A Trial Testing Early Vs Late Onset of EPO Alfa Treatment in Lower Risk MDS (EPO-PRETAR)

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

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)

Study Overview

• Status: Active, not recruiting
• Conditions: Myelodysplastic Syndromes
• Intervention / Treatment: Drug: EPREX

Detailed Description

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

1. Early onset arm: early onset of EPO ALFA 60000 IU/week , at patient inclusion
2. 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).

• Study Type: Interventional
• Enrollment (Estimated): 124
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Amiens, France
    • CHU Amiens
  • Angers, France, 49 000
    • CH Angers
  • Avignon, France, 84000
    • Ch Avignon
  • Bayonne, France, 64100
    • Centre Hospitalier de la Côte Basque
  • Belfort, France, 90015
    • Hôpital Nord Franche-Comté
  • Besançon, France, 25030
    • CHU de Besançon
  • Bobigny, France, 9300
    • Hopital Avicenne
  • Brest, France, 29609
    • Hopital Morvan
  • Caen, France, 14033
    • CHU de Caen
  • Cesson, France, 35510
    • CH de Sevigné
  • Cholet, France, 49325
    • CH de Cholet
  • Clermont-Ferrand, France, 63000
    • CHU Estaing
  • Corbeil-Essonnes, France, 91100
    • CHSF Gilles de Corbeil
  • Créteil, France, 94010
    • Hôpital Henri-Mondor
  • Grenoble, France, 38043
    • CHU de Grenoble
  • Le Mans, France, 72000
    • Clinique Victor Hugo
  • Le Mans cedex, France, 72000
    • Centre Hospitalier du Mans
  • Lille, France, 59160
    • Hôpital Saint-Vincent de Paul
  • Limoges, France, 87042
    • CHRU Limoges
  • Lyon, France, 69495
    • Centre hospitalier Lyon Sud
  • Marseille, France, 13273
    • IPC
  • Mont-de-Marsan, France, 40000
    • Centre Hospitalier du Mont de Marsan
  • Nantes, France, 44093
    • CHU de Nantes
  • Nice, France
    • CHU de Nice
  • Paris, France, 75475
    • Hopital St Louis T4
  • Perpignan, France, 66046
    • Centre Hospitalier Joffre-Perpignan
  • Pessac, France, 33604
    • Sophie Dimicoli-Salazar
  • Poitiers, France, 86021
    • CHU de Poitiers
  • Pringy, France, 74374
    • CHR d'Annecy
  • Périgueux, France, 24019
    • CH de Périgueux
  • Reims, France, 51092
    • CHRU de Reims
  • Rennes, France, 35033
    • CHU Pontchaillou
  • Rouen, France, 76038
    • Centre Henri Becquerel
  • Saint-Nazaire, France, 44600
    • CH Saint Nazaire
  • Strasbourg, France, 67098
    • Centre Hospitalier Universitaire de Strasbourg
  • Toulouse, France, 31059
    • Iuct Oncopole
  • Troyes, France, 10003
    • CH de Troyes
  • Valence, France, 26953
    • CH Valence
  • Vandœuvre-lès-Nancy, France, 54511
    • Chu Brabois

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 18 years
2. MDS according to WHO 2016 criteria, with low or int 1 classical IPSS
3. Non-RBC transfusion dependent anemia
4. Hb level between 9 and 10.5g/dl (at the center's lab)
5. 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)
6. Serum EPO level <500U/l
7. No other cause of anemia (including iron deficiency, vitamin B12 or B9 deficiency, hemolysis, hypothyroidism….)
8. Performance status <=2

Exclusion Criteria:

1. Higher risk MDS (IPSS intermediate-2 or high)
2. Del 5q
3. Baseline Hemoglobin level > 10.5 g/dl or <9g/dl
4. Transfusion threshold (based on age , comorbidities…) >9g/dl
5. Transfusion threshold less than 1 g/dl below baseline Hb level
6. RBC transfusion dependence. Patients may have received only one transfusion series for MDS prior to inclusion
7. CMML , if >10 % BM blasts or WBC>13.000/mm3
8. Uncontrolled hypertension
9. Uncontrolled cardiovascular disease including angina pectoris or cardiac failure
10. Renal failure: Creatinine clearance<40ml/min (using MDRD formula)
11. Pregnancy (positive bettaHCG) or nursing

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Early onset arm; Intervention: early onset of Eprex60000 IU/week , at patient inclusion	Drug: EPREX; 60 000 U/week for at least 12 weeks; Other Names: Epoetin alfa
Experimental: Delayed onset arm; 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; 60 000 U/week for at least 12 weeks; Other Names: Epoetin alfa

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Groupe Francophone des Myelodysplasies
• Investigators: Principal Investigator: Sophie Park, Prof, University Hospital, Grenoble

Study record dates

Study Major Dates

• Study Start (Actual): March 26, 2018
• Primary Completion (Actual): September 21, 2023
• Study Completion (Estimated): October 1, 2028

Study Registration Dates

• First Submitted: July 11, 2017
• First Submitted That Met QC Criteria: July 18, 2017
• First Posted (Actual): July 21, 2017

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 6, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: myelodysplastic syndrome; erythropoetin
• Additional Relevant MeSH Terms: Neoplasms; Hematologic Diseases; Precancerous Conditions; Bone Marrow Diseases; Preleukemia; Myelodysplastic Syndromes; Hematinics; Epoetin Alfa
• Other Study ID Numbers: GFM-EPO-PRETAR

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No