PRIMARY OBJECTIVE:~I. To assess the rate of undetectable minimal residual disease (MRD) (uMRD, by ClonoSEQ) in both peripheral blood and bone marrow after 15 cycles of treatment.~SECONDARY OBJECTIVES:~I. To assess best peripheral blood uMRD rate and best bone marrow uMRD rate by ClonoSEQ.~II. To assess progression-free survival (PFS). III. To assess overall response rate (ORR) and complete response (CR) rate. IV. To assess duration of response (DOR), time to next treatment (TTNT), and overall survival (OS).~V. To assess toxicities associated with pirtobrutinib and venetoclax.~CORRELATIVE RESEARCH OBJECTIVE:~I. To analyze the dynamics of MRD (by ClonoSEQ) and its association with response to treatment and clinical outcomes.~OUTLINE:~Patients receive pirtobrutinib and venetoclax orally on study. Patients also undergo computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) scans during screening and on study. Patients also undergo bone marrow aspiration and bone marrow biopsy, and collection of blood, tissue, stool, and saliva samples on study.
This phase II trial studies how well pirtobrutinib and venetoclax work in treating patients with chronic lymphocytic leukemia or small lymphocytic lymphoma. This study also seeks to adopt a blood test which shows a small number of cancer cells in the body after cancer treatment called minimal residual disease as a guide to determine length of treatment. Drugs used in chemotherapy, such as pirtobrutinib and venetoclax, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.