Phase II Trial GA101 Inbrutinib B CLL

Inclusion Criteria: * Patient information and written informed consent * Age 18 years or older * Immunophenotypically confirmed B-CLL (IWCLL2008 and Matutes score 4 or 5) * Binet stage C according to IWCLL 2008 criteria or Binet stage A and B with active disease could be considered for inclusion. * Patients with no prior treatment (chemotherapy, radiotherapy, immunotherapy) except steroids for less than 1 month * Absence of 17p deletion as assessed by FISH (\< 10 % positive nuclei) * Performance status ECOG \< 2 * CIRS (Cumulative Illness Rating Scale) ≤ 6 (see appendix 4 for calculation of CIRS score) Mandatory inclusion criteria for treatment with ibrutinib Hematology values must be within the following limits: * Absolute neutrophil count (ANC) \<1 G/L independent of growth factor support * Platelets \<100 G/L or \<50 G/L if bone marrow involvement independent of transfusion support in either situation Biochemical values within the following limits: * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x upper limit of normal (ULN) * Total bilirubin ≤ 1.5 x ULN unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin * Serum creatinine ≤ 2 x ULN or estimated Glomerular Filtration Rate (Cockroft Gault≥ 40 mL/min/1.73m2 * 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 3 months after the last dose of study drug. * 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. * Sign (or their legally-acceptable representatives 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: * Binet stage A and B without active disease according to IWCLL 2008 criteria * Known HIV seropositivity * Hepatitis B or C seropositivity (unless clearly due to vaccination) * Active hemolysis (isolated positive DAT is not an exclusion criteria) * Life expectancy \< 6 months * Patient refusal to perform the bone marrow biopsy for evaluation points * Clinically significant auto-immune anemia * Active second malignancy currently requiring treatment (except basal cell carcinoma in situ endometrial carcinoma and incidental prostate carcinoma) and/or less than 5 years CR after breast cancer * Any severe co-morbid conditions such as Class III or IV heart failure, myocardial infarction within months, unstable angina, ventricular tachyarrhythmias requiring ongoing treatment, severe chronic obstructive pulmonary disease with hypoxemia, uncontrolled diabetes mellitus, or uncontrolled hypertension * Concomitant disease requiring prolonged use of corticosteroids (\> 1 month) * Known hypersensitivity with anaphylactic reaction to humanized monoclonal antibodies or any of the study drugs * Contraindication to the use of Obinutuzumab. * Contraindication to use of Ibrutinib * Transformation to aggressive B-cell malignancy (e.g. diffuse large cell lymphoma, Hodgkin lymphoma, or prolymphocytic leukaemia) * Active bacterial, viral or fungal infection * Abnormal renal function with creatinine clearance \< 60 ml/min calculated according to the formula of Cockcroft and Gault * Total bilirubin, gamma glutamyltransferase or transaminase levels \> 2.5 ULN. * Any coexisting medical or psychological condition that would preclude participation in the required study procedures * Patient with mental deficiency preventing proper understanding of the requirements of treatment. * Pregnant or breastfeeding women. * Adult under law-control * Fertile male and female patients who cannot or do not wish to use an effective method of contraception, during and for 18 months after the final treatment used for the purposes of the study. * No affiliate to social security Mandatory exclusion criteria for treatment with Ibrutinib * Major surgery within 4 weeks of randomization. * Known central nervous system lymphoma. * History of stroke or intracranial hemorrhage within 6 months prior to randomization. * Requires anticoagulation with warfarin or equivalent vitamin K antagonists * Requires treatment with strong CYP3A inhibitors. * 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 Functional Classification. * Vaccinated with live, attenuated vaccines within 4 weeks of randomization. * Known history of human immunodeficiency virus (HIV) or active Hepatitis C Virus or active Hepatitis B Virus infection or any uncontrolled active systemic infection requiring intravenous (IV) antibiotics. * Any life-threatening illness, medical condition, or organ system dysfunction 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.