Study of Zanubrutinib in Japanese Participants With B-Cell Malignancies
Study Details
Study Description
Brief Summary
This is a Phase 1/2 study of zanubrutinib in Japanese participants with mature B-cell malignancies.
This study intends to assess the use of zanubrutinib as an investigational agent to develop new treatment options for Japanese participants with B-cell malignancies. No formal hypothesis testing will be performed given the small sample size.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Zanubrutinib
|
Drug: Zanubrutinib
Zanubrutinib at 160 mg orally twice daily
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Part 1: Number of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) [Until approximately 6 months after the last dose of zanubrutinib for the last participant who discontinues zanubrutinib or zanubrutinib becomes commercially available for the participant's disease, whichever is earlier]
- Part 1: Number of Participants Experiencing Treatment-Emergent Serious Adverse Events (SAEs) [Until approximately 6 months after the last dose of zanubrutinib for the last participant who discontinues zanubrutinib or zanubrutinib becomes commercially available for the participant's disease, whichever is earlier]
- Part 1: Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation of Treatment [Until approximately 6 months after the last dose of zanubrutinib for the last participant who discontinues zanubrutinib or zanubrutinib becomes commercially available for the participant's disease, whichever is earlier]
- Part 1: Maximum Plasma Concentration (Cmax) of zanubrutinib [Up to 29 days]
- Part 1: Area under plasma concentration-time curve Concentration (AUC) of zanubrutinib [Up to 29 days]
- Part 2: Overall response rate as assessed by Independent Review Committee (IRC) [Until approximately 6 months after the last dose of zanubrutinib for the last participant who discontinues zanubrutinib or zanubrutinib becomes commercially available for the participant's disease, whichever occurs first]
Secondary Outcome Measures
- Part 1: Bruton tyrosine kinase (BTK) occupancy in peripheral blood mononuclear cells [Predose up to 24 hours postdose]
- Part 1: Overall response rate (ORR) as assessed by the investigator [Until approximately 6 months after the last dose of zanubrutinib for the last participant who discontinues zanubrutinib or zanubrutinib becomes commercially available for the participant's disease, whichever is earlier]
- Part 1: Progression-free survival (PFS) as assessed by the investigator [Until approximately 6 months after the last dose of zanubrutinib for the last participant who discontinues zanubrutinib or zanubrutinib becomes commercially available for the participant's disease, whichever is earlier]
- Part 1: Duration of response as assessed by the investigator [Until approximately 6 months after the last dose of zanubrutinib for the last participant who discontinues zanubrutinib or zanubrutinib becomes commercially available for the participant's disease, whichever is earlier]
- Part 1: Time to response as assessed by the investigator [Until approximately 6 months after the last dose of zanubrutinib for the last participant who discontinues zanubrutinib or zanubrutinib becomes commercially available for the participant's disease, whichever is earlier]
- Part 2: Number of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) [Until approximately 6 months after the last dose of zanubrutinib for the last participant who discontinues zanubrutinib or zanubrutinib becomes commercially available for the participant's disease, whichever is earlier]
- Part 2: Number of Participants Experiencing Treatment-Emergent Serious Adverse Events (SAEs) [Until approximately 6 months after the last dose of zanubrutinib for the last participant who discontinues zanubrutinib or zanubrutinib becomes commercially available for the participant's disease, whichever is earlier]
- Part 2: Maximum Plasma Concentration (Cmax) of zanubrutinib [Predose up to 24 hours postdose Cycle 1 day 1 (C1D1) and Cycle 2 day 1 (C2D1)]
- Part 2: Number of Participants Experiencing AEs Leading to Discontinuation of Treatment [Until approximately 6 months after the last dose of zanubrutinib for the last participant who discontinues zanubrutinib or zanubrutinib becomes commercially available for the participant's disease, whichever is earlier]
- Part 2: Rate of complete response for chronic lymphocytic leukemia (CLL) as assessed by IRC [Until approximately 6 months after the last dose of zanubrutinib for the last participant who discontinues zanubrutinib or zanubrutinib becomes commercially available for the participant's disease, whichever is earlier]
- Part 2: Rate of complete response with incomplete marrow for CLL as assessed by IRC [Until approximately 6 months after the last dose of zanubrutinib for the last participant who discontinues zanubrutinib or zanubrutinib becomes commercially available for the participant's disease, whichever is earlier]
- Part 2: Rate of complete response for small lymphocytic lymphoma (SLL), mantle cell lymphoma (MCL), and Waldenström macroglobulinemia (WM) as assessed by IRC [Until approximately 6 months after the last dose of zanubrutinib for the last participant who discontinues zanubrutinib or zanubrutinib becomes commercially available for the participant's disease, whichever is earlier]
