Sulfasalazine in AML Treated by Intensive Chemotherapy: Elderly Patients-first Line Treatment

Inclusion Criteria:

• Patients aged 60 years or older

• With newly diagnosed acute myeloid leukemia (AML) (short course treatment withhydroxyurea and or steroids is acceptable). Patients with AML secondary to anantecedent Myelodysplastic Syndromes (MDS) or Myeloproliferative Neoplasms (MPN) areeligible, as those with therapy-related AML.

• Eligible for intensive chemotherapy in the investigator's opinion

• Leukaemia-associated immunophenotypes (LAIP) detected at screening allowing flowcytometry (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 thelimit of normal (ULN) and total and direct serum bilirubin ≤ 1.5 x ULN unlessconsidered due to leukemia Estimated glomerular filtration rate (GFR) ≥ 50 mL/minaccording 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 lastthree weeks

• Proven central nervous system leukemic involvement

• Favorable risk cytogenetics: t(15;17), t(8;21), inv(16) or t(16;16) or presence ofPML-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 studydose. Only hydroxyurea for the control of blood counts is permitted.

• Patients planned to received CPX-351 for myelodysplasia-related changes ortherapy-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) ormesalazine, other sulfonylarylamines sulfonamides or salicylates, or sulfasalazineexcipients 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 ongoingsigns/symptoms related to the infection without improvement despite appropriatetreatment).

• Other uncontrolled or active malignant disease within prior 12 months (excludingmyelodysplastic syndrome; cutaneous basal cell carcinoma, "in-situ" carcinoma of thecervix 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 maysignificantly impair absorption of oral study medications.

• Participation in another therapeutic interventional clinical study within 30 days ofenrolment.

• Administration of any therapy considered investigational (i.e., used fornon-approved indications(s) or in the context of a research investigation) within 5drug 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 arrhythmiaas estimated by the investigator or left-ventricule ejection fraction (LVEF) <53% asassessed by echocardiography or Multigated Acquisition Scan (MUGA), anteriortreatment by idarubicin and/or anthracyclines and anthracènediones beyond themaximum cumulative dose.

• Any contraindication to use cytarabine including degenerative and toxicencephalopathy.

• Any condition requiring treatment with digoxin.

• Any of concurrent severe and/or uncontrolled medical condition, which couldcompromise participation in the study.

• Females who are pregnant or breastfeeding.

• In a man whose sexual partner is a woman of childbearing potential, unwillingness orinability of the man or woman to use a highly effective contraceptive method for theentire treatment period and for at least 6 months after completion of protocoltreatment.

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 orinability to use a highly effective contraceptive method (as described above) forthe entire treatment period and for at least 6 months after the administration ofthe 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, personhospitalized without their consent by virtues of French Public Health Code articlesL 3212-1 and L3213-1 and who are not subject to the provisions of article L 1121-8.