Nivolumab and Ibrutinib in Treating Patients With Relapsed, Refractory, or High-Risk Untreated Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, or Richter Transformation

Inclusion Criteria

• Patients will have a diagnosis of CLL or small lymphocytic lymphoma (SLL), refractory to or relapsed after at least one prior standard therapy or untreated with deletion (del)(17p) by fluorescence in-situ hybridization (FISH) (high-risk cytogenetics) and have an indication for treatment by IWCLL 2008 criteria (Cohort 1) OR have been on ibrutinib for at least 9 months with measurable persistent disease (absolute lymphocyte count [ALC] > 4 K/muL, any lymph node > 1.5 cm by computed tomography [CT] scan, or > 30% lymphocytes on bone marrow aspirate differential) (Cohort 2), OR patients will have a diagnosis of RT, refractory to and/or relapsed after at least one prior standard therapy or untreated with del(17p) by FISH (high-risk cytogenetics) (Cohort 3)
• Eastern Cooperative Oncology Group (ECOG) performance status = = 160 mmHg or diastolic >= 100 mmHg)
• Known evidence of active cerebral/meningeal CLL; patients may have history of central nervous system (CNS) leukemic involvement if definitively treated with prior therapy and no evidence of active disease at the time of registration
• Active, uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia requiring steroid therapy
• Patients with autoimmune diseases are excluded: patients with a history of inflammatory bowel disease (including Crohn's disease and ulcerative colitis) are excluded from this study as are patients with a history of autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis, systemic lupus erythematosus, Wegener's granulomatosis)
• Patients with previous allogeneic stem cell transplant (SCT) within 6 months or with active acute or chronic graft-versus host disease are excluded; patients must be off immunosuppression for graft-versus host disease (GVHD) for at least 30 days before cycle 1 day 1
• Patients with organ allografts (such as renal transplant) are excluded
• History of interstitial lung disease or pneumonitis
• Patients who are on high dose steroid (> 10 mg daily of prednisone or equivalent) or immune suppression medications; Note: patients on high-dose steroids (doses > 10mg/day of prednisone or equivalent) or immune suppression medications are eligible provided these drugs are discontinued at least 3 days prior to starting on the study drugs
• Patients with uncontrolled active infection (viral, bacterial, and fungal) are not eligible
• Current or chronic hepatitis B or C infection, or known seropositivity for human immunodeficiency virus (HIV)
• Patient is pregnant or breast-feeding
• Concurrent use of investigational therapeutic agent
• Malabsorption syndrome or other condition that precludes enteral route of administration
• Concomitant use of warfarin or other vitamin K antagonists
• Requires treatment with a strong cytochrome P450 (CYP) family 3, subfamily A (3A) inhibitor
• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and/or would make the patient inappropriate for enrollment into this study