Biological Predictive Factors of Response to ESA in Low Risk MDS Patients

• Status: Completed
• Trial end date: 2018-05-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Association pour la recherche sur les Affections Malignes en Immunologie Sanguine
• Treatments: Epoetin Alfa; Hematinics

Criteria

Inclusion Criteria:

> 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

Exclusion Criteria:

• 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