Phase II Study of Low-Dose Intravenous Decitabine in Patients Aged > 60 Years With Acute Myeloid Leukemia Who Are Not Eligible for Standard Induction Chemotherapy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 238
- 试验地点
- 8
- 主要终点
- response rate (complete and partial remissions, antileukemic effect)
研究概览
简要总结
This study is an open-label phase II trial to investigate the efficacy and toxicity of low-dose decitabine (5-aza-2'-deoxycytidine) in elderly patients with acute myeloid leukemia (AML) not eligible for aggressive induction chemotherapy. AML patients above the age of 60 years (no upper age limit) who have not previously received and are not eligible for, standard induction treatment of their disease will be eligible for this trial. Decitabine will be administered as a 3 hour infusion at 15 mg/m2 three times daily on three consecutive days (total dose 135 mg/m2). In all patients with > 20000 WBC/µl, this treatment will be repeated 1 week later. In patients with white blood cells exceeding 50 000/μl, decitabine treatment will be preceded by cytoreductive doses of hydroxyurea.
详细描述
Hypothesis
If after 4 courses of Decitabine none out of 12 patients achieves a response (complete or partial remission, antileukemic effect), the protocol will be stopped. If at least one response is seen among the first 12 patients, 17 additional patients will be treated in an open, uncontrolled manner. If in 3 or more of these 29 patients a response is achieved, this treatment will be considered effective and will be studied further, otherwise it will be considered ineffective. At a preliminary analysis after recruitment of 29 patients, encouraging results (response rate, tolerability) are prompting continuation of recruitment, with a planned inclusion of at least 60 patients, until initiation of the planned large, controlled phase II follow-up trial. Unexpected toxicities will be carefully evaluated. 29 patients were needed for the first two steps of this phase II study, at least 60 patients are planned for the extension of the recruitment. Expected study duration for the first two steps was 15-20 months, with 35-40 months total when including the third step.
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
- 60 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients older than 60 years with acute myeloid leukemia (> 30 % bone marrow blasts) not qualifying for, or not consenting to, standard induction chemotherapy or immediate allografting
- •life expectancy > 3 months with successful treatment
- •performance status ECOG 0, 1, 2
- •age-adjusted normal cardiac, kidney, liver function (creatinine < 1.5 mg/dl unless leukemia-related, total bilirubin < 2.0 of upper normal limits)
- •patients with >50 000 leukocytes/µl in whom initial cytoreduction according to protocol is effective
- •written informed consent
排除标准
- •AML of FAB subtype M3
- •previous induction-type chemotherapy for MDS or AML
- •previous treatment with Decitabine, 5-azacytidine or ATRA
- •"low-dose" chemotherapy (e.g.hydroxyurea, cytosine arabinoside, melphalan) within 8 weeks prior to Decitabine treatment, except for cytoreduction of leukocytosis > 50 000/µl according to protocol - patients with > 50 000 leukocytes/µl in whom initial cytoreduction according to protocol is ineffective
- •treatment with cytokines within previous 4 weeks
- •concomitant use of any other investigational drug
- •other malignancy that is not in remission (previous chemotherapy for other malignancies is not an exclusion criteria)
- •cardiac insufficiency NYHA IV
- •HIV infection
- •other uncontrolled active infection
- •psychiatric disorder that interferes with treatment
- •known hypersensitivity to retinoids
- •contact lenses
研究组 & 干预措施
A
Decitabine 15 mg/m2 i.v. - single arm
干预措施: Decitabine 15 mg/m2 i.v. (Drug)
结局指标
主要结局
response rate (complete and partial remissions, antileukemic effect)
时间窗: after four treatment courses of Decitabine, after 6 months
次要结局
- overall survival(after 1 year)
- progression-free survival time(after 1 year)
- toxicity of Decitabine (alone and in combination with all-trans retinoic acid)(after 3-6 months)