Study of Zanubrutinib (BGB-3111) in Participants With Marginal Zone Lymphoma
- Registration Number
- NCT03846427
- Lead Sponsor
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 68
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Zanubrutinib Zanubrutinib Zanubrutinib 160 mg (two 80-mg capsules) orally twice daily with or without food until progressive disease, intolerable toxicity, or withdrawal of consent
- Primary Outcome Measures
Name Time Method Overall Response Rate (ORR) by Independent Review Committee (IRC) Assessment 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 Outcome Measures
Name Time Method ORR by Investigator Assessment 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.
Progression-free Survival (PFS) by Investigator Assessment 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
PFS Event-Free Rate by Investigator Assessment 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.
Overall Survival (OS) 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
DOR Event-Free Rate by Investigator Assessment 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.
Time to Treatment Failure (TTF) 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.
Time to Next Line of Therapy 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
Time to Next Line of Therapy Event-Free Rate 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.
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) PFS by IRC Assessment 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
Duration of Response (DOR) by Investigator Assessment 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.
Change From Baseline in EuroQol 5-dimension 5-level (EQ-5D-5L) Visual Analogue Score (VAS) 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.
Number of Participants With Adverse Events 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
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) DOR by IRC Assessment 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.
DOR Event-Free Rate by IRC Assessment 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.
ORR by IRC Assessment Using Positron Emission Tomography-Computed Tomography (PET-CT) 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
PFS Event-Free Rate by IRC Assessment 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.
OS Event-Free Rate 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.
TTF Event-Free Rate 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.
Time to Response (TTR) by Investigator Assessment 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
Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Global Health Status 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.
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) TTR by IRC Assessment 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.
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)
Trial Locations
- Locations (31)
Clinical Research Alliance, Inc
🇺🇸Westbury, New York, United States
The Charlotte Mecklenburg Hospital Authority
🇺🇸Charlotte, North Carolina, United States
The Saint George Hospital Kogarah
🇦🇺Kogarah, New South Wales, Australia
Princess Alexandra Hospital
🇦🇺Brisbane, Queensland, Australia
Box Hill Hospital
🇦🇺Box Hill, Victoria, Australia
Monash Health
🇦🇺Clayton, Victoria, Australia
The First Affiliated Hospital, Zhejiang University School of Medicine
🇨🇳Hangzhou, Zhejiang, China
University Hospital Vinohrady Hematology Department
🇨🇿Prague, Czechia
Centre de Lutte Contre Le Cancer Institut Bergonie
🇫🇷Bordeaux, France
Hopital de La Conception Aphm
🇫🇷Marseille Cedex, France
Hopital Saint Louis
🇫🇷Paris, France
Chu Hopital Lyon Sud
🇫🇷PierreBenite, France
Policlinico Sorsola Malpighi, Aou Di Bologna
🇮🇹Bologna, Italy
Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
🇮🇹Milano, Italy
Universita Degli Studi Di Modena Azienda Ospedaliere Policlinco
🇮🇹Modena, Italy
Azienda Ospedaliera S Maria Di Terni
🇮🇹Terni, Italy
Ao Citta Della Salute E Della Scienza Di Torino Presidio O
🇮🇹Torino, Italy
Severance Hospital Yonsei University Health System
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
North Shore Hospital
🇳🇿Takapuna, New Zealand
The Christie Hospital
🇬🇧Greater Manchester, United Kingdom
University College Hospital
🇬🇧London, United Kingdom
Royal Marsden Hospital
🇬🇧London, United Kingdom
Canberra Hospital
🇦🇺Garran, Australian Capital Territory, Australia
Concord Repatriation General Hospital
🇦🇺Concord, New South Wales, Australia
Flinders Medical Centre
🇦🇺Bedford PK, South Australia, Australia
Peninsula Private Hospital
🇦🇺Frankston, Victoria, Australia
Peking University Third Hospital
🇨🇳Beijing, Beijing, China
Henan Cancer Hospital
🇨🇳Zhengzhou, Henan, China
Institute of Hematology and Hospital of Blood Disease
🇨🇳Tianjin, Tianjin, China
Auckland City Hospital
🇳🇿Auckland, New Zealand
Beatson West of Scotland Cancer Centre
🇬🇧Glasgow, United Kingdom