Vyxeos and Gilteritinib for the Treatment of Relapsed or Refractory FLT-3 Mutated Acute Myeloid Leukemia

Inclusion Criteria

• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Male or female, aged >= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• FLT3-ITD or FLT3-TKD mutated AML (non-M3) in 1st or greater relapse or refractory to at least one prior line of AML directed therapy
• FLT3 testing must be confirmed at the time of disease relapse
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 times the institutional upper limit of normal (ULN)
• Total bilirubin < 2 times the institutional ULN (in the absence of Gilbert's syndrome)
• Creatinine < 2 times the institutional ULN or creatinine clearance > 60 mL/min/1.73m^2
• Left ventricular ejection fraction (LVEF) >= 50%
• Prior anthracycline exposure =< 368 mg/m^2 daunorubicin (or equivalent)
• Ability to take oral medication and willingness to adhere to the medication regimen
• For females of reproductive potential: use of highly effective contraception including double barrier methods (condoms with spermicidal jelly or foam and diaphragm with spermicidal jelly or foam), oral, Depo-Provera, or injectable contraceptives, intrauterine devices and tubal ligation
• For females of reproductive potential: negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 days and again within 24 hours of beginning study treatment
• For males of reproductive potential: use of condoms
• Breastfeeding mothers must agree to discontinue nursing
• Patients who have relapsed after and allogeneic stem cell transplant must have controlled grade =< 2 graft-versus-host disease (GVHD). Immunosuppression with tacrolimus or sirolimus is allowed at stable or tapering doses

Exclusion Criteria

• Patients may not be receiving any other investigational agents
• Patients with documented central nervous system involvement of AML
• Progression of AML while on prior gilteritinib therapy
• Patients must not have evidence of gastrointestinal (GI) tract abnormalities that would alter the absorption of oral medications
• Major surgery within two weeks of first dose of study drug. Patients must have recovered from the effects of any surgery performed greater than two weeks prior
• White blood cell (WBC) count >= 50,000 at the time study treatment begins. Use of hydroxyurea to maintain WBC < 50,000 is allowed up to the time that study treatment begins
• Predicted inability to tolerate standard induction chemotherapy
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• No other malignancies in addition to AML that are currently requiring treatment with the exception of: 1) basal cell or squamous cell carcinoma or the skin; 2) carcinoma in situ of the cervix or breast; 3) a history of breast cancer that is currently being managed with adjuvant endocrine therapy
• Grade >= 3 acute or chronic graft versus host disease after allogeneic stem cell transplant. No steroids for GVHD are allowed