A study of Gilteritinib combined with chemotherapy to treat Children, Adolescents and Young Adults with Relapsed or Refractory Acute Myeloid Leukemia (AML) with a FLT3 gene mutation

Prior treatment

• Subject has active clinically significant graft-versus-host disease (GVHD) or is on treatment with immunosuppressive drugs for treatment of active GVHD, with the exception of subjects being weaned from systemic corticosteroids where the subject is receiving ≤ 0.5 mg/kg of prednisone (or equivalent) daily dose for prior GVHD. Subject has received calcineurin inhibitors within 4 weeks prior to screening, unless used as GVHD prophylaxis
• Subject requires treatment with concomitant drugs that are strong inducers of cytochrome P450 (CYP)3A/P-glycoprotein (P-gp).

Other illness

• Subject has active malignant tumors other than AML.

Lab values

• Subject has uncontrolled or significant cardiovascular disease, including: • Diagnosed or suspected congenital long QT syndrome or any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes); any history of arrhythmia will be discussed with the sponsor’s medical monitor prior to subject’s entry into the study • Prolonged Fridericia-corrected QT interval (QTcF) interval on pre-entry electrocardiogram (ECG) (≥ 450 ms) • Any history of second- or third-degree heart block (may be eligible if the subject currently has a pacemaker) • Heart rate < 50 beats/minute on pre-entry ECG • Uncontrolled hypertension • Complete left bundle branch block
• Subject has hypokalemia and/or hypomagnesemia at Screening (defined as values below institutional lower limit of normal [LLN]). Repletion of potassium and magnesium levels during the screening period is allowed.

Other

• Subject has active central nervous system (CNS) leukemia.

• Phase 1: Subject is positive for FLT3 (ITD and/or TKD) mutation in bone marrow or blood as determined by the local institution. Phase 2: Subject is positive for the FLT3 (ITD) mutation in bone marrow or blood as determined by the local institution.
• Subject is aged ≥ 6 months and < 21 years of age* at the time of signing informed consent and/or assent, as applicable. * For phase 2: Enrollment of subjects from 6 months to less than 1 year (Group 3) and 1 year to less than 2 years (Group 2) will be dependent on the establishment of RP2D in the respective for age groups during phase 1.
• Subject has a diagnosis of AML according to The French–American–British (FAB) classification with ≥ 5% blasts in the bone marrow, with or without extramedullary disease (except subjects with active central nervous system (CNS) Leukemia). a) In the phase 1 portion of the study, subject must be in first or greater relapse or refractory to induction therapy with no more than 1 attempt at remission induction (up to 2 induction cycles). b) For the phase 2 portion of the study, subject must be refractory to or at the first hematologic relapse after first-line remission induction AML therapy (up to 2 induction cycles)