Inclusion Criteria:

1. Participant has a diagnosis of primary AML or AML secondary to myelodysplastic syndrome (MDS) according to World Health Organization (WHO) classification as determined by pathology review at the treating institution.
2. Participant is refractory to or relapsed after first-line AML therapy (with or without HSCT)

* Refractory to first-line AML therapy is defined as:

1. Participant did not achieve CR/CRi/CRp under initial therapy. A participant eligible for standard therapy must receive at least 1 cycle of an anthracycline containing induction block in standard dose for the selected induction regimen. A participant not eligible for standard therapy must have received at least 1 complete block of induction therapy seen as the optimum choice of therapy to induce remission for this participant.
2. Untreated first hematologic relapse is defined as:

1. Participant must have achieved a CR/CRi/CRp with first-line treatment and has hematologic relapse.
2. Participant is positive for FLT3 mutation in bone marrow or whole blood as determined by the central lab. A participant with rapidly proliferative disease and unable to wait for the central lab results can be enrolled based on a local test performed after completion of the last interventional treatment. Participants can be enrolled from a local test result if the participants have any of the following FLT3 mutations: FLT3-internal tandem duplication (ITD), FLT3-tyrosine kinase domain (TKD)/D835 or FLT3-TKD/I836.
3. Participant has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
4. Participant is eligible for preselected salvage chemotherapy.
5. Participant must meet the following criteria as indicated on the clinical laboratory tests:

1. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN)
2. Serum total bilirubin (TBL) ≤ 1.5 x ULN
3. Serum creatinine ≤ 1.5 x ULN or an estimated glomerular filtration rate of > 50 mL/min as calculated by the Modification of Diet in Renal Disease equation.
4. Participant is suitable for oral administration of study drug.
5. Participant agrees not to participate in another interventional study while on treatment.

Inclusion Criteria for COE:

Participant is eligible for the COE if they continue to meet all inclusion criteria from the main protocol in addition to the following when the participant is evaluated for eligibility to participate in the COE portion of the study:

1. Participant has received study treatment of either LoDAC, MEC or FLAG and has no response or progressive disease.
2. Participant have not received other antileukemic therapy after EOT (hydroxyurea is allowed for the control of peripheral leukemic blasts in participants with leukocytosis).
3. Participant agrees not to participate in another interventional study while on treatment.

Exclusion Criteria:

1. Participant was diagnosed as acute promyelocytic leukemia.
2. Participant has BCR-ABL-positive leukemia (chronic myelogenous leukemia in blast crisis).
3. Participant has AML secondary to prior chemotherapy for other neoplasms (except for MDS).
4. Participant is in second or later hematologic relapse or has received salvage therapy for refractory disease.
5. Participant has clinically active central nervous system leukemia..
6. Participant has been diagnosed with another malignancy, unless disease-free for at least 5 years. Participants with treated nonmelanoma skin cancer, in situ carcinoma or cervical intraepithelial neoplasia, regardless of the disease-free duration, are eligible for this study if definitive treatment for the condition has been completed. Participants with organ-confined prostate cancer with no evidence of recurrent or progressive disease are eligible if hormonal therapy has been initiated or the malignancy has been surgically removed or treated with definitive radiotherapy.
7. Participant has received prior treatment with ASP2215 or other FLT3 inhibitors (with the exception of sorafenib and midostaurin used in first-line therapy regimen as part of induction, consolidation and/or maintenance).
8. Participant has clinically significant abnormality of coagulation profile, such as disseminated intravascular coagulation.
9. Participant has had major surgery within 4 weeks prior to the first study dose.
10. Participant has radiation therapy within 4 weeks prior to the first study dose.
11. Participant has congestive heart failure New York Heart Association (NYHA) class 3 or 4 or participant with a history of congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram (ECHO) performed within 1 month prior to study entry results in a left ventricular ejection fraction (LVEF) that is ≥ 45%.
12. Participant with mean of triplicate Fridericia-corrected QT interval (QTcF) > 450 ms at Screening based on central reading.
13. Participant with Long QT Syndrome at Screening.
14. Participant with hypokalemia and hypomagnesemia at Screening (defined as values below lower limit of normal [LLN]).
15. Participant requires treatment with concomitant drugs that are strong inducers of CYP3A.
16. Participant requires treatment with concomitant drugs that are strong inhibitors or inducers of P-gp with the exception of drugs that are considered absolutely essential for the care of the participant.
17. Participant requires treatment with concomitant drugs that target serotonin 5-hydroxytryptamine receptor 1 (5HT1R) or 5-hydroxytryptamine receptor 2B (5HT2BR) receptors or sigma nonspecific receptor with the exception of drugs that are considered absolutely essential for the care of the participant.
18. Participant has an active uncontrolled infection.
19. Participant is known to have human immunodeficiency virus infection.
20. Participant has active hepatitis B or C or other active hepatic disorder.
21. Participant has any condition which makes the participant unsuitable for study participation.
22. Participant has active clinically significant (graft-versus-host disease) GVHD or is on treatment with systemic corticosteroids for GVHD.
23. Participant has an FLT3 mutation other than the following: FLT3-ITD, FLT3-TKD/D835 or FLT3-TKD/I836.

Exclusion Criteria for COE:

Participant will be excluded from participation in the COE if they meet any of the exclusion criteria listed in the main protocol or when the participant is evaluated for eligibility to participate in the COE portion of the study.