A Phase II Study of Dasatinib Therapy in Children and Adolescents With Newly Diagnosed Chronic Phase Chronic Myelogenous Leukemia or With Ph+ Leukemias Resistant or Intolerant to Imatinib
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 133
- 试验地点
- 109
- 主要终点
- Complete Hematologic Response (CHR) Rate
研究概览
简要总结
The purpose of this study is to determine whether dasatinib is safe and effective in children and adolescents with newly diagnosed chronic myeloid leukemia (CML), or in children with Ph+ acute lymphoblastic leukemia (ALL), accelerated or blast phases CML who relapse after imatinib or who are resistant or intolerant to imatinib. The side effects of this oral investigational drug in children and adolescents will be evaluated
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Day 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •CP-CML who prove resistant or intolerant to imatinib (Cohort 1)
- •Ph+ ALL, AP-CML, or BP-CML who are resistant or intolerant to or who relapse after imatinib therapy (Cohort 2)
- •Newly diagnosed, treatment naive CP-CML (Cohort 3)
- •Lansky or Karnofsky scale >50
- •Life expectancy ≥12 weeks
- •Adequate hepatic and renal function
- •Written informed consent
- •Target Population for the PK substudy must obtain written informed consent from subject, or from parents or legal guardians for minor subjects, according to local law and regulation
- •Target Population for the PK substudy subjects must have CP-CML and be taking daily dasatinib (tablets or PFOS) either as part of Cohort 1 or Cohort 3 of this protocol. Patients receiving commercial dasatinib tablets outside of this protocol may be invited to participate in this PK substudy
- •Target Population for the PK substudy subjects with CP-CML who are tolerating dasatinib tablet dose of at least 60 mg/m2 or dasatinib PFOS dose of at least 72 mg/m2
- •Target Population for the PK substudy prior exposure to imatinib or other TKI therapy is permissible
- •Target Population for the PK substudy subjects must meet relevant inclusion criteria
排除标准
- •Eligibility for potentially-curative therapy including hematopoietic stem-cell transplantation
- •Symptomatic CNS involvement (other than signs and symptoms caused by leptomeningeal disease)
- •Isolated extramedullary disease
- •Prior therapy with Dasatinib
- •Target Population for the PK substudy subjects participating in the PK substudy must comply with the relevant exclusion criteria
- •Target Population for the PK substudy subjects are not allowed to use proton pump inhibitors, H2 antagonists, CYP3A4 inhibitors and inducers when entering the PK substudy
- •Other inclusion/exclusion criteria may apply
研究组 & 干预措施
Cohort 1: Imatinib-resistant/intolerant CP-CML
Dasatinib 60 mg/m² tablet every day (QD) [with a maximum dose of 100 mg QD for subjects with high BSA] for minimum of 24 months, may continue as long as deriving clinical benefit
OR
Dasatinib 72 mg/m² powder for oral suspension (PFOS) QD [with a maximum dose of 120 mg QD for subjects with high BSA] for minimum of 24 months, may continue as long as deriving clinical benefit
干预措施: Dasatinib (Drug)
Cohort 2: Ph+ALL or AP- or BP-CML
Dasatinib 80 mg/m² tablet QD [with a maximum dose of 140 mg QD for subjects with high BSA] for minimum of 24 months, may continue as long as deriving clinical benefit
OR
Dasatinib 96 mg/m² PFOS QD [with a maximum dose of 170 mg QD for subjects with high BSA] for minimum of 24 months, may continue as long as deriving clinical benefit
干预措施: Dasatinib (Drug)
Cohort 3: Newly diagnosed, treatment naïve CP-CML
Dasatinib 60 mg/m² tablet QD [with a maximum dose of 100 mg QD for subjects with high BSA] for minimum of 24 months, may continue as long as deriving clinical benefit
OR
Dasatinib 72 mg/m² PFOS QD [with a maximum dose of 120 mg QD for subjects with high BSA] for minimum of 24 months, may continue as long as deriving clinical benefit
干预措施: Dasatinib (Drug)
结局指标
主要结局
Complete Hematologic Response (CHR) Rate
时间窗: From first dose of study therapy until 30 days after last dose (Assessed up to September 2016, approximately 90 months)
Complete Hematologic Response (CHR) rate is defined as the proportion of all treated participants who achieve a confirmed CHR while on-study, expressed as percentage. CHR is defined as including no more than 5% blasts in bone marrow and normal white blood cell count without blasts in peripheral blood, expressed as percentage. The denominator of the CHR response rate consists of all treated participants in Cohort 2, and the numerator is all participants in Cohort 2 achieving CHR. 95% confidence interval was calculated by Clopper-Pearson exact method.
