Waldenstrom MacroglobulinemiaNCT00039676
Clinical, Laboratory and Epidemiologic Characterization of Individuals and Families at High Risk of Hematologic Cancer
An observational study of Waldenstrom Macroglobulinemia and Chronic Lymphocytic Leukemia, run by National Cancer Institute (NCI) at 2 sites in United States.
Trial summary
Background: Individuals may be prone to develop blood or lymph node cancers (leukemia or lymphoma) for a variety of reasons, including genetic predisposition to these cancers, environmental exposures or other medical conditions. Read more about this study
- Who is it for?
- Ages 11 months and olderHealthy volunteers can take part
- Conditions the study is for
- Waldenstrom Macroglobulinemia, Chronic Lymphocytic Leukemia, Hodgkin Disease
- How many people
- 1,836 participants
- Where
- 2 sitesUnited States
- Study dates
- 8 Jul 2002to not given
- Phase
- Observational
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 11 months and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: General population with a family history of cancer
Who may be able to join
- On referral, persons >= 11 months will be included only because of personal history, and persons >=18 years can also be included because of personal or family history of the parameters listed below:
- A medical history of hematologic/ lymphoproliferative malignancy of an unusual type, pattern, or number or
- Known or suspected factor(s) predisposing to hematologic malignancy, either genetic and/or congenital factors (birth defects, metabolic phenotype, chromosomal anomalies or Mendelian traits associated with tumors), environmental exposure (medications, occupation, radiation, diet, infectious agents, etc.), or unusual demographic features (very young age of onset, multiple tumors, etc.)
- Personal and family medical history must be verified through questionnaires, interviews, and review of pathology slides and medical records. For familial neoplasms, two or more living affected cases among family members are generally required, although in selected instances exceptions may be made, e.g., for WM, one case plus a living 1st degree relative with an autoimmune condition will qualify a family for further investigations.
- Disease-specific considerations. Familial aggregation of any hematologic cancer(s) is eligible for study. Disease-specific procedures are outlined in appendices:
- Chronic lymphocytic leukemia (CLL)
Show all 11Show fewer
- Waldenstrom macroglobulinemia (WM)
- Non-Hodgkin lymphoma (NHL)
- Hodgkin lymphoma (HL)
- Mixed/miscellaneous hematologic and lymphoproliferative diseases
- Ability of subject or Legally Authorized Representative (LAR) to understand, and the willingness to sign, a written informed consent document.
Who cannot join
- Referred individuals for whom reported diagnoses cannot be verified;
- Referred individuals who decline informed consent.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
NIH National Cancer Institute - Shady Grove
Rockville, Maryland, 20850
About this study
Official title: Clinical, Laboratory, and Epidemiologic Characterization of Individuals and Families at High Risk of Blood and Lymph Node Malignancy
Background:
- Individuals may be prone to develop blood or lymph node cancers (leukemia or lymphoma) for a variety of reasons, including genetic predisposition to these cancers, environmental exposures or other medical conditions.
- Studies of people and families at high risk of cancer often lead to clues about their cause that may also be important regarding the sporadic occurrence of these cancers in the general population.
- Identifying genetic or environmental factors that play a role in the development of these diseases may be important in developing prevention trials, screening programs and treatments.
Read more
Objectives:
- Describe the cancers and other conditions in families with blood or lymph node cancer.
- Find and describe genes that may cause blood and lymph node cancer, and understand how they work in families.
- Use laboratory methods to try to determine if it is possible to identify who is at highest risk of blood or lymph node cancer.
- Test how genes act with other factors to alter the risk of disease, its severity or its manifestations in families.
Eligibility:
- Individuals of any age with a personal or family history of a blood or lymph node cancer.
- Individuals with a personal or family history of medical conditions or environmental exposures that may predispose to blood or lymph node cancer.
Design:
- Participants complete questionnaires about their personal and family medical history and provide consent for researchers to review their medical records and pathology materials related to their care and those of deceased relatives with blood or lymph node cancer, tumors, or other related illnesses for whom they are the legally authorized representative.
- Participants donate a sample of blood or cheek cells, or a lock of hair for genetic studies.
- Patients may also be evaluated at the NIH Clinical Center by one or more of the following specialists: cancer doctor or blood specialist, medical geneticist, research nurses or clinical social worker. They may have blood and urine tests and a cheek swab or mouth wash to collect cheek cells. Some patients may also be asked to have x-rays and routine imaging, such as CT scans or ultrasound tests, cell surface markers, skin biopsy, and, with special consents, bone marrow biopsy, MRI or PET scans, apheresis or fluorescein angiography and photography.
Read the detailed description
Background:
Persons may be prone to develop hematologic or lymphoproliferative cancer for a variety of reasons including: inherited predisposition of benign, premalignant, or malignant conditions; environmental exposures shared by family members; previous tumors or preneoplastic conditions; immune deficiency; or stochastic processes
Investigations of individuals and families at high risk of cancer often lead to etiologic clues that may be important in the sporadic counterparts of these cancers in the general population
Identification of etiologically important genetic factors could inform chemoprevention trials, screening programs, and treatment of hematologic and lymphoproliferative cancers
Objectives:
To evaluate and define the clinical spectrum and natural history of disease in syndromes predisposing to hematologic cancer
To evaluate potential precursor states of malignancy in families at risk
To quantify the risks of specific tumors in family members and define syndromic constellations
To identify, map, characterize, clone, and determine function of tumor susceptibility genes
To validate and test associations of biomarkers with risk
To identify genetic determinants, environmental factors, and gene-environmental interactions conferring cancer risk in individuals and families
To identify differences and similarities between the familial and sporadic condition
To educate and counsel study participants about their risk of hematologic malignancy including prevention recommendations and early detection activities when known
To develop syndrome-specific educational materials for medical professionals and high-risk family members
Eligibility:
On referral, persons >= 11 months will be included only because of personal history, and persons >/=18 years can also be included because of personal or family history of the parameters listed below:
- a medical history of hematologic/lymphoproliferative malignancy of an unusual type, pattern, or number or
- there are known or suspected factor(s) predisposing to hematologic malignancy, either genetic or congenital factors, environmental exposure, or unusual demographic features
- For familial neoplasms, two or more living affected cases among family members are generally required
Design:
This is a prospective study. Families are studied long-term using a cohort approach.
