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 Translocation of the MLL Gene at 11q23 or Advanced Hematologic Malignancies

Inclusion Criteria:

1. Male and female patients aged ≥ 18 years.

2. AML, ALL, acute mixed lineage leukemia, myelodysplastic syndrome (International
Prognostic Scoring System Int-2 or high-risk), myeloproliferative disorder, or
chronic myelogenous leukemia meeting the following criteria (NOTE: only patients
with acute leukemia with rearrangement of the MLL gene will be 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.

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 ≤1.5 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 involvement of the central nervous system by leukemia.

8. On immunosuppressive therapy.

9. Known active infection.

10. Pregnant or nursing females.