Bendamustine/Rituximab Followed by Venetoclax and Rituximab for Treatment of Chronic Lymphocytic Leukemia

Inclusion Criteria: * Age ≥ 18 years of age. * Diagnosed with CLL * To be considered CLL, the subject must have an absolute lymphocytosis in the blood of at least 5,000 lymphocytes per microliter, or bone marrow lymphocytosis greater than or equal to 30% of all nucleated cells. * Histologic and immunophenotypic analysis should demonstrate small to moderate size lymphocytes with flow cytometry demonstrating a certain population of lymphocytes. * No prior therapy for their disease. Topical or inhaled corticosteroids are permitted for other medical conditions, ie asthma or dermatologic reasons. * Eastern Oncology Cooperative Group (ECOG) performance score of ≤ 2. * Subjects with autoimmune hemolytic anemia or autoimmune thrombocytopenia will be eligible for treatment on this protocol regardless of disease stage upon discussion with the principal investigator. * An absolute neutrophil count \> 1.0 109/L; hemoglobin \> 8 g/dL; or a platelet count \> 50 x 109/L (unless due to bone marrow failure). * Adequate hepatic function * activated partial thromboplastin time (aPTT) and prothrombin time (PT) not to exceed 1.5x the upper limit of reference ranges. * Ability to understand and the willingness to sign a written informed consent document. * Women of child-bearing potential and men must agree to use adequate contraception (see below) for at least 90 days prior to study entry and for the duration of study participation. * For women of childbearing potential (WCBP): a negative serum β-human chorionic gonadotropin (βhCG) pregnancy test must be performed within 1 week before randomization (WCBP defined as a sexually mature woman who has not undergone surgical sterilization or who has not been naturally post-menopausal for at least 24 consecutive months \[women ≤ 55 years\] or 12 consecutive months \[women \> 55 years\]). * Male and female subjects who are not surgically sterile or postmenopausal must be willing to use medically acceptable methods of birth control from the first dose of study drug to 30 days after the last dose of study drug. Sexually active men, and women using oral contraceptive pills, should also use barrier contraception. Exclusion Criteria: * Subjects who have been previously treated for CLL or small lymphocytic lymphoma (SLL), except with corticosteroids for symptom relief. * Treatment with any of the following within 7 days prior to the first dose of study drug: * Steroid therapy for anti-neoplastic intent * moderate or strong cytochrome P450 3A (CYP3A) inhibitors * moderate or strong CYP3A inducers * Subject has known allergy to both xanthine oxidase inhibitors and/or rasburicase. * Subject has a significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, cardiovascular, or hepatic disease that in the opinion of the investigator would adversely affect his/her participating in this study. * Subject has evidence of other clinically significant uncontrolled condition(s) including, but not limited to: 1. Uncontrolled and/or active systemic infection (viral, bacterial or fungal) 2. 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. * Subject is known to be positive for HIV. (HIV testing is not required.) * New York Heart Association (NYHA) class II-IV heart failure or arrhythmia requiring treatment. * Pregnant or lactating women. Women and men of childbearing age should use effective contraception. * Subject has a history of active malignancies other than CLL within the past 2 years prior to study entry with the exception of: adequately treated in situ carcinoma of the cervix uteri, adequately treated basal cell carcinoma or localized squamous cell carcinoma of the skin, or previous malignancy confined and surgically resected (or treated with other modalities) with curative intent. * Subjects may receive intravenous immunoglobulin (IVIG) for hypogammaglobulinemia while on protocol. Subjects may receive erythropoietin, filgrastim, pegfilgrastim, or sargramostim while on protocol. * Subject has malabsorption syndrome or other condition that precludes enteral route of administration. * Subjects with known Richter's syndrome or a history of Richter's syndrome. * Subjects who are are actively being treated for a non-hematologic autoimmune disease, or are on other immunomodulatory agents (e.g. cyclosporine, tacrolimus, etc.) will be excluded. * Subjects who have received an allogeneic stem cell transplant. * History of allergic reactions attributed to compounds of similar chemical or biologic composition to BCL-2 inhibitors, bendamustine, or anti-CD20 monoclonal antibodies. * Administration or consumption of any of the following within 3 days prior to the first dose of study drug: * Grapefruit or grapefruit products * Seville oranges (including marmalade containing Seville oranges) * Star fruit