NCT03053440已完成3 期
A Phase 3, Randomized, Open-Label, Multicenter Study Comparing the Efficacy and Safety of the Bruton's Tyrosine Kinase (BTK) Inhibitors BGB-3111 and Ibrutinib in Subjects With Waldenström's Macroglobulinemia (WM)
BeiGene58 个研究点 分布在 11 个国家目标入组 201 人开始时间: 2017年1月25日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 201
- 试验地点
- 58
- 主要终点
- Percentage of Participants Achieving Either a Complete Response (CR) or Very Good Partial Response (VGPR) Using an Adaptation of the Response Criteria Updated at the Sixth International Workshop on WM as Assessed by an Independent Review Committee (IRC)
研究概览
简要总结
This study evaluated the safety, efficacy and clinical benefit of BGB-3111 (zanubrutinib) vs ibrutinib in participants with MYD88 Mutation Waldenström's Macroglobulinemia.
详细描述
This open-label, randomized study compared the efficacy and safety of the Bruton's Tyrosine Kinase (BTK) inhibitors BGB-3111 and ibrutinib in participants with Waldenström's Macroglobulinemia who require therapy. Participants had baseline bone marrow samples assayed for sequencing of the MYD88 gene. 201 participants with the MYD88 mutation were enrolled and randomized to receive 160 mg BGB-3111 orally twice per day (PO BID) (treatment Arm A) or to receive 420mg ibrutinib orally once per day (PO QD) (treatment Arm B) until disease progression or unacceptable toxicity.
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
- •Clinical and definitive histologic diagnosis of WM
- •Measurable disease, requiring treatment
- •Participants with no prior therapy for WM, must be considered inappropriate candidates for treatment with a standard chemoimmunotherapy regimen
- •Age ≥ 18 years old
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- •Adequate bone marrow function
- •Adequate renal and hepatic function
- •Electrocardiogram/multigated acquisition scan (ECHO/MUGA) demonstrating left ventricular ejection fraction (LVEF)≥ the lower limit of institutional normal
- •Participants may be enrolled who relapse after autologous stem cell transplant if they are at least 3 months after transplant, and after allogeneic transplant if they are at least 6 months post-transplant.
- •Females of childbearing potential must agree to use highly effective forms of birth control throughout the course of the study and at least up to 90 days after last dose of study drug. Males must have undergone sterilization- vasectomy, or utilize a barrier method
- •Life expectancy of > 4 months
排除标准
- •Prior exposure to a BTK inhibitor
- •Evidence of disease transformation at the time of study entry
- •Corticosteroids given with antineoplastic intent within 7 days, or chemotherapy given with antineoplastic intent, targeted therapy, or radiation therapy within 3 weeks, or antibody-based therapy within 4 weeks of the start of study drug
- •Major surgery within 4 weeks of study treatment
- •Toxicity of ≥ Grade 2 from prior anticancer therapy
- •History of other active malignancies within 2 years of study entry, with exception of (1) adequately treated in-situ carcinoma of cervix; (2) localized basal cell or squamous cell carcinoma of skin; (3) previous malignancy confined and treated locally with curative intent
- •Currently active, clinically significant cardiovascular disease such as uncontrolled arrhythmia, congestive heart failure, any Class 3 or 4 cardiac disease within 6 months of screening
- •QTcF prolongation (defined as a QTcF > 480 msec)
- •Active, clinically significant Electrocardiogram (ECG) abnormalities
- •Unable to swallow capsules or disease significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction
- •Uncontrolled active systemic infection or recent infection requiring parenteral anti-microbial therapy
- •Known human immunodeficiency virus (HIV), or active hepatitis B or hepatitis C
- •Pregnant or lactating women
- •Any life-threatening illness, medical condition, organ system dysfunction, need for profound anticoagulation, or bleeding disorder, which, in the investigator's opinion, could compromise the subject's safety
- •Any medications which are strong or moderate cytochrome P450, family 3, subfamily A (CYP3A) inhibitors or strong CYP3A inducers
- •NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Arm A : Ibrutinib
Experimental
Participants with the MYD88 mutation received Ibrutinib
干预措施: Ibrutinib (Drug)
Arm B: Zanubrutinib
Active Comparator
Participants with the MYD88 mutation received zanubrutinib
干预措施: BGB-3111 (Drug)
结局指标
主要结局
Percentage of Participants Achieving Either a Complete Response (CR) or Very Good Partial Response (VGPR) Using an Adaptation of the Response Criteria Updated at the Sixth International Workshop on WM as Assessed by an Independent Review Committee (IRC)
时间窗: Up to approximately 2 years and 7 months
Percentage of participants with CR, defined as normal serum immunoglobulin M (IgM) levels, disappearance of monoclonal protein by immunofixation, and negative cryoglobulinemia if cryoglobulinemia was positive at baseline, or VGPR, defined as ≥90% reduction in serum IgM level from baseline or normal serum IgM values.
次要结局
- Percentage of Participants Achieving Major Response Rate (MRR) as Assessed by IRC(Up to approximately 2 years and 7 months)
- Duration of Response (DOR) as Assessed by IRC(Up to approximately 2 years and 7 months)
- DOR as Assessed by IRC: Event -Free Rate(12 and 18 months from the date of randomization (up to approximately 2 years and 7 months))
- Percentage of Participants Achieving Either CR or VGPR in as Assessed by the Investigator(Up to approximately 5 years and 5 months)
- DOR as Assessed by the Investigator(Up to approximately 5 years and 5 months)
- DOR as Assessed by the Investigator: Event-Free Rate(24,36 and 48 months from the date of randomization (up to approximately 5 years and 5 months))
- Progression Free Survival (PFS) as Assessed by the IRC(Up to approximately 2 years and 7 months)
- PFS as Assessed by IRC: Event-Free Rate(12 and 18 months from the date of randomization (up to approximately 2 years and 7 months))
- PFS as Assessed by the Investigator(Up to approximately 5 years and 5 months)
- PFS as Assessed by the Investigator: Event-Free Rate(24,36 and 48 months from the date of randomization (up to approximately 5 years and 5 months))
- Percentage of Participants With Resolution of All Treatment-precipitating Symptoms(Up to approximately 5 years and 5 months)
- Percentage of Participants With an Anti-Lymphoma Effect(Up to approximately 5 years and 5 months)
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)(Up to approximately 5 years and 5 months)
研究者
研究点 (58)
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