Dexamethasone Added to Intensive Chemotherapy in Older Patients with Acute Myeloid Leukemia (AML)

Patients will receive dexamethasone in addition to induction and post-remission chemotherapy

The principal objective of the study is to determine whether adding dexamethasone to induction and post-remission therapy results in significant improvement of event-free survival (EFS) as compared with an historical cohort of the FILO LAM-SA 2007 trial.

Induction therapy: Idarabucin + Cyrarabine + Lomustine (ICL) + Dexamethasone. Idarubicin 8 mg/m²/day, IV over 15 minutes, D1 to D5; Cytarabine 100 mg/m²/d, IV continuous 24h-infusion D1 to D7; Lomustine 200 mg/m²/d, orally at D1; Dexamethasone 10 mg/12h, IV over 30 minutes, D1 to D3.

Post remission therapy: Idarabucin + Cyrarabine (IC) + Dexamethasone

Idarubicin 8 mg/m², IV over 15 minutes, D1; Cytarabine 50 mg/m²/12h, subcutaneous, D1 to D5; Dexamethasone 20 mg/d, IV over 30 minutes, D1.

Inclusion criteria

• > 60 years of age.
• Newly diagnosed AML according to the World Health Organization (WHO) 2016 either de novo AML or therapy-related AML (i.e AML arising after previous cytotoxic therapy or radiation)
• AML with favorable or intermediate cytogenetic risk according to Medical Research Council (MRC 2010) classification.
• Subjects should be eligible for intensive chemotherapy by Idarubicin, cytarabine, Lomustine.
• Eastern Cooperative Oncology Group (ECOG) performance status < 3 (appendix 1).
• SORROR score ≤ 3 (appendix 2).
• Adequate baseline organ function defined by the criteria below:

• Total bilirubin ≤ 1.5 x Upper Limit of Normal (ULN) unless bilirubin rise is due to Gilbert's syndrome
• Alanine Aminotransferase (ALAT) and Aspartate Transaminase (ASAT) ≤ 3xULN
• creatinin clearance (Cockcroft-Gault) ≥ 30 ml/min
• Unless considered due to leukemic organ involvement
• Adequate cardiac function with Left Ventricular Ejection Fraction (LVEF) ≥50%
• Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
• Women will be menopausal to be enrolled
• The patient must give written (personally signed and dated) informed consent before completing any study-related procedure which means assessment or evaluation that would not form part of the normal medical care of the patient and before the start of induction chemotherapy.
• Affiliated to the French Social Security (Health Insurance).

Exclusion criteria

• Acute promyelocytic leukemia (APL) or acute megakaryocytic leukemia (AML-FAB M7).
• AML with adverse cytogenetic risk according to the MRC 2010 classification.
• AML arising from myelodysplastic syndromes, myeloproliferative disorders or chronic myelo-monocytic leukemia according to WHO classification (2016).
• AML with Philadelphia chromosome or with BCR-ABL1.
• Known active central nervous system leukemia
• Previous anti-AML treatment other than hydroxyurea.
• Cumulative anthracycline dose equivalent to ≥550 mg/m².
• Treatment with an investigational drug within 30 days or 5 half-life whichever is longer, preceding the first dose of study medication.
• Prior history of cancer unless controlled for at least 2 years and except for basal cell carcinoma, non-melanoma skin cancer and in situ cervical carcinoma.
• Severe medical or mental condition precluding the administration of protocol treatments
• Any sign of active uncontrolled disease including but not restricted to cardiac disease, infections, hepatitis.
• Any severe chronic disease potentially interfering with the protocol including HIV infection, active hepatitis B or C.
• Any severe conditions inducing contra-indications to dexamethasone including uncontrolled diabetes, infections, hypertension, stomach ulcer, mental illness, myasthenia or glaucoma.
• Any serious medical condition, laboratory abnormality, or psychiatric illness that would place the participant at an unacceptable risk or prevent them from giving informed consent.
• Known active HIV, Hepatitis B or C infection.
• Pregnancy or breastfeeding.
• Patients who are incapacitated, under wardship, legal guardianship, or under the protection of the courts.
• Patients under State Medical Assistance (AME).