Back to resultsStudy to Evaluate Efficacy and Safety of BGB-3111 in Participants With Relapsed or Refractory Mantle Cell Lymphoma (MCL)
Primary Purpose
Refractory Mantle Cell Lymphoma, Relapsed Mantle Cell Lymphoma
Status
Completed
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Zanubrutinib
Sponsored by
About this trial
This is an interventional treatment trial for Refractory Mantle Cell Lymphoma
Eligibility Criteria
Key Inclusion Criteria:
- Diagnostic report had to include evidence for morphological and cyclin D1 or t (11; 14).
- Eastern Cooperative Oncology Group performance status of 0-2.
- Measurable disease by computed tomography/magnetic resonance imaging.
- Received prior regimens for MCL.
- Documented failure to achieve any response, (stable disease or progressive disease during treatment) or documented progressive disease after response to the most recent treatment regimen.
- Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x upper limit of normal (ULN).
- Total bilirubin ≤ 2 x ULN (unless documented Gilbert's syndrome).
- Life expectancy of > 4 months.
Key Exclusion Criteria:
- Current or history of central nervous system lymphoma.
- Prior exposure to a BTK inhibitor before enrollment.
- Prior corticosteroids with anti-neoplastic intent within 7 days.
- Major surgery within 4 weeks of screening.
- Toxicity must have recovered from prior chemotherapy.
- History of other active malignancies within 2 years of study entry.
- Currently clinically significant active cardiovascular disease.
- QT interval corrected with Fridericia's formula > 450 microseconds or other significant electrocardiogram abnormalities.
- Uncontrolled systemic infection or infection requiring parenteral anti-microbial therapy.
- Known human immunodeficiency virus infection, or active hepatitis B or hepatitis C infection (detected positive by polymerase chain reaction).
Note: Other protocol-defined Inclusion/Exclusion criteria may apply.
Sites / Locations
- Beijing Cancer Hospital
- Peking Union Medical College Hospital
- Fujian Medical University Union Hospital
- Nanfang Hospital of Southern Medical University
- Henan Cancer Province
- Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology
- Jiangsu Province Hospital
- The First Affiliated Hospital of Jinlin University
- Fudan University Cancer Center
- West China Hospital, Sichuan University
- Blood Diseases Hospital, Chinese Academy of Medical Sciences
- Tianjin Cancer Hospital
- The First Affiliated Hospital, College of Medicine, Zhejiang University
- Zhejiang Cancer Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Zanubrutinib
Arm Description
Zanubrutinib (160 milligrams) administered orally twice daily
Outcomes
Primary Outcome Measures
Overall Response Rate (ORR) As Assessed By Independent Review Committee
The ORR was assessed in accordance with the 2014 modification of the International Working Group on non-Hodgkin Lymphoma Criteria. The ORR was defined as the percentage of participants achieving a best overall response (BOR) of complete response (CR) or partial response (PR). The BOR was defined as the best response recorded from the start of zanubrutinib until data cut or start of new antineoplastic treatment. Participants with no post-baseline response assessment (due to any reason) were considered non-responders for BOR.
Secondary Outcome Measures
Progression-free Survival
Progression-free survival was defined as the time from the starting date of zanubrutinib to the date of first documentation of disease progression or death, whichever occurred first. Participants who did not have disease progression were censored at their last valid tumor assessment. A six-month progression-free survival rate was defined as no disease progression after treated with zanubrutinib for over six months (under control). The 95% confidence interval (CI) lower bound was 33.1 months while the upper bound could not be estimated.
Time To Response
Time to response was defined as the time from treatment initiation to the first documentation of response.
Duration Of Response
The duration of response was defined as the time from the date that the response criteria are first met to the date that Progressive Disease was objectively documented or death (whichever occurs first). Participants who did not have disease progression were censored at their last valid assessment.
ORR As Assessed By The Investigator
The ORR was assessed in accordance with the 2014 modification of the International Working Group on non-Hodgkin Lymphoma Criteria. The ORR was defined as the percentage of participants achieving a BOR of CR or PR. The BOR was defined as the best response recorded from the start of zanubrutinib until data cut or start of new antineoplastic treatment. Participants with no post-baseline response assessment (due to any reason) were considered non-responders for BOR. For this outcome measure, only investigator-assessed data are analyzed and reported because of the high rate of concordance between the Independent Review Committee and investigator assessments for the primary outcome measure of ORR.
Number Of Participants Experiencing Treatment -Emergent Adverse Events (AEs)
An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not. A summary of serious and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.
A treatment-emergent adverse event (TEAE) is defined as an AE that had an onset date or a worsening in severity from baseline (pretreatment) on or after the date of first dose of study drug up to 30 days following study drug discontinuation (Safety Follow-up visit) or initiation of new anticancer therapy, whichever comes first.
