A Phase III Multi-center, Open-label, Randomized Study of Imatinib Versus Nilotinib in Adult Patients With Newly Diagnosed Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 846
- 试验地点
- 32
- 主要终点
- Major Molecular Response Rate (MMR) at 12 Months Between All 3 Arms - With Imputation
研究概览
简要总结
In this study, the efficacy and safety of two nilotinib doses, 300 mg twice daily and 400 mg twice daily, were compared with imatinib 400 mg once daily in newly diagnosed patients with Philadelphia chromosome-positive (Ph+) Chronic Myelogenous Leukemia in the chronic phase (CML-CP).
An extension protocol was included in this study design to allow patients who did not show sufficient response to their assigned treatments the opportunity to receive imatinib 400 mg BID (option available until protocol amendment 7) or nilotinib 400 mg BID, using an abbreviated safety and efficacy assessment schedule.
详细描述
Primary objectives of this study:
- Compared the efficacy (major molecular response (MMR) rate at 12 months) of nilotinib at 400 mg bid with that of imatinib 400 mg qd in newly diagnosed, previously untreated Ph+ CML-CP patients.
- Compared the efficacy (MMR rate at 12 months) of nilotinib at 300 mg bid with that of imatinib 400 mg qd in newly diagnosed, previously untreated Ph+ CML-CP patients.
The Primary objectives of Extension Phase of the study:
- Characterized the safety and tolerability profile of nilotinib 400 mg BID after failure of imatinib or insufficiently responded to nilotinib 300 mg BID therapy and the safety and tolerability profile of imatinib therapy after failure of nilotinib therapy.
The study was designed to determine whether the treatment of newly diagnosed, previously untreated Ph+ CML-CP patients with either nilotinib 300 mg bid or 400 mg bid demonstrated improved efficacy compared to imatinib 400 mg qd. The primary efficacy endpoint was the rate of MMR defined as the proportion of patients who achieved ≥ 3 log reduction in BCR-ABL transcripts compared to either the standardized Baseline established in the IRIS trial (International Randomized Interferon versus STI571) (Cortes et al 2005) or to the BCR-ABL ratio ≤ 0.1% by International Scale, as detected by real-time quantitative polymerase chain reaction (RQ-PCR) at 12 months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Nilotinb 400 mg bid (investigating arm)
干预措施: nilotinib (Drug)
nilotinib 300mg bid (investigating arm)
干预措施: nilotinib (Drug)
imatinib 400mg QD (control arm)
干预措施: imatinib (Drug)
结局指标
主要结局
Major Molecular Response Rate (MMR) at 12 Months Between All 3 Arms - With Imputation
时间窗: Baseline, 12 months
MMR is defined as the percentage of participants in MMR (reduction of ≥ 3 logs in BCR-ABL transcripts compared to the standardized baseline established in IRIS, or ≤ 0.1% BCR-ABL/ABL % by international scale and measured by real-time quantitative polymerase chain reaction (RQ-PCR)) at 12 months.
Percentage of Participants With MMR at 12 Months Between All 3 Arms by Sokal Risk Group With Imputation
时间窗: 12 months
MMR is defined as the percentage of participants in MMR (reduction of ≥ 3 logs in BCR-ABL transcripts compared to the standardized baseline established in IRIS, or ≤ 0.1% BCR-ABL/ABL % by international scale and measured by real-time quantitative polymerase chain reaction (RQ-PCR)) at 12 months.
次要结局
- Rates of Durable MMR at 24 Months Between All 3 Arms(24 months)
- Rate of Complete Cytogenetic Response (CCyR) in Nilotinib Treatment Arms With Imatinib at 12 Months and Beyond 12 Months(12, 24, 36, 48, 60, 72 months (M))
- Rate of Major Molecular Response (MMR) at 12 Months Between Two Nilotinib Arms(12 months)
- Rate of MMR at 6 Months and Beyond in All 3 Treatment Arms(6, 12, 24, 36, 48, 60, 72, 84, 96, 108 and 120 months)
- Rate of a ≥ 4 Log Reduction in BCR-ABL Transcripts in Nilotinib Treatment Arms With Imatinib(at 6, 12, 24, 36, 48, 60, 72, 84, 96, 108 and 120 months)
- Rate of a ≥ 4.5 Log Reduction in BCR-ABL Transcripts in Nilotinib Treatment Arms With Imatinib(at 6, 12, 24, 36, 48, 60, 72, 84, 96, 108 and 120 months)
- Time to First MMR(up to 84 months)
- Duration of MMR(approx. 11 years)
- Time to Both a ≥ 4 and ≥ 4.5 Log Reduction in BCR-ABL Transcripts(up to 84 months)
- Duration of Both a ≥ 4 and ≥ 4.5 Log Reduction in BCR-ABL Transcripts(approx. 11 years)
- Rate of Hematologic Response(12 months, 24 months, Overall on Core study (approx. 11 years))
- Time to Complete Cytogenic Response (CCyR)(24 months)
- Duration of CCyR(up to 72 months)
- Progression-free Survival (PFS)(approx. 11 years)
- Event-free Survival (EFS)(approx. 11 years)
- Overall Survival (OS)(approx. 11 years)
- Actual Dose-intensity(approx. 11 years)
- Time to Progression to AP/BC(approx. 11 years)
- Pharmacokinetics: Cmax(any day after day 8 up to cycle 12 (each cycle = 28 days) and after at least 3 consecutive days without dose interruption or dose modification at pre-dose (0 hour), 1 hour, 2 hours, 3 hours, 5 hours, 8 hours, and 12 hours after dose administration)
- Pharmacokinetics: Cmin(any day after day 8 up to cycle 12 (each cycle = 28 days) and after at least 3 consecutive days without dose interruption or dose modification at pre-dose (0 hour), 1 hour, 2 hours, 3 hours, 5 hours, 8 hours, and 12 hours after dose administration)
- Pharmacokinetics: Tmax(any day after day 8 up to cycle 12 (each cycle = 28 days) and after at least 3 consecutive days without dose interruption or dose modification at pre-dose (0 hour), 1 hour, 2 hours, 3 hours, 5 hours, 8 hours, and 12 hours after dose administration)
- Pharmacokinetics: AUC0-last(any day after day 8 up to cycle 12 (each cycle = 28 days) and after at least 3 consecutive days without dose interruption or dose modification at pre-dose (0 hour), 1 hour, 2 hours, 3 hours, 5 hours, 8 hours, and 12 hours after dose administration)
- Rate of Hematologic Response on Nilotinib 400 mg BID Therapy After Insufficient Response During Core Treatment and Switch to Extension Phase (Extension)(Overall for Extension study for approx. 10 years)
- Rate of Complete Cytogenetic Response (CCyR) on Nilotinib 400 mg BID Therapy After Insufficient Response During Core Treatment and Switch to Extension Phase (Extension)(Overall for Extension study for approx. 10 years)
- Rate of Major Molecular Response (MMR) on Nilotinib 400 mg BID Therapy After Insufficient Response During Core Treatment and Switch to Extension Phase (Extension)(Overall for Extension study for approx. 10 years)
- Rate of ≥ 4.5 Log Reduction in BCR-ABL Transcripts on Nilotinib 400 mg BID Therapy After Insufficient Response During Core Treatment and Switch to Extension Phase (Extension)(Overall for Extension study for approx. 10 years)
- Rate of a ≥ 4 Log Reduction in BCR-ABL Transcripts on Nilotinib 400 mg BID Therapy After Insufficient Response During Core Treatment and Switch to Extension Phase (Extension)(Overall for Extension study for approx. 10 years)
- Presence of Newly Observed BCR-ABL Mutations in Patients Post-baseline and Correlate With Response to Treatment With Imatinib and Nilotinib (Extension)(Overall for Extension study for approx. 10 years)