Clinical and Biological Evaluation of Azacitidine in Transfusion-dependent Patients With Low and Intermediate-1 Risk MDS, and Low-risk CMML, Who Are Either Refractory to or Not Eligible for Treatment With Erythropoietin +/- G-CSF
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 17
- 主要终点
- Number of patients reaching transfusion independency after treatment with Azacitidine
研究概览
简要总结
Azacitidine has proved prolonged overall survival in patients with high-risk MDS. Minor pilot studies have shown that treatment with Azacitidine can induce transfusion independency in previous transfusion dependent patients with low-risk MDS. This study will evaluate the effect of Azacitidine in transfusion dependent patients with low-risk MDS (IPSS low or int-1) or low risk CMML. Included patients should first have failed, or considered not being eligible to, treatment with EPO +/- G-CSF. Our hypothesis is that Azacitidine can lead to transfusion independency in this group of patients. Those patients who do not respond to treatment with Azacitidine alone, will be given treatment with the combination of Azacitidine and EPO where our hypothesis is that Azacitidine can restore sensitivity to EPO.
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
- •Must be 18 years of age at the time of signing the informed consent form
- •MDS at IPSS Low or Int-1, or mixed MDS/MPD; either CMML with < 10% marrow blasts or RARS-T
- •Patients with high or intermediate probability for response according to the predictive model (see Hellstrom-Lindberg et al, Br J Haematol 99:344-51 1997)should be refractory to EPO / darbepoetin (equivalent to > 60 000 U of EPO / week for > 8 weeks) followed by EPO + G-CSF for > 8 weeks, or biosimilar drugs in equipotent doses, or EPO + G-CSF upfront for 8 weeks. Patients with low probability for response according to the predictive model, could be included without prior EPO/G-CSF treatment
- •Transfusion need >4 units over the last 8 weeks, or >8 units over the last 26 weeks.
- •Subject has signed the informed consent document.
- •Men and women of childbearing potential must use effective contraception during, and for up to 3 months after treatment.
排除标准
- •Pregnant or lactating females.
- •Patients who are eligible for curative treatment
- •Expected survival less than 24 weeks.
- •Symptomatic thrombocytopenia / active bleeding
- •Patients with JAK-2 positive RARS-T if eligible for new investigational drugs
- •Serum biochemical values as follows
- •Serum creatinine >2.0 mg/dL (177 micromol/L)
- •Serum aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) or alanine transaminase (ALT)/serum glutamate pyruvate transaminase (SGPT) >3.0 x upper limit of normal (ULN)
- •Serum total bilirubin >1.5 mg/dL (26 micromol/L)
- •Uncontrolled systemic infection
- •Considered not capable of following the study protocol
研究组 & 干预措施
Azacitidine +/- erythropoetin
干预措施: Azacitidine (Drug)
Azacitidine +/- erythropoetin
干预措施: Erythropoetin (Drug)
结局指标
主要结局
Number of patients reaching transfusion independency after treatment with Azacitidine
时间窗: Week 28
Hemoglobin level
时间窗: Week 28
次要结局
- Effect on leucocyte, platelet count(Week 28 and End of Trial)
- Hemoglobin level(End of Trial)
- Effect on bone marrow morphology and cytogenetics(Week 28 and End of Trial)
- Number of patients reaching transfusion independency after treatment with Azacitidine and Epo(End of Trial)
- Effect on genetic and epigenetic profile(Week 28)