Duvelisib and Nivolumab in Treating Patients with Richter Syndrome or Transformed Follicular Lymphoma

Inclusion Criteria

• Diagnosis of CLL or small lymphocytic lymphoma (SLL) meeting International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2018 criteria AND biopsy proven transformation to diffuse large B cell lymphoma (DLBCL), clinically consistent with Richter’s syndrome (RS) OR histologically diagnosed relapsed or refractory DLBCL including transformed follicular lymphoma (tFL) ineligible for or refractory to platinum containing salvage therapy for the dose escalation portion of the study. Patients ineligible for platinum therapy would be those with creatinine (Cr) >= 1.5, aspartate aminotransferase (AST)/alanine aminotransferase (ALT)/total bilirubin (Tbili) >= upper limit of normal (ULN), or Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2. For the dose expansion phase only patients with CLL with transformation to DLBCL or tFL will be eligible
• Patients must have received at least one prior therapy for either the transformed disease or the initial malignancy (CLL/SLL/DLBCL/follicular lymphoma)
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Absolute neutrophil count (ANC) >= 500/uL
• Platelet count >= 30,000/uL (unless due to bone marrow involvement)
• AST and ALT =< 2.5 ULN
• Total bilirubin =< 1.5 ULN (unless due to liver involvement, hemolysis, or Gilbert’s disease)
• Creatinine clearance >= 40 mL/min (Cockcroft-Gault estimated)
• Women of childbearing potential and men who are sexually active must be practicing a highly effective method of birth control during and after the study consistent with local regulations regarding the use of birth control methods for subjects participating in clinical trials. Men must agree to not donate sperm during and after the study. For females, these restrictions apply for 1 month after the last dose of study drug. For males, these restrictions apply for 7 months after the last dose of nivolumab and 30 days after the last dose of duvelisib
• Women of childbearing potential must have a negative serum (beta-human chorionic gonadotropin [beta-hCG]) or urine pregnancy test at screening. Women who are pregnant or breastfeeding are ineligible for this study
• Patients must sign an informed consent document indicating that they understand the purpose of and procedures required for the study, including biomarkers, and are willing to participate in the study

Exclusion Criteria

• Documented infection with human immunodeficiency virus (HIV) or chronic, active hepatitis B or C infection
• Any chemotherapy or monoclonal antibodies within 14 days or kinase inhibitors (except BTKi) within 5 half-lives before cycle 1, day 1 (C1D1). BTK inhibitors may be continued until 2 days prior to C1D1. Steroids are allowed for palliation of symptoms due to lymphoma
• Toxicity from previous therapy which has not resolved to grade 1 (or patient’s previous baseline)
• Other active malignancies except those treated with curative intent with no active disease at the time of study entry or those felt to be at low risk of progression or recurrence over the next 2 years (such as low risk prostate cancer on active surveillance)
• New York Heart Association (NYHA) class III/IV heart disease or other significant medical condition or organ system dysfunction which could compromise the subject’s safety or put the study outcomes at undue risk
• Uncontrolled systemic infection
• Unable to swallow capsules or significant malabsorption syndrome, symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction at the time of screening
• Patients who are pregnant or breastfeeding
• Patients with known central nervous system (CNS) involvement by CLL or lymphoma
• Patients who have undergone allogeneic stem cell transplant
• Patients with history of underlying significant autoimmune disease including inflammatory bowel disease, autoimmune adrenal insufficiency, multiple sclerosis, autoimmune neuropathy, Guillain-Barre syndrome, myasthenia gravis, systemic lupus erythematosus (SLE), polymyositis, scleroderma, autoimmune hepatitis. Patients with other autoimmune endocrine disease, rheumatoid arthritis, other arthropathies or dermatologic conditions, or positive autoimmune serology in the absence of documented disease at any point are eligible