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

This phase II, open-label, multicenter study evaluates zanubrutinib in patients aged 80 years and older with previously untreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who require treatment. CLL and SLL are slow-growing blood cancers that mainly affect older adults. Although zanubrutinib is an effective treatment, taking it continuously at the full dose may increase the risk of side effects over time, particularly in elderly patients. The study aims to assess whether a planned reduction in the dose of zanubrutinib after an initial period of treatment can maintain disease control while improving long-term tolerability.

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 \