Major Cytogenetic Response (MCyR) Rate
时间窗: From first dose of study therapy until 30 days after last dose (Assessed up to September 2016, approximately 90 months)
Major Cytogenetic Response (MCyR) rate is defined as the proportion of all treated participants who achieved a complete (0%) or partial (1%-35% Ph+ metaphases in at least 20 metaphases in bone marrow) cytogenetic response, expressed as percentage. The denominator of the MCyR response rate consists of all treated participants in Cohort 1, and the numerator is all participants in Cohort 1 achieving MCyR. 95% confidence interval was calculated by Clopper-Pearson exact method.
Complete Cytogenetic Response (CCyR) Rate
时间窗: From first dose of study therapy until 30 days after last dose (Assessed up to September 2016, approximately 90 months)
Complete Cytogenetic Response (CCyR) rate is defined as the proportion of all treated participants who achieve a CCyR while on-study, expressed as a percentage. CCyR rate is defined as 0% Ph+ metaphases in at least 20 metaphases in bone marrow. The denominator of the CCyR response rate consists of all treated participants in Cohort 3, and the numerator is all participants in Cohort 3 achieving CCyR. 95% confidence interval was calculated by Clopper-Pearson exact method.
次要结局
- Major Cytogenetic Response (MCyR) Rate in Cohort 2(From first dose of study therapy until 30 days after last dose (Assessed up to September 2016, approximately 90 months))
- Complete Hematologic Response (CHR) Rate in Cohorts 1 and 3(From first dose of study therapy until 30 days after last dose (Assessed up to September 2016, approximately 90 months))
- Rate of Best Cytogenetic Response(From first dose of study therapy until 30 days after last dose (Assessed up to September 2016, approximately 90 months))
- Time to Major Cytogenetic Response (MCyR)(From first dose until MCyR criteria are met (assessed up to September 2016, approximately 90 months))
- Duration of Major Cytogenetic Response (MCyR)(From first day criteria are met for MCyR until the date PD is reported or death (assessed up to September 2016, approximately 90 months))
- Time to Complete Cytogenetic Response (CCyR)(From first dose until CCyR criteria are met, assessed up to September 2016 (approximately 90 months))
- Duration of Complete Cytogenetic Response (CCyR)(From first day criteria are met for CCyR until the date of progressive disease or death (assessed up to September 2016, approximately 90 months))
- Progression-Free Survival (PFS)(174 Months)
- Time to Complete Hematologic Response (CHR)(From first dose until CHR criteria are met, assessed up to September 2016 (approximately 90 months))
- Duration of Complete Hemotologic Response (CHR)(From first day criteria are met for CHR until date of disease progression or death (assessed up to September 2016, approximately 90 months))
- Disease-Free Survival(168 Months)
- Overall Survival (OS)(174 Months)
- Major Molecular Response (MMR) Rate(From date of first treatment to date of MMR (assessed up to Jan 2025, approximately 15 years and 10 months))
- Complete Molecular Response (CMR) Rate(From date of first treatment to date of CMR (assessed up to Jan 2025, approximately 15 years and 10 months))
- Major Cytogenetic Response (MCyR) Rate up to 2 Years(24 months)
- Complete Cytogenetic Response (CCyR) Rate up to 2 Years(24 months)
- Major Molecular Response (MMR) Rate up to 7.5 Years(90 months)
- Complete Molecular Response (CMR) Rate up to 7.5 Years(90 months)