STop and Restart Acalabrutinib In fRail Patients With Previously Untreated Chronic Lymphocytic Leukemia

Inclusion Criteria: * Age \> 70 years or older * Eastern Cooperative Oncology Group (ECOG) performance status \< 2 * Previously untreated CLL or Small Lymphocytic Lymphoma (SLL) * CLL or SLL requiring treatment according to the iwCLL 2018 criteria2 * Total Cumulative Illness Rating Scale (CIRS) score \> 6 or 30 \< CrCl \< 69 mL/min * Both patients with or without TP53 disruption 17p deletion and/or TP53 mutations) can be included * Patients can be included whatever their IGHV mutational status * Patients with therapy-controlled cardiovascular comorbidities and/or anticoagulation (novel oral anticoagulant alone, aspirin alone, heparin alone) can be included (patients treated by vitamin K antagonist or dual anti-platelet therapy cannot be included) * Life expectancy \> 6 months * Adequate hematology values: absolute neutrophil count ≥ 0.75 x 109/L, platelet count ≥ 50 x 109/L. * Adequate liver function as indicated by a total bilirubin \<1.5, aspartate transaminase and alanine transaminase ≤3 the institutional upper limits of normal values, unless directly attributable to CLL * Signed (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 specify biology analysis, and are willing to participate in the study. Exclusion Criteria: * Known HIV seropositivity * Evidence of other clinically significant uncontrolled condition(s) including, but not limited to: * Uncontrolled and/or active systemic infection (viral, bacterial or fungal) * Known history of human immunodeficiency virus, serologic status reflecting active hepatitis B virus or hepatitis C virus infection, any uncontrolled active systemic infection along with subjects who are on ongoing anti-infective treatment and subjects who have received vaccination with a live attenuated vaccine within 4 weeks before the first dose of study treatment 1. Subjects who are hepatitis B core antibody (anti-HBc) positive and who are hepatitis B surface antibody (anti-HBs) negative will need to have a negative hepatitis B virus Polymerase Chain Reaction (PCR) result before enrollment. Those who are hepatitis B surface antigen (HBsAg) positive or hepatitis B virus PCR positive will be excluded. 2. Subjects who are hepatitis C virus antibody positive will need to have a negative hepatitis C virus PCR result before enrollment. Those who are hepatitis C virus PCR positive will be excluded * Active and uncontrolled autoimmune cytopenia, including autoimmune hemolytic anemia (AIHA) (isolated positive Direct Antiglobulin Testing (DAT) is not an exclusion criteria) and idiopathic thrombocytopenic purpura (ITP). * Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura. * Patients treated by vitamin K antagonist or dual anti-platelet therapy * History of bleeding diathesis (e.g. hemophilia or von Willebrand disease) * History of confirmed progressive multifocal leukoencephalopathy (PML). * Concurrent severe diseases which exclude the administration of therapy : * heart insufficiency New York Heart Association (NYHA) grade III/IV, Left Ventricular Ejection Fraction (LEVF) \< 50% and or Recirculation Fraction (RF) \< 30%, myocardial infarction within the past 6 months prior to study * Significant cardiovascular disease such as symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of Screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional (Subjects with controlled, asymptomatic atrial fibrillation are allowed to enroll on study) * severe chronic obstructive lung disease with hypoxemia * history of stroke or intra-cranial hemorrhage within the last 6 months * severe diabetes mellitus * uncontrolled hypertension * impaired renal function with creatinine clearance \< 30 ml/min according the formula of Cockcroft and Gault * Patient who requires treatment with proton-pump inhibitors (e.g., omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole). Subjects receiving proton-pump inhibitors who switch to H2-receptor antagonists or antacids are eligible for enrollment in this study. * Disease significantly affecting gastrointestinal function (malabsorption syndrome, stomach or small bowel resection) * Evidence for Richter syndrome * Treatment with any of the following within 7 days prior to the first dose of study drug: steroid therapy for anti-neoplastic intent. * A significant history of renal, neurologic, psychiatric, endocrine, metabolic, immunologic, cardiovascular, or hepatic disease that, in the opinion of the investigator, would adversely affect the patient's participation in this study or interpretation of study outcomes * Major surgery within 30 days prior to the first dose of study treatment. * History of prior other malignancy that could affect compliance with the protocol or interpretation of results, with the exception of the following: * curatively treated basal cell carcinoma or squamous cell carcinoma of the skin or carcinoma in situ of the cervix at any time prior to study. * other cancers not specified above that have been curatively treated by surgery and/or radiation therapy from which patient is disease-free for ≥ 5 years without further treatment * Adult under law-control * Fertile male patients who cannot or do not wish to use an effective method of contraception, during and for 12 months after the final treatment used for the purposes of the study * No affiliation to social security