Fred Hutchinson Cancer Center
This phase II trial tests how well tacabrutideg and sonrotoclax, with response-guided addition of obinutuzumab, works in treating patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Tacabrutideg is a drug that degrades a protein called Bruton's tyrosine kinase (BTK). By degrading BTK, tacabrutideg inhibits the activation of signaling pathways that help cancer cells survive, inhibiting the growth of cancer cells that express the BTK protein. Sonrotoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking BCL-2, a protein needed for cancer cell survival. Obinutuzumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Giving tacabrutideg together with sonrotoclax may kill more cancer cells than giving either drug alone, and giving obinutuzumab after initial treatment with tacabrutideg and sonrotoclax may improve disease response in patients whose CLL or SLL didn't respond completely to initial treatment.
OUTLINE: Patients receive tacabrutideg orally (PO) once daily (QD) on days 1-28 of cycles 1-14 and sonrotoclax PO QD on days 1-28 of cycles 3-14. Cycles repeat every 28 days for up to 14 cycles in the absence of disease progression or unacceptable toxicity. Patients who are minimal residual disease (MRD) positive after cycle 14 continue receiving tacabrutideg PO QD and sonrotoclax PO QD on days 1-28 of cycles 15-20 and also receive obinutuzumab intravenously (IV) on days 8, 9, 15 and 22 of cycle 15 and day 8 of cycles 16-20. Cycles repeat every 28 days for up to 6 additional cycles in the abs…
Inclusion Criteria: * Age \>= 18 at time of study enrollment who are capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol * Confirmed diagnosis of CLL/SLL by 2018 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria * Meets criteria for treatment for iwCLL criteria * Measurable disease, as defined by at least one of the following: * At least one lymph node \> 1.5 cm in longest diameter, as measurable by computed tomography (CT) or magnetic resonance imag…
Given PO
Given PO
Given IV
Undergo TTE
Undergo collection of blood samples
Undergo CT
Undergo MUGA