An International, Phase 3, Open-Label, Randomized Study of BGB-3111 Compared With Bendamustine Plus Rituximab in Patients With Previously Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma (CLL/SLL)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 590
- 试验地点
- 158
- 主要终点
- Cohort 1: Progression-free Survival (PFS) as Determined by Independent Central Review (ICR)
研究概览
简要总结
To compare efficacy between zanubrutinib versus bendamustine and rituximab in patients with previously untreated CLL/SLL, as measured by progression free survival assess by Independent Central Review.
详细描述
This is a global phase 3, open label, randomized study of zanubrutinib versus bendamustine plus rituximab (B+R) in participants with previously untreated chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL), including participants without del(17p) [Cohort 1] and participants with del(17p) [Cohort 2 and Cohort 3]. Participants in Cohort 1 are randomized 1:1 to zanubrutinib (Arm A) or bendamustine plus rituximab (Arm B). Randomization will be stratified by age, Binet stage, immunoglobulin variable region heavy chain (IGHV) mutational status, and geographic region. Participants in Cohort 2 will receive treatment with zanubrutinib. Participants in Cohort 3 will receive treatment with zanubrutinib and venetoclax.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Unsuitable for chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab (FCR)
- •Confirmed diagnosis of CD20-positive CLL or SLL, requiring treatment
- •Measurable disease by imaging
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
- •Life expectancy ≥ 6 months
- •Adequate bone marrow function
- •Adequate renal and hepatic function
排除标准
- •Previous systemic treatment for CLL/SLL
- •Requires ongoing need for corticosteroid treatment
- •Known prolymphocytic leukemia or history of or suspected Richter's transformation.
- •Clinically significant cardiovascular disease
- •Prior malignancy within the past 3 years, except for curatively treated basal or squamous cell skin cancer, non-muscle-invasive bladder cancer, carcinoma in situ of the cervix of breast, or localized Gleason score 6 prostate cancer
- •History of severe bleeding disorder
- •History of stroke or intracranial hemorrhage within 6 months before the first dose of study drug
- •Severe or debilitating pulmonary disease
- •Inability to swallow capsules or disease affecting gastrointestinal function
- •Active infection requiring systemic treatment
- •Known central nervous system involvement by leukemia or lymphoma
- •Underlying medical condition that will render the administration of study drug hazardous or obscure interpretation of toxicity or AEs
- •Known infection with human immunodeficiency virus (HIV) or active hepatitis B or C infection
- •Major surgery ≤ 4 weeks prior to start of study treatment
- •Pregnant or nursing females
- •Vaccination with live vaccine within 35 days prior to the first dose of study drug.
- •Ongoing alcohol or drug addiction
- •Known hypersensitivity to zanubrutinib, bendamustine, rituximab, or venetoclax (as applicable) or any other ingredients of the study drugs
- •Requires ongoing treatment with strong cytochrome P450 (CYP3A) inhibitor or inducer
- •Concurrent participation in another therapeutic clinical study
- •NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Cohort 1: Bendamustine + Rituximab
Participants will receive bendamustine plus rituximab for up to six 28-day cycles (Arm B)
干预措施: Bendamustine (Drug)
Cohort 1: Bendamustine + Rituximab
Participants will receive bendamustine plus rituximab for up to six 28-day cycles (Arm B)
干预措施: Rituximab (Drug)
Cohort 1: Zanubrutinib
Participants will receive zanubrutinib until unacceptable toxicity or disease progression (Arm A)
干预措施: Zanubrutinib (Drug)
Cohort 1a (China only): Bendamustine + Rituximab
Participants will receive bendamustine plus rituximab for up to six 28-day cycles (Arm B, China only)
干预措施: Bendamustine (Drug)
Cohort 1a (China only): Bendamustine + Rituximab
