A Clinical Trial to Assess the Efficacy and Safety of the Combination of a Drug Call Quizartinib With Chemotherapy (FLAG-IDA) in Patients With Acute Myeloid Leukemia That Has Not Responded to the First Treatment or That Has Returned After the First Treatment

Inclusion Criteria:

1. Written informed consent in accordance with national, local, and institutionalguidelines. The patient must provide informed consent prior to the first screeningprocedure. Informed consent form must be signed by the patient and the Investigator.
2. Patients aged ≥ 18 years old and ≤70 years old at the time of screening.
3. First R/R AML defined as:

• First relapse after frontline intensive chemotherapy (with or without prioralloSCT), irrespectively of the duration of the first CR. Patients previouslytreated with a FLT3 inhibitor different from quizartinib, can be included.
• First refractory disease (defined as patients not achieving at least a PR afterfirst induction cycle and/or not achieving CR/CRi after first 2 cycles). Patientspreviously treated with a FLT3 inhibitor different from quizartinib, can beincluded.

4. Non-APL AML.
5. Considered for intensive approach as per Investigator judgment.
6. ECOG 0-2.
7. No contraindications for quizartinib.
8. No contraindications for intensive chemotherapy.
9. No severe organ function abnormalities.
10. No active relevant GVHD.
11. For the Phase II, FLT3-ITD patients will represent 50% of the study cohort (FLT3-TKDare not excluded but included in the FLT3-ITD-WT group).
12. Female patients of child-bearing potential must have a negative serum pregnancy testat screening and agree to use reliable methods of contraception upon enrollment,during the treatment period and for 6 months following the last dose ofinvestigational drug or cytarabine, whichever is later.
13. Male patients must use a reliable method of contraception (if sexually active with afemale of child-bearing potential) upon enrollment, during the treatment period, andfor 6 months following the last dose of investigational drug or cytarabine, whicheveris later.

Exclusion Criteria:

1. Patients with genetic diagnosis of acute promyelocytic leukemia.
2. Blastic phase of bcr/abl chronic myeloid leukemia.
3. Patients with other neoplastic disease, for whom the Investigator has clinicalsuspicion of active disease at the time of enrollment. Note: Patients with adequatelytreated early stage squamous cell carcinoma of the skin, basal cell carcinoma of theskin, or cervical intraepithelial neoplasia are eligible for this study. Hormonal oradjuvant therapies will be allowed for breast cancer or prostate cancer if they are ona stable dose for at least 2 weeks prior to first dose.
4. Presence of any severe psychiatric disease or physical condition/comorbidity that,according to the physician´s criteria, contraindicates the inclusion of the patient inthe clinical trial
5. Serum creatinine ≥ 250 μmol/l (≥ 2.5 mg/dL) (unless it is attributable to AMLactivity).
6. Bilirubin, alkaline phosphatase, or SGOT >3 times the upper normal limit (unless it isattributable to AML activity).
7. Uncontrolled or significant cardiovascular disease, including any of the following:

• Symptomatic bradycardia of less than 50 beats per minute, unless the subject hasa pacemaker.
• QTcF >450 ms at screening. Note: QTcF will be derived from the mean of triplicatereadings.
• Diagnosis of or suspicion of long QT syndrome (including family history of longQT syndrome)
• History of clinically relevant ventricular arrhythmias (e.g., ventriculartachycardia, ventricular fibrillation, or Torsade de Pointes).
• History of second- (Mobitz II) or third-degree heart block (subjects withpacemakers are eligible if they have no history of fainting or clinicallyrelevant arrhythmias while using the pacemaker).
• History of uncontrolled angina pectoris or myocardial infarction within 6monthsprior to Screening.
• History of New York Heart Association Class 3 or 4 heart failure.
• Complete left bundle branch block.
• Right bundle branch and left anterior hemiblock (bifascicular block)
• Infarction (MI) within 3 months.
• Systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥ 110 mmHg
• A previously known left ventricle ejection fraction <45%

8. Uncontrolled (i.e., clinically unstable) infection requiring parenteral antibiotics,antivirals, or antifungals within one week prior to first dose; however, prophylacticuse of these agents is acceptable even if parenteral.
9. Active hepatitis B or hepatitis C infection.
10. Previously known and documented human immunodeficiency virus (HIV) infection (HIVtesting is not required as part of this study).
11. Active acute or chronic GVHD requiring prednisone >10 mg or equivalent corticosteroiddaily
12. Any patients with known significant impairment in gastrointestinal function orgastrointestinal disease that may significantly alter the absorption of quizartinib
13. History of hypersensitivity to any excipients in the quizartinib tablets.
14. Females who are pregnant or breastfeeding.
15. Isolated extramedullary R/R AML.
16. Only applicable to patients screened after the first cohort of 34 patients of thePhase II has been achieved (e.g., FLT3-ITD negative): patients must have aconfirmation of FLT3-ITD status at relapse, and this must correspond to thenon-achieved cohort (e.g. FLT3-ITD positive).