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 \<20 mg daily) is allowed
* Patients with multiple basal cell carcinomas that undergo sequential Moh's excisions with interim observation
* Allogeneic hematologic stem cell transplant within 6 months of starting study treatment or active graft vs. host disease (GVHD) requiring treatment or prophylaxis
o Patients with a history of an allogeneic stem cell transplant \> 6 months prior to starting study treatment should be stable, off of immunosuppression for at least 2 months.
* Any active systemic infection requiring systemic antibiotics or other uncontrolled, active infections
* Positive Human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV) antibody test
o For HCV and HBV, patients with evidence of prior infection also excluded
* Evidence of other clinically significant uncontrolled condition(s) including, but not limited to:
* Uncontrolled and/or active systemic infection (viral, bacterial or fungal)
* Chronic hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment. Note: subjects with serologic evidence of prior vaccination to HBV (i.e. hepatitis B surface (HBs) antigen negative-, anti-HBs antibody positive and anti-hepatitis B core (HBc) antibody negative) or positive anti-HBc antibody from intravenous immunoglobulins (IVIG) may participate
* Uncontrolled, not disease-related autoimmune hemolytic anemia or ITP
* History of stroke or intracranial hemorrhage
* History of severe bleeding disorder (hemophilia A or B, von Willebrand disease (VWD)), history of spontaneous bleeding requiring blood transfusions or other medical intervention, history of life-threatening hemorrhage within 3 months of first dose.
* Currently active gastrointestinal disease, including colitis, inflammatory bowel disease and diarrhea requiring therapy
* Currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or Class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification; or a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to enrollment
* Cardiac history of CHF requiring treatment or Ejection Fraction ≤ 50% or chronic stable angina
* Use of Coumadin for anticoagulation (other anticoagulants permitted)
* Lactating or pregnant
* Unable to swallow capsules or malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction resulting in malabsorption or chronic diarrhea
* Concurrent administration of medications or foods that are strong inhibitors or inducers of CYP3A (see Appendix D)
* Treatment with any of the following within 7 days prior to the first dose of study drug:
* Steroid therapy for anti-neoplastic intent (defined as prednisone or equivalent \>20 mg daily)
* Moderate or strong cytochrome P450 3A (CYP3A) inhibitors (see Appendix D for examples)
* Moderate or strong CYP3A inducers (see Appendix D for examples)
* Administration or consumption of any of the following within 7 days prior to the first dose of study drug:
* Grapefruit or grapefruit products
* Seville oranges (including marmalade containing Seville oranges)
* Star fruit
