Roginolisib (IOA-244) With Venetoclax and Rituximab for Refractory/Relapsed Chronic Lymphocytic Leukemia (CLL)

Inclusion Criteria: * Patients with relapsed/refractory CLL who meet iwCLL criteria for requiring treatment. * Patients with measurable disease as defined by at least one of: circulating lymphocytosis \> 5000 B cells/microliter, bone marrow involvement \> 30%, palpable splenomegaly or lymph nodes \> 1.5 cm. Computer tomography (CT) at screening must be performed and followed every 2 cycles (1 cycle = 28 days). * Patients must have received at least two prior therapies for CLL including systemic therapy containing a covalent BTK inhibitor. * Patients willing to undergo a pre-treatment and on treatment bone marrow biopsy. * Age ≥18 years, at the time of signing the IRB approved informed consent. Because no dosing or adverse event data are currently available on the use of venetoclax in combination with roginolisib in participants \<18 years of age, children are excluded from this study, but will be eligible for future pediatric trials. * Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2. * Participants must meet the following organ and marrow function as defined below: * Platelet count ≥50 x 109/L\^\^\^ * Total bilirubin ≤ 1.5 ×institutional upper limit of normal (ULN)\* * AST(SGOT)/ALT(SGPT) ≤3.0 × institutional ULN * Creatinine clearance ≥ 60 mL/min\*\* * \^\^\^Thrombocytopenia due to marrow involvement of CLL: \> 30 x 109/L for the safety run-in, and 20 x 109/L for the randomized portion of the study * \*unless increase attributed to leukemic …