An Open Label, Randomized (2:1) Phase IIb Study of Dasatinib Versus Imatinib in Patients With Chronic Phase Chronic Myeloid Leukemia Who Have Not Achieved an Optimal Response to 3 Months of Therapy With 400 mg Imatinib
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 262
- 试验地点
- 87
- 主要终点
- Percentage of Patients Achieving Major Molecular Response (MMR) After 12 Months of CML Treatment
研究概览
简要总结
The purpose of this study is to test the hypothesis that patients with CML who have not achieved optimal response after 3 months of treatment with imatinib will have a better response by switching to dasatinib compared to staying on their original imatinib regimen.
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
- •Chronic Phase (CP)-CML Ph+ patients with complete hematologic response (CHR) but without one log BCR-ABL reduction (BCR-ABL level >10% IS) 3 months of imatinib 400mg treatment. (Imatinib transient dose adjustments due to Adverse Event (AEs) are allowed with a maximum of 2 weeks interruption of treatment with imatinib (cumulative) within the 3 month period before randomization). Imatinib monotherapy must have been started within 6 months of CP-CML diagnosis (Ph + /BCR-ABL detection)
- •Currently tolerating imatinib 400mg QD. Patients with prior imatinib treatment interruption or dose reductions are required to be on treatment with 400 mg imatinib for two weeks immediately prior to randomization to ensure tolerance to imatinib
- •Eastern Co-Operative Group (ECOG) performance status = 0 - 2
- •Adequate renal function defined as serum creatinine ≤3 times the institutional upper limit of normal (ULN)
- •Adequate hepatic function defined as: total bilirubin ≤2.0 times the institutional ULN; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 times the institutional ULN
排除标准
- •Previous diagnosis of accelerated phase or blast crisis
- •Subjects with clonal evolution in Ph+ cells observed in ≥2 metaphases at baseline bone marrow cytogenetic test, unless the same abnormalities were present at diagnosis. Patients with no evidence of clonal evolution, including those patients whose cytogenetic testing fails or bone marrow aspiration is a dry tap at 3 months, are eligible for the study
- •Subjects with less than CHR after 3 months of imatinib treatment or lost CHR after initial achievement
- •Documented T315I/A, F317L, or V299L mutations (if already available - not required for screening)
- •A serious uncontrolled medical disorder or active infection that would impair the ability of the subject to receive protocol therapy
研究组 & 干预措施
Arm 1: Imatinib (≥400 mg)
Imatinib ≥400 mg tablets by mouth once daily (QD) or twice daily (BID) up to 60 months
干预措施: Imatinib (Drug)
Arm 2: Dasatinib (100 mg)
Dasatinib 100 mg tablet by mouth QD up to 60 months
干预措施: Dasatinib (Drug)
结局指标
主要结局
Percentage of Patients Achieving Major Molecular Response (MMR) After 12 Months of CML Treatment
时间窗: At 12 months after Day 1 initiation of 1st line treatment with imatinib or imatinib at any dose, after less than optimal response to first-line imatinib.
Major Molecular Response, is defined as a 3-log reduction in BCR-ABL transcripts from the standardized baseline, which represents 100% on the international scale, so a 3-log reduction is fixed at 0.1% for MMR; N/A = not applicable. 95% CI is Clopper-Pearson(Exact) two-sided 95% confidence intervals. P-value is based on Cochran-Mantel-Haenszel (CMH) test stratified by Sokal score(high, intermediate, low, and unknown) and time between 3 month molecular analysis and randomization (\<=4 weeks vs \>4 weeks).
次要结局
- Median Time to Major Molecular Response (MMR)(From randomization to study completion. Approximately 115 months)
- Time to Molecular Response (MR)^4.5(From randomization to study completion. Approximately 115 months)
- Progression Free Survival (PFS)(From randomization to study completion. Approximately 115 months)
- Overall Survival (OS)(From randomization to study completion. Approximately 115 months)