IMPACT-AML: A Randomized Pragmatic Clinical Trial for Relapsed or Refractory Acute Myeloid Leukemia.

Inclusion Criteria:

• Non-Acute promyelocytic leukemia (APL) AML defined according World HealthOrganization (WHO) 2022 (or International Consensus Classification (ICC) 2022)criteria

• 1st or 2nd relapse or refractory according to European leukemia Network (ELN) 2022

• Patient is clinically candidate to both low intensity therapy and high dosechemotherapy in the opinion of the physician

• Both low intensity therapy and high dose chemotherapy to which patient is candidateare available and can be provided as per local practice

• No specific treatment protocol can be rationally considered better suited to patientneeds.This specifically include, but is not limited to: i) the availability of a drug that is already demonstrated superior to comparatorarm and can be considered the only standard of care ii) specific contraindicationsrelated to fitness or any medical conditions that deem to avoid one of the two armsof this randomization iii) patient willingness to avoid one of the two arm of thisrandomization iv) lack of social support that make unfeasible one of the two arm ofthis randomization

• Male or Female, aged>18 years

• Eastern Cooperative Oncology Group (ECOG) performance status <4

• A female participant is eligible to participate if she is not pregnant and notbreastfeeding. If Women of childbearing potential (WOCBP), negative serum pregnancytest within 14 days of starting treatment must be obtained. WOCBP must adopt highlyeffective birth control methods, according to guideline "Recommendation related tocontraception and pregnancy testing in clinical trials". Male patient and his femalepartner who is of childbearing potential must use 2 methods of birth control (acondom as a barrier method of contraception and one of the highly effective birthcontrol methods, according to guideline "Recommendation related to contraception andpregnancy testing in clinical trials". Use of- and compliance to- birth controlmethods are required beginning at the screening visit and continuing until 6 monthsfollowing last treatment with study drug.

• Participant is willing and able to give informed consent for participation in thestudy

Exclusion Criteria:

• Known contraindication to the study drug that will be selected by the treatingphysician within the list of high or low intensity treatment, according to mostupdate version of Summary of Product Characteristics (SmPC) (e.g. hypersensitivity,allergy, organ failure precluding treatment)

• Participation in another clinical trial with any investigational agents within 14days or 5 drug half-lives (whatever comes first) prior to randomization

• Active infections or other clinical conditions that in the opinion of theinvestigator make the patient ineligible to receive study treatment.