A Phase 1, Open-Label, Dose-Escalation & Expanded Cohort, Continuous IV Infusion, Multi-center Study of the Safety, Tolerability,PK & PD of EPZ-5676 in Treatment Relapsed/Refractory Patients With Leukemias Involving

Inclusion Criteria:

1. Male and female patients aged ≥ 18 years.
2. Patients with relapsed /refractory AML, ALL, or MLL with rearrangement of the MLL gene, including 11q23 or PTD, are eligible for the expanded cohort:

   * At least one prior therapy;
   * Refractory disease on most recent therapy, or disease recurrence following remission on most recent therapy;
   * Received and failed all known effective therapies for their disease;
   * Not a candidate for allogeneic stem cell transplantation
   * \> 10% blasts or biopsy-documented leukemia cutis or myeloid sarcoma.
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
4. Patients must have the following clinical laboratory values:

   * Serum creatinine ≤2 mg/dL or creatinine clearance \> 60 mL/minute;
   * Total bilirubin ≤2.0 times the ULN for the institution, unless considered due to Gilbert's syndrome;
   * ALT or AST ≤ twice the upper limit of normal (ULN), unless considered due to organ leukemic involvement;
   * Absolute neutrophil count ≥1,000/µL (unless due to documented leukemic involvement of the bone marrow at the time of study entry)
   * Platelets ≥100,000/µL (unless due to documented leukemic involvement of the bone marrow at the time of study entry).
   * PT or aPTT \< 1.5 times the ULN
5. Able and willing to give written informed consent.
6. Life expectancy of at least 3 months

Exclusion Criteria:

1. Uncontrolled intercurrent illness or psychiatric illness/social situations that would limit compliance with study requirements.
2. Active heart disease
3. Receiving any other standard treatment for their hematologic malignancy.
4. Receiving strong CYP3A4 inhibitors/ inducers.
5. Known history of cerebrovascular accident in the past 6 months.
6. Known bleeding diathesis.
7. Known, active (symptomatic) involvement of the central nervous system by leukemia.
8. On immunosuppressive therapy.
9. Known active infection.
10. Pregnant or nursing females.