Testing the Addition of a New Drug, Venetoclax, to the Usual Treatment (Ibrutinib and Rituximab) for Waldenstrom's Macroglobulinemia/Lymphoplasmacytic Lymphoma

Summary

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PRIMARY OBJECTIVE: I. To compare the rate of complete response (CR) in previously untreated participants with Waldenstrom's macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) who are treated upfront with ibrutinib, rituximab and venetoclax (IRV) versus (vs.) ibrutinib and rituximab (IR) regimen...

PRIMARY OBJECTIVE: I. To compare the rate of complete response (CR) in previously untreated participants with Waldenstrom's macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) who are treated upfront with ibrutinib, rituximab and venetoclax (IRV) versus (vs.) ibrutinib and rituximab (IR) regimen. SECONDARY OBJECTIVES: I. To compare overall response rates (ORR) in WM participants treated upfront with IRV vs. those treated with IR. II. To compare progression free survival (PFS), time to next treatment, duration of response in WM participants treated upfront with IRV vs. those treated with IR. III. To compare the rate of very good partial response (VGPR) or better in WM participants treated upfront with IRV vs. those treated with IR. IV. To evaluate the safety of the IRV regimen as compared to IR regimen in participants with WM. V. To evaluate the time to CR in WM participants treated upfront with IRV and those treated with IR. VI. To evaluate the ORR in participants who progress on treatment with IR and are crossed over to treatment with IRV. VII. To compare overall survival (OS) in WM participants treated upfront with IRV vs. those treated with IR. BANK OBJECTIVE: I. To bank specimens for future correlative studies. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive ibrutinib orally (PO) once daily (QD) on days 1-28 of cycles 1-24 and rituximab intravenously (IV) on days 1, 8, 15, and 22 of cycles 1 and 5. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Patients with progressive disease during Arm I may receive ibrutinib, rituximab, and venetoclax as in Arm II for up to an additional 24 cycles. ARM II: Patients receive ibrutinib PO QD on days 1-28 of cycles 1-24, rituximab IV on days 1, 8, 15, and 22 of cycles 1 and 5, and venetoclax PO QD on days 1-28 of cycles 2-24. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for up to 5 years.

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