Study to Evaluate Efficacy and Safety of BGB-3111 in Participants With Relapsed or Refractory Mantle Cell Lymphoma (MCL)

Phase 2

Completed

• Conditions: Refractory Mantle Cell Lymphoma; Relapsed Mantle Cell Lymphoma
• Interventions: Drug: Zanubrutinib

• Registration Number: NCT03206970
• Lead Sponsor: BeiGene

Brief Summary

The primary objective of this study was to evaluate the efficacy of zanubrutinib in participants with centrally confirmed relapsed or refractory MCL.

Detailed Description

Not available

Study Timeline

• Study Start: 2017-03-02
• Study First Submitted: 2017-06-29
• Study First Submitted QC: 2017-06-29
• Study First Posted: 2017-07-02
• Primary Completion: 2019-02-15
• Results First Submitted: 2020-03-31
• Results First Submitted QC: 2020-05-01
• Results First Posted: 2020-05-13
• Study Completion: 2020-09-08
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-23
• Last Update Posted: 2024-10-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 86

Inclusion Criteria

1. Diagnostic report had to include evidence for morphological and cyclin D1 or t (11; 14).
2. Eastern Cooperative Oncology Group performance status of 0-2.
3. Measurable disease by computed tomography/magnetic resonance imaging.
4. Received prior regimens for MCL.
5. 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.
6. Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x upper limit of normal (ULN).
7. Total bilirubin ≤ 2 x ULN (unless documented Gilbert's syndrome).
8. Life expectancy of > 4 months.

Key

Exclusion Criteria

1. Current or history of central nervous system lymphoma.
2. Prior exposure to a BTK inhibitor before enrollment.
3. Prior corticosteroids with anti-neoplastic intent within 7 days.
4. Major surgery within 4 weeks of screening.
5. Toxicity must have recovered from prior chemotherapy.
6. History of other active malignancies within 2 years of study entry.
7. Currently clinically significant active cardiovascular disease.
8. QT interval corrected with Fridericia's formula > 450 microseconds or other significant electrocardiogram abnormalities.
9. Uncontrolled systemic infection or infection requiring parenteral anti-microbial therapy.
10. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Zanubrutinib	Zanubrutinib	Zanubrutinib (160 milligrams) administered orally twice daily

Primary Outcome Measures

Name	Time	Method
Overall Response Rate (ORR) As Assessed By Independent Review Committee	Up to 1 year and 11 months	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

Name	Time	Method
ORR As Assessed By The Investigator	Up to 3 years and 6 months	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 AEs Leading To Treatment Discontinuation	From the initiation of study drug until 30 days after the last dose (Up to 3 years and 6 months)	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 To Response	Up to 3 years and 6 months	Time to response was defined as the time from treatment initiation to the first documentation of response.
Duration Of Response	Up to 3 years and 6 months	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.
Number Of Participants Experiencing Treatment -Emergent Adverse Events (AEs)	From the initiation of study drug until 30 days after the last dose (Up to 3 years and 6 months)	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.
Progression-free Survival	Up to 3 years and 6 months	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.

Trial Locations

Locations (13)

Henan Cancer Hospital; 🇨🇳 Zhengzhou, Henan, China

Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology; 🇨🇳 Wuhan, Hubei, China

The First Hospital of Jilin University; 🇨🇳 Changchun, Jilin, China

Fudan University Shanghai Cancer Center; 🇨🇳 Shanghai, Shanghai, China

Institute of Hematology and Hospital of Blood Disease; 🇨🇳 Tianjin, Tianjin, China

Tianjin Medical University Cancer Institute and Hospital; 🇨🇳 Tianjin, Tianjin, China

The First Affiliated Hospital, Zhejiang University School of Medicine; 🇨🇳 Hangzhou, Zhejiang, China

Beijing Cancer Hospital; 🇨🇳 Beijing, Beijing, China

Fujian Medical University Union Hospital; 🇨🇳 Fuzhou, Fujian, China

Nanfang Hospital of Southern Medical University; 🇨🇳 Guangzhou, Guangdong, China

Jiangsu Province Hospital; 🇨🇳 Nanjing, Jiangsu, China

West China Hospital, Sichuan University; 🇨🇳 Chengdu, Sichuan, China

Zhejiang Cancer Hospital; 🇨🇳 Hangzhou, Zhejiang, China