Phase II, Open-label, Prospective Single-arm, Multi-center Clinical Trial to Evaluate if Adding Venetoclax to Patients on Covalent BTKi For 1L CLL Can Achieve Deep Durable Remissions (by UMRD 10^-4) to Allow Off-treatment Period
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 118
- 试验地点
- 39
- 主要终点
- uMRD4 Rate at EOCT
研究概览
简要总结
The main purpose of the study is to evaluate if adding venetoclax to participants receiving cBTKi for the 1L CLL can achieve deep durable remissions of undetectable measurable residual disease [uMRD < or 10^-4 in peripheral blood (PB)] by end of combination treatment (EOCT) to allow off-treatment period.
The acronym BRAVE stands for Btki Responders to Achieve deep remission (or off-treatment periods) with VEnetoclax.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Diagnosed with CLL and currently receiving a stable dose of cBTKi (i.e., ibrutinib, acalabrutinib, or zanubrutinib) for at least 6 months for 1L treatment with a response of at least a PR per iwCLL criteria
- •Eastern Cooperative Oncology Group (ECOG) performance score of less than or equal to (</=) 2
- •Adequate renal and liver function
排除标准
- •Prior B-cell lymphoma (Bcl-2) inhibitor therapy
- •Anti-cluster of differentiation 20 (CD20) therapy within the month prior to screening
- •Progressive or stable disease on cBTKi
- •Transformation of CLL to aggressive non-Hodgkin lymphoma (NHL) (Richter's transformation or pro-lymphocytic leukemia)
- •History of cardiomyopathy
- •Hypersensitivity to venetoclax or to any of the excipients (e.g., trehalose)
- •Clinically significant cardiovascular disease
- •Active bleeding or history of bleeding diathesis
- •Pregnant women and nursing mothers
- •Uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia
研究组 & 干预措施
Venetoclax Added to cBTKi (Commercially Prescribed)
Participants will receive venetoclax, orally, once daily (QD) with a starting ramp-up dose of 20 milligrams (mg) on Day 1 of Cycle 1 (cycle length= 28 days). The dose will increase weekly; thereafter, treatment will continue with venetoclax at the target dose of 400 mg, QD from Week 5 up to Day 28 of Cycle 12. Participant will discontinue from venetoclax and/or cBTKi after 12 cycles. Participants with detectable measurable residual disease with the presence of less than 1 CLL cell in 10,000 leukocytes (< 10^-4) (MRD4) or uMRD4 with partial response (PR) may continue receiving cBTKi-monotherapy (i.e. ibrutinib or acalabrutinib, or zanubrutinib) as previously prescribed by the investigator according to the prescribing label.
干预措施: cBTKi Monotherapy (Drug)
Venetoclax Added to cBTKi (Commercially Prescribed)
Participants will receive venetoclax, orally, once daily (QD) with a starting ramp-up dose of 20 milligrams (mg) on Day 1 of Cycle 1 (cycle length= 28 days). The dose will increase weekly; thereafter, treatment will continue with venetoclax at the target dose of 400 mg, QD from Week 5 up to Day 28 of Cycle 12. Participant will discontinue from venetoclax and/or cBTKi after 12 cycles. Participants with detectable measurable residual disease with the presence of less than 1 CLL cell in 10,000 leukocytes (< 10^-4) (MRD4) or uMRD4 with partial response (PR) may continue receiving cBTKi-monotherapy (i.e. ibrutinib or acalabrutinib, or zanubrutinib) as previously prescribed by the investigator according to the prescribing label.
干预措施: Venetoclax (Drug)
结局指标
主要结局
uMRD4 Rate at EOCT
时间窗: Cycle 12 Day 28 (Cycle length= 28 Days)
uMRD4 will be assessed using next generation sequencing (NGS) (sensitivity 10\^-4) from PB.
次要结局
- CR/CRi Rate at EOCT as Determined by the Investigator According to International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Guidelines(Up to approximately 12 months)
- Overall Response Rate (ORR) at EOCT as Determined by the Investigator According to iwCLL Guidelines(Up to approximately 12 months)
- PR Rate at EOCT as Determined by the Investigator According to iwCLL Guidelines(Up to approximately 12 months)
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(Up to approximately 13 months)
- Number of Participants Who Withdrew Prematurely from the Study(Up to approximately 12 months)
- Overall Survival (OS)(Up to approximately 48 months)
- Progression-free Survival (PFS) as Determined by the Investigator According to iwCLL Guidelines(Up to approximately 48 months)
- Event-free Survival (EFS) as Determined by the Investigator According to iwCLL Guidelines(Up to approximately 48 months)
- Duration of Response (DOR) in Participants With CR/CRi or PR as Determined by the Investigator According to iwCLL Guidelines(Up to approximately 12 months)
- DOR in Participants With CR or CRi as Determined by the Investigator According to iwCLL Guidelines(Up to approximately 12 months)
- Time to Next CLL Treatment (TTNT)(Up to approximately 12 months)