A Phase 3, Open-Label, Randomized Study of BGB-16673 Compared to Investigator's Choice in Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma Previously Exposed to Covalent BTK Inhibitors
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 153
- 试验地点
- 109
- 主要终点
- Progression-Free Survival (PFS) by IRC
研究概览
简要总结
The purpose of this study is to investigate the efficacy and safety of BGB-16673 compared with investigator's choice (bendamustine plus rituximab or high-dose methylprednisolone plus rituximab or chlorambucil plus obinutuzumab) in participants with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) previously exposed to covalent Bruton tyrosine kinase inhibitor(s) (cBTKi).
详细描述
Chronic lymphocytic leukemia and small lymphocytic lymphoma are types of blood cancer that affects people around the world. People with CLL and SLL suffer from enlarged lymph nodes, spleen, or liver, or have symptoms like night sweats, weight loss and fever. They have shorter life expectancy compared to healthy people. There is an urgent need for new treatment to prolong life and control disease-related symptoms.
In this study, participants with R/R CLL or SLL who were previously exposed to a covalent BTKi will receive BGB-16673 or the investigator's choice of bendamustine plus rituximab or high-dose methylprednisolone plus rituximab or chlorambucil plus obinutuzumab. The main purpose of this study is to compare the length of time that participants live without their CLL or SLL worsening between those participants who receive BGB-16673 versus the investigator's choice of treatment. Approximately 150 participants will be included in this study in Mainland China and Taiwan. Participants will be randomly allocated to receive either BGB-16673 or the investigator's choice of treatment.
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
- •Confirmed diagnosis of CLL/SLL, requiring treatment, based on 2018 international workshop on chronic lymphocytic leukemia (iwCLL) criteria.
- •Previously received treatment for CLL/SLL with a covalent BTKi.
- •Measurable disease by computer tomography/magnetic resonance imaging for patients with SLL.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- •Adequate bone marrow function
- •Adequate kidney and liver function
- •Adequate blood clotting function
排除标准
- •Known prolymphocytic leukemia or history of, or currently suspected, Richter's transformation
- •2. Prior autologous stem cell transplant (unless ≥ 3 months after transplant) or chimeric antigen receptor-T cell (unless ≥ 6 months after cell infusion)
- •History of severe allergic reactions or hypersensitivity to the active ingredient and excipients of study treatment (BGB-16673, bendamustine, rituximab, chlorambucil, or obinutuzumab)
- •Current or history of central nervous system involvement
- •History of ischemic stroke or intracranial hemorrhage within 6 months before first dose of study drug
- •History of confirmed progressive multifocal leukoencephalopathy.
- •Active fungal, bacterial, and/or viral infection requiring parenteral systemic therapy
- •Clinically significant cardiovascular disease
- •NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Arm B: Investigator's Choice
Participants will receive investigator's choice of bendamustine plus rituximab or high-dose methylprednisolone plus rituximab or chlorambucil plus obinutuzumab for up to six 28-day cycles.
Participants with unequivocal disease progression confirmed by Independent Review Committee (IRC) may cross over to receive treatment with BGB-16673 at the Investigator's discretion
干预措施: Obinutuzumab (Drug)
Arm A: BGB-16673 Monotherapy
Participants will receive BGB-16673 once daily until any of the treatment discontinuation criteria are met
干预措施: BGB-16673 (Drug)
Arm B: Investigator's Choice
Participants will receive investigator's choice of bendamustine plus rituximab or high-dose methylprednisolone plus rituximab or chlorambucil plus obinutuzumab for up to six 28-day cycles.
Participants with unequivocal disease progression confirmed by Independent Review Committee (IRC) may cross over to receive treatment with BGB-16673 at the Investigator's discretion
干预措施: Bendamustine (Drug)
Arm B: Investigator's Choice
Participants will receive investigator's choice of bendamustine plus rituximab or high-dose methylprednisolone plus rituximab or chlorambucil plus obinutuzumab for up to six 28-day cycles.
Participants with unequivocal disease progression confirmed by Independent Review Committee (IRC) may cross over to receive treatment with BGB-16673 at the Investigator's discretion
干预措施: Rituximab (Drug)
Arm B: Investigator's Choice
Participants will receive investigator's choice of bendamustine plus rituximab or high-dose methylprednisolone plus rituximab or chlorambucil plus obinutuzumab for up to six 28-day cycles.
Participants with unequivocal disease progression confirmed by Independent Review Committee (IRC) may cross over to receive treatment with BGB-16673 at the Investigator's discretion
干预措施: BGB-16673 (Drug)
Arm B: Investigator's Choice
Participants will receive investigator's choice of bendamustine plus rituximab or high-dose methylprednisolone plus rituximab or chlorambucil plus obinutuzumab for up to six 28-day cycles.
Participants with unequivocal disease progression confirmed by Independent Review Committee (IRC) may cross over to receive treatment with BGB-16673 at the Investigator's discretion
干预措施: Methylprednisolone (Drug)
Arm B: Investigator's Choice
Participants will receive investigator's choice of bendamustine plus rituximab or high-dose methylprednisolone plus rituximab or chlorambucil plus obinutuzumab for up to six 28-day cycles.
Participants with unequivocal disease progression confirmed by Independent Review Committee (IRC) may cross over to receive treatment with BGB-16673 at the Investigator's discretion
干预措施: Chlorambucil (Drug)
结局指标
主要结局
Progression-Free Survival (PFS) by IRC
时间窗: Approximately 23 Months
PFS is defined as time from the date of randomization to the date of first disease progression or death, whichever occurs first, as determined by IRC using modified 2018 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria for participants with R/R CLL and the Lugano Classification for patients with R/R SLL.
次要结局
- PFS as Assessed by the Investigator(Approximately 12 Months)
- Overall Survival (OS)(Approximately 21 Months)
- Overall Response Rate (ORR) by IRC and Investigator Assessment(Approximately 23 Months)
- Rate of Partial Response with Lymphocytosis (PR-L) or Higher Determined by Investigator Assessment(Approximately 23 Months)
- Time to Next Anti-CLL/SLL Treatment (TTNT)(Approximately 14 Months)
- Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)(Approximately 14 Months)
- Change from baseline in European Organization of Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Chronic Lymphocytic Leukemia Module 17 Items (QLQ-CLL17) Symptom Burden and Physical Condition Scales(Baseline and up to approximately 23 Months)
- Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Cancer Questionnaire -Core 30 (EORTC QLQ-C30) Global Health Status (GHS)/Quality of Life (QoL) and Physical Functioning Scales(Baseline and up to approximately 23 Months)
- Duration of Response (DOR) by IRC and Investigator Assessment(Approximately 9 Months)
- Time to Response (TTR) by IRC and Investigator Assessment(Approximately 6 Months)