FLUCLORIC
Etude prospective de phase III randomisée multicentrique comparant 2 types de conditionnement d’intensité réduite (clofarabine/busulfan versus fludarabine/busulfan) chez des patients adultes éligibles à une allogreffe de cellules souches hématopoïétiques et porteurs d’une leucémie aigue myéloblastique
Type d'essai : Académique / Institutionnel
Etat de l'essai : Ouvert
Situation thérapeutique : Hématologie ( Greffe / Car-t , GvH )
Etablissement(s) participant(s)
Dr Raynier DEVILLIER
Détails de l'essai
Objectif principal
To compare 2-year overall survival (OS) between patients with AML in complete remission receiving either a CloB2A2 or a FB2A2 RIC regimen for allo-SCT.
Résumé / schéma de l'étude
-1/J-7 before graft : Patient should be included.
Hospitalisation for conditionning regimen and graft :
After registration for the study, the following treatment plan is to be followed : FB2A2 arm or CloB2A2 arm.
Graft infusion on Day 0 : only peripheral blood stem cells will be accepted; CD34 target dose is 4 × 10^6 per Kg body weight, with a minimum of 2 ×106 per Kg body weight.
GVHD prophylaxis.
In case of sibling donor : Cyclosporine A (CsA) 3mg/kg/day IV from day -3.
In case of unrelated donor: Cyclosporine A (CsA) 3mg/kg/day IV from day -3+Mycophenolate Mofetil (MMF) oral; 500mg x 4/d from day -3.
Follow up visits: Graft+30 days, Graft+60 days, Graft+90/100 days, 6, 9, 12months and 24 months.
Experimental treatment : The CloB2 arm:
-30 mg/m2/day IV clofarabine for 5 days (day-6 to day-2).
-130 mg/m2/day IV busulfan once daily for 2 days (day -4 and -3).
– ATG (Thymoglobuline®) 2.5 mg/Kg/day IV for 2 consecutive days (day -2 and -1).
Corticosteroids may be used in profilaxis.
Comparator : FB2A2 arm:
-30 mg/m2/day IV fludarabine for 5 days (day-6 to day-2).
-130 mg/m2/day IV busulfan once daily for 2 days (day -4 and -3).
– ATG (Thymoglobuline®) 2.5 mg/Kg/day IV for 2 consecutive days (day -2 and -1).
Critère(s) d'inclusion
Main inclusion criteria
- Age ≥ 18 years old.
- De novo or secondary AML (according to ELN 2022 classification) in complete cytological remission at time of transplant (bone marrow blast count < 5%).
- Patients in first or second line therapy are allowed.
- Patient eligible to a RIC regimen: patients aged ≥ 60 year old or <60 year old with co-morbidity(ies).
- Patient with a related or an unrelated matched donor 10/10.
- Graft using peripheral blood stem cells.
- Performance status ECOG 0 – 2.
- Written informed consent.
- Previous allograft allowed.
Critère(s) de non-inclusion
Main exclusion criteria
- Pro-myelocytic leukemia.
- Patient eligible to a myeloablative conditioning regimen.
- Patient with haploidentical, mismatched unrelated donor or umbilical cord blood.
- Pregnant or breastfeeding woman or patient refusing contraceptive mesures.
- HIV positive.
- Active Hepatitis B or C.
- Left ventricular ejection fraction < 50%.
- DLCO < 40%.
- Uncontrolled infection.
- Uncontrolled haemolytic anaemia.
- Creatinine clearance < 50 ml/min (evaluated by MDRD or CKDEPI).
- Serum bilirubine < 30 mmol/l, Cytolysis >5 the upper limit range.
- Previous or concurrent second malignancy except for adequately treated basal cell carcinoma of the skin, curatively treated in situ carcinoma of the cervix, curatively treated solid cancer, with no evidence of disease for at least 2 years.
- Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
- Absence of written informed consent.
Calendrier prévisionnel
Lancement de l’étude : Septembre 2023
Fin estimée des inclusions : Septembre 2026
Nombre de patients à inclure : 302
Coordonnateur de l'étude
Dr Patrice CHEVALLIER
CHU NANTES
Promoteur de l'étude
CHU NANTES