Study of Zanubrutinib in Older Patients With Previously Untreated Chronic Lymphocytic Leukemia (CLL)

Inclusion Criteria: * Participant who understands and voluntarily signs and dates an informed consent form prior to any studyspecific assessments/procedures being conducted, including consent for specific biology analysis * Must be able to adhere to the trial visit schedule and other protocol requirements * ≥ 80 years at the time of signing the informed consent form (ICF) with no upper age limit * Previously untreated and documented CLL or small lymphocytic lymphoma (SLL), with a Royal Marsden Hospital (RMH) or Matutes Score of 4 or 5. For SLL a detectable clone with a CLL phenotype in the peripheral blood is a prerequisite for trial participation. * Participant requiring treatment according to 2018 IWCLL guidelines * ECOG performance status 0 to 2 * Life expectancy \> 6 months * Adequate hematopoietic function within 7 days before the participant's enrollment * ANC ≥ 0.75 G/L * And Platelets ≥ 50 G/L Note: Platelets transfusions may be administered during screening to meet this requirement * Hemoglobin level \> 9g/dL, regardless of transfusion * Adequate renal function defined by a Creatinine Clearance ≥ 30 ml/min calculated according to MDRD or CKD-EPI or Cockcroft-Gault (using actual body weight). * Adequate liver function, as indicated by a total bilirubin \<1.5 x ULN, AST and ALT \<3 x ULN value, unless directly attributed to the participant's CLL/SLL or to Gilbert's Syndrome (the ULN is based on institutionalvalues) * Participant covered by any social security system * Participant who understands and speaks the country official language unless local regulation authorizes independent translator Exclusion Criteria: * Any prior CLL or SLL-specific therapies, even including rituximab used for autoimmune cytopenias. * Clinically significant cardiovascular disease including the following: 1. Myocardial infarction within 6 months prior to ICF signature 2. Unstable angina within 3 months prior to ICF signature 3. NYHA class III or IV heart failure 4. Uncontrolled hypertension 5. History of clinically significant arrhythmias (including sustained ventricular tachycardia, ventricular fibrillation, or torsades de pointes). 6. History of Mobitz II second- or third-degree heart block without permanent pacemaker 7. Known LVEF \<50% as determined by echocardiography or multiple uptake gated acquisition (MUGA) scan * Child-Pugh liver cirrhosis * Clinical evidence for Central Nervous System involvement by CLL * Severe chronic obstructive lung disease with hypoxemia * Severe diabetes mellitus * Disease significantly affecting gastrointestinal function (malabsorption syndrome, stomach or small bowel resection) * Active or non-active autoimmune hemolytic anemia (AIHA) (isolated positive DAT is not an exclusion criterion, but reticulocytes/haptoglobin levels must be in lab normal ranges) or idiopathic thrombocytopenic purpura (ITP), requiring steroid therapy with \> 20 mg daily of prednisone dose or equivalent. * Any prior history of Richter transformation or DLBCL * Any evidence or suspicion of Richter transformation or DLBCL during screening * Active malignancy other than the one treated in this trial. Prior history of malignancies unless the participant has been free of the disease for ≥ 2 years. However, participants with the following history /conditions that have been treated with a curative intent are allowed: 1. Non-invasive basal cell or epidermoid carcinoma (non melanoma) 2. In situ carcinoma of the cervix 3. In situ carcinoma of the breast 4. Incidental histologic finding of prostate cancer (T1a or T1b) using the tumor, nodes, metastasis \[TNM\] clinical staging system 5. Woman with adjuvant endocrine therapy (I.e., hormonotherapy) after breast cancer treatment can be enrolled if hormonotherapy was started for ≥ 2 years * History of stroke or intracranial hemorrhage within 6 months prior to ICF signature. * Major surgery 28 days before the ICF signature * History or known bleeding disorders (e.g hemophilia or von Willebrand disease) * Active Hepatitis C Virus (HCV) infection (RNA PCR-positive). Participants who received treatment for HCV infection that was intended to eradicate the virus may participate if hepatitis C RNA levels are undetectable * Active Hepatitis B Virus (HBV) infection (DNA PCR-positive). Participants with evidence of prior HBV infection but who are PCR-negative are permitted in the trial but should receive prophylactic antiviral therapy during the entire treatment with active monitoring of viral load in the blood * Patient with a positive HIV test before enrollment are eligible provided that they are stable on antiretroviral therapy for at least 4 weeks, have a CD4 count ≥ 200/uL, have an undetectable viral load, and have not had a history of opportunistic infection attributable to AIDS within the last 12 months.Known or suspected hypersensitivity or anaphylaxis to trial intervention including active substance or to any of the excipients. * Requires or receiving anticoagulation with warfarin or dual antiplatelets therapy equivalent vitamin K antagonists (other anticoagulants allowed: novel oral anticoagulant alone, aspirin alone, heparin alone). * Requires treatment with a strong/moderate cytochrome CYP3A4 inhibitor/inducer. * Participation in another clinical study who would compromise the participation to the current study. * Vaccinated with live, attenuated vaccines within 6 months of ICF * Use of any standard or experimental anti-cancer drug therapy within 28 days before the start (Day 1) of study treatment * Corticosteroid use \> 20 mg per day within 1 week before the first dose of trial intervention, except as indicated for other medical conditions, such as inhaled steroid for asthma, topical steroid use, or as premedication for administration of trial intervention or contrast. * Any significant medical conditions, or laboratory abnormality or psychiatric illness likely to interfere with participation in this clinical trial or affect interpretation of trial outcomes (according to the investigator's decision) * Any uncontrolled and/or active significant infection (eg, bacterial, viral, or fungal; including participants with positive cytomegalovirus PCR). * Participant deprived of their liberty by a judicial or administrative decision * Participant hospitalized without consent * Adult participant under legal protection