The study design and evaluation vary by the specific type of familial neoplasm being studied
The overall approach to eligible families includes defining affection status, characterization of disease, localization of genetic loci, identification of genes, evaluation of phenotype/genotype correlations, estimation of risk of the disease associated with carrier
status and identification of other risk factors that modify penetrance (genetic, environmental, and host factors)
- Conditions
- Waldenstrom Macroglobulinemia, Chronic Lymphocytic Leukemia, Hodgkin Disease, NonHodgkin Lymphoma, Mixed Lymphoproliferative Disease
- Keywords
- Genetics, Risk Factors, Natural History, Lymphoma, Leukemia, Lymph Node Cancer
- Medical subject headings
- Waldenstrom Macroglobulinemia, Leukemia, Lymphocytic, Chronic, B-Cell, Hodgkin Disease, Lymphoma, Non-Hodgkin, Lymphoma, Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Standard | People that have blood or lymph node cancer, or a family history of leukemia or lymphoma. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Spectrum and Natural History
To define the clinical spectrum and natural history of familial blood and lymph node malignancies and susceptibility states over time.
Measured: Ongoing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2002 (estimated)
- Study start8 Jul 2002
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Waldenstrom MacroglobulinemiaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Family based
- Time perspective
- Prospective
- Enrolment
- 1,836 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Douglas R Stewart, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00039676
- Sponsor's protocol ID
- 020210
- Other IDs
- 02-C-0210
- Status last verified
- 2 Jun 2026
- First submitted
- 6 Jun 2002
- Last updated
- 13 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Berndt SI, Camp NJ, Skibola CF, Vijai J, Wang Z, Gu J, Nieters A, Kelly RS, Smedby KE, Monnereau A, Cozen W, Cox A, Wang SS, Lan Q, Teras LR, Machado M, Yeager M, Brooks-Wilson AR, Hartge P, Purdue MP, Birmann BM, Vajdic CM, Cocco P, Zhang Y, Giles GG, Zeleniuch-Jacquotte A, Lawrence C, Montalvan R, Burdett L, Hutchinson A, Ye Y, Call TG, Shanafelt TD, Novak AJ, Kay NE, Liebow M, Cunningham JM, Allmer C, Hjalgrim H, Adami HO, Melbye M, Glimelius B, Chang ET, Glenn M, Curtin K, Cannon-Albright LA, Diver WR, Link BK, Weiner GJ, Conde L, Bracci PM, Riby J, Arnett DK, Zhi D, Leach JM, Holly EA, Jackson RD, Tinker LF, Benavente Y, Sala N, Casabonne D, Becker N, Boffetta P, Brennan P, Foretova L, Maynadie M, McKay J, Staines A, Chaffee KG, Achenbach SJ, Vachon CM, Goldin LR, Strom SS, Leis JF, Weinberg JB, Caporaso NE, Norman AD, De Roos AJ, Morton LM, Severson RK, Riboli E, Vineis P, Kaaks R, Masala G, Weiderpass E, Chirlaque MD, Vermeulen RCH, Travis RC, Southey MC, Milne RL, Albanes D, Virtamo J, Weinstein S, Clavel J, Zheng T, Holford TR, Villano DJ, Maria A, Spinelli JJ, Gascoyne RD, Connors JM, Bertrand KA, Giovannucci E, Kraft P, Kricker A, Turner J, Ennas MG, Ferri GM, Miligi L, Liang L, Ma B, Huang J, Crouch S, Park JH, Chatterjee N, North KE, Snowden JA, Wright J, Fraumeni JF, Offit K, Wu X, de Sanjose S, Cerhan JR, Chanock SJ, Rothman N, Slager SL. Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia. Nat Commun. 2016 Mar 9;7:10933. doi: 10.1038/ncomms10933.
PubMed 26956414Rotunno M, McMaster ML, Boland J, Bass S, Zhang X, Burdett L, Hicks B, Ravichandran S, Luke BT, Yeager M, Fontaine L, Hyland PL, Goldstein AM; NCI DCEG Cancer Sequencing Working Group; NCI DCEG Cancer Genomics Research Laboratory; Chanock SJ, Caporaso NE, Tucker MA, Goldin LR. Whole exome sequencing in families at high risk for Hodgkin lymphoma: identification of a predisposing mutation in the KDR gene. Haematologica. 2016 Jul;101(7):853-60. doi: 10.3324/haematol.2015.135475. Epub 2016 Jun 13.
PubMed 27365461Goldin LR, McMaster ML, Rotunno M, Herman SE, Jones K, Zhu B, Boland J, Burdett L, Hicks B, Ravichandran S, Luke BT, Yeager M, Fontaine L, Goldstein AM, Chanock SJ, Tucker MA, Wiestner A, Marti G, Caporaso NE. Whole exome sequencing in families with CLL detects a variant in Integrin beta 2 associated with disease susceptibility. Blood. 2016 Nov 3;128(18):2261-2263. doi: 10.1182/blood-2016-02-697771. Epub 2016 Sep 14. No abstract available.
PubMed 27629550