An observational study in Waldenstrom Macroglobulinemia, Lymphoplasmacytic Lymphoma and Monoclonal B-Cell Lymphocytosis, sponsored by National Heart, Lung, and Blood Institute (NHLBI). Recruiting at 1 site in United States. Open to participants aged 18 Years to 110 Years. Per ClinicalTrials.gov, last updated 2026-11-10.
Sponsored by National Heart, Lung, and Blood Institute (NHLBI) · Observational
Background
The development of new technologies now allow scientists to investigate the molecular basis and clinical manifestations of monoclonal B cell lymphocytosis (MBL), chronic lymphocytic leukemia(CLL)/small lymphocytic lymphoma (SLL), lymphoplasmacytic lymphoma (LPL)/Waldenstrom macroglobulinemia (WM), and splenic marginal zone lymphoma (SMZL). Applying these methods in a natural history study can help identify processes involved in disease progression, and possibly lead to the discovery or validation of treatment targets.
Objectives
Study the history of MBL/CLL/SLL/LPL/WM/SMZL in patients prior to and after treatment. Characterize clinical, biologic and molecular events of disease stability and progression of patients enrolled on this protocol.
Eligibility:
Design
Patients are typically followed every 6 to 24 months in the clinic and have blood drawn. Patients may be asked to undergo additional testing, including bone marrow biopsy and aspiration, lymph node biopsy, positron emission tomography, and CT and MRI scans. Some of these tests (e.g., blood draw) may be required to monitor CLL/SLL and LPL/WM. Other tests (e.g., lymph node biopsy) may not be clinically indicated, but patients may be asked to undergo these procedures for research purposes.
No treatment will be administered on this study. If a patients requires treatment for their cancer, available NIH clinical trials and alternative treatment options will be discussed with the patient.
The purpose of this protocol is to collect blood, tissue (bone marrow and lymph node biopsies) and/or imaging studies (PET and CT scans) from patients with monoclonal B cell lymphocytosis (MBL), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), lymphoplasmacytic lymphoma (LPL)/Waldenstrom macroglobulinemia (WM), and splenic marginal zone lymphoma (SMZL).
Assessments will be used for clinical and translational research investigating the molecular basis of MBL, CLL/SLL, LPL/WM, SMZL and their clinical manifestations. New technologies now permit the simultaneous characterization of pathogenic events ranging from the control of gene expression to the characterization of the molecular events of cell-cell interactions. Applying these methods to MBL/CLL/SLL/LPL/WM/SMZL in the context of a natural history protocol can help unravel cellular pathways involved in pathogenesis and disease progression and lead to the discovery or the validation of therapeutic targets. MBL/CLL/SLL/LPL/WM/SMZL is an incurable disease for which there are no reliable cell lines and only a few mouse models. There is an urgent need to obtain a flow of primary samples to advance research into pathogenesis and novel treatment approaches.
Eligibility:
Patients will be typically followed every 6-12 months for the first 2 years and every 12-24 months thereafter. Interim visits may occur at the discretion of the research team. Patients may donate cellular products or tissues as appropriate for research purposes. Clinical information will be obtained and stored in a central databank.
Objectives:
Endpoints:
524 studies on the registry are indexed under Waldenstrom Macroglobulinemia; 62 are open to participants now.
This study's planned enrollment of 1,000 is above the median of 150 across 40 observational studies indexed under Waldenstrom Macroglobulinemia.
Browse Waldenstrom Macroglobulinemia studies →National Heart, Lung, and Blood Institute (NHLBI) is the lead sponsor of 1,143 studies on the registry; 71 are open to participants now.
Of its 58 completed or terminated interventional studies of FDA-regulated products, 51 (88%) have results posted.
Counted across the registry records on this site, refreshed daily.
Patients with monoclonal B cell lymphocytosis (MBL), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), lymphoplasmacytic lymphoma (LPL)/Waldenstr(SqrRoot)(Delta)m macroglobulinemia (WM), and splenic marginal zone lymphoma (SMZL).
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Diagnosis of CLL/SLL will be made according to the updated criteria of the NCI Working Group.
OR
Diagnosis of LPL/WM. LPL is defined as the presence of an intertrabecular pattern of bone marrow infiltration by small lymphocytes showing plasmacytoid/plasma cell differentiation. WM, comprising >95% of LPL cases, describes the clinical syndrome of LPL associated with an IgM monoclonal gammopathy of any concentration. The remaining cases may be IgA, IgM, or non-secreting LPL. Immunophenotyping is required for diagnosis
EXCLUSION CRITERIA:
1. None
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Line of therapy
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Patients with monoclonal B cell lymphocytosis (MBL), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), lymphoplasmacytic lymphoma (LPL)/Waldenstr(SqrRoot)(Delta)m macroglobulinemia (WM), and splenic marginal zone lymphoma (SMZL).
Study the natural history of MBL/CLL/SLL in patients prior to the time when their disease requires treatment.
Treatment free survival, measured as the time from diagnosis or last therapy to the development of active disease that requires treatment at which time patients will be able to change to a treatment protocol or seek treatment outside of NIH.
Time frame: Ongoing
Characterize clinical, biological and molecular events of disease stability and progression of patients enrolled on this protocol
Describe the underlying biologic heterogeneity of tumor cells in relation to treatment free survival
Time frame: Ongoing
Started May 2008 (actual).
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
Contact study teamGet an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Waldenstrom Macroglobulinemia →
National Heart, Lung, and Blood Institute (NHLBI) →