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

Myelodysplastic Syndromes Clinical Trial

— EPO-PRETAR  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03223961
• Other study ID #: GFM-EPO-PRETAR
• Status: Recruiting
• Phase: Phase 3
• Start date: March 26, 2018
• Est. completion date: May 16, 2024

Study information

• Verified date: November 2020
• Source: Groupe Francophone des Myelodysplasies
• Contact: Sophie Park, Prof
• Phone: +33 (0)4 76 76 62 77
• Email: spark[@]chu-grenoble.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 124
• Est. completion date: May 16, 2024
• Est. primary completion date: May 16, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Myelodysplastic Syndromes
• Preleukemia

Intervention

Drug:
• EPREX
60 000 U/week for at least 12 weeks

Locations

Country	Name	City	State
France	Chu Amiens	Amiens
France	CH Angers	Angers
France	CH Avignon	Avignon
France	Centre Hospitalier de La Cote Basque	Bayonne
France	Hopital Nord Franche-Comté	Belfort
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	Clinique Victor Hugo	Le Mans
France	Centre Hospitalier du Mans	Le Mans cedex
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	CH de Périgueux	Périgueux
France	Centre Hospitalier Joffre-Perpignan	Perpignan
France	Sophie Dimicoli-Salazar	Pessac
France	CHU de Poitiers	Poitiers
France	CHR d'Annecy	Pringy
France	CHRU de Reims	Reims
France	CHU Pontchaillou	Rennes
France	Centre Henri Becquerel	Rouen
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

Sponsors (1)

Lead Sponsor	Collaborator
Groupe Francophone des Myelodysplasies

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Erythroid response (according to IWG 2006 criteria)	Erythroid response (according to IWG 2006 criteria) after 12 weeks of EPO ALFA treatment	12 weeks
Secondary	response duration to EPO ALFA	response duration to EPO ALFA measured from the date of enrollment until failure	4 years
Secondary	Overall survival	Overall survival measured from the date of enrollment to death or the date of last contact	4 years