PRIMARY OBJECTIVES:~I. To characterize the safety of treatment with daratumumab and ibrutinib for previously untreated chronic lymphocytic leukemia (CLL).~II. To determine the complete response rate (CR) at the post cycle 12 response assessment following treatment with daratumumab and ibrutinib for previously untreated chronic lymphocytic leukemia (CLL).~SECONDARY OBJECTIVES:~I. To characterize the activity of daratumumab and ibrutinib as measured by overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and time-to-next treatment.~TERTIARY OBJECTIVES:~I. To measure pharmacodynamic parameters in B cells including drug occupancy of BTK and B cell receptor signaling during treatment.~II. To determine the influence of this combination on T cell and natural killer (NK) cell number and function.~III. To assess for development of mutations that may confer resistance to this combination.~IV. To assess the ability of daratumumab to clear CLL in the peripheral blood and association of CD38 expression on CLL cells with response.~OUTLINE:~Patients receive daratumumab intravenously (IV) on days 1, 8, 15, and 22 of courses 1-2, days 1 and 15 of courses 3-6, and day 1 of subsequent courses. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Beginning course 2, patients also receive ibrutinib orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.~After completion of study treatment, patients are followed up every 12 weeks for up to 2 years.
This phase Ib trials studies the side effects of daratumumab and ibrutinib and how well they work in treating patients with symptomatic chronic lymphocytic leukemia. Monoclonal antibodies, such as daratumumab, may interfere with the ability of cancer cells to grow and spread. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving daratumumab and ibrutinib may work better in treating patients with chronic lymphocytic leukemia.