A Study of XY0206 Versus Salvage Chemotherapy In Patients With Relapsed or Refractory AML With FLT3-ITD-Mutation (ALIVE)

Inclusion Criteria:

1. Age≥18 years old.
2. Subject has a diagnosis of primary AML or AML secondary to myelodysplastic syndrome (MDS) according to World Health Organization (WHO) classification as determined bypathology review at the treating institution.
3. Subject is refractory to or relapsed after prior AML therapy (with or withouthematopoietic stem cell transplant ):

• Advanced relapse after first-line AML therapy is defined as: the patientsachieved Complete remission without minor residual diseases/completeremission/complete remission with partial hematologic recovery/complete remissionwith incomplete hematologic recovery/complete remission with incomplete plateletrecovery/Morphologic leukemia- free state(CRMRD-/CR/CRh/CRi/CRp/MLFS )afterfirst-line treatment and relapsed after 12 months with hematological relapse;
• Patients with relapsed / refractory AML.
• Refractory to first-line AML therapy is defined as:the patient did not achieveCRMRD-/CR/CRh/CRi/CRp/MLFS under initial therapy.A subject eligible for standardtherapy must receive at least 1 cycle of an anthracycline containing inductionblock in standard dose for the selected induction regimen. A subject not eligiblefor standard therapy must have received at least 1 complete block of inductiontherapy seen as the optimum choice of therapy to induce remission for thissubject.
• Early relapse:Relapse within 12 months after consolidation therapy afterachieving CRMRD-/CR/CRh/CRi/CRp/MLFS.
• Relapse after 12 months but nonresponse to conventional chemotherapy afterachieving CRMRD-/CR/CRh/CRi/CRp/MLFS.
• Second or more relapse.
• Patients who cannot tolerate intensive chemotherapy develop disease progressionduring continuous treatment with low-intensity drugs.
• Persistence of extramedullary leukemia.

4. Patient is positive for FLT3-ITD mutation in bone marrow or whole blood.
5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
6. Expected survival ≥12 weeks .
7. Patient must meet the following criteria as indicated on the clinical laboratorytests:

• Serum creatinine ≤ 1.5 x ULN or an estimated glomerular filtration rate of ≥50mL/min .
• Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 xupper limit of normal (ULN)
• Serum total bilirubin (TBL) ≤ 1.5 x ULN.
• Fridericia's Heart Rate Correction Formula (QTcF) interval ≤480 msec.

8. Female patients of childbearing potential must have a negative serum pregnancy testwithin 14 days prior to the first study drug administration.Female patients ofchildbearing potential and male must be surgically sterile or willing to use highlyeffective birth control upon enrollment, during the treatment period, and for 6 monthsfollowing the last dose of investigational drug.
9. The subject should be willing to provide evidence of valid diagnosis before treatmentor undergo bone marrow puncture or biopsy for diagnosis, and receive bone marrowpuncture or biopsy for efficacy evaluation after treatment.
10. Patients volunteered to participate in this study and signed the informed consentform.

Exclusion Criteria:

1. Patient was diagnosed as acute promyelocytic leukemia (APL), or Philadelphiachromosome（BCR-ABL）-positive leukemia (chronic myelogenous leukemia in blast crisis).
2. Patients who received live vaccine (including live attenuated vaccine) within 4 weeksbefore randomization and/or planed to receive live vaccine after enrollment.
3. Presence of FLT3-tyrosine kinase domain(TKD) mutation.
4. Patients were prior failed adequate treatment with FLT3 inhibitors.
5. AML with Central Nervous System Leukemia.
6. Patient has AML secondary to prior chemotherapy for other neoplasms, except for MDS.
7. Patients with other malignant tumors past or present,unless whose Disease-freesurvival period≥5 years.Non-melanin skin cancer, carcinoma in situ, or cervicalintraepithelial neoplastic lesions with completed radical treatment (regardless ofdisease-free survival),and subjects with prostate cancer confined to the prostate andwith no evidence of disease recurrence or progression,if they have started hormonaltherapy or have undergone surgery to remove the malignancy or have undergone radicalradiotherapy,will be eligible for the study.
8. Pretrial treatment conditions:

• Patients who received hematopoietic stem cell transplantation within the 2 monthsbefore enrollment,or having clinically significant graft-versus-host disease (GVHD) or receiving systemic cortisol hormone therapy for GVHD.
• Patients who received chemotherapy, biological therapy, targeted anti-tumortherapy within 14 days before the first use of the drug in this study or within 5half-lives of the drug, or radiation therapy within 28 days.
• Patients who participated in other clinical trials and received trial drugswithin 28 days to the first study dose.
• Patients who have had major surgery or significant traumatic injury within 28days to the first study dose or planted to require major surgery during studytreatment.

9. Concurrent disease conditions:

• Patients are hepatitis B surface antigen or core antibody actives positive,andhepatitis B virus(HBV) DNA ≥2000IU/mL or 1×104 copy/mL.
• Patients are hepatitis C virus (HCV) antibody actives positive and HCV-RNAquantification is above the upper limit of normal at each center.
• Human immunodeficiency virus (HIV) seropositivity.
• Patient has clinically obvious gastrointestinal abnormalities that may affect theintake, transport, or absorption of drugs (such as inability to swallow, chronicdiarrhea, intestinal obstruction, etc),patients with total gastrectomy or majorgastrectomy (Billroth II), patients with a clear gastrointestinal bleedingtendency,or major gastrointestinal bleeding considered possible by theinvestigator.
• Patient has uncontrolled epilepsy history.
• Patient has uncontrolled hypertension defined as systolic blood pressure greaterthan 160 mmHg or diastolic pressure greater than 100 mmHg, despite optimalmedical management and optimal measurement.
• Patient has clinically significant abnormal serum lipase or amylase indicatorsduring screening.
• Patient has refractory intractable hypokalemia or hypomagnesemia.
• Patient has clinically significant abnormality of coagulation profile, such asdisseminated intravascular coagulation (DIC), hemophilia.
• Patient has congestive heart failure New York Heart Association (NYHA) class 3 or 4 or patient with a history of congestive heart failure NYHA class 3 or 4 in thepast, unless a screening echocardiogram performed within 1 month before studyentry results in a left ventricular ejection fraction that is ≥ 45%.
• Patients with second degree (Mobitz II) or third degree atrioventricular blockdisease (except for patients who use the pacemaker) or complete left bundlebranch block.
• Patients with new clinically significant arrhythmias (except for sinustachycardia caused by anemia, infection and AML) or patients with previousarrhythmias that require long-term use of drugs with QT-prolonging effects.
• Patients with any one of the following diseases within 6 months prior torandomization:myocardial infarction,unstable angina pectoris,Patients undergoingcoronary artery bypass graft(CABG) or peripheral artery bypassimplantation,congestive heart-failure,Cerebrovascular events (including cerebralhemorrhage and cerebral infarction, etc.),Deep venous thrombosis (except for deepvenous thrombosis due to peripherally inserted central venous catheter (PICC)catheterization),pulmonary embolism and other diseases that the researcherconsiders inappropriate to participate in this study.
• Patients with diagnosed or suspected long QT syndrome at screening (including afamily history of long QT syndrome).
• Patient has an active uncontrolled infection.
• Patient has severe unhealed wounds, ulcers, or fractures.
• Females who are pregnant or breastfeeding.
• Patients are not suitable for the study in the investigator's opinion.