- Part 2: Rate of very good partial response (VGPR) or better for WM as assessed by IRC [Until approximately 6 months after the last dose of zanubrutinib for the last participant who discontinues zanubrutinib or zanubrutinib becomes commercially available for the participant's disease, whichever is earlier]
- Part 2: Major response rate (partial response or better) for WM as assessed by IRC [Until approximately 6 months after the last dose of zanubrutinib for the last participant who discontinues zanubrutinib or zanubrutinib becomes commercially available for the participant's disease, whichever is earlier]
- Part 2: Rate of partial response or better for CLL as assessed by IRC [Until approximately 6 months after the last dose of zanubrutinib for the last participant who discontinues zanubrutinib or zanubrutinib becomes commercially available for the participant's disease, whichever is earlier]
- Part 2: Overall response rate (ORR) by disease type as assessed by the investigator [Until approximately 6 months after the last dose of zanubrutinib for the last participant who discontinues zanubrutinib or zanubrutinib becomes commercially available for the participant's disease, whichever is earlier]
- Part 2: Progression-free survival (PFS) as assessed by IRC [Until approximately 6 months after the last dose of zanubrutinib for the last participant who discontinues zanubrutinib or zanubrutinib becomes commercially available for the participant's disease, whichever is earlier]
- Part 2: Duration of response as assessed by IRC [Until approximately 6 months after the last dose of zanubrutinib for the last participant who discontinues zanubrutinib or zanubrutinib becomes commercially available for the participant's disease, whichever is earlier]
- Part 2: Time to response as assessed by IRC [Until approximately 6 months after the last dose of zanubrutinib for the last participant who discontinues zanubrutinib or zanubrutinib becomes commercially available for the participant's disease, whichever is earlier]
- To assess the efficacy of zanubrutinib as measured by overall survival [Overall survival defined as time from start of study treatment to death due to any cause]
Eligibility Criteria
Criteria
Key Inclusion Criteria:
-
Participants with Confirmed diagnosis of mature B-cell neoplasms including chronic lymphocytic leukemia/ small lymphocytic lymphoma, mantle cell lymphoma, follicular lymphoma, marginal zone lymphoma and Waldenström's macroglobulinemia
-
Relapsed/refractory disease defined as disease that relapsed after, or been refractory to, at least 1 prior therapy
-
Meeting at least one of criteria for requiring treatment
-
Measurable disease by computed tomography (CT)/ magnetic resonance imaging (MRI) for mantle cell lymphoma (MCL), marginal zone lymphoma (MZL) and follicular lymphoma (FL) participants and by serum immunoglobulin (Ig) M level > 0.5 g/dL for WM participants
-
Eastern Cooperative Oncology Group performance status of 0, 1, or 2
-
Life expectancy of > 4 months
Key Exclusion Criteria:
-
Known central nervous system involvement by lymphoma/leukemia
-
Known plasma cell neoplasm, prolymphocytic leukemia, history of or currently suspected Richter's syndrome
-
Prior allogeneic stem cell transplant
-
Systemic chemotherapy or radiation therapy within 2 weeks prior to first dose of zanubrutinib
-
Active fungal, bacterial, and/or viral infection requiring systemic therapy
-
Prior therapy with B-cell receptor inhibitor (eg, Bruton tyrosine kinase, phosphoinositide 3 kinase delta, and/or spleen tyrosine kinase inhibitor) or B-cell lymphoma 2 inhibitor (eg, venetoclax/ABT-199)
-
Pregnant, lactating, or nursing women
-
Autoimmune anemia and/or thrombocytopenia that is poorly responsive to corticosteroids or other standard therapy
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Nagoya University Hospital | Nagoya | Aichi | Japan | 003-0804 |
| 2 | Toyohashi Municipal Hospital | Toyohashi | Aichi | Japan | 441-8570 |
| 3 | Matsuyama Red Cross Hospital | Matsuyama | Ehime | Japan | 790-8524 |
| 4 | Kurume University Hospital | Kurume | Fukuoka | Japan | 830-0011 |
| 5 | National Hospital Organization Hokkaido Cancer Center | Sapporo | Hokkaido | Japan | 003-0904 |
| 6 | Aiiku Hospital | Sapporo | Hokkaido | Japan | 064-0804 |
| 7 | Kobe City Medical Center General Hospital | Kobe | Hyogo | Japan | 650-0047 |
| 8 | Yokohama Municipal Citizen's Hospital | Yokohama | Kanagawa | Japan | 240-8555 |
| 9 | Kanagawa Cancer Center Hospital | Yokohama | Kanagawa | Japan | 241-8515 |
| 10 | National Cancer Center Hospital | Chuo-ku | Tokyo | Japan | 104-0045 |
| 11 | Aomori Prefectural Central Hospital | Aomori | Japan | 030-8553 | |
| 12 | Chiba-Ken Cancer Center | Chiba | Japan | 260-8727 | |
| 13 | Gifu Municipal Hospital | Gifu | Japan | 500-8513 | |
| 14 | The Japanese Red Cross Nagasaki Genbaku Hospital | Nagasaki | Japan | 852-8511 | |
| 15 | National Hospital Organization Okayama Medical Center | Okayama | Japan | 701-1192 |
Sponsors and Collaborators
- BeiGene
Investigators
- Study Director: William Novotny, M.D, BeiGene
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- BGB-3111-111
- JapicCTI-195047