NCT00769327已完成2 期
Front-line Treatment of Philadelphia Positive (Ph Pos), BCRABL Positive, Chronic Myeloid Leukemia (CML) With Two Tyrosine Kinase Inhibitors (TKI) (Nilotinib and Imotinib) A Phase II Exploratory Multicentric Centre.
适应症
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 129
- 试验地点
- 37
- 主要终点
- Complete cytogenetic response rate
研究概览
简要总结
RATIONALE: Nilotinib and imatinib mesylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
PURPOSE: This phase II trial is studying how well giving nilotinib together with imatinib mesylate works in treating patients with early chronic phase chronic myelogenous leukemia.
详细描述
OBJECTIVES:
Primary
- To assess the complete cytogenetic response rate at 12 months in patients with Philadelphia chromosome- and BCR-ABL-positive early chronic phase chronic myelogenous leukemia treated with nilotinib and imatinib mesylate.
Secondary
- To assess the complete cytogenetic response rate at 6 and 24 months in these patients.
- To assess the major and complete molecular response rate at 6, 12, and 24 months in these patients.
- To assess the frequency and the types of BCR-ABL kinase domain mutations at 24 months during and for 3 years after study treatment.
- To assess the rate of failures and the time to failure at 12, 24, and 60 months in these patients.
- To assess compliance, toxicity, and adverse events in these patients.
- To understand the relationship between response, gene expression profile, biomarkers, and drug plasma concentrations in these patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 120 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •Cytologically and cytogenetically confirmed chronic myelogenous leukemia meeting the following criteria:
- •Early chronic phase disease (< 6 months from diagnosis)
- •Philadelphia chromosome-positive disease
- •BCR-ABL-positive
- •PATIENT CHARACTERISTICS:
- •WHO performance status 0-1
- •ALT and AST = 2.5 times upper limit of normal (ULN) (5.0 times ULN if considered due to leukemia)
- •Alkaline phosphatase = 2.5 times ULN (unless considered due to leukemia)
- •Serum bilirubin = 1.5 times ULN
- •Serum creatinine = 1.5 times ULN
- •Serum amylase = 1.5 times ULN
- •Serum lipase = 1.5 times ULN
- •Normal serum levels of the following or correctable with supplements:
- •Potassium
- •Total calcium (corrected for serum albumin)
- •Magnesium
- •Phosphorus
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective barrier method contraception during study and for up to 3 months following completion of study treatment
- •No impaired cardiac function, including any of the following:
- •LVEF < 45% by MUGA scan or echocardiogram
- •Uncontrolled congestive heart failure
- •Uncontrolled hypertension
- •Uncontrolled angina pectoris
- •Myocardial infarction within the past 12 months
- •No significant electric heart abnormalities, including any of the following:
- •History or active ventricular or atrial tachyarrhythmias
- •Congenital long QT syndrome and/or QTc > 450 msec on screening ECG
- •No history of acute (within one year) or chronic pancreatitis
- •No impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
- •No acute or chronic liver or renal disease considered unrelated to leukemia
- •No known diagnosis of HIV infection
- •No 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
- •No other primary malignancy that is currently clinically significant or requires active intervention
- •PRIOR CONCURRENT THERAPY:
- •More than 2 weeks since prior major surgery and recovered
- •More than 30 days since prior imatinib mesylate, with a washout period of ≥ 7 days
- •More than 4 weeks since prior investigational drug
- •No prior hematopoietic stem cell transplantation
- •No concurrent therapeutic coumarin derivates (i.e., warfarin, acenocoumarol, phenprocoumon)
- •No concurrent medications that would prolong the QT interval
- •No concurrent chemotherapy, investigational agents, radiotherapy, or biologic therapy
- •Prior treatment with hydroxyurea or anagrelide allowed
排除标准
- 未提供
结局指标
主要结局
Complete cytogenetic response rate
时间窗: At 12 months from study entry
次要结局
- Safety and tolerability(At 24 months from study entry)
- Major and complete molecular response rate(At at 6, 12 and 24 months from study entry)
- Relationship between response, the gene expression profile, the biomarkers of leukemic cells, and plasma concentrations of nilotinib and imatinib mesylate(At 24 months from study entry)
- Complete cytogenetic response(At at 6 and 24 months from study entry)
- Development of BCR-ABL kinase domain mutations (number, timing, and type)(At at 24 months during and for 3 years after study treatment)
- Rate of failures and the time to failure(At 12, 24, and 60 months from study entry)
- Frequency and type of adverse events (AE) and severe AE(At 24 months from study entry)
研究者
研究点 (37)
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