A Phase I Study of Alisertib + R-EPOCH for Treatment of Myc-Positive Aggressive B-cell Lymphomas

Inclusion Criteria: * ≥18 y/o (no upper age limit) * ECOG PS ≤2 * Disease - Histologically or cytologically documented newly diagnosed (stages II, III or IV) Myc-positive DLBCL, transformed follicular lymphoma, or high-grade unclassifiable with features intermediate between DLBCL and Burkitt lymphoma * Myc Positive lymphoma is defined by: * Positive for Myc gene rearrangement by fluorescence in-situ hybridization (FISH) involving various breakpoints (e.g. 8-14, 8-22 and 2-8) AND concurrent gene rearrangements in bcl-2 and/or bcl-6 by FISH OR * Myc and Bcl-2 overexpression defined by \> 40% Myc and \> 70% Bcl-2 expression by IHC. Patients may enroll in the study based on the local laboratory evaluation, but these should be confirmed by the UNC Hematopathology Laboratory retrospectively * Positive for CD20 via immunophenotyping * Prior Treatment: Previously untreated or who received a maximum of one cycle of combination chemotherapy (i.e. R-CHOP, R-EPOCH, or R-hyperCVAD) within 4 weeks of study entry except patients who require dose reduction after the first cycle of off-study R-EPOCH. * Measurable disease as assessed by 2 dimensional measurements by CT (≥ 1.5 cm). * Adequate organ function as demonstrated by: * Bone marrow function (without platelet transfusion or myeloid growth factor support within two weeks of screening) as demonstrated by: * Hemoglobin ≥ 8 g/dL * Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3 * Platelet count ≥75,000/mm3 * And hepatic and…