PRIMARY OBJECTIVE:~I. To determine the proportion of patients who have treatment-free remission 6 months after discontinuation of acalabrutinib in patients who complete 24 cycles of frontline therapy.~SECONDARY OBJECTIVES:~I. To determine clinical factors associated with a treatment-free remission of more than 6 months after discontinuation of acalabrutinib.~II. To determine the treatment-free remission length. III. To evaluate the efficacy of re-treatment with acalabrutinib plus obinutuzumab in patients who relapse.~EXPLORATORY OBJECTIVES:~I. To characterize the effects of limited-duration acalabrutinib plus obinutuzumab therapy on the clonal architecture as determined by genome-wide genotyping and analysis (GWAs) and whole exome sequencing (WES).~II. To determine the frequency of BTK and PLCG2 mutation in patients relapsing after limited-duration acalabrutinib plus obinutuzumab therapy.~OUTLINE:~Patients receive acalabrutinib orally (PO) twice a day (BID) every 12 hours starting on day 1 of cycle 1, and obinutuzumab intravenously (IV) over 4-6 hours on days 1 and 2 of cycle 3, and day 1 of cycles 4-8. Patients who do not achieve a complete response or remission after cycle 8 may receive single-agent acalabrutinib therapy PO BID for an additional 6 cycles at the discretion of their treating physician. Patients who are in partial response or who have stable disease receive an additional 6 cycles of acalabrutinib PO BID and obinutuzumab IV. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.~After completion of study treatment, patients are followed up at 30 days then every 3 months.
This phase II trial investigates the how well acalabrutinib and obinutuzumab work in treating patients with chronic lymphocytic leukemia (CLL). Acalabrutinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with obinutuzumab may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Giving acalabrutinib and obinutuzumab may help to control disease progression in CLL patients who have not received treatment for CLL.