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:

Male and female patients aged ≥ 18 years.

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.
Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

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
Able and willing to give written informed consent.
Life expectancy of at least 3 months

Exclusion Criteria:

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