24 reported
Secondary	Time to Response (TTR) by Investigator Assessment	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	Up to approximately 3 years and 2.5 months
Secondary	TTR by IRC Assessment	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.	Up to approximately 3 years and 2.5 months
Secondary	Change From Baseline in EuroQol 5-dimension 5-level (EQ-5D-5L) Visual Analogue Score (VAS)	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.	Baseline to Cycle 30 (28 days per cycle)
Secondary	Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Global Health Status	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.	Baseline to Cycle 30 (28 days per cycle)
Secondary	Number of Participants With Adverse Events	Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), including laboratory tests, physical exams, and vital signs	From first dose to 30 days after last dose of study drug (Up to approximately 3 years and 2.5 months)
Secondary	Area Under the Curve From Time 0 to 6 Hours (AUC0-6)		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)
Secondary	Apparent Oral Clearance (CL/F) of Zanubrutinib		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)
Secondary	Maximum Observed Concentration (Cmax)		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)
Secondary	Elimination Half Life (t1/2)		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)