Study of BTK Inhibitor Zanubrutinib in Participants With Relapsed/Refractory Non-GCB Type Diffuse Large B Cell Lymphoma

NCT ID: NCT03145064

Last Updated: 2024-10-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 41 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-06-30
• Study Completion Date: 2020-09-03

Brief Summary

Screening (up to 28 days); daily treatment until disease progression, unacceptable toxicity or death, withdrawal of consent, lost to follow-up, or study termination from sponsor; treatment (up to 2 years), safety follow-up (30 days); survival follow-up until data cutoff for final analysis.

Detailed Description

This is a single-arm, multicenter, open-label Phase 2 study to evaluate efficacy, safety, tolerability of BGB-3111 (zanubrutinib) in participants with relapsed/refractory non-germinal center B-cell (GCB) type diffuse large B-cell lymphoma (DLBCL).

The study will enroll approximately 40 participants treated with zanubrutinib (160 milligrams [mg]) twice daily (BID). All participants in the study were treated until disease progression, unacceptable toxicity, death, withdrawal of consent, or the study was terminated by the sponsor for final analysis. At the time of final analysis, participants who remained on treatment were considered for participation in the extension study when eligible. A treatment cycle consisted of 28 days.

Conditions

Diffuse Large B-cell Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Zanubrutinib

Participants received zanubrutinib BID.

Group Type: EXPERIMENTAL

Zanubrutinib

Intervention Type: DRUG

Administered at a dose of 160 mg BID orally.

Interventions

Zanubrutinib

Administered at a dose of 160 mg BID orally.

Intervention Type: DRUG

Other Intervention Names

BGB-3111; BRUKINSA

Eligibility Criteria

Inclusion Criteria

1. Histologically confirmed non-germinal center DLBCL, by immunohistochemistry using the Hans algorithm:

1. Cluster of differentiation 10 (CD10)- and B-cell lymphoma 6 protein (BCL6)-,

2. CD10-, BCL6+, but maximal unique match+

2. Men and women ≥ 18 years of age.

3. Eastern Cooperative Oncology Group performance status of 0-2.

4. Measurable disease was defined as at least 1 lymph node > 1.5 centimeters in longest diameter and measurable in 2 perpendicular dimensions.

5. All participants must have provided fresh tumor biopsy or recent tumor tissue samples (within 2 years of study entry [informed consent form signed]).

6. Received at least one prior therapy for DLBCL that included anthracycline-based chemotherapy.

7. Participant not eligible for or refused intensive chemotherapy and hematopoietic stem cell transplant.

8. Documented failure to achieve at least partial response with, or documented disease progression after response to, the most recent treatment regimen.

9. Neutrophils ≥ 1 x 10^9/liter (L) independent of growth factor support within 7 days of study entry.

10. Platelets ≥ 75 x 10^9/L, independent of growth factor support or transfusion within 7 days of study entry.

11. Creatinine clearance of ≥ 30 milliliters/minute (as estimated by the Cockcroft-Gault equation or estimated glomerular filtration rate).

12. Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x upper limit of normal (ULN).

13. Bilirubin ≤ 2 x ULN (unless documented Gilbert's syndrome), then up to 5 x ULN allowed.

14. Independent of erythropoietin support or transfusion within 7 days of first dose of study drug.

15. International normalized ratio ≤ 1.5 and activated partial thromboplastin time ≤ 1.5 x ULN.

16. Participants may be enrolled who relapsed after autologous stem cell transplant if they are at least 6 months after transplant, participants should have had no active infections (that is, fungal or viral).

17. Females of childbearing potential must have agreed to use highly effective forms of birth control throughout the course of the study and at least up to 90 days after last dose of study drug. Highly effective forms of birth control were defined as abstinence, hysterectomy, bilateral oophorectomy with no menstrual bleeding for up to 6 months, intrauterine contraception, hormonal methods such as contraceptive injection, oral contraceptive. Males must have undergone sterilization-vasectomy, or utilized a barrier method where the female partner utilized the effective forms of birth control noted above.

18. Life expectancy of > 3 months.

19. Able to provide written informed consent and could understand and comply with the requirements of the study.

6. History of other active malignancies within 2 years of study entry, with exception of (1) adequately treated in-situ carcinoma of cervix; (2) localized basal cell or squamous cell carcinoma of skin; (3) previous malignancy confined and treated locally (surgery or other modality) with curative intent.

7. Currently active clinically significant cardiovascular disease such as uncontrolled arrhythmia, congestive heart failure, any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification, or history of myocardial infarction within 6 months of screening. Left ventricular ejection fraction is lower than 50% measured by echocardiography.

8. QTcF (Fridericia's correction) > 450 milliseconds or other significant electrocardiogram abnormalities including second degree atrioventricular (AV) block Type II, or third-degree AV block.

9. Unable to swallow capsules or disease significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction.

10. Uncontrolled systemic infection or infection requiring parenteral anti-microbial therapy.

11. Known human immunodeficiency virus, or active hepatitis B or hepatitis C infection (detected positive by polymerase chain reaction).

12. Pregnant or lactating women.

13. Any life-threatening illness, medical condition or organ system dysfunction, which, in the investigator's opinion, could compromise the participant's safety, or put the study at risk.

14. On medications that were strong cytochrome P450 (CYP), family 3, subfamily A (CYP3A) inhibitors or CYP3A inducers.

Exclusion Criteria

1. Current or history of central nervous system lymphoma.

2. Prior exposure to a BTK inhibitor.

3. Prior corticosteroids (at dosages equivalent to prednisone > 20 mg/day) given with anti-neoplastic intent within 7 days, prior chemotherapy, targeted therapy, or radiation therapy within 3 weeks, or antibody-based therapies or Chinese anti-cancer herbal therapies within 4 weeks of the start of study drug.

4. Major surgery within 4 weeks of screening.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

BeiGene

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: PRINCIPAL_INVESTIGATOR

BeiGene

Locations

Beijing Cancer Hospital

Beijing, Beijing Municipality, China

Harbin Medical University Cancer Hospital

Harbin, Heilongjiang, China

Henan Cancer Hospital

Zhengzhou, Henan, China

The First Affiliated Hospital of Soochow University Branch Shizi

Suzhou, Jiangsu, China

The First Hospital of Jilin University

Changchun, Jilin, China

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, China

Rui Jin Hospital Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, China

West China Hospital, Sichuan University

Chengdu, Sichuan, China

Institute of Hematology and Hospital of Blood Disease

Tianjin, Tianjin Municipality, China

Tianjin Medical University Cancer Institute and Hospital

Tianjin, Tianjin Municipality, China

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, China

Countries

China

References

Yang H, Xiang B, Song Y, Zhang H, Zhao W, Zou D, Lv F, Bai O, Liu A, Li C, Tan Z, Wang W, Gui H, Novotny W, Huang J, Li Y. Zanubrutinib monotherapy for patients with relapsed or refractory non-germinal center diffuse large B-cell lymphoma: results from a phase II, single-arm, multicenter, study. American Society of Clinical Oncology. 2020

Reference Type: BACKGROUND

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

CTR20170091

Identifier Type: REGISTRY

Identifier Source: secondary_id

BGB-3111-207

Identifier Type: -

Identifier Source: org_study_id