Duvelisib and Venetoclax in Patients With Relapsed or Refractory Peripheral T-cell Lymphoma (PTCL)

This is an open-label, phase I/II study of duvelisib in combination with Venetoclax for patients with relapsed/refractory NHL. Duvelisib is an FDA approved, marketed product used to treat certain patients with leukemia and lymphoma and Venetoclax, which is approved for treatment of certain patients with acute myeloid leukemia. The combination of these two drugs is experimental. Experimental means that it is not approved by the United States Food and Drug Administration (FDA). The researchers want to find out how safe it is to combine these drugs and how well this combination can work for your cancer.

Inclusion Criteria: * Phase I: Histologically confirmed relapsed/refractory PTCL, except the following lymphoma subtypes: cutaneous T-cell lymphoma (CTCL) and T-cell-prolymphocytic leukemia (TPLL). * Phase II: same as phase I * Disease that has progressed during or relapsed after at least two previous therapies. * ECOG performance status ≤ 2 * Adequate hepatic function defined as: o Serum aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 x upper limit of normal (ULN), bilirubin ≤ 1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin * Adequate renal function as defined by: o Creatinine clearance ≥ 30 mL/min; calculated by the Cockcroft Gault formula or measured by 24 hours urine collection * Patients must meet the following hematologic criteria at screening, unless they have significant bone marrow involvement confirmed on biopsy: * Absolute neutrophil count ≥ 1500 cells/mm3 (1.5 x 109/L) or ≥ 1000 cells/mm3 (1.5 x 109/L) with bone marrow involvement. Growth factor use is allowed in order to achieve this * Platelet count ≥ 50,000 cells/mm3 (50 x 109/L) independent of transfusion within 7 days of screening * Hemoglobin ≥8 g/dL (without transfusion support.) Exclusion Criteria: * Phase I and Phase II: * Patients eligible for Hematopoietic stem cell transplantation (HSCT) * Cutaneous T-cell lymphoma (CTCL) and T-cell-prolymphocytic leukemia (TPLL) * Suspected and confirmed central nervous system involvement * Previous treatment with venetoclax or a PI3K inhibitor. * Active malignancy other than NHL requiring ongoing therapy, with the exception of hormonal therapy (i.e. castration-sensitive prostate cancer stable on testosterone blockade) * Patients receiving cancer therapy (i.e., chemotherapy, radiation therapy, immunotherapy, biologic therapy, surgery) within 2 weeks of Cycle 1/Day 1 with the following exceptions: * For patients on targeted therapies, a washout of least five half-lives is required * Patients who experience clinical deterioration may start therapy after a shorter washout period with prior approval by the PI * Corticosteroid therapy (prednisone or equivalent \