Clinical Trials Search at Vanderbilt-Ingram Cancer Center

Inclusion Criteria:

All patients must be enrolled on APEC14B1 and consented to Eligibility Screening (Part A) prior to enrollment and treatment on AAML1831

Patients must be less than 22 years of age at the time of study enrollment

Patient must be newly diagnosed with de novo AML according to the 2016 World Health Organization (WHO) classification with or without extramedullary disease * Patient must have 1 of the following: * >= 20% bone marrow blasts (obtained within 14 days prior to enrollment) * In cases where extensive fibrosis may result in a dry tap, blast count can be obtained from touch imprints or estimated from an adequate bone marrow core biopsy * 20% bone marrow blasts with one or more of the genetic abnormalities associated with childhood/young adult AML as provided in the protocol (sample obtained within 14 days prior to enrollment) * A complete blood count (CBC) documenting the presence of at least 1,000/uL (i.e., a white blood cell \[WBC\] count >= 10,000/uL with >= 10% blasts or a WBC count of >= 5,000/uL with >= 20% blasts) circulating leukemic cells (blasts) if a bone marrow aspirate or biopsy cannot be performed (performed within 7 days prior to enrollment)

ARM C: Patient must be >= 2 years of age at the time of Late Callback

ARM C: Patient must have FLT3/ITD allelic ratio > 0.1 as reported by Molecular Oncology

ARM C: Patient does not have any congenital long QT syndrome or congenital heart block

ARM C: Females of reproductive potential must agree to use effective contraception during treatment and for at least 6 months after the last dose of gilteritinib

ARM C: Lactating women must agree not to breastfeed during treatment with gilteritinib and for 2 months after the last dose of gilteritinib

ARM C: Males of reproductive potential must agree to use effective contraception during treatment and for at least 4 months after the last dose of gilteritinib

ARM D: Patient must be >= 2 years of age at the time of Late Callback

ARM D: Patient must have one of the clinically relevant non-ITD FLT3 activating mutations as reported by Foundation Medicine

ARM D: Females of reproductive potential must agree to use effective contraception during treatment and for at least 6 months after the last dose of gilteritinib

ARM D: Lactating women must agree not to breastfeed during treatment with gilteritinib and for 2 months after the last dose of gilteritinib

ARM D: Males of reproductive potential must agree to use effective contraception during treatment and for at least 4 months after the last dose of gilteritinib

NEUROPSYCHOLOGICAL TESTING: Patient must be enrolled on Arm A or Arm B. Patients who transfer to Arm C or Arm D are not eligible

NEUROPSYCHOLOGICAL TESTING: Patient must be 5 years or older at the time of enrollment

NEUROPSYCHOLOGICAL TESTING: English-, French- or Spanish-speaking

NEUROPSYCHOLOGICAL TESTING: No known history of neurodevelopmental disorder prior to diagnosis of AML (e.g., Down syndrome, fragile X, William syndrome, mental retardation)

NEUROPSYCHOLOGICAL TESTING: No significant visual or motor impairment that would prevent computer use or recognition of visual test stimuli

All patients and/or their parents or legal guardians must sign a written informed consent

All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met



Exclusion Criteria:

Fanconi anemia

Shwachman Diamond syndrome

Patients with constitutional trisomy 21 or with constitutional mosaicism of trisomy 21

Telomere disorders

Germline predispositions known, or suspected by the treating physician to increase risk of toxicity with AML therapy

Any concurrent malignancy

Juvenile myelomonocytic leukemia (JMML)

Philadelphia chromosome positive AML

Mixed phenotype acute leukemia

Acute promyelocytic leukemia

Acute myeloid leukemia arising from myelodysplasia

Therapy-related myeloid neoplasms

Patients with persistent cardiac dysfunction prior to enrollment, defined as ejection fraction (EF) 50% (preferred method Biplane Simpson's EF) or if EF unavailable, shortening fraction (SF) 24%. \*Note: if clinically safe and feasible, repeat echocardiogram is strongly advised in order to confirm cardiac dysfunction following clinical stabilization, particularly if occurring in the setting of sepsis or other transient physiologic stressor. If the repeat echocardiogram demonstrates an EF >= 50%, the patient is eligible to enroll and may receive an anthracycline-containing Induction regimen

Administration of prior anti-cancer therapy except as outlined below: * Hydroxyurea * All-trans retinoic acid (ATRA) * Corticosteroids (any route) * Intrathecal therapy given at diagnosis * In particular, strong inducers of CYP3A4 and/or P-glycoprotein (P-gp) should be avoided from the time of enrollment until it is determined whether the patient will receive gilteritinib. Patients receiving gilteritinib will be required to avoid strong CYP3A4 inducers and/or strong P-gp inducers for the duration of the study treatment

Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential

Lactating females who plan to breastfeed their infants

Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation

ARM D: Patient does not have any congenital long QT syndrome or congenital heart block