NCT04840602 · National Cancer Institute (NCI)
Testing the Combination of Venetoclax and Rituximab, in Comparison to the Usual Treatment (Ibrutinib and Rituximab) for Waldenstrom's Macroglobulinemia/Lymphoplasmacytic Lymphoma
What this study is about
This phase II trial studies the effects of venetoclax and rituximab in comparison to ibrutinib and rituximab 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.
View original scientific description
This phase II trial studies the effects of venetoclax and rituximab in comparison to ibrutinib and rituximab 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.
Interventions
PROCEDURE
Biospecimen Collection
Undergo blood sample collection
PROCEDURE
Bone Marrow Aspiration
Undergo bone marrow biopsy and aspiration
PROCEDURE
Bone Marrow Biopsy
Undergo bone marrow biopsy and aspiration
PROCEDURE
Computed Tomography
Undergo CT or PET/CT
DRUG
Ibrutinib
Given PO
PROCEDURE
Positron Emission Tomography
Undergo PET/CT
BIOLOGICAL
Rituximab
Given IV
DRUG
Venetoclax
Given PO
DRUG
Zanubrutinib
Given PO
Primary outcome measures
Very good partial response or better (VGPR or better) rate
Time frame: Up to 5 years
A Cochran-Mantel-Haenszel test will be performed to compare the VGPR in the ibrutinib plus rituximab or zanubrutinib alone arm and the venetoclax plus rituximab arm accounting for the stratification factor of prior rituximab, and VGPR or better rate will be reported in each study arm with a binomial confidence interval.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
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 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 greater than 4.0 centipoises, WM associated glomerulonephritis or renal disease, bulky disease, or constitutional symptoms. Constitutional symptoms
Where
- Tucson, Arizona
- Irvine, California
- Coral Gables, Florida
- Coral Springs, Florida
- Deerfield Beach, Florida
- Doral, Florida
- Hollywood, Florida
- Jacksonville, Florida
- Miami, Florida
- North Miami, Florida
- Plantation, Florida
- Nampa, Idaho
And 91 more locations — see the full list below.
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Jul 14, 2026 · Source of record for eligibility and locations