RecruitingNot Applicable

Cancer in Inherited Bone Marrow Failure Syndromes

United States4,000 participantsStarted 2001-11-28

Plain-language summary

Background: A prospective cohort of Inherited Bone Marrow Failure Syndrome (IBMFS) will provide new information regarding cancer rates and types in these disorders. Pathogenic variant(s) in IBMFS genes are relevant to carcinogenesis in sporadic cancers. Patients with IBMFS who develop cancer differ in their genetic and/or environmental features from patients with IBMFS who do not develop cancer. These cancer-prone families are well suited for cancer screening and prevention trials targeting those at increased genetic risk of cancer. Carriers of IBMFS pathogenic variant(s) are at increased risk of cancer. The prototype disorder is Fanconi's Anemia (FA); other IBMFS will also be studied. Objectives: To determine the types and incidence of specific cancers in patients with an IBMFS. To investigate the relevance of IBMFS pathogenic variant(s) in the carcinogenesis pathway of the sporadic counterparts of IBMFS-associated cancers. To identify risk factors for IBMFS-related cancers in addition to the primary germline pathogenic variant(s). To determine the risk of cancer in IBMFS carriers. Eligibility: North American families with a proband with an IBMFS. IBMFS suspected by phenotype, confirmed by pathogenic variant(s) in an IBMFS gene, or by clinical diagnostic test. Fanconi's anemia: birth defects, marrow failure, early onset malignancy; positive chromosome breakage result. Diamond-Blackfan anemia: pure red cell aplasia; elevated red cell adenosine deaminase. Dyskeratosis congenita: dysplastic nails, lacey pigmentation, leukoplakia; marrow failure. Shwachman-Diamond Syndrome: malabsorption; neutropenia. Amegakaryocytic thrombocytopenia: early onset thrombocytopenia. Thrombocytopenia absent radii: absent radii; early onset thrombocytopenia. Severe Congenital Neutropenia: neutropenia, pyogenic infections, bone marrow maturation arrest. Pearson's Syndrome: malabsorption, neutropenia, marrow failure, metabolic acidosis; ringed sideroblasts. Other bone marrow failure syndromes: e.g. Revesz Syndrome, WT, IVIC, radio-ulnar synostosis, ataxia-pancytopenia. First degree relatives of IBMFS-affected subjects as defined here, i.e. siblings (half or full), biologic parents, and children. Grandparents of IBMFS-affected subjects. Patients in the general population with sporadic tumors of the types seen in the IBMFS (head and neck, gastrointestinal, and anogenital cancer), with none of the usual risk factors (e.g. smoking, drinking, HPV). Design: Natural history study, with questionnaires, clinical evaluations, clinical and research laboratory test, review of medical records, cancer surveillance. Primary endpoints are all cancers, solid tumors, and cancers specific to each type of IBMFS. Secondary endpoints are markers of pre-malignant conditions, such as leukoplakia, serum or tissue evidence of carcinogenic viruses, and bone marrow morphologic myelodyplastic syndrome or cytogenetic clones.

Who can participate

Age range

1 Day – 100 Years

Sex

ALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion criteria

Family members include first degree relatives of IBMFS-affected subjects as defined here, i.e. siblings (half or full), biologic parents, and children. Grandparents of IBMFS-affected subjects are also included, specifically for Hypothesis 4. The age range will be from birth to old age (grandparents of probands).
Patients in the general population with sporadic tumors of the types seen in the IBMFS (head and neck, gastrointestinal, and anogenital cancer), with none of the usual risk factors for those tumors (e.g. smoking, drinking, HPV). These patients will be further evaluated for an IBMFS by the referring physician under the guidance of the study investigators and if diagnosed with an IBMFS or if not diagnosed but highly suspicious for an IBMFS, would be eligible for inclusion in the Field and Clinic Center cohorts.

Exclusion criteria

Affected: An individual who meets any of the following criteria will be excluded from participation in this study:

Questions worth asking your doctor

Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.

1Since this study is tracking cancer risk and biology in people with conditions like Fanconi Anemia, Dyskeratosis Congenita, and Diamond Blackfan Anemia over time, would enrolling help my care team catch early signs of cancer that might otherwise be missed?
2This trial is comparing patients with inherited bone marrow failure syndromes to healthy controls — does that mean my family members might also need to participate, and what would that involve for them practically?
3Because this is a Phase NA observational registry rather than a treatment trial, what exactly would I be asked to do — like how often would I need to come in, provide samples, or complete follow-up — and how would that fit into my current care schedule?
4The study is measuring how specific genetic mutations affect cancer risk — if a mutation is identified in me through this research, would that information be shared with me and my care team, and could it change my treatment plan?
5Given that this is a long-term observational study and I may already be receiving standard treatment for my condition, is there any reason my doctor would recommend a different clinical trial or treatment path instead of, or alongside, joining this registry?

Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.

Questions for the trial coordinator

The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.

1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?

A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.

What they're measuring

Cohort of Families with IBMFS

Timeframe: Ongoing

Biology of Patients Compared with Healthy Controls

Timeframe: Ongoing

Differences Between Patients and Healthy Controls

Timeframe: Ongoing

Risk of Cancer with Specific Mutations

Timeframe: Ongoing

Trial details

NCT IDNCT00027274

SponsorNational Cancer Institute (NCI)

Sponsor typeNIH

Study typeOBSERVATIONAL

Contact for this trial

NCI Family Study Referrals

(800) 518-8474 ncifamilystudyreferrals@mail.nih.gov

View on ClinicalTrials.gov More Diamond Blackfan Anemia trials

Plain-language summary

Who can participate

Age range

1 Day – 100 Years

Sex

ALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion criteria

Family members include first degree relatives of IBMFS-affected subjects as defined here, i.e. siblings (half or full), biologic parents, and children. Grandparents of IBMFS-affected subjects are also included, specifically for Hypothesis 4. The age range will be from birth to old age (grandparents of probands).
Patients in the general population with sporadic tumors of the types seen in the IBMFS (head and neck, gastrointestinal, and anogenital cancer), with none of the usual risk factors for those tumors (e.g. smoking, drinking, HPV). These patients will be further evaluated for an IBMFS by the referring physician under the guidance of the study investigators and if diagnosed with an IBMFS or if not diagnosed but highly suspicious for an IBMFS, would be eligible for inclusion in the Field and Clinic Center cohorts.

Exclusion criteria

Affected: An individual who meets any of the following criteria will be excluded from participation in this study: