A Randomized, Open-label, Multi-center, Phase II Study of Asciminib Versus Best Available Therapy in Chinese Patients With Chronic Myelogenous Leukemia in Chronic Phase (CML-CP), Previously Treated With 2 or More Tyrosine Kinase Inhibitors
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 84
- 试验地点
- 1
- 主要终点
- Major molecular response rate of asciminib
研究概览
简要总结
The purpose of this Chinese bridging study is to evaluate the efficacy, safety, tolerability and pharmacokinetics of asciminib versus best available therapy in Chinese patients with Chronic Myelogenous Leukemia in chronic phase, previously treated with 2 or more tyrosine kinase inhibitors to support related indication registration in China.
The primary objective of the study is to evaluate the Major Molecular Response (MMR) rate of asciminib treatment at 24 weeks.
详细描述
The purpose of this Chinese bridging study is to evaluate the efficacy, safety, tolerability and pharmacokinetics (PK) of asciminib versus best available therapy (BAT) in Chinese patients with Chronic Myelogenous Leukemia in chronic phase (CML-CP), previously treated with 2 or more tyrosine kinase inhibitors (TKIs) to support related indication registration in China.
This study will enroll the participants 1) who failed their most recent TKI therapy by meeting the definition of treatment failure as per the 2013 European Leukemia Net (ELN) guidelines, or 2) who were intolerant to the most recent TKI therapy and must have BCR-ABL1 ratio > 0.1% IS at screening.
Eligible participants will be randomized into asciminib arm or the BAT arm on a 2:1 ratio, to receive asciminib treatment (continuous 40 mg BID) or BAT from Day 1 until the end of study treatment period defined as 96 weeks after the last participant receives the first dose.
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 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosed as CML-CP:
- •Participants must meet all of the following laboratory values at the screening visit:
- •< 15% blasts in peripheral blood and bone marrow < 30% blasts plus promyelocytes in peripheral blood and bone marrow < 20% basophils in the peripheral blood
- •50 x 10^9/ L (≥ 50,000/mm3) platelets Transient prior therapy related thrombocytopenia (< 50,000/mm3 for ≤ 30 days prior to screening) is acceptable No evidence of extramedullary leukemic involvement, with the exception of hepatosplenomegaly
- •Prior treatment with a minimum of 2 prior ATP-competitive TKIs.
- •Failure (adapted from the 2013 European Leukemia Net (ELN) Guidelines) or intolerance to the most recent TKI therapy at the time of screening.
- •Evidence of typical BCR-ABL1 transcript [e14a2 and/or e13a2] at the time of screening which are amenable to standardized RQ-PCR quantification
排除标准
- •Known presence of the T315I mutation at any time prior to study entry
- •Known second chronic phase of CML after previous progression to AP/BC
- •Previous treatment with a hematopoietic stem cell transplantation
- •Participants planning to undergo allogeneic hematopoietic stem cell transplantation
- •Cardiac or cardiac repolarization abnormality, including any of the following:
- •History within 6 months prior to starting study treatment of myocardial infarction, angina pectoris, coronary artery bypass graft Clinically significant cardiac arrhythmias , complete left bundle branch block, high-grade AV block QTcF at screening ≥450 msec (male participants), ≥460 msec (female participants)
- •Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:
- •Risk factors for Torsades de Pointes including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia Concomitant medication(s) with a "Known risk of Torsades de Pointes" that cannot be discontinued or replaced 7 days prior to starting study drug by safe alternative medication.
- •Inability to determine the QTcF interval
- •History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis
- •Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
asciminb arm
Patients will receive asciminib (40 mg BID continuous)
干预措施: asciminib (Drug)
best available treatment arm
Patients will receive best available therapy chosen by investigator
干预措施: best available treatment (Other)
结局指标
主要结局
Major molecular response rate of asciminib
时间窗: week 24
Evaluate the major molecular response rate at 24 weeks in asciminib arm
次要结局
- Overall survival(Up to all participants received at least 96 weeks of randomized study treatment, plus 30 days for safety follow up)
- Cytogenetic response (CyR) rate(24, 48, 96 weeks)
- Major molecular response rate of best available treatment arm(week 24)
- Major molecular response rate of both asciminib arm and BAT armn time points(Up to all participants received at least 96 weeks of randomized study treatment, except week 24)
- major molecular response rate by all scheduled data collection time points(Up to all participants received at least 96 weeks of randomized study treatment)
- Time to major molecular response rate(Up to all participants received at least 96 weeks of randomized study treatment)
- Duration of major molecular response(Up to all participants received at least 96 weeks of randomized study treatment)
- Progression free survival(Up to all participants received at least 96 weeks of randomized study treatment, plus 30 days for safety follow up)
- Pharmacokinetics (PK) parameter of asciminib: Cmax(Week 2 Day 1 (W2D1))
- PK parameter of asciminib: Tmax(Week 2 Day 1 (W2D1))
- PK parameter of asciminib: Ctrough(Week 2 Day 1 (W2D1))
- PK parameter of asciminib: AUCtau(Week 2 Day 1 (W2D1))
- PK parameter of asciminib: AUClast(Week 2 Day 1 (W2D1))