Study of Zanubrutinib in Japanese Participants With B-Cell Malignancies

Mature B-cell Malignancies Clinical Trial

Official title:

A Phase 1/2 Study of Zanubrutinib in Japanese Patients With Mature B-Cell Malignancies

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04172246
• Other study ID #: BGB-3111-111
• Secondary ID: JapicCTI-195047
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: January 29, 2020
• Est. completion date: September 30, 2024

Study information

• Verified date: February 2024
• Source: BeiGene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 55
• Est. completion date: September 30, 2024
• Est. primary completion date: May 10, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Mature B-cell Malignancies
• Neoplasms

Intervention

Drug:
• Zanubrutinib
Zanubrutinib at 160 mg orally twice daily

Locations

Country	Name	City	State
Japan	Aomori Prefectural Central Hospital	Aomori
Japan	Chiba-Ken Cancer Center	Chiba
Japan	National Cancer Center Hospital	Chuo-ku	Tokyo
Japan	Gifu Municipal Hospital	Gifu
Japan	Kobe City Medical Center General Hospital	Kobe	Hyogo
Japan	Kurume University Hospital	Kurume	Fukuoka
Japan	Matsuyama Red Cross Hospital	Matsuyama	Ehime
Japan	The Japanese Red Cross Nagasaki Genbaku Hospital	Nagasaki
Japan	Nagoya University Hospital	Nagoya	Aichi
Japan	National Hospital Organization Okayama Medical Center	Okayama
Japan	Aiiku Hospital	Sapporo	Hokkaido
Japan	National Hospital Organization Hokkaido Cancer Center	Sapporo	Hokkaido
Japan	Toyohashi Municipal Hospital	Toyohashi	Aichi
Japan	Kanagawa Cancer Center Hospital	Yokohama	Kanagawa
Japan	Yokohama Municipal Citizen's Hospital	Yokohama	Kanagawa

Sponsors (1)

Lead Sponsor	Collaborator
BeiGene

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	Part 1: Maximum Plasma Concentration (Cmax) of zanubrutinib		Up to 29 days
Primary	Part 1: Area under plasma concentration-time curve Concentration (AUC) of zanubrutinib		Up to 29 days
Primary	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	Part 1: Bruton tyrosine kinase (BTK) occupancy in peripheral blood mononuclear cells		Predose up to 24 hours postdose
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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