Acalabrutinib, Umbralisib, and Ublituximab (AU2) In Relapsed and Untreated CLL

Inclusion Criteria: * Confirmed diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) per International Workshop on CLL (iwCLL) 2018 criteria.1 * Participants must have an indication for treatment as defined by iwCLL 2018 criteria.1 * Participants must have measurable disease, defined as lymphocytosis \> 5,000 / μL, or palpable or CT measurable lymphadenopathy ≥ 1.5 cm, or bone marrow involvement ≥ 30%. * For enrollment to Cohort 1: Participants must have relapsed or refractory disease as per iwCLL 2018 criteria,1 and must have received no more than 2 prior lines of anti-cancer therapy. * For enrollment to Cohort 2: Participants must have previously untreated disease (i.e. must not have received any prior systemic therapy for CLL or SLL). * Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of umbralisib, acalabrutinib, and ublituximab in participants \< 18 years of age and CLL is extremely rare in this population, children are excluded from this study. * ECOG performance status ≤ 2 (Karnofsky ≥ 60%, see Appendix A). * Participants must have adequate organ and marrow function as defined below: * Total bilirubin ≤ 1.5 × institutional upper limit of normal (ULN) (unless due to hemolysis or Gilbert's disease, in which ≤ 3 × institutional ULN is acceptable) * AST (SGOT) and ALT (SGPT) ≤ 2.5 × institutional ULN, OR * AST (SGOT) and ALT (SGPT) ≤ 5 × institutional ULN if there is hemolysis or documented …