The Protein Tyrosine Kinase Inhibitor Nilotinib as First-line Treatment of Ph+ Chronic Myeloid Leucemia (CML) in Early Chronic Phase: a Phase II Exploratory, Multicenter Study. GIMEMA Protocol CML 0307. EUDRACT 2007-000597-22.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 74
- 试验地点
- 37
- 主要终点
- Complete cytogenetic response (CCgR ) rate
研究概览
简要总结
Treating Ph pos CML with Imatinib is very effective since the majority of the patients achieve a complete cytogenetic response and a major molecular response and are alive and progression-free after 5 years. However, the great majority of responding patients are not leukemia-free and may be at risk of progression, molecular, cytogenetic and clinical, at any time. In case of disease progression due to Imatinib failure, nilotinib has been found to be very effective, as expected from the preclinical profile of the drug, that is much more potent against BCR-ABL and inhibits nearly all the imatinib-resistant BCR-ABL mutants. For these reasons, nilotinib is going to be registered for the treatment of imatinib-resistant CMl patients. For the same reasons, nilotinib is expected to be more efficient than imatinib also front-line, based on the principle that we should aim at preventing the emergence of resistance better that at treating resistance once it has emerged. This expectation can be tested safely, because the "toxicity profile" of Nilotinib may be even more convenient than that of Imatinib, due to the lower frequency of edema and fluid retention.
详细描述
Study Phase:
Phase II, Prospective, multicentric, non randomized, open label
Objectives:
The primary objective of the trial is to investigate the cytogenetic and molecular effects of the protein tyrosine kinase (PTK) inhibitor nilotinib in the treatment of early chronic phase Ph+ CML.
The secondary objectives are:
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
- •Patients with a cytologic and cytogenetic confirmed diagnosis of Ph+ CML.
- •Age ≥ 18 years old
- •Early CP (within 6 months from diagnosis)
- •No prior treatment with any antileukemic drugs with the exception of Hydroxyurea (HU) and Anagrelide.
- •WHO performance status of ≤ 2
- •Normal serum level of potassium, total calcium corrected for serum albumin, magnesium and phosphorus, or correctable with supplements
- •ALT and AST ≤ 2.5 x ULN or ≤ 5.0 x ULN if considered due to leukaemia.
- •Alkaline phosphatase ≤ 2.5 x ULN unless considered due to leukemia.
- •Serum bilirubin ≤ 1.5 x ULN
- •Serum creatinine ≤ 1.5 x ULN
- •Serum amylase ≤ 1.5 x ULN and serum lipase ≤ 1.5 x ULN.
- •Written informed consent prior to any study procedures being performed.
- •Exclusion criteria:
- •Impaired cardiac function, including LVEF < 45% as determined by MUGA scan or echocardiogram, uncontrolled congestive heart failure, uncontrolled hypertension
- •History of myocardial infarction within three months, or uncontrolled angina pectoris.
- •Significant electric heart abnormalities, including history or presence of significant ventricular or atrial tachyarrhythmias, congenital long QT syndrome and/or QTc > 450 msec on screening ECG (using the QTcF formula).
- •Patients with ventricular pacemakers and clinically significant bradycardias.
- •Patients with heart blocks.
- •History of acute or chronic pancreatitis.
- •Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of nilotinib (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
- •Use of therapeutic coumarin derivates (i.e. warfarin, acenocoumarol, phenprocoumon).
- •Acute or chronic liver or renal disease considered unrelated to leukaemia
- •Other concurrent severe and/or uncontrolled medical conditions (e.g., uncontrolled diabetes, active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol
- •Patients who are currently receiving treatment with any of the medications listed in Appendix E and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug. The medications listed in Appendix E have the potential to prolong QT, with the exception of HU and Anagrelide.
- •Patients who have received any antileukemic agents and treatments, including HSCT, with the exception of HU and Anagrelide.
- •Patients who have received any investigational drug ≤ 4 weeks.
- •Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy.
- •Patients who are pregnant or breast feeding, or adults of reproductive potential not employing an effective method of birth control. (Women of childbearing potential must have a negative serum pregnancy test within 48 hrs prior to administration of nilotinib). Post menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Male and female patients must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug.
- •Treatment with any hematopoietic colony-stimulating growth factors (e.g. G-CSF, GM-CSF) 1 week prior to starting study drug.
- •Patients who have received immunotherapy 1 week prior to starting study drug or who have not recovered from side effects of such therapy.
- •Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory).
- •Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention.
- •Patients unwilling or unable to comply with the protocol.
排除标准
- 未提供
结局指标
主要结局
Complete cytogenetic response (CCgR ) rate
时间窗: At 1 year
次要结局
- The development of bcr-abl mutation during the treatment with AMN107 (number and type)(At 1 year)
- To describe any SAE(At 1 year)
- The kinetics of haematologic, cytogenetic and molecular response to AMN107(At 1 year)
- The safety and tolerability of nilotinib treatment at the dose of 300 mg b.i.d(At 1 year)
- The complete and the partial cytogenetic response rate(At 6 months)
- The major molecular response (MMR) rate(At 1 year)