Biological Predictive Factors of Response to Erythropoiesis Stimulating Agent (ESA) in Low Risk Myelodysplastic Syndromes (MDS) Patients
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 70
- 主要终点
- Determination of the Red score on the prediction of response to ESA
研究概览
简要总结
In this trial, the investigators would like to understand why a small percentage of patients will be refractory to ESA (independently of International prognostic scoring system (IPSS) and % of blasts). In a retrospective study of the "Groupe Francophone des Myélodysplasies (GFM)" , the investigators showed that about 43% of patients are refractory or will relapse after initial response to ESA and it has been shown that these patients have a poorer survival. The investigators plan to give a 12-week treatment of Epoetin alfa or zeta in low risk MDS patients and measure different biological factors to predict response to ESA:
- evaluation by flow cytometry before and after treatment of the degree of dyserythropoiesis and dysgranulopoiesis which could explain the primary resistance or loss of response of a subset of patients,
- screening by molecular biology of predictive factors of response to ESA,
- Iron homeostasis will be measured via hepcidin, GDF-15 and ferritin levels.
详细描述
Lower risk MDS patients, with LOW and INT-1 IPSS score, with anemia Hb<10g/dl, requiring or not Red blood cel (RBC) transfusions, treated by erythropoiesis stimulating agent (ESA) according to national French recommendations ( epoetin zeta 40000 UI/week in lower risk MDS, <10% blasts, with Hb<10g/dl and sEPO<500UI/l, for 12 weeks).
BM aspirates are collected prospectively at T0 and at W12 of ESA treatment.
BM aspirates will be collected prospectively at inclusion in all 70 patients, after 12 weeks, in 70 patients.
Fresh bone marrow samples will be centralized at Cochin hospital for flow cytometry analysis of dyserythropoiesis and gene sequencing (Hematology laboratory, Cochin, Paris). "Ogata flow cytometry score" will be assessed locally in Mulhouse, Creteil, Tours, Grenoble or Cochin. Patients have been reevaluated at week 12 by flow cytometry "Ogata score".
Blood plasma will be been collected for analysis of GDF-15 and hepcidin, and sent to Cochin (Institut Cochin, Paris). Hepcidin level was measured by LC-MS/MS method in Louis Mourier Hospital.
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 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •> 18y patients
- •with MDS subtypes :
- •refractory anemia (RA), refractory anemia with ringed sideroblasts (RARS), refractory anemia with excess of blasts (RAEB) with <10 % blasts (according to FAB classification) CMML with white blood cell (WBC) <13.000/mm3
- •RA, RARS, RCMD, RAEB-1, CMML-1 with WBC <13.000/mm3 (according to OMS classification), 5q- syndrome
- •Low int-1 IPSS score
- •With hemoglobin (Hb)<10 g/dL or red blood cell transfusion (RBC) transfusion dependent
- •treated by ESA according to national French recommendations
- •without renal insufficiency
- •with ECOG PERFORMANCE STATUS <2
排除标准
- •higher risk MDS (IPSS intermediate-2 or high)
- •CMML with >10 % of BM blasts or WBC>13.000/mm3
- •Non-controlled hypertension
- •Cardio-vascular disease :uncontrolled, angina pectoris, cardiac insufficiency,
- •Renal insufficiency : Creatinine clearance<40ml/min
- •EPO level>500UI/l
- •Systemic infection or inflammatory chronic disease
- •Serum folates<2 ng/mL or vitamin B12 <200 pg/mL
- •Other causes of anemia (eg hemolysis, hemorrhage, iron deficiency)
- •Pregnancy (positive betaHCG) or nursing
- •Women of childbearing age without effective contraception why?
- •Hypersensitivity to Darbepoietin alfa or other ESA
- •Patient unable to understand the protocol or to follow adequately
- •History of epilepsy
- •History of thrombosis
- •Concomitant thalidomide or lenalidomide treatment
研究组 & 干预措施
epoetin zeta
Patients received epoetin zeta (Retacrit®) 40000UI/week subcutaneously during 12 weeks.
干预措施: Epoetin Zeta (Drug)
结局指标
主要结局
Determination of the Red score on the prediction of response to ESA
时间窗: 5 years
The flow cytometry (FCM) "Red score" described by Mathis et al, Leukemia 2013, ranges from 0 to 7 and includes CD36 and CD71 CV and Hb levels.
Determination of hepcidin levels on the prediction of response to ESA
时间窗: 5 years
Mean and median values of hepcidin (ng/ml)
Determination of Ogata FCM score on the prediction of response to ESA
时间窗: 5 years
The "Ogata FCM score" described by Ogata et al, Haematologica 2009, ranges from 0 to 4 and includes parameters of dysgranulopoiesis and excess of CD34+ blasts
Determination of GDF-15 levels on the prediction of response to ESA
时间窗: 5 years
Mean and median values of GDF15 (pg/ml) levels
Determination of the number of molecular gene mutations on the prediction of response to ESA
时间窗: 5 years
Gene mutations numbers, assessed by next generation sequencing on a 39 gene panel
次要结局
- Response rate to ESA(5 years)