Mature B-cell Malignancies
Conditions
Keywords
relapsed/refractory chronic lymphocytic leukemia, relapsed/refractory small lymphocytic lymphoma, treatment-naïve chronic lymphocytic leukemia, treatment-naïve /small lymphocytic lymphoma, relapsed/refractory mantle cell lymphoma, relapsed/refractory marginal zone lymphoma, relapsed/refractory follicular lymphoma, relapsed/refractory Waldenström macroglobulinemia, treatment-naïve Waldenström macroglobulinemia
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.
Interventions
DRUGZanubrutinib
Zanubrutinib at 160 mg orally twice daily
Sponsors
BeiGene
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion 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/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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 1: Bruton tyrosine kinase (BTK) occupancy in peripheral blood mononuclear cells | Predose up to 24 hours postdose |
| 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 |
| 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 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 |
Countries
Japan
Outcome results
None listed