PRIMARY OBJECTIVE:~I. To determine the overall response rate (ORR) of rituximab, venetoclax, and bortezomib in relapsed/refractory diffuse large B-cell lymphoma.~SECONDARY OBJECTIVES:~I. To describe the safety profile of rituximab, venetoclax, and bortezomib in diffuse large B-cell lymphoma (DLBCL).~II. To describe the progression free survival of subjects enrolled to the study.~III. To describe the median overall survival of subjects enrolled to the study. IV. To describe the complete remission (CR) rate, the partial remission (PR) rate and the duration of response (DoR) of rituximab, venetoclax, and bortezomib in relapsed/refractory DLBCL.~EXPLORATORY OBJECTIVE:~I. To describe the association of BCL2 expression status, measured by immunohistochemistry (IHC), with ORR, CR and PR rates.~OUTLINE:~Patients receive rituximab intravenously (IV) on day -1 of cycle 1, then on day 1 of cycles 2-6. Patients also receive venetoclax orally (PO) once daily (QD) on days 1-14 and bortezomib IV or subcutaneously (SC) on day -1 of cycle 1, then on days 1, 8, and 15 of subsequent cycles. Treatment repeats every 28 days for up to 6 cycles for rituximab and up to 26 cycles for venetoclax and bortezomib in the absence of disease progression or unacceptable toxicity.~After completion of study treatment, patients are followed up at 30 days.
This phase II trial studies how well rituximab, venetoclax, and bortezomib work in treating patients with diffuse large B-cell lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Immunotherapy with monoclonal antibodies, such as rituximab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Venetoclax and bortezomib may stop the growth of tumor cells by blocking some of the proteins needed for cell growth. Giving rituximab, venetoclax, and bortezomib may slow or stop the growth of cancer cells in patients with diffuse large B-cell lymphoma.