ClinicalTrials.gov record NCT00923507

Natural History Study of 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)

Record copied from ClinicalTrials.gov: Oct 10, 2026AI summaries generated: Sep 28, 2026

Natural History Study of 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)

StatusRecruitingThe study is currently enrolling participants. Only the study team can say whether a particular person can join.
Study typeObservationalA study in which researchers do not assign participants to a treatment or other intervention. They observe or measure what happens, which may include study visits, tests, questionnaires or a review of medical records.
Age18 years old to 110 years old
SexAll
LocationUnited States
AI summaryWhat this study is about, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

This is a prospective, observational natural history study for people with MBL, CLL/SLL, LPL/WM, or SMZL. Participants are followed over time with clinic visits, blood draws, and sometimes tissue samples or imaging. No treatment is given on the study; clinical data and samples are collected for research into disease course and biology.

What it is studying. The study aims to describe the natural history of these B‑cell disorders and to characterize clinical, biological, and molecular events associated with disease stability and progression.

What the researchers hope to learn. Scientific goals include describing the history of MBL/CLL/SLL/LPL/WM/SMZL before and after treatment, characterizing clinical, biologic and molecular events of stability and progression, providing blood and tissue linked to clinical data for translational studies, and supporting development of novel treatment approaches.

What this study is about

The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.

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:

  • Diagnosis of CLL/SLL and on treatment/previously treated/nearing treatment
  • Diagnosis of LPL/WM
  • As of February 5, 2025, patients with MBL and SMZL will no longer be enrolled.
  • Age greater than or equal to 18 years.
  • ECOG performance status of 0-2.

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.

Eligibility

The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.

Inclusion criteria

  • Diagnosis of CLL/SLL will be made according to the updated criteria of the NCI Working Group.
  • on treatment or previously treated
  • requiring or nearing first-line treatment
  • 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
  • Age greater than or equal to 18 years.
  • ECOG performance status of 0-2.
  • Able to comprehend the investigational nature of the protocol and provide informed consent

Exclusion criteria

  • None

Study description and what participation involves

The study's detailed description, as published on ClinicalTrials.gov.

Show the detailed description from the registry

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:

  • Diagnosis of MBL/CLL/SLL/LPL/WM/SMZL
  • Age greater than or equal to 18 years.
  • ECOG performance status of 0-2.
  • Design:

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:
  • Describe the history of MBL/CLL/SLL/WM/SMZL in patients prior to and after treatment.
  • Apply the expertise and available technologies of the investigators to advance our understanding of disease pathogenesis by studying MBL/CLL/SLL and closely related B-cell malignancies, LPL/WM and SMZL
  • Develop novel treatment approaches for CLL/SLL/LPL/WM/SMZL.
  • Provide evaluation, diagnostic studies and monitoring for patients on study.
  • Provide blood and tissue linked to clinical and biologic information for translational studies.
  • Endpoints:
  • 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 evaluated for a treatment protocol or seek treatment outside of NIH.
AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

Participants are followed long-term with clinic visits and blood draws—typically every 6–12 months for the first 2 years and every 12–24 months thereafter, with interim visits as needed. You may be asked to give blood and to donate cellular products or tissue for research; the study may also perform or request bone marrow biopsy and aspiration, lymph node biopsy, PET scans, CT scans, and MRI scans. Some tests (for example blood draws) may be required for clinical monitoring of CLL/SLL and LPL/WM, while other procedures may be requested only for research purposes. No treatment is given on this study; clinical information will be stored in a central databank and patients who require treatment will be evaluated for treatment protocols or other options.

How the study is structured. This is a prospective cohort (observational) study. Patients are typically followed in clinic every 6–12 months for the first 2 years and every 12–24 months thereafter, with blood draws at follow-up visits. Participants may be asked to provide tissue samples (bone marrow and lymph node biopsies) and to undergo imaging studies (PET, CT, MRI) for research. No treatment is provided on this protocol; clinical information and samples are stored for research.

Questions you could ask

These questions are suggestions for a conversation with the study team or your own clinician, not advice.

  • The registry lists this study under Waldenstrom Macroglobulinemia; Lymphoplasmacytic Lymphoma; Monoclonal B-Cell Lymphocytosis; Small Lymphocytic Lymphoma; CLL (Chronic Lymphocytic Leukemia). Does it apply to my diagnosis?
  • This is an observational study, so the study itself gives no treatment. What would taking part involve for me, and would it change my usual care?
  • The listed sites are in United States. Is any of them reachable for me, and does the study help with travel?
  • Which of the eligibility criteria would need to be checked with tests before I could join?

More on splenic marginal zone lymphoma

This trial is also listed on this site under Waldenström macroglobulinemia.

Clinical trials12 trials listed for splenic marginal zone lymphomaEvery trial the registry lists for splenic marginal zone lymphoma, with recruitment status, phase and sites, updated from ClinicalTrials.gov.See all trials →Research updatesWhat changed in splenic marginal zone lymphoma researchLatest monthly update: July 2026. Includes: Slow disease course. New research summarized each month in plain language, with links to every source paper.Read the latest update →

Important dates

Study start
May 29, 2008
Target enrollment
1000 participants (estimated)
Last updated on registry
Sep 28, 2026
Data verified
Oct 10, 2026

Sponsor and research team

The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.

Lead sponsor
National Heart, Lung, and Blood Institute (NHLBI)

Central study contact

If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.

Participating sites (1)

Terms used on this page · explanations by MedicalUpdates.ai

natural history study
A study that follows how a condition changes over time without assigning an experimental treatment. It may involve study visits and tests, and is often used to plan future trials.
ECOG performance status
A scale from 0 to 5 that describes how a person's condition affects daily activity. 0 means fully active; 1 means restricted in strenuous activity; 2 means able to self-care but unable to work; higher numbers mean more limitation.
biopsy
Removal of a small piece of tissue so it can be examined under a microscope. 'Biopsy-proven' or 'histologically confirmed' means the diagnosis was confirmed by examining tissue under a microscope.
positron emission tomography
A scan in which a small amount of a radioactive tracer is injected so that activity in tissues can be seen. Often combined with a CT or MRI scan.
CT
An X-ray scan that builds detailed cross-section images of the body. 'High-resolution' CT (HRCT) is used to look closely at the lungs.
MRI
A scan that uses magnets and radio waves, not X-rays, to make detailed pictures of the inside of the body. Some implants and metal objects mean a person cannot have one.
investigational
A treatment that is being tested and has not been approved for this use. It may be approved for a different condition. Being studied does not mean it works or is available outside the study.
informed consent
The process of explaining a study, including its risks and what participation involves, so that a person can decide freely whether to take part. Consent is usually documented in writing, and a participant can choose to leave the study later.
INCLUSION CRITERIA
The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
EXCLUSION CRITERIA
The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.
Endpoints
Something the study measures to judge its results, such as a symptom score, a blood test or survival. Outcomes are grouped as primary, secondary and sometimes exploratory.

The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.

← Back to clinical trials