Oral Decitabine Plus Ivosidenib as First Line for Older/Unfit Adult AML Patients

The goal of this clinical trial is to learn if the combination of oral decitabine plus ivosidenib works to treat naïve adult patients with acute myeloid leukemia (AML) with IDH1 R132 mutation older than 60 years old or those who are older than 18 years old with defined comorbidities that make them not suitable for standard induction therapy. The main objectives of this clinical trial are: * Asses the Complete Remission (CR) and Complete Remission with incomplete marrow recovery (CRi) rates of this treatment. * Determine the incidence and severity of all adverse events (AEs). All participants will receive oral ivosidenib and oral decitabine in treatment cycles of 28 days until disease progression, lack of clinical benefit or the end of the study. Patients who achieve CR/CRi will be elegible to receive allogeneic stem cell transplantation.

Inclusion Criteria: 1. Morphological diagnosis of AML (WHO criteria 2022) 2. Newly diagnosed AML. 3. IDH1 R132 mutations (centrally assessed by PCR and NGS). A patient will be allowed to be included with local result after approval of the medical monitor. 4. Subject must have an Eastern Cooperative Oncology Group (ECOG) Performance status of 0 to 2 if ≥ 60 years of age, or 0 to 3 if ≥ 18 to 60 years. 5. Age ≥ 18 years with comorbidities contraindicating intensive chemotherapy; or age ≥ 60 years. * ≥ 60 years of age; * or ≥ 18 to 60 with at least one of the following co-morbidities: * ECOG Performance Status of 2 or 3; * Cardiac history of CHF requiring treatment or Ejection Fraction ≤ 55% or chronic stable angina; * DLCO ≤ 65% or FEV1 ≤ 65% or significant history of chronic pulmonary obstructive; * Creatinine clearance ≥ 25 mL/min to \< 50 ml/min * Moderate hepatic impairment with total bilirubin \> 1.5 to ≤ 3.0 × ULN * Non active/controlled prior neoplastic disease * Any other patient´s comorbidity or disease condition that the physician judges to be incompatible with intensive chemotherapy must be reviewed and approved by the PETHEMA medical monitor before study enrolment (e.g, prior MDS or MPS, high-risk cytogenetics) 6. Patients \ 2.5 × ULN (unless considered to be due to leukemic disease, in which case it should be approved by the PETHEMA medical monitor) 11. Subject has a white blood cell count \> 30 × 109/L that is not controlled using hydrea or 1 gr/sqm/day per 1 day of cytarabine. 12. Contraindications for IVO or oral decitabine according to the SmPC. 13. Patient has a heart rate-corrected QT interval using Fridericia's method QT for corrected heart rate (QTcF) ≥450 msec or any other factor that increases the risk of QT prolongation or arrhythmic events (e.g., hypokalemia, family history of long QT interval syndrome). Patients with prolonged QTcF interval in the setting of bundle branch block may participate in the trial.