A MULTICENTER PHASE 3 RANDOMIZED, OPEN-LABEL STUDY OF BOSUTINIB VERSUS IMATINIB IN ADULT PATIENTS WITH NEWLY DIAGNOSED CHRONIC PHASE CHRONIC MYELOGENOUS LEUKEMIA
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 536
- 试验地点
- 182
- 主要终点
- Percentage of Participants With Major Molecular Response (MMR) at Month 12
研究概览
简要总结
Phase 3, 2-arm, randomized, open label trial. Patients will be randomized to receive bosutinib or imatinib for the duration of the study.
详细描述
The study will be open for enrollment until the planned number of approximately 500 Philadelphia Chromosome Positive (Ph+) patients have been randomized (approximately 250 Ph+ patients in each treatment arm; a total of approximately 530 Ph+ and Ph- patients). All patients will be treated and/or followed for approximately 5 years (240 weeks) after randomization until the study has closed. Patients who discontinue study therapy early due to disease progression or intolerance to study medication will continue to be followed yearly for survival for up to approximately 5 years (240 weeks) after randomization.
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
盲法说明
NOTE: Value was Open Label in old format; This study has an open-label design. Although most efficacy studies have a double blind design, this is not feasible in this trial, due to the complexity of the dose reduction and dose escalation schemes with tablets of various sizes, dosage strengths, as well as the number of tablets that would be required daily. However, the opportunity for bias is mitigated by the use of objective outcome measures (MMR, CCyR, CHR). The Investigators will be instructed to ensure that laboratory/pathology personnel are blinded to treatment information. For these reasons, an open-label, randomized study is appropriate.
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
- •Molecular diagnosis of CP CML of ≤ 6 months (from initial diagnosis).
- •Adequate hepatic, renal and pancreatic function.
- •Age ≥ 18 years.
排除标准
- •Any prior medical treatment for CML, including tyrosine kinase inhibitors (TKIs), with the exception of hydroxyurea and/or anagrelide treatment, which are permitted for up to 6 months prior to study entry (signature of ICF) if suitably approved for use in the subject's region.
- •Any past or current Central Nervous System (CNS) involvement, including leptomeningeal leukemia.
- •Extramedullary disease only.
- •Major surgery or radiotherapy within 14 days of randomization.
- •History of clinically significant or uncontrolled cardiac disease.
- •Known seropositivity to human immunodeficiency virus (HIV), current acute or chronic hepatitis B (hepatitis B surface-antigen positive), hepatitis C, cirrhosis or evidence of decompensated liver disease. Patients with resolved Hepatitis B can be included.
- •Recent or ongoing clinically significant GI disorder, e.g. Crohn's Disease, Ulcerative Colitis, or prior total or partial gastrectomy.
- •History of another malignancy within 5 years with the exception of basal cell carcinoma or cervical carcinoma in situ or stage 1 or 2 cancer that is considered adequately treated and currently in complete remission for at least l2 months.
- •Current, or recent (within 30 days, or 5 half-lives of investigational product) participation in other clinical trials of investigational agents and/or containing interventional procedures deemed contrary to the objectives and conduct of this trial.
研究组 & 干预措施
Bosutinib
Bosutinib, 400 mg, oral administration once a day
干预措施: Bosutinib (Drug)
Imatinib
Imatinib, 400 mg, oral administration once a day
干预措施: Imatinib (Drug)
结局指标
主要结局
Percentage of Participants With Major Molecular Response (MMR) at Month 12
时间窗: Month 12
MMR was defined as a ratio of breakpoint cluster region to abelson (BCR-ABL/ABL) less than or equal to (\<=) 0.1 percent (%) on the international scale (IS) (greater than or equal to \[\>=\] 3 log reduction from standardized baseline in ratio of BCR-ABL to ABL transcripts \[\>=3000 ABL required\]) by quantitative reverse transcriptase polymerase chain reaction (RT-qPCR). The percentage of participants with MMR at Month 12 are reported.
次要结局
- Kaplan-Meier Estimate of Probability of Retaining Complete Cytogenetic Response (CCyR) at Month 48(Month 48)
- Percentage of Participants With Complete Cytogenetic Response (CCyR) Up to Month 12(Up to Month 12)
- Kaplan-Meier Estimate of Probability of Retaining Major Molecular Response (MMR) at Month 48(Month 48)
- Cumulative Incidence of Event Free Survival (EFS) Events(Up to Month 60)
- Overall Survival (OS) Rate(Up to Month 60)
- Percentage of Participants With Major Molecular Response (MMR) Up to Month 18(Up to Month 18)