Tafasitamab, Acalabrutinib, and Obinutuzumab for the Treatment of Previously Untreated Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma

PRIMARY OBJECTIVE: I. Evaluate safety and measurable residual disease negativity. SECONDARY OBJECTIVE: I. Evaluate early indications of efficacy based on response. EXPLORATORY OBJECTIVES: I. Determine progression-free survival. II. Determine overall survival. III. Define the population based on molecular correlates and determinants of CLL or SLL. IV. Associations between molecular correlates and determinants of CLL/SLL and response. V. Correlative Studies for T cell function. VI. Patient-reported quality of life (QOL) outcomes. OUTLINE: Patients receive obinutuzumab intravenously (IV) over a rate titrated up to 400 mg/hour on days 1, 2, 8, and 15 for cycle 1 then on day 1 for cycles 2-6 and tafasitamab IV over 1.5-2 hours on days 1, 4, 8, 15, and 22 for cycle 2, on days 1, 8, 15, and 22 for cycles 3-4, and on days 1 and 15 for cycles 5-7. Patients also receive acalabrutinib orally (PO) twice daily (BID) of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection and computed tomography (CT) scans throughout the trial. Patients may undergo an echocardiography (ECHO) at baseline as clinically indicated and may also undergo bone marrow biopsy and/or aspiration at baseline and/or follow-up. After completion of study treatment, patients are followed up every 3 months for 2 years.