A Trial Testing Early vs Late Onset of EPO Alfa Treatment in Lower Risk MDS

Study Overview
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Brief Summary
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This is an open-label, randomized, multicenter, phase III study Patients with baseline Hb comprised between 9 and 10.5g/dl will be randomized to receive EPO Alfa 60000 UI/week for at least 12 weeks: Either at diagnosis Or at the Hb threshold chosen for RBC transfusions (must be < 9g/dl)

Detailed Description
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in this trial we will compare the early introduction of EPO alfa to the delayed introduction in lower risk MDS with non RBC transfusion dependent anemia. At enrollment patients will be randomised in the 2 arms (early and delayed start of EPO alfa). Treatment Regimen Epoetin alfa 60000 UI/week for at least 12 weeks Early onset arm: early onset of EPO ALFA 60000 IU/week , at patient inclusion Delayed onset arm: late introduction of EPO ALFA 60000 IU/week, whenever the patient reaches the level chosen RBC transfusions (based on age, comorbidities, anticipated tolerance of anemia).

Official Title
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A Randomized Trial Testing Early vs Late Onset of EPO Alfa Treatment in Lower Risk MDS With Non RBC Transfusion Dependent Anemia and Without Del 5q

Conditions
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Myelodysplastic Syndromes

Intervention / Treatment
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* Drug: EPREX


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years MDS according to WHO 2016 criteria, with low or int 1 classical IPSS Non-RBC transfusion dependent anemia Hb level between 9 and 10.5g/dl (at the center's lab) Hb level should be at least 1g/dl higher than the Hb threshold chosen to start RBC transfusions based on age, comorbidities and predicted clinical tolerance of anemia (this transfusion threshold should be chosen between 8 and 9g/dl) Serum EPO level <500U/l No other cause of anemia (including iron deficiency, vitamin B12 or B9 deficiency, hemolysis, hypothyroidism….) Performance status <=2 Exclusion Criteria: Higher risk MDS (IPSS intermediate-2 or high) Del 5q Baseline Hemoglobin level > 10.5 g/dl or <9g/dl Transfusion threshold (based on age , comorbidities…) >9g/dl Transfusion threshold less than 1 g/dl below baseline Hb level RBC transfusion dependence. Patients may have received only one transfusion series for MDS prior to inclusion CMML , if >10 % BM blasts or WBC>13.000/mm3 Uncontrolled hypertension Uncontrolled cardiovascular disease including angina pectoris or cardiac failure Renal failure: Creatinine clearance<40ml/min (using MDRD formula) Pregnancy (positive bettaHCG) or nursing

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: randomazed study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Early onset arm<br>Intervention: early onset of Eprex60000 IU/week , at patient inclusion | Drug: EPREX<br>* 60 000 U/week for at least 12 weeks<br>* Other names: Epoetin alfa;|
| Experimental: Delayed onset arm<br>Intervention: late introduction of Eprex60000 IU/week, whenever the patient reaches the level chosen RBC transfusions (based on age, comorbidities, anticipated tolerance of anemia). | Drug: EPREX<br>* 60 000 U/week for at least 12 weeks<br>* Other names: Epoetin alfa;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to RBC transfusion dependence in non RBC transfusion dependent lower risk MDS patients with anemia with early (at inclusion of the patient) versus delayed onset,( at the threshold chosen for RBC transfusion) of EPO ALFA | RBC transfusion dependence will be defined by requirement of at least transfusions of 2 PRBC within an interval of less than 8 weeks, given for Hb <8g/dl or <9g/dl according to comorbidities and in the absence of other cause of anemia (bleeding, surgery…), taking into account only transfusions given at least 12 weeks after onset of treatment with EPO ALFA. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Erythroid response (according to IWG 2006 criteria) | Erythroid response (according to IWG 2006 criteria) after 12 weeks of EPO ALFA treatment | 12 weeks | 
| response duration to EPO ALFA | response duration to EPO ALFA measured from the date of enrollment until failure | 4 years | 
| Overall survival | Overall survival measured from the date of enrollment to death or the date of last contact | 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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myelodysplastic syndrome, erythropoetin