Early Clonal Dynamics During Venetoclax Treatment for Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)

This study aims to study the clonal dynamics and kinetics of response during the ramp-up phase of venetoclax in chronic lymphocytic leukemia (CLL). Key Eligibility Criteria: 1. Diagnosis of CLL/SLL (treatment naive or relapsed/refractory) 2. Must have designated hematologist/oncologist who has agreed to assume care and continue venetoclax after the ramp-up phase is complete 3. Age \>=18 years 4. ECOG 0-2 Design: Patients with CLL/SLL will enroll on the study. Subjects will be treated at the NIH Clinical Center for the duration of the ramp-up phase of venetoclax. After the ramp-up phase is complete, subjects will be transitioned to the care of their local hematologist/oncologist and receive venetoclax monotherapy or in combination with other agent(s) at the discretion of the treating oncologist. Subjects will have the option to follow-up at the NIH every 6 months (from initiation of venetoclax) and at (suspected) progression. Study Objectives: Primary Objective: -Determine the proportion of subjects with clonal shift during the ramp-up phase of venetoclax Secondary Objective: -Determine response kinetics of venetoclax therapy in the peripheral blood, lymph nodes and bone marrow Exploratory Objectives: * Assess relationship between clonal shifts and minimal residual disease (MRD) status, progression free survival (PFS) and overall survival (OS) * Assess immunologic changes in the peripheral blood and bone marrow during venetoclax treatment * Assess circulating-tumor DNA in response to treatment during venetoclax treatment * Compare the proportion of subjects with early clonal shift between patients receiving only venetoclax and patients receiving venetoclax and BTKi overlap during the ramp-up