A Trial of Epigenetic Priming in Patients With Newly Diagnosed Acute Myeloid Leukemia

Prior treatment

• Use of concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol.
• Use of investigational agents within 30 days or any anticancer therapy for this malignancy within 2 weeks before study entry with the exception of IT therapy, hydroxyurea, or low-dose cytarabine as specified in the protocol document. The patient must have recovered from all acute toxicities from any previous therapy.
• Any significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results.
• Prior chemotherapy, with the exception of hydroxyurea or low-dose cytarabine as specified in the protocol document. The patient must have recovered from all acute toxicities from any previous therapy.

Other illness

• Down syndrome
• Kostmann syndrome
• Shwachman syndrome
• Other bone marrow failure syndromes or low grade (\<5% bone marrow blasts) MDS.
• Systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment).

Other

• Acute promyelocytic leukemia (APL)
• BCR-ABL1 chronic myeloid leukemia in blast crisis (CML-BC)
• Juvenile myelomonocytic leukemia (JMML)
• Fanconi anemia (FA)
• Pregnant or lactating.
• Patients with treatment related myeloid neoplasms with cumulative anthracyclines greater than 230 mg/m2 doxorubicin equivalents.

• Diagnostic criteria: Patients must have one of the following diagnoses:
  • Acute myeloid leukemia fulfilling the criteria of the WHO Classification (see Appendix I), or
  • \>5% but \< 20% marrow myeloblasts and evidence of a clonal de novo AML genetic abnormality \[e.g., t(8;21), inv(16), t(9;11)\], or
  • Myeloid sarcoma (also referred to as extramedullary myeloid tumor, granulocytic sarcoma, or chloroma), with or without evidence of a leukemia process in the bone marrow or peripheral blood, with confirmation of myeloid differentiation, or
  • High grade myelodysplastic syndrome (MDS) with greater than 5% blasts, or
  • Patients with treatment related myeloid neoplasms including AML and MDS, provided their cumulative anthracycline dose has not exceeded 230 mg/m2 doxorubicin equivalents.
• Other criteria - Patients must meet all the following criteria:
  • Age \> 28 days and \< 22 years at time of study entry inclusive, and
  • No prior therapy for this malignancy except for one dose of intrathecal therapy and the use of hydroxyurea or low-dose cytarabine (100-200 mg/m2 per day for one week or less for hyperleukocytosis), and
  • Written informed consent according to institutional guidelines, and
  • Female patients of childbearing potential must have a negative pregnancy test within 2 weeks prior to enrollment, and
  • Male and female participants of reproductive potential must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment.