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

INCLUSION CRITERIA:

   - 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.

EXCLUSION CRITERIA:

   - Down syndrome

   - Acute promyelocytic leukemia (APL)

   - BCR-ABL1 chronic myeloid leukemia in blast crisis (CML-BC)

   - Juvenile myelomonocytic leukemia (JMML)

   - Fanconi anemia (FA)

   - Kostmann syndrome

   - Shwachman syndrome

   - Other bone marrow failure syndromes or low grade (<5% bone marrow blasts) MDS.

   - 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.

   - 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).

   - Pregnant or lactating.

   - 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.

   - Patients with treatment related myeloid neoplasms with cumulative anthracyclines
   greater than 230 mg/m2 doxorubicin equivalents.