Testing the Combination of Venetoclax and Rituximab, in Comparison to the Usual Treatment (Ibrutinib Plus Rituximab or Zanubrutinib Alone) for Waldenstrom's Macroglobulinemia/Lymphoplasmacytic Lymphoma

Recruiting now · Phase 2

Conditions studied: Lymphoplasmacytic Lymphoma, Waldenstrom Macroglobulinemia

In brief

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.

Key facts

Study ID

NCT04840602

Run by

National Cancer Institute (NCI)

People needed

92

Starts

2022-01-05

Expected to finish

2028-03-31

Last updated by the study team

2026-07-29

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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 status must be performed within 28 days prior to registration
• Participants must have at least one of the criteria to require therapy for WM including:
• Anemia
• Thrombocytopenia
• Neuropathy related to WM
• Symptomatic hyperviscosity or serum viscosity levels ≥ 4.0 centipoises
• WM associated glomerulonephritis or renal disease, bulky disease, or constitutional symptoms
• Constitutional symptoms can be described as:
• Unintentional weight loss >= 10% within the previous 6 months prior to screening
• Fevers higher than 100.5 degrees Fahrenheit (F) or 38.0 degrees Celsius (C) for 2 or more weeks prior to screening without evidence of infection
• Night sweats for more than 1 month prior to screening without evidence of infection
• Clinically relevant fatigue which is not relieved by rest due to WM
• Participants who require ongoing use or received a moderate or strong CYP3A inducer, moderate or strong CYP3A inhibitor, P-gp inhibitor within 7 days prior to the first dose of study drug will be excluded from the study. If such participants can be safely switched to an alternative agent, then the participants will be eligible to enroll
• Participants must not have had prior systemic therapy. Prior therapy with rituximab will be allowed as long as the last rituximab dose was at least 6 months prior to registration
• Participants must be >= 18 years of age
• Participants must have history and physical exam within 28 days prior to registration
• Participants must have Zubrod performance status =< 2
• Participants must have evidence of adequate renal function, as defined by creatinine clearance (CrCl) >= 30 mL/min. Values must be obtained within 14 days prior to registration
• Total bilirubin =< 1.5 x IULN (institutional upper limit of the norm) (within 14 days prior to registration)
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT) =< 3 x IULN (within 14 days prior to registration)
• Alkaline phosphatase =< 3 x IULN (within 14 days prior to registration)
• Platelet count >= 50,000 cells/mm\^3 (within 14 days prior to registration)

Where it is running

• University of Arizona Cancer Center-North Campus — Tucson, Arizona, United States (enrolling)
• City of Hope at Irvine Lennar — Irvine, California, United States (enrolling)
• UM Sylvester Comprehensive Cancer Center at Coral Gables — Coral Gables, Florida, United States (enrolling)
• UM Sylvester Comprehensive Cancer Center at Coral Springs — Coral Springs, Florida, United States (enrolling)
• UM Sylvester Comprehensive Cancer Center at Deerfield Beach — Deerfield Beach, Florida, United States (enrolling)
• UM Sylvester Comprehensive Cancer Center at Doral — Doral, Florida, United States (enrolling)
• UM Sylvester Comprehensive Cancer Center at Hollywood — Hollywood, Florida, United States (enrolling)
• Mayo Clinic in Florida — Jacksonville, Florida, United States (enrolling)
• University of Miami Miller School of Medicine-Sylvester Cancer Center — Miami, Florida, United States (enrolling)
• UM Sylvester Comprehensive Cancer Center at Kendall — Miami, Florida, United States (enrolling)
• University of Miami Sylvester Comprehensive Cancer Center at Sole Mia — North Miami, Florida, United States (enrolling)
• UM Sylvester Comprehensive Cancer Center at Plantation — Plantation, Florida, United States (enrolling)
• Saint Alphonsus Cancer Care Center-Nampa — Nampa, Idaho, United States (enrolling)
• Centralia Oncology Clinic — Centralia, Illinois, United States (enrolling)
• Carle at The Riverfront — Danville, Illinois, United States (enrolling)
• Cancer Care Specialists of Illinois - Decatur — Decatur, Illinois, United States (enrolling)
• Carle Physician Group-Effingham — Effingham, Illinois, United States (enrolling)
• Crossroads Cancer Center — Effingham, Illinois, United States (enrolling)
• Carle Physician Group-Mattoon/Charleston — Mattoon, Illinois, United States (enrolling)
• Loyola University Medical Center — Maywood, Illinois, United States (enrolling)
• Cancer Care Center of O'Fallon — O'Fallon, Illinois, United States (enrolling)
• Southern Illinois University School of Medicine — Springfield, Illinois, United States (enrolling)
• Springfield Clinic — Springfield, Illinois, United States (enrolling)
• Springfield Memorial Hospital — Springfield, Illinois, United States (enrolling)
• Banner University Medical Center - Tucson — Tucson, Arizona, United States (enrolling)

Full record on ClinicalTrials.gov

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