Clinical trial NCT05068440: Treatment of CD79B Mutant Relapsed/Refractory Diffuse Large B-Cell Lymphoma With Bruton Tyrosine Kinase Inhibitor Zanubrutinib
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Relapsed Diffuse Large B-cell Lymphoma
Refractory Diffuse Large B-cell Lymphoma
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2021-10-05
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Overall response rate (ORR)
timeFrame: approximately 2 years
Secondary outcomes:
measure: Overall response rate (ORR)
timeFrame: approximately 3.5 years
measure: Complete response rate (CRR)
timeFrame: approximately 3.5 years
measure: Duration of response (DOR)
timeFrame: approximately 3.5 years
measure: Progression-free survival (PFS)
timeFrame: approximately 3.5 years
measure: Time to response (TTR)
timeFrame: approximately 3.5 years
measure: Overall survival (OS)
timeFrame: approximately 3.5 years
measure: Number of participants with adverse events
timeFrame: approximately 3.5 years
Other outcomes:
Locations:
city: Hefei
country: China
facility: Anhui Provincial Cancer Hospital Aka West Branch of Anhui Province Hospital
state: Anhui
city: Beijing
country: China
facility: Beijing Friendship Hospital, Capital Medical University
state: Beijing
city: Fuzhou
country: China
facility: Fujian Cancer Hospital
state: Fujian
city: Guangzhou
country: China
facility: Sun Yat Sen University Cancer Center
state: Guangdong
city: Guangzhou
country: China
facility: Guangdong Provincial Peoples Hospital Huifu Branch
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangzhou Medical University
state: Guangdong
city: Shantou
country: China
facility: The First Affiliated Hospital of Shantou University Medical College
state: Guangdong
city: Haikou
country: China
facility: Hainan Cancer Hospital
state: Hainan
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Wuhan
country: China
facility: Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
city: Wuhan
country: China
facility: Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology
state: Hubei
city: Changsha
country: China
facility: The Second Xiangya Hospital of Central South University
state: Hunan
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University Branch Donghu
state: Jiangxi
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Shenyang
country: China
facility: Liaoning Cancer Hospital and Institute
state: Liaoning
city: Shanghai
country: China
facility: Rui Jin Hospital Shanghai Jiao Tong University School of Medicine
state: Shanghai
city: Taiyuan
country: China
facility: Shanxi Provincial Cancer Hospital
state: Shanxi
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
city: Tianjin
country: China
facility: Institute of Hematology and Hospital of Blood Disease
state: Tianjin
city: Kunming
country: China
facility: Yunnan Cancer Hospital
state: Yunnan
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang University College of Medicine Second Affiliated Hospital
state: Zhejiang
city: Taizhou
country: China
facility: Taizhou Hospital of Zhejiang
state: Zhejiang
Study officials:
affiliation: BeiGene
name: Study Director
role: STUDY_DIRECTOR
References: