Venetoclax and Selinexor in Treating Patients with Relapsed or Refractory High Risk Hematologic Malignancies

Primary: * Escalation: Identify the maximum tolerated dose(s) (MTD) and recommended phase 2 dose(s) (RP2D) of SEL-VEN combination therapy in patients with diffuse large B-cell lymphoma (DLBCL) and acute myeloid leukemia (AML). * Expansion: Determine the overall response rate of SEL-VEN combination therapy in patients with relapsed/refractory hematologic malignancies. Exploratory Objectives: * To explore biomarkers of response to SEL-VEN therapy. * To determine the progression free survival (PFS) and overall survival (OS) of SEL-VEN combination therapy. OUTLINE: This is a dose-escalation study. Patients receive venetoclax orally (PO) once daily (QD) on days 1-28. Patients with DLBCL receive selinexor PO on days 1, 8, 15, and 22 of each cycle. Patients with venetoclax-naive AML are treated with selinexor on days 8, 15, and 22 of cycle 1, followed by days 1, 8, 15, and 22 of subsequent cycles. Venetoclax-refractory AML patients begin both drugs on cycle 1 day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 28 days and every 3 months for 2 years.