Clinical and Biological Effects of 5-Azacitidine Five Days/Monthly Schedule in Symptomatic Low-risk Myelodysplastic Syndromes (MDSs)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 28
- 试验地点
- 7
- 主要终点
- To evaluate the toxicity of five days monthly 5-Aza treatment schedule in patients with low-risk MDS (IPSS 0-1).
研究概览
简要总结
Azacitidine will be given at a dose of 75 mg/sqm (s.c) daily for 5 consecutive days every 28 days (every month) for a total of 8 courses to low risk MDSs according to IPSS scoring system. In fact, several studies produced high rates of trilineage responses, reduces the risk of progression to acute myeloid leukemia (AML) in high-risk MDS and improves the quality of life (QoL). The use of 5-Aza in the earlier phases of MDS could reduce the proliferative advantage of MDS clone and favour the regrowth of normal hematopoiesis.
详细描述
5-Azacitidine(5-AZA) is the most promising drug for treatment MDSs. When administered at a dose of 75mg/m2/day subcutaneously for 7 days, every 28 days (every month), 5-Aza produces high rates of trilineage responses, reduces the risk of progression to AML in high-risk MDS and improves the QoL. The use of 5-Aza in the earlier phases of MDS could reduce the proliferative advantage of MDS clone and favour the regrowth of normal hematopoiesis. Other doses or schedules could improve its efficacy. Gene expression profile studies in MDS patients who are sensitive or resistant to 5-AZA are lacking and data coming from these studies could be useful to clarify the mechanisms of 5-azacitidine and optimize the therapy.
Objectives of the study
Primary:
- To evaluate the efficacy (hematologic response) and toxicity of 5-Aza five days monthly treatment schedule in patients with low-risk MDS (IPSS 0-INT1)
Secondary:
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with low-risk (IPSS 0-INT1) MDS according to WHO classification, presenting one or more of the followings:
- •Symptomatic anemia requiring RBC transfusion supportive therapy previously unresponsive to EPO or not expected to respond to EPO
- •Thrombocytopenia requiring platelet transfusion with or without muco-cutaneous haemorrhagic syndrome
- •Persistent (> 3 months) absolute neutrophil count less then 1,5 x 109/L, with or without infections, requiring or not myeloid growth factor therapy
- •≥ 18 years old.
- •Life expectancy ≥ 3 months.
- •ECOG performance Status Grade 0-
- •Serum bilirubin levels ≤ 1.5 upper limit of the normal (ULN)
- •Serum GOT and GPT levels ≤ 2x UNL.
- •Creatinine levels ≤ 1.5x UNL.
- •Negative serum β-human chorionic gonadotropin (β-HCG) pregnancy test 24 hours prior to beginning of therapy with 5-AZA, for fertile women.
- •Written informed consent.
排除标准
- •Patients with MDS according to WHO classification with INT-2 or high IPSS risk.
- •Life expectancy < 3 months.
- •ECOG performance Status Grade >
- •Serum bilirubin levels >1.5 upper limit of the normal (ULN).
- •Serum GOT and GPT levels > 2 x UNL.
- •Creatinine levels >1.5 x UNL.
- •Pregnancy or breast feeding.
- •Insulin-dependent diabetes and uncontrolled non insulin-dependent diabetes.
- •Severe cardiac or pulmonary disease incompatible with the conduction of the protocol.
- •Patient with a clear indication to receive long-term anticoagulant therapy.
- •Other active hematologic or solid tumors.
- •Severe CNS disease.
- •Malignant hepatic tumors.
- •Hypersensitivity to mannitol or azacitidine.
- •No written informed consent.
研究组 & 干预措施
Azacytidine
Azacitidine will be given at a dose of 75mg/sqm subcutaneous daily for 5 consecutive days every 28 days (every month) for a total of 8 courses. 5-Aza dosages will be adjusted.
干预措施: Azacytidine (Drug)
结局指标
主要结局
To evaluate the toxicity of five days monthly 5-Aza treatment schedule in patients with low-risk MDS (IPSS 0-1).
时间窗: 36 months
To evaluate the efficacy (hematologic response) of five days monthly 5-Aza treatment schedule in patients with low-risk MDS (IPSS 0-1).
时间窗: 36 months
次要结局
- To evaluate the QoL by the FACT-An questionnaire(36 months)
研究者
Domenico Russo
Full Professor of Hematology
Università degli Studi di Brescia