Administration of Gilteritinib to eliminate MRD in patients with AML and FLT3-ITD mutation.

Prior treatment

• Subjects with secondary AML, including treatment-related [e.g., due to prior anthracycline use], as well as subjects with progression of antecedent hematological disorder [e.g., MDS, MPN or MDS/MPN ‘overlap’ syndrome].
• Subjects with a serious concurrent illness that in the opinion of the Investigator would pose an undue risk to the subject participating in the clinical study (such as active/uncontrolled infection at the time of screening).

Other illness

• History of clinically significant medical conditions or any other reason that the investigator determines would interfere with the subject's participation in this study or would make the subject an unsuitable candidate to receive study drug.
• Subjects with a diagnosis of human immunodeficiency virus (HIV), active hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection. Subjects with HBV inactive carrier status and/or HCV with low viral titres on antivirals (non-exclusionary medications) are eligible. Low viral hepatitis titre is defined per institutional guidelines.
• Known hypersensitivity to the active substance or to any of the excipients of Gilteritinib.
• Has a known psychiatric or substance abuse disorder that would interfere with the participant’s ability to cooperate with the requirements of the study.
• Malabsorption syndrome or other condition that precludes oral route of administration.

Other

• Subjects with acute promyelocytic leukemia.
• Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 180 days after the last dose of Gilteritinib.
• Patients not willing to comply with effective contraception.

• Patients must provide signed and dated informed consent for the study that has been approved by an Independent Ethics Committee (IEC) and the relevant Institution Review Board (IRB) of each participating centre, before performing any screening or study procedure.
• Female patients of reproductive potential using hormonal contraceptives should add a barrier method of contraception.
• Female subjects of child-bearing potential are eligible if they commit to contraception and if they are not pregnant, breastfeeding, nor considering becoming pregnant during the study or for at least 6 months after the last dose of Gilteritinib.
• If male, and subject is sexually active with female partner(s) of childbearing potential, he must agree, to use effective contraception during treatment and for at least 4 months after the last dose of Gilteritinib.
• Subjects must be willing and able to return to the clinical site for adequate follow-up and to comply with the protocol as required.
• Patients with positive MRD (by PCR-NGS for FLT3-ITD) after 2 cycles of intensive chemotherapy in combination with an FLT3- inhibitor will be eligible for enrolment.
• Adult male or female patients.. Aged 18 – 75 years old on the day of signing informed consent.
• Subjects must have a new diagnosis of primary/de novoFLT3-ITD mutated AML according to the WHO criteria (2017).
• Body weight >40kg.
• Subjects must be willing and able to comply with the relevant procedures, according to the protocol.
• Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of < 2 (See Appendix 1: ECOG Performance Status).
• Subjects must have an estimated life expectancy of >3 months.
• Female patients of childbearing potential: negative serum pregnancy test at the screening visit and negative urine pregnancy test within seven days prior to starting treatment with Gilteritib.
• Female patients of reproductive potential must agree to use an effective method of contraception during treatment with Gilteritinib and for at least 6 months after stopping Gilteritinib.