Treatment of CD79B Mutant Relapsed/Refractory Diffuse Large B-Cell Lymphoma With Bruton Tyrosine Kinase Inhibitor Zanubrutinib

Refractory Diffuse Large B-cell Lymphoma Clinical Trial

Official title:

A Phase 2, Single-Arm, Open-Label, Multicenter Study of the Bruton Tyrosine Kinase Inhibitor Zanubrutinib in Patients With CD79B Mutant Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05068440
• Other study ID #: BGB-3111-218
• Secondary ID: CTR20210786
• Status: Recruiting
• Phase: Phase 2
• Start date: August 11, 2021
• Est. completion date: December 30, 2024

Study information

• Verified date: July 2023
• Source: BeiGene
• Contact: BeiGene
• Phone: 1.877.828.5568
• Email: clinicaltrials[@]beigene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Study consists of a single arm to explore the efficacy and safety of zanubrutinib in participants with CD79B mutant Relapsed/Refractory Diffuse Large B-Cell Lymphoma.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 66
• Est. completion date: December 30, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Histologically confirmed DLBCL based on the World Health Organization (WHO) 2008 classification of tumors of hematopoietic and lymphoid tissue.

2. Positive CD79B mutation confirmed by the central laboratory.

3. Previously received at least 1 line of adequate systemic anti-DLBCL therapy, defined as an anti-CD20 antibody-based chemoimmunotherapy for at least 2 consecutive cycles, unless participants had disease progression before Cycle 2

4. Relapsed or refractory (R/R) disease before study entry, defined as either

1. Recurrent disease after having achieved disease remission (CR or partial response [PR]) at the completion of the latest treatment regimen.

2. Stable disease or PD at the completion of the latest treatment regimen

5. Ineligible for high dose therapy/stem cell transplantation, which is defined as

meeting any of the following criteria:

1. Significant organ dysfunction (eg, left ventricular ejection fraction < 50% by echocardiogram or multiple gated acquisition scan [MUGA], diffuse lung capacity for carbon monoxide < 60% predicted by pulmonary function test, creatinine clearance < 70 mL/min shown by nuclear medicine scan or 24-hour urine collection) or comorbidities precluding the use of high dose therapy/stem cell transplantation on the basis of unacceptable risk of treatment-related morbidity

2. Failure to achieve CR or PR with salvage therapy.

3. Failure to collect stem cells or unable to perform stem cell collection as assessed by the investigator.

Exclusion Criteria:

1. Participants who have NHL other than classical histology DLBCL (DLBCL, not otherwise specified), eg, participants with DLBCL transformed from indolent lymphomas, primary mediastinal (thymic) large B-cell lymphoma, primary cutaneous DLBCL, primary effusion lymphoma, and central nervous system (CNS) lymphoma.

2. History of allogeneic stem cell transplantation or chimeric antigen receptor (CAR) T-cell therapy.

3. Prior exposure to a Bruton's tyrosine kinase (BTK) inhibitor.

4. Receipt of the following treatment at the time indicated before the first dose of

study drug:

1. Corticosteroid given with antineoplastic intent within 2 weeks, but a short course (= 7 days) of systemic corticosteroid treatment at doses = 20 mg/day prednisone equivalent for control of lymphoma-related symptoms is allowed prior to enrollment provided that it is tapered off within 5 days after initiation of study treatment.

2. Chemotherapy or radiotherapy within 2 weeks.

3. Monoclonal antibody within 2 weeks.

4. Investigational therapy within 2 weeks.

5. Chinese patent medicine with antineoplastic intent within 2 weeks.

5. History of other active malignancies within 2 years before study entry, with the exception of (1) adequately treated in-situ carcinoma of the cervix; (2) localized basal cell or squamous cell carcinoma of the skin; (3) previous malignancy confined and treated locally (surgery or other modality) with curative intent. Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse
• Refractory Diffuse Large B-cell Lymphoma
• Relapsed Diffuse Large B-cell Lymphoma

Intervention

Drug:
• Zanubrutinib
administered orally as capsules

Locations

Country	Name	City	State
China	Beijing Friendship Hospital, Capital Medical University	Beijing	Beijing
China	The First Hospital of Jilin University	Changchun	Jilin
China	Hunan Cancer Hospital	Changsha	Hunan
China	The Second Xiangya Hospital of Central South University	Changsha	Hunan
China	West China Hospital, Sichuan University	Chengdu	Sichuan
China	Fujian Cancer Hospital	Fuzhou	Fujian
China	Guangdong Provincial Peoples Hospital Huifu Branch	Guangzhou	Guangdong
China	Sun Yat Sen University Cancer Center	Guangzhou	Guangdong
China	The First Affiliated Hospital of Guangzhou Medical University	Guangzhou	Guangdong
China	Hainan Cancer Hospital	Haikou	Hainan
China	The First Affiliated Hospital, Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	Zhejiang University College of Medicine Second Affiliated Hospital	Hangzhou	Zhejiang
China	Harbin Medical University Cancer Hospital	Harbin	Heilongjiang
China	Anhui Provincial Cancer Hospital Aka West Branch of Anhui Province Hospital	Hefei	Anhui
China	Yunnan Cancer Hospital	Kunming	Yunnan
China	The First Affiliated Hospital of Nanchang University Branch Donghu	Nanchang	Jiangxi
China	Rui Jin Hospital Shanghai Jiao Tong University School of Medicine	Shanghai	Shanghai
China	The First Affiliated Hospital of Shantou University Medical College	Shantou	Guangdong
China	Liaoning Cancer Hospital and Institute	Shenyang	Liaoning
China	Shanxi Provincial Cancer Hospital	Taiyuan	Shanxi
China	Taizhou Hospital of Zhejiang	Taizhou	Zhejiang
China	Institute of Hematology and Hospital of Blood Disease	Tianjin	Tianjin
China	Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology	Wuhan	Hubei
China	Union Hospital of Tongji Medical College, Huazhong University of Science and Technology	Wuhan	Hubei
China	Henan Cancer Hospital	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
BeiGene

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall response rate (ORR)	Defined as the proportion of participants who achieved complete response (CR) or partial response (PR) by investigator assessment according to the Lugano classification for Non-Hodgkin's Lymphoma (NHL).	approximately 2 years
Secondary	Overall response rate (ORR)	Defined as the proportion of participants who achieved complete response (CR) or partial response (PR) by Independent Review Committee assessment according to the Lugano classification for Non-Hodgkin's Lymphoma (NHL).	approximately 3.5 years
Secondary	Complete response rate (CRR)	Defined as the proportion of participants with a documented CR determined by the Independent Review Committee and by investigator assessment	approximately 3.5 years
Secondary	Duration of response (DOR)	DOR is defined as the time from the date of the first documented response (PR or better) after treatment initiation until the date of first documented disease progression or death, whichever occurs first. Determined by the Independent Review Committee and by investigator assessment	approximately 3.5 years
Secondary	Progression-free survival (PFS)	PFS is defined as time from start of treatment to the first documentation of disease progression or death, whichever occurs first as determined by the Independent Review Committee and by investigator assessment	approximately 3.5 years
Secondary	Time to response (TTR)	TTR is defined as the time from start of treatment to first documentation of response of Partial Response (PR) or better as determined by the Independent Review Committee and by investigator assessment	approximately 3.5 years
Secondary	Overall survival (OS)	OS defined as the time from start of treatment to the date of death due to any cause	approximately 3.5 years
Secondary	Number of participants with adverse events	Number of participants with adverse events and serious adverse events, including clinical laboratory measurements, physical examination, and vital signs	approximately 3.5 years