Number Of Participants Experiencing AEs Leading To Treatment Discontinuation
An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to the study drug or not. A summary of serious and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03206970
Brief Title
Study to Evaluate Efficacy and Safety of BGB-3111 in Participants With Relapsed or Refractory Mantle Cell Lymphoma (MCL)
Official Title
A Single-Arm, Open-Label, Multicenter Phase 2 Study to Evaluate Efficacy and Safety of BGB-3111, a Bruton's Tyrosine Kinase (BTK) Inhibitor, in Subjects With Relapsed or Refractory Mantle Cell Lymphoma (MCL)
Study Type
Interventional
2. Study Status
Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
March 2, 2017 (Actual)
Primary Completion Date
February 15, 2019 (Actual)
Study Completion Date
September 8, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
BeiGene
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The primary objective of this study was to evaluate the efficacy of zanubrutinib in participants with centrally confirmed relapsed or refractory MCL.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Refractory Mantle Cell Lymphoma, Relapsed Mantle Cell Lymphoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
86 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Zanubrutinib
Arm Type
Experimental
Arm Description
Zanubrutinib (160 milligrams) administered orally twice daily
Intervention Type
Drug
Intervention Name(s)
Zanubrutinib
Other Intervention Name(s)
BGB-3111
Intervention Description
Administered as specified in the treatment arm.
Primary Outcome Measure Information:
Title
Overall Response Rate (ORR) As Assessed By Independent Review Committee
Description
The ORR was assessed in accordance with the 2014 modification of the International Working Group on non-Hodgkin Lymphoma Criteria. The ORR was defined as the percentage of participants achieving a best overall response (BOR) of complete response (CR) or partial response (PR). The BOR was defined as the best response recorded from the start of zanubrutinib until data cut or start of new antineoplastic treatment. Participants with no post-baseline response assessment (due to any reason) were considered non-responders for BOR.
Time Frame
Up to 1 year and 11 months
Secondary Outcome Measure Information:
Title
Progression-free Survival
Description
Progression-free survival was defined as the time from the starting date of zanubrutinib to the date of first documentation of disease progression or death, whichever occurred first. Participants who did not have disease progression were censored at their last valid tumor assessment. A six-month progression-free survival rate was defined as no disease progression after treated with zanubrutinib for over six months (under control). The 95% confidence interval (CI) lower bound was 33.1 months while the upper bound could not be estimated.
Time Frame
Up to 3 years and 6 months
Title
Time To Response
Description
Time to response was defined as the time from treatment initiation to the first documentation of response.
Time Frame
Up to 3 years and 6 months
Title
Duration Of Response
Description
The duration of response was defined as the time from the date that the response criteria are first met to the date that Progressive Disease was objectively documented or death (whichever occurs first). Participants who did not have disease progression were censored at their last valid assessment.
Time Frame
Up to 3 years and 6 months
Title
ORR As Assessed By The Investigator
Description
The ORR was assessed in accordance with the 2014 modification of the International Working Group on non-Hodgkin Lymphoma Criteria. The ORR was defined as the percentage of participants achieving a BOR of CR or PR. The BOR was defined as the best response recorded from the start of zanubrutinib until data cut or start of new antineoplastic treatment. Participants with no post-baseline response assessment (due to any reason) were considered non-responders for BOR. For this outcome measure, only investigator-assessed data are analyzed and reported because of the high rate of concordance between the Independent Review Committee and investigator assessments for the primary outcome measure of ORR.
Time Frame
Up to 3 years and 6 months
Title
Number Of Participants Experiencing Treatment -Emergent Adverse Events (AEs)
Description
An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not. A summary of serious and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.
A treatment-emergent adverse event (TEAE) is defined as an AE that had an onset date or a worsening in severity from baseline (pretreatment) on or after the date of first dose of study drug up to 30 days following study drug discontinuation (Safety Follow-up visit) or initiation of new anticancer therapy, whichever comes first.
Time Frame
From the initiation of study drug until 30 days after the last dose (Up to 3 years and 6 months)
Title
Number Of Participants Experiencing AEs Leading To Treatment Discontinuation
Description
An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to the study drug or not. A summary of serious and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.
Time Frame
From the initiation of study drug until 30 days after the last dose (Up to 3 years and 6 months)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
Diagnostic report had to include evidence for morphological and cyclin D1 or t (11; 14).
Eastern Cooperative Oncology Group performance status of 0-2.
Measurable disease by computed tomography/magnetic resonance imaging.
Received prior regimens for MCL.
Documented failure to achieve any response, (stable disease or progressive disease during treatment) or documented progressive disease after response to the most recent treatment regimen.
Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x upper limit of normal (ULN).
Total bilirubin ≤ 2 x ULN (unless documented Gilbert's syndrome).
Life expectancy of > 4 months.
Key Exclusion Criteria:
Current or history of central nervous system lymphoma.
Prior exposure to a BTK inhibitor before enrollment.
Prior corticosteroids with anti-neoplastic intent within 7 days.
Major surgery within 4 weeks of screening.
Toxicity must have recovered from prior chemotherapy.
History of other active malignancies within 2 years of study entry.
Currently clinically significant active cardiovascular disease.
QT interval corrected with Fridericia's formula > 450 microseconds or other significant electrocardiogram abnormalities.
Uncontrolled systemic infection or infection requiring parenteral anti-microbial therapy.
Known human immunodeficiency virus infection, or active hepatitis B or hepatitis C infection (detected positive by polymerase chain reaction).
Note: Other protocol-defined Inclusion/Exclusion criteria may apply.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
BeiGene
Official's Role
Principal Investigator
Facility Information:
Facility Name
Beijing Cancer Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100142
Country
China
Facility Name
Peking Union Medical College Hospital
City
Beijing
State/Province
Beijing
Country
China
Facility Name
Fujian Medical University Union Hospital
City
Fuzhou
State/Province
Fujian
Country
China
Facility Name
Nanfang Hospital of Southern Medical University
City
Guangzhou
State/Province
Guangdong
Country
China
Facility Name
Henan Cancer Province
City
Zhengzhou
State/Province
Henan
Country
China
Facility Name
Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology
City
Wuhan
State/Province
Hubei
Country
China
Facility Name
Jiangsu Province Hospital
City
Nanjing
State/Province
Jiangsu
Country
China
Facility Name
The First Affiliated Hospital of Jinlin University
City
Chang chun
State/Province
Jilin
Country
China
Facility Name
Fudan University Cancer Center
City
Shanghai
State/Province
Shanghai
Country
China
Facility Name
West China Hospital, Sichuan University
City
Chengdu
State/Province
Sichuan
Country
China
Facility Name
Blood Diseases Hospital, Chinese Academy of Medical Sciences
City
Tianjin
State/Province
Tianjin
Country
China
Facility Name
Tianjin Cancer Hospital
City
Tianjin
State/Province
Tianjin
Country
China
Facility Name
The First Affiliated Hospital, College of Medicine, Zhejiang University
City
Hangzhou
State/Province
Zhejiang
Country
China
Facility Name
Zhejiang Cancer Hospital
City
Hangzhou
State/Province
Zhejiang
Country
China
12. IPD Sharing Statement
Plan to Share IPD
Yes
Citations:
Citation
Yuqin Song, Keshu Zhou, Dehui Zou, Jianfeng Zhou, Jianda Hu, Haiyan Yang, Huilai Zhang, Jie Ji, Wei Xu, Jie Jin, Fangfang Lv, Ru Feng, Sujun Gao, Daobin Zhou, Haiyi Guo, Aihua Wang, James Hilger, Jane Huang, William Novotny, Muhtar Osman, Jun Zhu; Safety and Activity of the Investigational Bruton Tyrosine Kinase Inhibitor Zanubrutinib (BGB-3111) in Patients with Mantle Cell Lymphoma from a Phase 2 Trial. Blood 2018; 132 (Supplement 1): 148. doi: https://doi.org/10.1182/blood-2018-99-117956
Results Reference
result
PubMed Identifier
32461234
Citation
Song Y, Zhou K, Zou D, Zhou J, Hu J, Yang H, Zhang H, Ji J, Xu W, Jin J, Lv F, Feng R, Gao S, Guo H, Zhou L, Elstrom R, Huang J, Novotny W, Wei R, Zhu J. Treatment of Patients with Relapsed or Refractory Mantle-Cell Lymphoma with Zanubrutinib, a Selective Inhibitor of Bruton's Tyrosine Kinase. Clin Cancer Res. 2020 Aug 15;26(16):4216-4224. doi: 10.1158/1078-0432.CCR-19-3703. Epub 2020 May 27.
Results Reference
result
PubMed Identifier
34152395
Citation
Tam CS, Opat S, Simpson D, Cull G, Munoz J, Phillips TJ, Kim WS, Rule S, Atwal SK, Wei R, Novotny W, Huang J, Wang M, Trotman J. Zanubrutinib for the treatment of relapsed or refractory mantle cell lymphoma. Blood Adv. 2021 Jun 22;5(12):2577-2585. doi: 10.1182/bloodadvances.2020004074.
Results Reference
result
PubMed Identifier
35303070
Citation
Song Y, Zhou K, Zou D, Zhou J, Hu J, Yang H, Zhang H, Ji J, Xu W, Jin J, Lv F, Feng R, Gao S, Guo H, Zhou L, Huang J, Novotny W, Kim P, Yu Y, Wu B, Zhu J. Zanubrutinib in relapsed/refractory mantle cell lymphoma: long-term efficacy and safety results from a phase 2 study. Blood. 2022 May 26;139(21):3148-3158. doi: 10.1182/blood.2021014162.
Results Reference
derived
Learn more about this trial
Study to Evaluate Efficacy and Safety of BGB-3111 in Participants With Relapsed or Refractory Mantle Cell Lymphoma (MCL)
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