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

Phase 2
Active, not recruiting
Conditions
Relapsed Diffuse Large B-cell Lymphoma
Refractory Diffuse Large B-cell Lymphoma
Interventions
Registration Number
NCT05068440
Lead Sponsor
BeiGene
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
66
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
ZanubrutinibZanubrutinibadministered orally
Primary Outcome Measures
NameTimeMethod
Overall response rate (ORR)approximately 2 years

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).

Secondary Outcome Measures
NameTimeMethod
Overall survival (OS)approximately 3.5 years

OS defined as the time from start of treatment to the date of death due to any cause

Overall response rate (ORR)approximately 3.5 years

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).

Complete response rate (CRR)approximately 3.5 years

Defined as the proportion of participants with a documented CR determined by the Independent Review Committee and by investigator assessment

Duration of response (DOR)approximately 3.5 years

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

Time to response (TTR)approximately 3.5 years

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

Progression-free survival (PFS)approximately 3.5 years

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

Number of participants with adverse eventsapproximately 3.5 years

Number of participants with adverse events and serious adverse events, including clinical laboratory measurements, physical examination, and vital signs

Trial Locations

Locations (25)

Anhui Provincial Cancer Hospital Aka West Branch of Anhui Province Hospital

🇨🇳

Hefei, Anhui, China

Beijing Friendship Hospital, Capital Medical University

🇨🇳

Beijing, Beijing, China

Fujian Cancer Hospital

🇨🇳

Fuzhou, Fujian, China

Sun Yat Sen University Cancer Center

🇨🇳

Guangzhou, Guangdong, China

Guangdong Provincial Peoples Hospital Huifu Branch

🇨🇳

Guangzhou, Guangdong, China

The First Affiliated Hospital of Guangzhou Medical University

🇨🇳

Guangzhou, Guangdong, China

The First Affiliated Hospital of Shantou University Medical College

🇨🇳

Shantou, Guangdong, China

Hainan Cancer Hospital

🇨🇳

Haikou, Hainan, China

Harbin Medical University Cancer Hospital

🇨🇳

Harbin, Heilongjiang, China

Henan Cancer Hospital

🇨🇳

Zhengzhou, Henan, China

Union Hospital of Tongji Medical College, Huazhong University of Science and Technology

🇨🇳

Wuhan, Hubei, China

Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology

🇨🇳

Wuhan, Hubei, China

The Second Xiangya Hospital of Central South University

🇨🇳

Changsha, Hunan, China

Hunan Cancer Hospital

🇨🇳

Changsha, Hunan, China

The First Affiliated Hospital of Nanchang University Branch Donghu

🇨🇳

Nanchang, Jiangxi, China

The First Hospital of Jilin University

🇨🇳

Changchun, Jilin, China

Liaoning Cancer Hospital and Institute

🇨🇳

Shenyang, Liaoning, China

Rui Jin Hospital Shanghai Jiao Tong University School of Medicine

🇨🇳

Shanghai, Shanghai, China

Shanxi Provincial Cancer Hospital

🇨🇳

Taiyuan, Shanxi, China

West China Hospital, Sichuan University

🇨🇳

Chengdu, Sichuan, China

Institute of Hematology and Hospital of Blood Disease

🇨🇳

Tianjin, Tianjin, China

Yunnan Cancer Hospital

🇨🇳

Kunming, Yunnan, China

The First Affiliated Hospital, Zhejiang University School of Medicine

🇨🇳

Hangzhou, Zhejiang, China

Zhejiang University College of Medicine Second Affiliated Hospital

🇨🇳

Hangzhou, Zhejiang, China

Taizhou Hospital of Zhejiang

🇨🇳

Taizhou, Zhejiang, China

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