Efficacy of Gilteritinib in Combination With FLAI as Induction Therapy of FLT3-positive Acute Myeloid Leukemia

Prior treatment

• Patient has been diagnosed with another malignancy, unless disease-free for at least 3 years. Subjects with treated nonmelanoma skin cancer, in situ carcinoma or cervical intraepithelial neoplasia, papillary thyroid carcinoma, regardless of the disease-free duration, are eligible for this study if definitive treatment for the condition has been completed. Subjects 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.
• Patient has had major surgery within 4 weeks prior to the first study dose.
• Patient has radiation therapy within 4 weeks prior to the first study dose.
• Patient has active hepatitis B or C or other active hepatic disorder. Chronic conditions previously cured or in active prophylaxis are allowed in the study

Other illness

• Patient has an active uncontrolled infection.
• Patient has active human immunodeficiency virus infection.
• Patient has infections, comorbidities or any disease, condition or alteration that per judgment of the investigator may be jeopardized by therapy

Lab values

• 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 the past, unless a screening echocardiogram performed within 1 month prior to study entry results in a left ventricular ejection fraction that is ≥ 45%.
• Patients receiving any other investigational or commercial agents or therapies administered with the intention to treat their malignancy with the exception of Hydroxyurea (HU) or 6-Mercaptopurine (6MP) in patients who need to continue this agent to maintain WBC count ≤10,000/mm3. HU and 6MP must be discontinued at the time of initiation of study medications.

Other

• Patient was diagnosed as acute promyelocytic leukemia.
• Patient has BCR-ABL-positive leukemia or chronic myelogenous leukemia in blast crisis.
• Patient has clinically active central nervous system leukemia.

• The patient is ≥ 18 and ≤65 years old.
• The patient has an Eastern Cooperative Oncology Group (ECOG) performance score (PS) of 0 to 2.
• The patient has adequate baseline organ function, including cardiac, renal, and hepatic function:
  • Left ventricular ejection fraction (LVEF) ≥institutional lower limit of normal as measured by multigated acquisition (MUGA) scan or 2-dimensional (2-D) echocardiography (ECHO) within 21 days before start of therapy and no clinically significant abnormalities on a 12-lead electrocardiogram (ECG).
  • ECG: QTcF≤450 male ≤480 female
  • 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.
  • Bilirubin ≤3 times the upper limit of normal ULN mg/dL except for Gilbert's condition
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 times the upper limit of normal (ULN)., except if due to leukemic involvement.
• Patient is positive at diagnosis for FLT3 activating mutation in bone marrow or whole blood.
• Diagnosis of untreated AML according to WHO 2016, non-APL
• If the patient is a woman of childbearing potential (WOCBP), she must have a negative serum or urine pregnancy test at screening within 1 week before treatment.
• The patient (male and female) agrees to use two acceptable contraceptive methods for the duration of time on the study and continue to use acceptable contraceptive methods for 6 months after the end of treatment
• The patient has signed informed consent before initiation of any study-specific procedures or treatment.
• The patient is able to adhere to the study visit schedule and other protocol requirements, including follow-up for survival assessment