Trial of DFP-10917 vs Non-Intensive or Intensive Reinduction for AML Patients in 2nd/3rd/4th Salvage

Inclusion Criteria:

1. Histologically or pathologically confirmed diagnosis of AML based on WHOclassification that has relapsed after, or is refractory to, two, three, or fourprior induction regimens that may have included intensive chemotherapy (e.g., "7+3"cytarabine and daunorubicin), epigenetic therapy (i.e., azacitidine or decitabine),or targeted therapy (e.g., FLT-3, IDH-1/2, BCL-2, monoclonal antibody).

(Relapse is defined as reemergence of ≥5% leukemia blasts in bone marrow or ≥1%blasts in peripheral blood ≥90 days after first CR or CR without complete plateletrecovery (CRp). Refractory AML is defined as persistent disease ≥28 days afterinitiation of intensive induction therapy (up to two induction cycles) or relapse <90 days after first CR or CRp. Refractory disease for patients undergoinghypomethylating agent induction is defined as lack of remission following at least 2cycles of epigenetic therapy without reduction in bone marrow blast status.) Patients with a history of IPSS-R high or very high risk MDS that transformed to AMLduring treatment with hypomethylating drugs and then relapse following or arerefractory to a subsequent AML induction regimen may be enrolled as Second SalvageAML patients. Additionally, patients with a history of MPN in accelerated phase (MPN-AP) or high-risk primary myelofibrosis (PMF) that transformed to AML duringtreatment with hypomethylating drugs and then relapse following or are refractory toa subsequent AML induction regimen may be enrolled as Second Salvage AML patients.

2. Aged ≥ 18 years.

3. ECOG Performance Status of 0, 1 or 2.

4. Adequate clinical laboratory values (i.e., plasma creatinine <2.5 x upper limit ofnormal (ULN) for the institution, bilirubin <2.5 x ULN, alanine transaminase (ALT)and aspartate transaminase (AST) ≤2.5 x ULN).

5. Absence of active central nervous system (CNS) involvement by leukemia. Patientswith previously diagnosed CNS leukemia are eligible if the CNS leukemia is undercontrol and intrathecal treatment may continue throughout the study.

6. Absence of uncontrolled intercurrent illnesses, including uncontrolled infections,cardiac conditions, or other organ dysfunctions.

7. Signed informed consent prior to the start of any study specific procedures.

8. Women of child-bearing potential must have a negative serum or urine pregnancy test.

9. Male and female patients must agree to use acceptable contraceptive methods for theduration of the study and for at least one month after the last drug administration.

Exclusion Criteria:

1. The interval from prior treatment to time of study drug administration is < 2 weeksfor cytotoxic agents or < 5 half-lives for noncytotoxic agents. Exceptions: Use ofhydroxyurea is allowed before the start of study and is to be discontinued prior tothe initiation of study treatment. At the investigator's discretion, for patientswith significant leukocytosis that develops during the early treatment cycles,hydroxyurea may be administered. The hydroxyurea should be discontinued as soon asclinically appropriate.

2. Any >grade 1 persistent clinically significant toxicities from prior chemotherapy.

3. Inadequate Cardiac (left ventricular ejection fraction ≤40%) function.

4. White blood cell (WBC) count >15,000/μL (Note: Patients considered for possiblevenetoclax-containing regimen must have WBC ≤10k/μL prior to initiating venetoclaxtreatment).

5. For patients with prior hematopoietic stem cell transplant (HSCT):

6. Less than 3 months since HSCT

7. Acute Graft versus Host Disease (GvHD) >Grade 1

8. Chronic GvHD >Grade 1

9. Any concomitant condition that in the opinion of the investigator could compromisethe objectives of this study and the patient's compliance.

10. A pregnant or lactating woman.

11. Current malignancies of another type. Exceptions: Patients may participate if theyhave previously treated and currently controlled prostate cancer, or adequatelytreated in situ cervical cancer or basal cell skin cancer, or other malignancieswith no evidence of disease for 2 years or more.

12. Patient has acute promyelocytic leukemia (APL).

13. Patients with known HIV, active HBV or active HCV infection (note: testing for theseinfections is not required). For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, ifindicated. Patients with a history of hepatitis C virus (HCV) infection must havebeen treated and cured. For patients with HCV infection who are currently ontreatment, they are eligible if they have an undetectable HCV viral load.

14. Documented or known clinically significant bleeding disorder.