National Cancer Institute (NCI)
This phase II trial studies the effects of venetoclax and rituximab in comparison to ibrutinib and rituximab or zanubrutinib in treating patients with previously untreated Waldenstrom's macroglobulinemia/lymphoplasmacytic lymphoma. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Rituximab is a monoclonal antibody. It binds to a protein called CD20, which is found on B cells (a type of white blood cell) and some types of cancer cells. This may help the immune system kill cancer cells. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Zanubrutinib, a type of tyrosine kinase inhibitor, blocks a protein called BTK, which may help keep cancer cells from growing. Giving venetoclax and rituximab may work better in treating patients with previously untreated Waldenstrom's macroglobulinemia than ibrutinib with rituximab or zanubrutinib alone.
PRIMARY OBJECTIVE: I. To compare the rate of very good partial response or better (VGPR or better) in previously untreated participants with Waldenström's macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) who are treated upfront with ibrutinib + rituximab (IR) or zanubrutinib alone (Z) versus (vs.) venetoclax +/- rituximab (VR) regimen. SECONDARY OBJECTIVES: I. To compare overall response rates (ORR) in WM participants treated upfront with ibrutinib + rituximab or zanubrutinib alone vs. venetoclax + rituximab. II. To compare progression-free survival (PFS), time to next treatment, du…
Inclusion Criteria: * Participants must have had a confirmed diagnosis of Waldenstrom's macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL). Participants must have measurable disease as determined by IgM protein quantification. * IgM Spike: ≥ 500 mg/dL (≥ 5 g/L) * Extramedullary disease: The manifestation of a lymphoid mass outside of the bone marrow, resulting in enlargement in extramedullary organs such as the lymph nodes or spleen. Note: all participants must have measurable IgM spike, but are not required to have extramedullary disease * Testing to establish baseline disease stat…
Undergo blood sample collection
Undergo bone marrow biopsy and aspiration
Undergo bone marrow biopsy and aspiration
Undergo CT or PET/CT
Given PO
Undergo PET/CT
Given IV
Given PO
Given PO