Clinical trial NCT03223961: A Trial Testing Early vs Late Onset of EPO Alfa Treatment in Lower Risk MDS
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Myelodysplastic Syndromes
Keywords: myelodysplastic syndrome
erythropoetin
Lead sponsor: Groupe Francophone des Myelodysplasies
Sponsor class: OTHER
First posted: 2017-07-21
Enrollment: 124
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: randomazed study
Primary purpose: TREATMENT

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).

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: 12 weeks
Secondary outcomes:
measure: Erythroid response (according to IWG 2006 criteria)
timeFrame: 12 weeks
measure: response duration to EPO ALFA
timeFrame: 4 years
measure: Overall survival
timeFrame: 4 years
Other outcomes:
Locations:
city: Amiens
country: France
facility: Chu Amiens
city: Angers
country: France
facility: CH Angers
city: Avignon
country: France
facility: CH Avignon
city: Bayonne
country: France
facility: Centre Hospitalier de La Cote Basque
city: Belfort
country: France
facility: Hopital Nord Franche-Comté
city: Besançon
country: France
facility: CHU de Besançon
city: Bobigny
country: France
facility: Hopital Avicenne
city: Brest
country: France
facility: Hôpital Morvan
city: Caen
country: France
facility: CHU de Caen
city: Cesson
country: France
facility: CH de Sevigné
city: Cholet
country: France
facility: CH de Cholet
city: Clermont-Ferrand
country: France
facility: CHU Estaing
city: Corbeil-Essonnes
country: France
facility: CHSF Gilles de Corbeil
city: Créteil
country: France
facility: Hôpital Henri-Mondor
city: Grenoble
country: France
facility: CHU de Grenoble
city: Le Mans cedex
country: France
facility: Centre Hospitalier du Mans
city: Le Mans
country: France
facility: Clinique Victor Hugo
city: Lille
country: France
facility: Hopital Saint-Vincent de Paul
city: Limoges
country: France
facility: CHRU Limoges
city: Lyon
country: France
facility: Centre Hospitalier Lyon Sud
city: Marseille
country: France
facility: IPC
city: Mont-de-Marsan
country: France
facility: Centre Hospitalier du Mont de Marsan
city: Nantes
country: France
facility: CHU de Nantes
city: Nice
country: France
facility: CHU de Nice
city: Paris
country: France
facility: Hopital St Louis T4
city: Perpignan
country: France
facility: Centre Hospitalier Joffre-Perpignan
city: Pessac
country: France
facility: Sophie Dimicoli-Salazar
city: Poitiers
country: France
facility: CHU de Poitiers
city: Pringy
country: France
facility: CHR d'Annecy
city: Périgueux
country: France
facility: CH de Périgueux
city: Reims
country: France
facility: CHRU de Reims
city: Rennes
country: France
facility: CHU Pontchaillou
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Saint-Nazaire
country: France
facility: CH Saint Nazaire
city: Strasbourg
country: France
facility: Centre Hospitalier Universitaire de STRASBOURG
city: Toulouse
country: France
facility: IUCT Oncopole
city: Troyes
country: France
facility: CH de Troyes
city: Valence
country: France
facility: CH Valence
city: Vandœuvre-lès-Nancy
country: France
facility: CHU Brabois
Study officials:
affiliation: University Hospital, Grenoble
name: Sophie Park, Prof
role: PRINCIPAL_INVESTIGATOR
References: