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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03846427




Registration number
NCT03846427
Ethics application status
Date submitted
11/10/2018
Date registered
19/02/2019
Date last updated
26/10/2024

Titles & IDs
Public title
Study of Zanubrutinib (BGB-3111) in Participants With Marginal Zone Lymphoma
Scientific title
A Phase 2, Open-label Study of Zanubrutinib (BGB-3111) in Patients With Relapsed or Refractory Marginal Zone Lymphoma
Secondary ID [1] 0 0
2018-001284-24
Secondary ID [2] 0 0
BGB-3111-214
Universal Trial Number (UTN)
Trial acronym
MAGNOLIA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Marginal Zone Lymphoma 0 0
MZL 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Zanubrutinib

Experimental: Zanubrutinib - Zanubrutinib 160 mg (two 80-mg capsules) orally twice daily with or without food until progressive disease, intolerable toxicity, or withdrawal of consent


Treatment: Drugs: Zanubrutinib
Zanubrutinib at a dose of 160 mg orally twice a day (BID)
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Response Rate (ORR) by Independent Review Committee (IRC) Assessment
Assessment method [1] 0 0
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
Timepoint [1] 0 0
Up to approximately 3 years and 2.5 months
Secondary outcome [1] 0 0
ORR by Investigator Assessment
Assessment method [1] 0 0
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.
Timepoint [1] 0 0
Up to approximately 3 years and 2.5 months
Secondary outcome [2] 0 0
ORR by IRC Assessment Using Positron Emission Tomography-Computed Tomography (PET-CT)
Assessment method [2] 0 0
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
Timepoint [2] 0 0
Up to approximately 3 years and 2.5 months
Secondary outcome [3] 0 0
Progression-free Survival (PFS) by Investigator Assessment
Assessment method [3] 0 0
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
Timepoint [3] 0 0
Up to approximately 3 years and 2.5 months
Secondary outcome [4] 0 0
PFS Event-Free Rate by Investigator Assessment
Assessment method [4] 0 0
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.
Timepoint [4] 0 0
Up to 3 years and 2.5 months after first participant enrolled; Month 24 reported
Secondary outcome [5] 0 0
PFS by IRC Assessment
Assessment method [5] 0 0
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
Timepoint [5] 0 0
Up to approximately 3 years and 2.5 months
Secondary outcome [6] 0 0
PFS Event-Free Rate by IRC Assessment
Assessment method [6] 0 0
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.
Timepoint [6] 0 0
Up to 3 years and 2.5 months after first participant enrolled; Month 24 reported
Secondary outcome [7] 0 0
Overall Survival (OS)
Assessment method [7] 0 0
OS is defined as the time from first study drug administration to the date of death due to any cause
Timepoint [7] 0 0
Up to approximately 3 years and 2.5 months
Secondary outcome [8] 0 0
OS Event-Free Rate
Assessment method [8] 0 0
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.
Timepoint [8] 0 0
Up to 3 years and 2.5 months after first participant enrolled; Month 24 reported
Secondary outcome [9] 0 0
Duration of Response (DOR) by Investigator Assessment
Assessment method [9] 0 0
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.
Timepoint [9] 0 0
Up to approximately 3 years and 2.5 months
Secondary outcome [10] 0 0
DOR Event-Free Rate by Investigator Assessment
Assessment method [10] 0 0
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.
Timepoint [10] 0 0
Up to 3 years and 2.5 months after first participant enrolled; Month 24 reported
Secondary outcome [11] 0 0
DOR by IRC Assessment
Assessment method [11] 0 0
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.
Timepoint [11] 0 0
Up to approximately 3 years and 2.5 months
Secondary outcome [12] 0 0
DOR Event-Free Rate by IRC Assessment
Assessment method [12] 0 0
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.
Timepoint [12] 0 0
Up to 3 years and 2.5 months after first participant enrolled; Month 24 reported
Secondary outcome [13] 0 0
Time to Treatment Failure (TTF)
Assessment method [13] 0 0
TTF is defined as the time from study treatment start to the date of discontinuation of study drug due to any reason.
Timepoint [13] 0 0
Up to approximately 3 years and 2.5 months
Secondary outcome [14] 0 0
TTF Event-Free Rate
Assessment method [14] 0 0
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.
Timepoint [14] 0 0
Up to 3 years and 2.5 months after first participant enrolled; Month 24 reported
Secondary outcome [15] 0 0
Time to Next Line of Therapy
Assessment method [15] 0 0
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
Timepoint [15] 0 0
Up to approximately 3 years and 2.5 months
Secondary outcome [16] 0 0
Time to Next Line of Therapy Event-Free Rate
Assessment method [16] 0 0
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.
Timepoint [16] 0 0
Up to 3 years and 2.5 months after first participant enrolled; Month 24 reported
Secondary outcome [17] 0 0
Time to Response (TTR) by Investigator Assessment
Assessment method [17] 0 0
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
Timepoint [17] 0 0
Up to approximately 3 years and 2.5 months
Secondary outcome [18] 0 0
TTR by IRC Assessment
Assessment method [18] 0 0
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.
Timepoint [18] 0 0
Up to approximately 3 years and 2.5 months
Secondary outcome [19] 0 0
Change From Baseline in EuroQol 5-dimension 5-level (EQ-5D-5L) Visual Analogue Score (VAS)
Assessment method [19] 0 0
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.
Timepoint [19] 0 0
Baseline to Cycle 30 (28 days per cycle)
Secondary outcome [20] 0 0
Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Global Health Status
Assessment method [20] 0 0
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.
Timepoint [20] 0 0
Baseline to Cycle 30 (28 days per cycle)
Secondary outcome [21] 0 0
Number of Participants With Adverse Events
Assessment method [21] 0 0
Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), including laboratory tests, physical exams, and vital signs
Timepoint [21] 0 0
From first dose to 30 days after last dose of study drug (Up to approximately 3 years and 2.5 months)
Secondary outcome [22] 0 0
Area Under the Curve From Time 0 to 6 Hours (AUC0-6)
Assessment method [22] 0 0
Timepoint [22] 0 0
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 outcome [23] 0 0
Apparent Oral Clearance (CL/F) of Zanubrutinib
Assessment method [23] 0 0
Timepoint [23] 0 0
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 outcome [24] 0 0
Maximum Observed Concentration (Cmax)
Assessment method [24] 0 0
Timepoint [24] 0 0
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 outcome [25] 0 0
Elimination Half Life (t1/2)
Assessment method [25] 0 0
Timepoint [25] 0 0
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)

