Rituximab + High-Dose Methylprednisolone Debulking Prior to Venetoclax for CLL & SLL Patients

The purpose of the study is to investigate whether the combination of rituximab and high dose methylprednisolone can be given together, can reduce the amount of cancer cells that are present prior to starting venetoclax, and therefore make it safer to take venetoclax. Patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) will be treated in this study. Subjects will be assessed for their risk of tumor lysis syndrome (TLS), a potentially serious side effect associated with venetoclax and rituxan. TLS is caused by the fast breakdown of cancer cells. TLS can lead to kidney failure or abnormal heart rhythm. Depending on their TLS risk, patients will be assigned to one of two treatment arms. Patients who are at high risk for TLS at baseline will receive HDMP/Rituximab for 1 cycle before beginning venetoclax. Patients who are at low risk for TLS at baseline will not receive HDMP/Rituximab and will instead start directly with venetoclax. Once the proper dose of venetoclax is reached, both arms will continue venetoclax for up to 2 years and receive rituximab for 5 cycles. The purpose is to determine if HDMP/Rituximab prior to venetoclax is efficient at reducing tumor burden and lowering the risk of developing TLS. Although all of these drugs are approved by the FDA for the treatment of patients with CLL or SLL, and although the combination of rituximab and venetoclax is approved by the FDA for the treatment of patients with CLL or SLL, the combination and dosing schedule in this trial are considered experimental.