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). Risk stratification will not be possible without the submission of viable samples. Given there are multiple required samples, bone marrow acquisition techniques such as frequent repositioning or performing bilateral bone marrow testing should be considered to avoid insufficient material for required studies. Consider a repeat marrow prior to starting treatment if there is insufficient diagnostic material for the required studies.

• 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 (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).

Exclusion Criteria:

• Patients with myeloid neoplasms with germline predisposition are not eligible.

• Fanconi anemia.

• Shwachman Diamond syndrome.

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

• Any other known bone marrow failure syndrome.

• 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.

• 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.

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