Assessing Minimal Residual Disease by Next- Generation Sequencing to Minimize Exposure in People With CLL or SLL Who Have Been Treated With Venetoclax

Screening Phase Inclusion Criteria:

* ≥ 18-years-old
* Diagnosis of chronic lymphocytic leukemia or small lymphocytic lymphoma confirmed by the enrolling institution
* Receiving treatment or planning to receive treatment within 30 days with a venetoclax-based regimen as defined below:

  * Venetoclax monotherapy
  * Venetoclax in combination with anti CD20 monoclonal antibody (Patients must have completed the anti CD20 monoclonal antibody portion of the regimen prior to discontinuing therapy)
* Patient has or will have specimen to identify the CLL or SLL clone(s) for future MRD assessments by clonoSEQ® defined as any of the following:

  * 3-5 bone marrow aspirate slides (banked), 3-5 FFPE slides (banked), banked tumor cells or banked DNA collected from the patient at any time from original diagnosis of CLL or SLL to present
  * Peripheral blood, marrow, or lymph node involvement for fresh sample collection
* The screening ID sample (high disease burden sample) can be sent prior to start of venetoclax-based therapy to identify the clone for tracking.

Study Intervention Phase Inclusion Criteria:

* Patients must have received venetoclax-based therapy for at least 6 months (including dose interruptions)
* If receiving venetoclax in combination with anti-CD20 monoclonal antibody, patients must have completed or discontinued the anti CD20 monoclonal antibody portion of the regimen prior to discontinuing therapy
* Patients must have two MRD-negative assessments (defined by ≥ 10\^-5 sensitivity) on the peripheral blood by the clonoSEQ® assay at least 28 days apart. Given that MRD status is a dynamic endpoint which may improve with time, if a patient is screen failure based on MRD status (i.e. MRD positive at the 10-5 sensitivity), they may be rescreened to assess for study eligibility.
* Patients must have achieved a complete or partial remission with the venetoclax-based regimen. Criteria for remission are per iwCLL 2018 guidelines. For this protocol, bone marrow biopsy/aspirate evaluation is not necessary to determine remission status.

Exclusion Criteria (both study phases):

* Ongoing participation in a clinical trial that supplies venetoclax and/or anti CD20 monoclonal antibody
* Unwilling or unable to participate in all required study evaluations and procedures.
* Unable to understand the purpose and risks of the study and to provide a signed and dated informed consent form (ICF) and authorization to use protected health information (in accordance with national and local patient privacy regulations).