Participants will receive bendamustine plus rituximab for up to six 28-day cycles (Arm B, China only)
干预措施: Rituximab (Drug)
Cohort 1a (China only): Zanubrutinib
Participants will receive zanubrutinib until unacceptable toxicity or disease progression (Arm A, China only)
干预措施: Zanubrutinib (Drug)
Cohort 2: Zanubrutinib
Participants will receive zanubrutinib until unacceptable toxicity or disease progression (Arm C)
干预措施: Zanubrutinib (Drug)
Cohort 3: Venetoclax + Zanubrutinib
Approximately 110 participants, 50 without del17p and 60 with del[17p] or TP53 mutation will receive zanubrutinib plus venetoclax; Participants will also receive zanubrutinib starting on Cycle 1 Day 1 then daily for a minimum of 27 cycles, or until unacceptable toxicity or disease progression, whichever occurs first. Participants will receive venetoclax starting Cycle 4 Day 1 according to a 5-week dose-up schedule then daily until unacceptable toxicity, disease progression, or for a maximum of 24 cycles. Each cycle is 28 days. (Arm D)
干预措施: Zanubrutinib (Drug)
Cohort 3: Venetoclax + Zanubrutinib
Approximately 110 participants, 50 without del17p and 60 with del[17p] or TP53 mutation will receive zanubrutinib plus venetoclax; Participants will also receive zanubrutinib starting on Cycle 1 Day 1 then daily for a minimum of 27 cycles, or until unacceptable toxicity or disease progression, whichever occurs first. Participants will receive venetoclax starting Cycle 4 Day 1 according to a 5-week dose-up schedule then daily until unacceptable toxicity, disease progression, or for a maximum of 24 cycles. Each cycle is 28 days. (Arm D)
干预措施: Venetoclax (Drug)
结局指标
主要结局
Cohort 1: Progression-free Survival (PFS) as Determined by Independent Central Review (ICR)
时间窗: Up to approximately 3 years and 7 months (as of cut-off date of 07MAY2021)
PFS is defined as the time from randomization until first documentation of progression or death from any cause, whichever occurs first, as assessed by the ICR per 2008 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) guidelines with modifications for treatment-related lymphocytosis in participants with CLL and the Revised Criteria for Response for Malignant Lymphoma in participants with small lymphocytic lymphoma (SLL).
次要结局
- Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs)(Up to 5 years)
- Pooled Cohort 1/1a: Progression-free Survival (PFS) Between Treatment Groups Determined by Investigator Assessment (IA)(Up to 5 years)
- Cohort 2: Overall Response Rate (ORR)(Up to 5 years)
- Cohort 2: Progression-free Survival (PFS)(Up to 5 years)
- Cohort 2: Duration of Response (DOR)(Up to 5 years)
- Cohort 3: Overall Response Rate (ORR)(Up to 5 years)
- Cohort 3: Area-Under-Curve From Time 0 to 12 Hours Postdose (AUC0-12) of Zanubrutinib(Predose up to 12 hours postdose)
- Cohort 1: Overall Response Rate (ORR) Between Treatment Groups as Determined by ICR(Up to 5 years)
- Pooled Cohort 1/1a: Overall Response Rate (ORR) Between Treatment Groups(Up to 5 years)
- Cohort 3: Progression-free Survival (PFS)(Up to 5 years)
- Cohort 3: Rate of Undetectable Minimal Residual Disease (MRD4)(Up to 5 years)
- Cohort 1: Patient-reported Outcomes as Assessed by the (European Quality Of Life 5D 5L) EQ-5D-5L Questionnaire(Up to 5 years)
- Cohort 1: Progression-free Survival (PFS) Between Treatment Groups Determined by Investigator Assessment (IA)(Up to 5 years)
- Cohort 1: Overall Survival (OS) Between Treatment Groups as Determined by the ICR(Up to 5 years)
- Pooled Cohort 1/1a: Duration of Response (DOR) Between Treatment Groups(Up to 5 years)
- Cohort 3: Duration of Response (DOR)(Up to 5 years)
- Cohort 1: Duration of Response (DOR) Between Treatment Groups as Determined by the ICR(Up to 5 years)
- Cohort 1: Patient-reported Outcomes as Assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Questionnaire.(Up to 5 years)
- Cohort 1 Zanubrutinib Only Arms: Area-Under-Curve From Time 0 to 12 Hours Postdose (AUC0-12)(Predose up to 12 hours postdose)
- Apparent Rate of Clearance of Zanubrutinib From Plasma (CL/F)CL/F(Predose up to 12 hours postdose)