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

Refractory Mantle Cell Lymphoma Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03206970
• Other study ID #: BGB-3111-206
• Secondary ID: CTR20160888
• Status: Completed
• Phase: Phase 2
• Start date: March 2, 2017
• Est. completion date: September 8, 2020

Study information

• Verified date: October 2021
• Source: BeiGene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 86
• Est. completion date: September 8, 2020
• Est. primary completion date: February 15, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Key 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.

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Mantle-Cell
• Refractory Mantle Cell Lymphoma
• Relapsed Mantle Cell Lymphoma

Intervention

Drug:
• Zanubrutinib
Administered as specified in the treatment arm.

Locations

Country	Name	City	State
China	Beijing Cancer Hospital	Beijing	Beijing
China	Peking Union Medical College Hospital	Beijing	Beijing
China	The First Affiliated Hospital of Jinlin University	Chang chun	Jilin
China	West China Hospital, Sichuan University	Chengdu	Sichuan
China	Fujian Medical University Union Hospital	Fuzhou	Fujian
China	Nanfang Hospital of Southern Medical University	Guangzhou	Guangdong
China	The First Affiliated Hospital, College of Medicine, Zhejiang University	Hangzhou	Zhejiang
China	Zhejiang Cancer Hospital	Hangzhou	Zhejiang
China	Jiangsu Province Hospital	Nanjing	Jiangsu
China	Fudan University Cancer Center	Shanghai	Shanghai
China	Blood Diseases Hospital, Chinese Academy of Medical Sciences	Tianjin	Tianjin
China	Tianjin Cancer Hospital	Tianjin	Tianjin
China	Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology	Wuhan	Hubei
China	Henan Cancer Province	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
BeiGene

Country where clinical trial is conducted

China, 

References & Publications (3)

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 — View 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 — View 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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Up to 1 year and 11 months
Secondary	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.	Up to 3 years and 6 months
Secondary	Time To Response	Time to response was defined as the time from treatment initiation to the first documentation of response.	Up to 3 years and 6 months
Secondary	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.	Up to 3 years and 6 months
Secondary	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.	Up to 3 years and 6 months
Secondary	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.	From the initiation of study drug until 30 days after the last dose (Up to 3 years and 6 months)
Secondary	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.	From the initiation of study drug until 30 days after the last dose (Up to 3 years and 6 months)