A Randomized, Open-label Study of Ponatinib Versus Nilotinib in Patients With Chronic Myeloid Leukemia in Chronic Phase Following Resistance to Imatinib
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- 入组人数
- 44
- 试验地点
- 1
- 主要终点
- Percentage of Participants With Major Molecular Response (MMR)
研究概览
简要总结
The purpose of this study is to compare the efficacy and safety of 2 starting doses of ponatinib compared to nilotinib in participants with imatinib-resistant chronic myeloid leukemia (CML) in chronic phase (CP).
详细描述
This is a multi-center, randomized study to demonstrate the efficacy and safety of 2 starting doses of ponatinib as a treatment for CP-CML compared to nilotinib. Eligible participants must have chronic phase chronic myeloid leukemia (CP-CML), be resistant to first-line imatinib treatment and have received no other tyrosine kinase inhibitors (TKIs).
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
- •Have CP-CML and are resistant to first-line imatinib treatment.
- •Be male or female ≥18 years old.
- •Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Have adequate renal function as defined by the following criterion:
- •Serum creatinine ≤1.5 × upper limit of normal (ULN) for institution.
- •Have adequate hepatic function as defined by all of the following criteria:
- •Total serum bilirubin ≤1.5 × ULN, unless due to Gilbert's syndrome
- •Alanine aminotransferase (ALT) ≤2.5 × ULN or ≤5 × ULN if leukemic infiltration of the liver is present
- •Aspartate aminotransferase (AST) ≤2.5 × ULN or ≤5 × ULN if leukemic infiltration of the liver is present.
- •Have normal pancreatic status as defined by the following criterion:
- •Serum lipase and amylase ≤1.5 × ULN.
排除标准
- •Have previously been treated with any approved or investigational TKIs other than imatinib or treated with imatinib within 14 days prior to receiving study drug.
- •Have previously been treated with any anti-CML therapy other than hydroxyurea, including interferon, cytarabine, immunotherapy, or any cytotoxic chemotherapy, radiotherapy, or investigational therapy.
- •Underwent autologous or allogeneic stem cell transplant.
- •Are in CCyR or MMR.
- •Have clinically significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to:
- •Any history of myocardial infarction (MI), unstable angina, cerebrovascular accident, or transient ischemic attack (TIA)
- •Any history of peripheral vascular infarction, including visceral infarction
- •Any history of a revascularization procedure, including vascular surgery or the placement of a stent
- •History of venous thromboembolism, including deep venous thrombosis, superficial venous thrombosis, or pulmonary embolism, within 6 months prior to enrollment
- •Congestive heart failure (New York Heart Association [NYHA] class III or IV) within 6 months prior to enrollment or left ventricular ejection fraction (LVEF) less than 45% or less than the institutional lower limit of normal (whichever is higher) within 6 months prior to enrollment.
研究组 & 干预措施
Cohort A: Ponatinib 30 mg
Ponatinib 30 mg, tablets, orally, once daily (QD) until achievement of major molecular response (MMR) up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to 42 months.
干预措施: Ponatinib 30 mg QD (Drug)
Cohort B: Ponatinib 15 mg
Ponatinib 15 mg, tablets, orally, QD until achievement of MMR up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to 45 months.
干预措施: Ponatinib 15 mg QD (Drug)
Cohort C: Nilotinib 400 mg
Nilotinib 400 mg, tablets, orally, twice daily up to approximately 42 months.
干预措施: Nilotinib 400 mg BID (Drug)
结局指标
主要结局
Percentage of Participants With Major Molecular Response (MMR)
时间窗: Up to 12 months
MMR is defined as the percentage of participants achieving a ratio of ≤0.1% Breakpoint Cluster Region-Abelson (BCR ABL) to ABL transcripts on the international scale (≤0.1% BCR-ABL/ABL\[IS\]) at any time within 12 months after randomization.
次要结局
- Percentage of Participants With Treatment Emergent Arterial Occlusive Events (TE-AOEs), Treatment Emergent Venous Thromboembolic Events (TE-VTE), Adverse Events (AEs), and Serious AEs (SAEs)(From first dose up to 30 days post last dose (Up to approximately 46 months))
- Percentage of Participants With Complete Cytogenetic Response (CCyR)(Up to 12 months)
- Percentage of Participants With Molecular Response (MR)(From Month 3 to every 3 months up to 48 months)
- Percentage of Participants With MR1(Month 3)
- Time to Response(Up to approximately 60 months)
- Duration of Response(Up to approximately 60 months)
- Percentage of Participants Who Achieved/Maintained Complete Hematologic Response (CHR)(3 months after the first dose of study treatment)
- Percentage of Participants With Treatment Emergent AEs Leading to Treatment Discontinuation, Dose Reduction and Dose Interruption(From first dose up to end of treatment (Up to approximately 45 months))
- Percentage of Participants With Major Cytogenetic Response (MCyR)(Up to 12 months)
- Progression-free Survival (PFS)(Up to end of study (approximately 60 months))
- Overall Survival(Up to end of study (approximately 60 months))
- Percentage of Participants With Progression to Accelerated Phase (AP) or Blast Phase (BP)-CML(Up to end of study (Up to approximately 60 months))