A PHASE 4 SAFETY AND EFFICACY STUDY OF BOSUTINIB (BOSULIF (REGISTERED)) IN PATIENTS WITH PHILADELPHIA CHROMOSOME POSITIVE CHRONIC MYELOID LEUKEMIA PREVIOUSLY TREATED WITH ONE OR MORE TYROSINE KINASE INHIBITORS
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 发起方
- Pfizer
- 入组人数
- 163
- 试验地点
- 48
- 主要终点
- Percentage of Participants With Cumulative Confirmed Major Cytogenetic Response (MCyR) in 2nd and 3rd Line Chronic Phase (CP) Participants
研究概览
简要总结
The purpose of this study is to fulfill the post-authorization commitment made by Pfizer to the European Medicines Agency in providing additional safety and efficacy data in approximately 150 Philadelphia Chromosome Positive Chronic Myeloid Leukemia patients with high unmet medical need, including 75 Chronic Phase, Accelerated Phase or Blast Phase patients in the fourth or later line treatment setting (i.e., after treatment with at least 3 other Tyrosine Kinase Inhibitors).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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 Philadelphia Chromosome positive Chronic Myeloid Leukemia or Confirmed BCR-ABL1 (Abelson-break point cluster) Positive if Philadelphia Chromosome negative Chronic Myeloid Leukemia (from initial diagnosis).
- •Prior treatment with 1 or more tyrosine kinase inhibitor drugs (imatinib, dasatinib and/or nilotinib) for Philadelphia Chromosome positive Chronic Myeloid Leukemia (CML).
- •Any Chronic Myeloid Leukemia disease phase, as long as the patient is unable to receive treatment with imatinib, dasatinib and/or nilotinib for any reason.
排除标准
- •Participation in any other clinical studies involving investigational drug(s) within 14 days or within 3 half-lives of drug levels in blood (whichever is longer) prior to the first dose of bosutinib.
- •Prior treatment with bosutinib.
- •Prior treatment with ponatinib.
- •Known T315I or V299L mutation.
研究组 & 干预措施
Bosutinib
干预措施: Bosutinib (Drug)
结局指标
主要结局
Percentage of Participants With Cumulative Confirmed Major Cytogenetic Response (MCyR) in 2nd and 3rd Line Chronic Phase (CP) Participants
时间窗: Up to 1 year (52 weeks)
Confirmed MCyR: confirmed (complete cytogenetic response\[CCyR\] or partial cytogenetic response\[PCyR\]) by 1 year for participants entering the study without CCyR or maintenance of confirmed CCyR for at least 1 year after treatment start with bosutinib for participants entering the study with CCyR or at least major molecular response(MMR) by 1 year and a deeper molecular response compared to baseline. Participants with baseline PCyR that did not achieve CCyR were counted as nonresponders. Initial cytogenetic (in absence of MMR) responses must have been confirmed by 2 consecutive assessments \>=28 days apart. CCyR: 0% Ph+ cells from \>=20 metaphases from conventional cytogenetics or \<1% Ph+ cells from \>= 200 cells from fluorescent in situ hybridization(FISH). PCyR: 1 to 35% Ph+ cells. MMR: \<=0.1% BCR-ABL1 on the international scale (IS) with at least 10,000 ABL1 transcripts assessed by central laboratory.
Percentage of Participants With Cumulative Confirmed Major Cytogenetic Response (MCyR) in 4th or Later Line Chronic Phase (CP) Participants
时间窗: Up to 1 year (52 weeks)
Confirmed MCyR: confirmed CCyR or PCyR by 1 year for participants entering the study without CCyR or maintenance of confirmed CCyR for at least 1 year after treatment start with bosutinib for participants entering the study with CCyR or at least MMR by 1 year and a deeper molecular response compared to baseline. Participants with baseline PCyR that did not achieve CCyR were counted as nonresponders. Initial cytogenetic (in absence of MMR) responses must have been confirmed by 2 consecutive assessments \>=28 days apart. CCyR: 0% Ph+ cells from \>=20 metaphases from conventional cytogenetics or \<1% Ph+ cells from \>= 200 cells from fluorescent in situ hybridization(FISH). PCyR: 1 to 35% Ph+ cells. MMR: \<=0.1% BCR-ABL1 on the IS with at least 10,000 ABL1 transcripts assessed by central laboratory.
Percentage of Participants With Cumulative Confirmed Overall Hematological Response (OHR) in Accelerated Phase (AP) Chronic Myelogenous Leukemia (CML) Participants
时间窗: Up to 1 year (52 weeks)
Confirmed OHR was defined as complete hematological response (CHR) or return to chronic phase (RCP) by 1 year in AP and BP participants. CHR was defined as white blood cells (WBC) \<10\*10\^9/L, peripheral blood basophils \<5%, no peripheral blood myelocytes, promyelocytes, myeloblasts in the differential, platelet count \<450\*10\^9/L, spleen not palpable. Hematologic responses must be of \>=4 weeks duration confirmed by 2 assessments \>=4 weeks apart.
次要结局
- Percentage of Participants With Cumulative Confirmed Overall Hematological Response (OHR) in Participants With Accelerated Phase (AP) Chronic Myelogenous Leukemia (CML)(Up to 4 years)
- Percentage of Participants With Cumulative Best Response(Up to 4 years)
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious AEs(First dose of study drug up to 28 days after last dose (up to maximum of 4 years))
- Percentage of Participants With Cumulative Major Molecular Response (MMR)(Up to 4 years)
- Percentage of Participants With Major Cytogenetic Response (MCyR) at Months 3, 6, 12, 18 and 24(Months 3, 6, 12, 18, and 24)
- Percentage of Participants With Cumulative Major Cytogenetic Response (MCyR)(Up to 4 years)
- Percentage of Accelerated Phase Participants With Confirmed Overall Hematological Response (OHR) at Month 3, 6, 9, 12, 18, and 24(Months 3, 6, 9, 12, 18, and 24)
- Percentage of Participants With Cumulative Confirmed Complete Hematological Response (CHR)(Up to 4 years)
- Kaplan-Meier Estimate of Probability of Retaining Complete Cytogenetic Response (CCyR) at Month 36(At Month 36)
- Kaplan-Meier Estimate of Probability of Retaining Major Molecular Response (MMR) at Month 36(At Month 36)
- Number of Participants With Laboratory Abnormalities Based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03(First dose of study drug up to 28 days after last dose (up to maximum of 4 years))
- Number of Participants With Grade 3 or 4 Treatment Emergent Adverse Events (TEAEs) Based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0(First dose of study drug up to 28 days after last dose (up to maximum of 4 years))
- Number of Participants With Treatment Related Treatment Emergent Adverse Events (TEAEs)(First dose of study drug up to 28 days after last dose (up to maximum of 4 years))