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

Phase 3

Active, not recruiting

• Conditions: Myelodysplastic Syndromes
• Interventions: Drug: EPREX

• Registration Number: NCT03223961
• Lead Sponsor: Groupe Francophone des Myelodysplasies

Brief Summary

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

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 Timeline

• Study First Submitted: 2017-07-11
• Study First Submitted QC: 2017-07-18
• Study First Posted: 2017-07-21
• Study Start: 2018-03-26
• Primary Completion: 2023-09-21
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-06
• Last Update Posted: 2025-03-11
• Study Completion: 2028-10-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 124

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Early onset arm	EPREX	Intervention: early onset of Eprex60000 IU/week , at patient inclusion
Delayed onset arm	EPREX	Intervention: late introduction of Eprex60000 IU/week, whenever the patient reaches the level chosen RBC transfusions (based on age, comorbidities, anticipated tolerance of anemia).

Primary Outcome Measures

Name	Time	Method
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	12 weeks	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.

Secondary Outcome Measures

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

Trial Locations

Locations (39)

CH Angers; 🇫🇷 Angers, France

CH Avignon; 🇫🇷 Avignon, France

Centre Hospitalier de La Cote Basque; 🇫🇷 Bayonne, France

Hopital Nord Franche-Comté; 🇫🇷 Belfort, France

CH Saint Nazaire; 🇫🇷 Saint-Nazaire, France

Centre Hospitalier Universitaire de STRASBOURG; 🇫🇷 Strasbourg, France

IUCT Oncopole; 🇫🇷 Toulouse, France

CH de Troyes; 🇫🇷 Troyes, France

CH Valence; 🇫🇷 Valence, France

CHU Brabois; 🇫🇷 Vandœuvre-lès-Nancy, France

Chu Amiens; 🇫🇷 Amiens, France

CHU de Besançon; 🇫🇷 Besançon, France

Hopital Avicenne; 🇫🇷 Bobigny, France

Hôpital Morvan; 🇫🇷 Brest, France

CHU de Caen; 🇫🇷 Caen, France

CH de Sevigné; 🇫🇷 Cesson, France

CH de Cholet; 🇫🇷 Cholet, France

CHU Estaing; 🇫🇷 Clermont-Ferrand, France

CHSF Gilles de Corbeil; 🇫🇷 Corbeil-Essonnes, France

Hôpital Henri-Mondor; 🇫🇷 Créteil, France

CHU de Grenoble; 🇫🇷 Grenoble, France

Centre Hospitalier du Mans; 🇫🇷 Le Mans cedex, France

Clinique Victor Hugo; 🇫🇷 Le Mans, France

Hopital Saint-Vincent de Paul; 🇫🇷 Lille, France

CHRU Limoges; 🇫🇷 Limoges, France

Centre Hospitalier Lyon Sud; 🇫🇷 Lyon, France

IPC; 🇫🇷 Marseille, France

Centre Hospitalier du Mont de Marsan; 🇫🇷 Mont-de-Marsan, France

CHU de Nantes; 🇫🇷 Nantes, France

CHU de Nice; 🇫🇷 Nice, France

Hopital St Louis T4; 🇫🇷 Paris, France

Centre Hospitalier Joffre-Perpignan; 🇫🇷 Perpignan, France

Sophie Dimicoli-Salazar; 🇫🇷 Pessac, France

CHU de Poitiers; 🇫🇷 Poitiers, France

CHR d'Annecy; 🇫🇷 Pringy, France

CH de Périgueux; 🇫🇷 Périgueux, France

CHRU de Reims; 🇫🇷 Reims, France

CHU Pontchaillou; 🇫🇷 Rennes, France

Centre Henri Becquerel; 🇫🇷 Rouen, France