Phase 2 Study to Assess Activity & Safety of Front-line Ibrutinib + Rituximab in Unfit Chronic Lymphocytic Leukemia

Inclusion Criteria: 1. 18 years of age or older. 2. Diagnosis of CLL meeting IWCLL criteria. 3. The diagnosis of CLL requires a history of lymphocytosis with a B-lymphocyte count ≥5,000/μL. Prolymphocytes may comprise no more than 55% of blood lymphocytes. 4. Active disease meeting at least 1 of the following IWCLL 2008 criteria for requiring treatment: 1. Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia or thrombocytopenia. 2. Massive (ie, at least 6 cm below the left costal margin), progressive, or symptomatic splenomegaly. 3. Massive nodes (ie, at least 10 cm in longest diameter), progressive, or symptomatic lymphadenopathy. 4. Progressive lymphocytosis with an increase of more than 50% over a 2-month period or a lymphocyte doubling time (LDT) of less than 6 months (which may be extrapolated). Lymphocyte doubling time can be obtained by linear regression extrapolation of ALCs obtained at intervals of 2 weeks over an observation period of 2 to 3 months. For patients with initial blood lymphocyte counts of less than 30 x 109/L (30,000/μL), LDT should not be used as a single parameter to define indication for treatment. In addition, factors contributing to lymphocytosis or lymphadenopathy other than CLL (eg, infections) should be excluded. 5. Constitutional symptoms, defined as 1 or more of the following disease-related symptoms or signs: * Unintentional weight loss \>10% within the previous 6 months prior to screening * Significant fatigue (inability to work or perform usual activities) * Fevers higher than 38.0°C for 2 or more weeks without evidence of infection; or * Night sweats for more than 1 month without evidence of infection * Measurable nodal disease by computed tomography (CT). Measurable nodal disease is defined as at least one lymph node \>1.5 cm in longest diameter in a site that has not been previously irradiated. An irradiated lesion may be assessed for measurable disease only if there has been documented progression in that lesion since radiotherapy has ended. 5. No prior treatment. 6. Total CIRS \>6 and/or creatinine clearance \<70 ml/min \[Cockcroft-Gault\]). 7. Hematology values within the following limits: Absolute neutrophil count (ANC) ≥1 x 109/L (ie, ≥1000/μL) independent of growth factor support. Platelets ≥50,000/mm3 if bone marrow involvement independent of transfusion support 8. Biochemical values within the following limits: 1. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 x upper limit of normal (ULN) 2. Total bilirubin ≤1.5 x ULN unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin 3. Serum creatinine ≤2 x ULN or estimated Glomerular Filtration Rate (Cockroft Gault) ≥40 mL/min 9. 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 not to 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 3 months after the last dose of study drug. 10. Women of childbearing potential must have a negative serum (beta-human chorionic gonadotropin \[β-hCG\]) or urine pregnancy test at Screening. Women who are pregnant or breastfeeding are ineligible for this study. 11. A signed (or signed by their legally-acceptable representatives) 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: 1. Any significant concurrent, uncontrolled medical condition or organ system dysfunction and/or laboratory abnormality or psychiatric disease which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue risk or prevent the subject from signing the informed consent form. 2. Pregnant or lactating females 3. Known presence of alcohol and/or drug abuse. 4. Any potential subject who meets any of the following criteria will be excluded from participating in the study. 5. Major surgery within 4weeks of randomization. 6. Uncontrolled autoimmune hemolytic anemia or thrombocytopenia. 7. Known central nervous system lymphoma. 8. History of stroke or intracranial hemorrhage within 6 months prior to randomization, or of a significant cerebrovascular disease in the past 6 months or ongoing event with active symptoms or sequelae. 9. Requires anticoagulation with warfarin or equivalent vitamin K antagonists (eg, phenprocoumon) in any moment of the study. 10. Requires treatment with strong CYP3A inhibitors. 11. Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of Screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association 12. Vaccinated with live, attenuated vaccines within 4 weeks of randomization. 13. Known history of human immunodeficiency virus (HIV) positive serology for HIV; active Hepatitis B Virus infection or positive serology for Hepatitis B (HBV) defined as a positive test for HBsAg and HBV-DNA; active Hepatitis C or HCV-RNA positive; any uncontrolled active systemic infection requiring intravenous (IV) antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, chronic chest infection; history of tuberculosis within the last five years or recent exposure to tuberculosis equal to or less than 6 months. 14. Richter's syndrome (RS), concomitant or past malignancy. Subjects who have been free of malignancy for at least 5 years, or have a history of completely resected non-melanoma skin cancer, or successfully treated in situ carcinoma are eligible.