Clinical Trials

Inclusion Criteria:

- All patients must be enrolled on APEC14B1 and consented to Eligibility Screening (Part
A) prior to enrollment and treatment on AAML1831. Submission of diagnostic specimens
must be done according to the Manual of Procedures

- 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

Eligibility last updated 6/20/22. Questions regarding updates should be directed to the study team contact.