A Phase 1 Dose Escalation and Expanded Cohort Study of EPZ-5676 in the Treatment of Pediatric Patients With Relapsed/Refractory Leukemias Bearing a Rearrangement of the MLL Gene

Inclusion Criteria: 1. Age: \>3 months to \<18 years of age. 2. Diagnosis: Patients must have documented relapsed/refractory ALL, AML, or acute leukemia of ambiguous lineage and meet the following criteria: * Patients must have at least received an appropriate induction therapy regimen. Patients with persistent leukemia after induction therapy, or with recurrence of leukemia at any time during the course of treatment (including allogeneic HSCT) are eligible; * Patients must have \> 10% leukemic blasts in the bone marrow; * Patients must have rearrangement involving the MLL gene, including reciprocal chromosomal translocations involving 11q23 by FISH, cytogenetic analysis, polymerase chain reaction (PCR) or next-generation sequencing (NGS) OR partial tandem duplication (PTD) of MLL by PCR or NGS. 3. Therapeutic Options: Patients must be ineligible or inappropriate for other treatment regimens known to have curative potential. 4. Performance Level: Karnofsky \> 50% for pts \> 12 years; Lansky \> 50% for pts \< 12 years of age. 5. Prior Therapy: Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study. Myelosuppressive Chemotherapy: * 14 days must have elapsed since the completion of cytotoxic therapy * Patients may receive hydroxyurea, low-dose cytarabine and/or glucocorticoids to control peripheral blood leukemic cell counts at study entry * At least 7 days since the completion of therapy with hematopoietic growth factors * At least 7 days since the completion of therapy with a biologic agent * At least 21 days since receipt of chimeric antigen receptor therapy or other modified T cell therapy * At least 60 days from prior total body irradiation (TBI) * At least 60 days must have elapsed from hematopoietic stem cell transplantation (HSCT) 6. Renal and Hepatic Function: Patient must have adequate renal and hepatic functions as indicated by the following laboratory values: * Patient must have a calculated creatinine clearance or radioisotope GFR \> 60mL/min/1.73m2 or a normal serum creatinine based on age/gender * Total bilirubin \< 1.5 x ULN for age or normal conjugated bilirubin * ALT and AST \< 3 x ULN (unless attributed to leukemic involvement) 7. Cardiac Function: Patient must have a shortening fraction (SF) of \> 27% or an ejection fraction (EF) of \> 50% by echocardiogram or MUGA scan. Exclusion Criteria: 1. Patients with CNS 3 disease or symptomatic CNS disease 2. Clinically active heart disease including prolonged QTc or prolonged PR interval, or history of arrhythmias 3. On immunosuppressive or other anti-leukemic therapy, excluding patients receiving glucocorticoids for management of circulating blast count or patients on a stable dose (\<20mg/m2/day prednisone or equivalent) of systemic or topical glucocorticoid therapy with ≤ Grade 1 GvHD or tapering dose of calcineurin inhibitor 4. Patients with known bleeding diathesis or prothrombin time (PT) or aPTT \>1.5 x ULN or fibrinogen \<0.5 x LLN 5. Receiving prophylactic use of hematopoietic colony stimulating factors 6. Known history of infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus (HBsAg positive) or hepatitis C virus (anti-HCV positive) 7. Being actively treated for another concurrent malignancy 8. Pregnant or nursing females; 9. Male patients not willing to use a condom 10. Uncontrolled intercurrent illness including, but not limited to uncontrolled infection, significant graft-versus-host-disease (GvHD) (Grade 2-4), or psychiatric illness/social situations that would limit compliance with study requirements 11. Patients who are concurrently receiving strong inducers/inhibitors of CYP3A 12. Patients with known history of Trisomy 21 (Down Syndrome), history of congenital immunodeficiency or inherited marrow failure disorder. 13. Patients with known bleeding diathesis, or PT (Prothrombin time) or aPTT (activated partial thromboplastin time) \> 1.5x ULN or \<0.5x LLN.