Eligibility
Key inclusion criteria
Key

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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
19/02/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
4/05/2022
Sample size
Target
Accrual to date
Final
68
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
Canberra Hospital - Garran
Recruitment hospital [2] 0 0
Concord Repatriation General Hospital - Concord
Recruitment hospital [3] 0 0
The Saint George Hospital Kogarah - Kogarah
Recruitment hospital [4] 0 0
Princess Alexandra Hospital - Brisbane
Recruitment hospital [5] 0 0
Flinders Medical Centre - Bedford PK
Recruitment hospital [6] 0 0
Box Hill Hospital - Box Hill
Recruitment hospital [7] 0 0
Monash Health - Clayton
Recruitment hospital [8] 0 0
Peninsula Private Hospital - Frankston
Recruitment postcode(s) [1] 0 0
2605 - Garran
Recruitment postcode(s) [2] 0 0
2139 - Concord
Recruitment postcode(s) [3] 0 0
2217 - Kogarah
Recruitment postcode(s) [4] 0 0
4102 - Brisbane
Recruitment postcode(s) [5] 0 0
5042 - Bedford PK
Recruitment postcode(s) [6] 0 0
3128 - Box Hill
Recruitment postcode(s) [7] 0 0
3168 - Clayton
Recruitment postcode(s) [8] 0 0
3199 - Frankston
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
New York
Country [2] 0 0
United States of America
State/province [2] 0 0
North Carolina
Country [3] 0 0
China
State/province [3] 0 0
Beijing
Country [4] 0 0
China
State/province [4] 0 0
Henan
Country [5] 0 0
China
State/province [5] 0 0
Tianjin
Country [6] 0 0
China
State/province [6] 0 0
Zhejiang
Country [7] 0 0
Czechia
State/province [7] 0 0
Prague
Country [8] 0 0
France
State/province [8] 0 0
Bordeaux
Country [9] 0 0
France
State/province [9] 0 0
Marseille Cedex
Country [10] 0 0
France
State/province [10] 0 0
Paris
Country [11] 0 0
France
State/province [11] 0 0
PierreBenite
Country [12] 0 0
Italy
State/province [12] 0 0
Bologna
Country [13] 0 0
Italy
State/province [13] 0 0
Milano
Country [14] 0 0
Italy
State/province [14] 0 0
Modena
Country [15] 0 0
Italy
State/province [15] 0 0
Terni
Country [16] 0 0
Italy
State/province [16] 0 0
Torino
Country [17] 0 0
Korea, Republic of
State/province [17] 0 0
Seoul Teugbyeolsi
Country [18] 0 0
New Zealand
State/province [18] 0 0
Auckland
Country [19] 0 0
New Zealand
State/province [19] 0 0
Takapuna
Country [20] 0 0
United Kingdom
State/province [20] 0 0
Glasgow
Country [21] 0 0
United Kingdom
State/province [21] 0 0
Greater Manchester
Country [22] 0 0
United Kingdom
State/province [22] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
BeiGene
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Study Director
Address 0 0
BeiGene
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT03846427