Clinical trial NCT04172246: Study of Zanubrutinib in Japanese Participants With B-Cell Malignancies
Official title: A Phase 1/2 Study of Zanubrutinib in Japanese Patients With Mature B-Cell Malignancies
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Mature B-cell Malignancies
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
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2019-11-21
Enrollment: 55
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Part 1: Number of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)
timeFrame: 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
measure: Part 1: Number of Participants Experiencing Treatment-Emergent Serious Adverse Events (SAEs)
timeFrame: 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
measure: Part 1: Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation of Treatment
timeFrame: 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
measure: Part 1: Maximum Plasma Concentration (Cmax) of zanubrutinib
timeFrame: Up to 29 days
measure: Part 1: Area under plasma concentration-time curve Concentration (AUC) of zanubrutinib
timeFrame: Up to 29 days
measure: Part 2: Overall response rate as assessed by Independent Review Committee (IRC)
timeFrame: 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 outcomes:
measure: Part 1: Bruton tyrosine kinase (BTK) occupancy in peripheral blood mononuclear cells
timeFrame: Predose up to 24 hours postdose
measure: Part 1: Overall response rate (ORR) as assessed by the investigator
timeFrame: 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
measure: Part 1: Progression-free survival (PFS) as assessed by the investigator
timeFrame: 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
measure: Part 1: Duration of response as assessed by the investigator
timeFrame: 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
measure: Part 1: Time to response as assessed by the investigator
timeFrame: 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
measure: Part 2: Number of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)
timeFrame: 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
measure: Part 2: Number of Participants Experiencing Treatment-Emergent Serious Adverse Events (SAEs)
timeFrame: 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
measure: Part 2: Maximum Plasma Concentration (Cmax) of zanubrutinib
timeFrame: Predose up to 24 hours postdose Cycle 1 day 1 (C1D1) and Cycle 2 day 1 (C2D1)
measure: Part 2: Number of Participants Experiencing AEs Leading to Discontinuation of Treatment
timeFrame: 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
measure: Part 2: Rate of complete response for chronic lymphocytic leukemia (CLL) as assessed by IRC
timeFrame: 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
measure: Part 2: Rate of complete response with incomplete marrow for CLL as assessed by IRC
timeFrame: 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
measure: Part 2: Rate of complete response for small lymphocytic lymphoma (SLL), mantle cell lymphoma (MCL), and Waldenström macroglobulinemia (WM) as assessed by IRC
timeFrame: 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
measure: Part 2: Rate of very good partial response (VGPR) or better for WM as assessed by IRC
timeFrame: 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
measure: Part 2: Major response rate (partial response or better) for WM as assessed by IRC
timeFrame: 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
measure: Part 2: Rate of partial response or better for CLL as assessed by IRC
timeFrame: 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
measure: Part 2: Overall response rate (ORR) by disease type as assessed by the investigator
timeFrame: 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
measure: Part 2: Progression-free survival (PFS) as assessed by IRC
timeFrame: 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
measure: Part 2: Duration of response as assessed by IRC
timeFrame: 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
measure: Part 2: Time to response as assessed by IRC
timeFrame: 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
measure: To assess the efficacy of zanubrutinib as measured by overall survival
timeFrame: Overall survival defined as time from start of study treatment to death due to any cause
Other outcomes:
Locations:
city: Nagoya
country: Japan
facility: Nagoya University Hospital
state: Aichi
city: Toyohashishi
country: Japan
facility: Toyohashi Municipal Hospital
state: Aichi
city: Chibashi
country: Japan
facility: Chiba Cancer Center
state: Chiba
city: Matsuyamashi
country: Japan
facility: Matsuyama Red Cross Hospital
state: Ehime
city: KurumeShi
country: Japan
facility: Kurume University Hospital
state: Fukuoka
city: SapporoShi
country: Japan
facility: National Hospital Organization Hokkaido Cancer Center
state: Hokkaido
city: SapporoShi
country: Japan
facility: Aiiku Hospital
state: Hokkaido
city: KobeShi
country: Japan
facility: Kobe City Medical Center General Hospital
state: Hyogo
city: Yokohamashi
country: Japan
facility: Kanagawa Cancer Center
state: Kanagawa
city: ChuoKu
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
city: Aomori
country: Japan
facility: Aomori Prefectural Central Hospital
city: Gifu
country: Japan
facility: Gifu Municipal Hospital
city: Nagasaki
country: Japan
facility: The Japanese Red Cross Nagasaki Genbaku Hospital
city: Okayama
country: Japan
facility: National Hospital Organization Okayama Medical Center
city: YokohamaShi
country: Japan
facility: Yokohama Municipal Citizens Hospital
Study officials:
affiliation: BeiGene
name: Study Director
role: STUDY_DIRECTOR
References: