A Multicenter, Single Arm Study to Assess Efficacy and Safety of Nilotinib 300mg Twice Daily in Patients With Philadelphia Positive Chronic Myeloid Leukemia in Chronic Phase (Ph+ CML-CP) Who Are Intolerant to Prior Tyrosine Kinase Inhibitors (TKIs).
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Molecular Response (MR4.0) Rate: Percentage of Patients Who Have Achieved a 4.0-log Reduction in BCR-ABL Level Within 12 Months and 24 Months
研究概览
简要总结
The purpose of this Australian study was to assess the efficacy and safety of nilotinib 300mg twice daily in patients with chronic myeloid leukemia chronic phase who were intolerant but responsive to 1st line treatment with imatinib or dasatinib. Eligible patients have been previously treated with imatinib or dasatinib for at least 3 months and are experiencing non-hematologic toxicity whilst having documented responses that meet PBS authority for 1st line treatment of CML without current MR4.5.
详细描述
The study was planned to enroll 130 patients to achieve the sample size requirement for a meaning full conclusion. Study got terminated with 20 patients because of slow recruitment. Therefore, due to small sample size, the results cannot be considered clinical significant.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •Written informed consent prior to screening procedures
- •Eastern Cooperative Oncology Grou (ECOG) Performance Status of 0, 1, or
- •Patient with diagnosis of Ph+ CML-CP associated with BCR-ABL quantifiable by RQ-PCR (IS).
- •Patient has received a minimum of 3 months of imatinib or dasatinib treatment (any dose) since initial diagnosis with a documented response.
- •Patient is eligible for Pharmaceutical Benefits Scheme (PBS) reimbursed 1st line TKI treatment.
- •Patient has experienced non-hematological Adverse Events (AE(s)) of any grade, which persisted for at least 1 month despite supportive care or recurred at any grade at least once. Patients who, at the Investigator's discretion, require immediate discontinuation due to the severity of the adverse event are also eligible.
- •No other current or planned anti-leukemia therapies.
- •Adequate organ function.
- •Potassium, Magnesium and Total Calcium above Lower limit of normal.
- •life expectancy of more than 12 months in the absence of any intervention
排除标准
- •Prior treatment with nilotinib.
- •Prior Accelerated Phase (AP), Blast Crisis (BC) or allogeneic-transplant (unless the patient received an autologous transplant and was in Chrionic Phase (CP) prior to transplant and never in AP or BC).
- •Patient has documented Molecular Response (MR) 4.5 at the time of study entry
- •Patients with atypical BCR-ABL transcript not quantifiable by standard RQ-PCR.
- •Known impaired cardiac function.
- •Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug.
- •Pregnant or breast feeding (lactating) women.
- •Women of child-bearing potential unwilling or unable to use highly effective contraception.
研究组 & 干预措施
Nilotinib
Nilotinib was administered orally at 300 mg BD at approximately 12 hour intervals which had to be taken without food. The capsules were to be swallowed whole with water and no food should have been consumed for at least 2 hours before and at least 1 hour after the dose was taken. Prior to the first dose of nilotinib, patients were required to have an imatinib or dasatinib washout period of at least 3 days. Therapy with nilotinib was to be continued for up to 24 months while on study.
干预措施: Nilotinib (Drug)
结局指标
主要结局
Molecular Response (MR4.0) Rate: Percentage of Patients Who Have Achieved a 4.0-log Reduction in BCR-ABL Level Within 12 Months and 24 Months
时间窗: Baseline, 48 weeks (12 months), 96 weeks (24 months)
Molecular Response (MR4.0) rate is defined as the percentage of patients who have achieved a 4-log reduction in BCR-ABL levels at 12 months and 24 months following the commencement of nilotinib therapy. Breakpoint cluster region - Abelson murine leukemia (BCR-ABL) levels are measured in patients by real-time quantitative polymerase chain reaction (RQ-PCR) testing of peripheral blood by the 24 months following the commencement of nilotinib therapy. MR4.0 corresponds to a BCR-ABL ratio 0.01% international scale (IS) using RQ-PCR. If a post-baseline value for BCR-ABL is \< 0.1 X the baseline value, the patients were classified as achieving a 1 log reduction in BCR-ABL.
Deep Molecular Response (MR4.5) Rate: Percentage of Patients Who Have Achieved a 4.5-log Reduction in BCR-ABL Level Within 24 Month
时间窗: Baseline, 96 weeks (24 months)
Deep Molecular Response (MR4.5) rate is defined as the percentage of patients who have achieved a 4.5 -log reduction in Breakpoint cluster region - Abelson murine leukemia (BCR-ABL) levels. BCR-ABL levels are measured in patients by real-time quantitative polymerase chain reaction (RQ-PCR) testing of peripheral blood by the 24 months following the commencement of nilotinib therapy. MR4.5 corresponds to a BCR-ABL ratio 0.0032% international scale (IS) using RQ-PCR. If a post-baseline value for BCR-ABL is \< 0.1 X the baseline value, the patient were classified as achieving a 1 log reduction in BCR-ABL.
Major Molecular Response (MMR) Rate: Percentage of Patients Who Have Achieved a 3 Log Reduction in BCR-ABL Levels Within 12 Months and 24 Months
时间窗: Baseline, 48 weeks (12 months), 96 weeks (24 months)
Major Molecular Response (MMR) rate is defined as the percentage of patients who have achieved a 3 log reduction in BCR-ABL levels at 12 months and at 24 months following the commencement of nilotinib therapy. Breakpoint cluster region - Abelson murine leukemia (BCR-ABL) levels are measured in patients by real-time quantitative polymerase chain reaction (RQ-PCR) testing of peripheral blood at the 12 and 24 months following the commencement of nilotinib therapy. MMR corresponds to a BCR-ABL ratio 0.1% international scale (IS) using RQ-PCR. If a post-baseline value for BCR-ABL is \< 0.1 \* the baseline Value, the patient will be classified as achieving a 1 log drop.
Duration of Prior TKI Therapy for Patients Based on MR4.5 Achievement Status Within 24 Months
时间窗: Baseline, 96 weeks (24 months)
Breakpoint cluster region - Abelson murine leukemia (BCR-ABL) levels are measured in patients by real-time quantitative polymerase chain reaction (RQ-PCR) testing of peripheral blood by the 24 months following the commencement of nilotinib therapy. Deep molecular response (MR4.5) rate was defined as the percentage of patients who have achieved a 4.5-log reduction (MR4.5) in BCR-ABL levels during the 24 months following the commencement of nilotinib therapy. MR4.5 corresponds to a BCR-ABL ratio 0.0032% IS using RQ-PCR. If a post-baseline value for BCR-ABL is \< 0.1 X the baseline value, the patient were classified as achieving a 1 log reduction in BCR-ABL.
Number of Patients With MR4.5 Response by Baseline BCR-ABL Response Level Within 24 Months
时间窗: Baseline, 96 weeks (24 months)
Deep Molecular Response (MR4.5) rate is defined as the percentage of patients who have achieved a 4.5 -log reduction in Breakpoint cluster region - Abelson murine leukemia (BCR-ABL) levels. BCR-ABL levels are measured in patients by real-time quantitative polymerase chain reaction (RQ-PCR) testing of peripheral blood by the 24 months following the commencement of nilotinib therapy. MR4.5 corresponds to a BCR-ABL ratio 0.0032% international scale (IS) using RQ-PCR. If a post-baseline value for BCR-ABL is \< 0.1 X the baseline value, the patient were classified as achieving a 1 log reduction in BCR-ABL.
次要结局
- Kinetics of Molecular Response: Percentage of Patients With no Response Based on BCR-ABL Over Time After the Switch to Nilotinib(Baseline, week 4, 8, 12, 24, 36, 48, 60, 72, 84, 96)
- Kinetics of Molecular Response: Percentage of Patients With MMR Based on BCR-ABL Over Time After the Switch to Nilotinib(Baseline, week 4, 8, 12, 24, 36, 48, 60, 72 and 96)
- Kinetics of Molecular Response: Percentage of Patients With MR4.0 Based on BCR-ABL Over Time After the Switch to Nilotinib(Baseline, week 4, 8, 12, 24, 36, 48, 60, 72, 84, 96)
- Kinetics of Molecular Response: Percentage of Patients With MR4.5 Based on BCR-ABL Over Time After the Switch to Nilotinib(Baseline, week 4, 8, 12, 24, 36, 48, 60, 72, 84, 96)
- Kaplan-Meier Estimates of Time to Deep Molecular Response (MR4.5)(96 weeks (24 months))
- Time to Progression-free Survival (PFS)(96 weeks (24 months))
- Time to Event Free Survival (EFS)(96 weeks (24 months))
- Number of Patients With Events Reported at Baseline That Have Shown an Improvement in Non-hematological AE Severity Compared to Week 12 Visit(Baseline, week 12 (month 3))
- Mean M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML)(Baseline, week 12, 24, 48, 96)