Acute myeloid leukemia (AML) is a heterogeneous clonal myeloid neoplasm where abnormal proliferation and impaired differentiation of hematopoietic stem and myeloid progenitor cells impedes normal hematopoiesis. Sulfasalazine (SSZ) is a broadly available, well tolerated anti-inflammatory medicine approved for the treatment of ulcerative colitis and rheumatoid arthritis. Intact SSZ, but not its metabolites 5-aminosalicylic acid and sulfapyridine, competitively inhibits xCT.21 SSZ is thus an ideal candidate for drug repurposing in AML.The purpose of this phase I study is to evaluate the safety and feasibility of such strategy, provide preliminary signals of efficacy, and identify potential biomarkers

Inclusion Criteria:

• Patients aged 60 years or older
• With newly diagnosed acute myeloid leukemia (AML) (short course treatment with hydroxyurea and or steroids is acceptable). Patients with AML secondary to an antecedent Myelodysplastic Syndromes (MDS) or Myeloproliferative Neoplasms (MPN) are eligible, as those with therapy-related AML.
• Eligible for intensive chemotherapy in the investigator's opinion
• Leukaemia-associated immunophenotypes (LAIP) detected at screening allowing flow cytometry (FCM)-based Minimal Residual Disease monitoring (Phase II only).
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2
• Aspartate transaminase (AST) and Alanine transaminanse (ALT) ≤ 3.0 times upper the limit of normal (ULN) and total and direct serum bilirubin ≤ 1.5 x ULN unless considered due to leukemia Estimated glomerular filtration rate (GFR) ≥ 50 mL/min according to the MDRD equation
• Written informed consent obtained prior to any screening procedures
• Eligible for National Health Insurance in France

Exclusion Criteria:

• Myeloid Sarcoma with < 20% bone marrow blasts
• Patient who has received a vaccine injection with live-attenuated virus in the last three weeks
• Proven central nervous system leukemic involvement
• Favorable risk cytogenetics: t(15;17), t(8;21), inv(16) or t(16;16) or presence of PML-RARA, RUNX1-RUNX1T1 or CBFB-MYH11 fusion transcript.
• Presence of FLT3-ITD or TKD mandating treatment with midostaurin.
• Concurrent therapy with any cytotoxic drug within 3 weeks before the first study dose. Only hydroxyurea for the control of blood counts is permitted.
• Patients planned to received CPX-351 for myelodysplasia-related changes or therapy-related AML.

Previous treatment with sulfasalazine in the last 5 years or ongoing treatment with sulfasalazine or 5-aminosalicylic acid (5-ASA) for ulcerative colitis or inflammatory rheumatisms.

• History of allergy SSZ, one of its metabolites (5-aminosalicylic acid, 5-ASA) or mesalazine, other sulfonylarylamines sulfonamides or salicylates, or sulfasalazine excipients History of allergic reaction to idarubicin or idarubicin excipients
• History of allergic reaction to cytarabine or cytarabine excipients
• Known glucose 6-phosphate dehydrogenase deficiency.
• Known acute intermittent porphyria or porphyria variegata.
• Uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate treatment).
• Other uncontrolled or active malignant disease within prior 12 months (excluding myelodysplastic syndrome; cutaneous basal cell carcinoma, "in-situ" carcinoma of the cervix or breast, or other local malignancy excised).
• Known human immunodeficiency virus (HIV) infection or HIV-related malignancy.
• Clinically active hepatitis B or hepatitis C infection.
• Inability to swallow. Known malabsorption syndrome or other condition that may significantly impair absorption of oral study medications.
• Participation in another therapeutic interventional clinical study within 30 days of enrolment.
• Administration of any therapy considered investigational (i.e., used for non-approved indications(s) or in the context of a research investigation) within 5 drug half-lives (whichever is longer) prior to the first dose of study drug.
• Previous treatment by anthracyclines
• Any contraindication to use anthracyclines including uncontrolled coronary disease, severe renal failure, severe hepatic failure, recent myocardial infarction, symptomatic congestive heart failure, severe cardiomyopathy, significant arrhythmia as estimated by the investigator or left-ventricule ejection fraction (LVEF) <53% as assessed by echocardiography or Multigated Acquisition Scan (MUGA), anterior treatment by idarubicin and/or anthracyclines and anthracènediones beyond the maximum cumulative dose.
• Any contraindication to use cytarabine including degenerative and toxic encephalopathy.
• Any condition requiring treatment with digoxin.
• Any of concurrent severe and/or uncontrolled medical condition, which could compromise participation in the study.
• Females who are pregnant or breastfeeding.
• In a man whose sexual partner is a woman of childbearing potential, unwillingness or inability of the man or woman to use a highly effective contraceptive method for the entire treatment period and for at least 6 months after completion of protocol treatment.

Highly effective contraception methods include: combined (estrogen and progestogen containing) hormonal methods associated with inhibition of ovulation, intra-uterine device; surgical sterilization (including bilateral tubal occlusion, partner's vasectomy) or sexual abstinence if this is the preferred and usual lifestyle of the patient.

Male patients must not freeze or donate sperm starting at screening and throughout the treatment period and 3 months after the administration of the final dose of study medication.

- In a heterosexually active woman of childbearing potential, unwillingness or inability to use a highly effective contraceptive method (as described above) for the entire treatment period and for at least 6 months after the administration of the final dose of study medication.

Women are not regarded as of childbearing potential if they are post-menopausal (at least 2 years without menses) or are surgically sterile (at least 1 month before enrollment).

Female patients must not donate or retrieve, for their own use, ova from the time of screening and throughout the treatment period, and for 12 weeks after the administration of the final dose of study medication.

Female patients must agree not to breastfeed from the time of screening and throughout the protocol period, and for (5 half-lives) days after the administration of the final dose of study medication.

Adults subjects to a legal protection order or unable to give their consent

- Persons deprived of their freedom by judicial or administrative decision, person hospitalized without their consent by virtues of French Public Health Code articles L 3212-1 and L3213-1 and who are not subject to the provisions of article L 1121-8.