Clinical trial NCT03206970: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Refractory Mantle Cell Lymphoma
Relapsed Mantle Cell Lymphoma
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2017-07-02
Enrollment: 86
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Primary outcomes:
measure: Overall Response Rate (ORR) As Assessed By Independent Review Committee
timeFrame: Up to 1 year and 11 months
Secondary outcomes:
measure: Progression-free Survival
timeFrame: Up to 3 years and 6 months
measure: Time To Response
timeFrame: Up to 3 years and 6 months
measure: Duration Of Response
timeFrame: Up to 3 years and 6 months
measure: ORR As Assessed By The Investigator
timeFrame: Up to 3 years and 6 months
measure: Number Of Participants Experiencing Treatment -Emergent Adverse Events (AEs)
timeFrame: From the initiation of study drug until 30 days after the last dose (Up to 3 years and 6 months)
measure: Number Of Participants Experiencing AEs Leading To Treatment Discontinuation
timeFrame: From the initiation of study drug until 30 days after the last dose (Up to 3 years and 6 months)
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital
state: Fujian
city: Guangzhou
country: China
facility: Nanfang Hospital of Southern Medical University
state: Guangdong
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Wuhan
country: China
facility: Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology
state: Hubei
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
city: Tianjin
country: China
facility: Institute of Hematology and Hospital of Blood Disease
state: Tianjin
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital
state: Tianjin
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
Study officials:
affiliation: BeiGene
name: Study Director
role: PRINCIPAL_INVESTIGATOR
References:
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
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.
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.
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.