Phase I Study of Venetoclax Plus DA-EPOCH-R for the Treatment of Aggressive B-Cell Lymphomas

• Adults age 18-80 years

• Histologically confirmed, biopsy-proven diagnosis of DLBCL, BCLu, HGBCL, or TiNHL.

⁃ Richter's transformation from Chronic Lymphocytic Leukemia (CLL) is not eligible.

• Subjects with DLBCL, BCLu, HGBCL NOS, or HGBCL with translocations of MYC and BCL2 and/or BCL6, must have had no prior chemotherapy for lymphoma. Steroids for palliation prior to enrollment are allowed.

• Subjects with TiNHL are eligible if they have received no prior cytotoxic chemotherapy for lymphoma. Steroids, rituximab, and external beam radiation therapy as prior therapy for indolent lymphoma is allowed.

• Ann Arbor stage II-IV disease (Stage I primary mediastinal B-cell lymphoma will also be eligible)

• Ability to provide signed Informed Consent Form

• Ability and willingness to comply with the requirements of the study protocol

• Measureable disease (defined as at least 1.5 cm in diameter).

• Adequate organ and bone marrow function:

• Absolute neutrophil count (ANC) at least 1,000/mm3

• Platelet count at least 100,000/mm3.

• Total bilirubin at most1.5 x the upper limit of the normal range (ULN), except Gilbert's disease

• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) at most 3 x ULN.

• Calculated creatinine clearance at least 30 mL/min.