Cancer in Inherited Bone Marrow Failure Syndromes
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ClinicalTrials.gov Identifier: NCT00027274 |
Recruitment Status :
Recruiting
First Posted : November 30, 2001
Last Update Posted : January 25, 2023
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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..
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Condition or disease |
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Diamond Blackfan Anemia Dyskeratosis Congenita Fanconi Anemia Shwachman Diamond Syndrome Inherited Bone Marrow Failure Syndrome, Aplastic Anemia |

Study Type : | Observational |
Estimated Enrollment : | 4000 participants |
Observational Model: | Family-Based |
Time Perspective: | Other |
Official Title: | Etiologic Investigation of Cancer Susceptibility in Inherited Bone Marrow Failure Syndromes: A Natural History Study |
Actual Study Start Date : | November 28, 2001 |

Group/Cohort |
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1
All families with a member who has one of the relevant syndromes.
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- Cohort of Families with IBMFS [ Time Frame: Ongoing ]Establish a cohort of families with IBMFS
- Biology of Patients Compared with Healthy Controls [ Time Frame: Ongoing ]Compare biology of IBMFS patients with general populations
- Differences Between Patients and Healthy Controls [ Time Frame: Ongoing ]Identify differences between patients with IBMFS who develop cancer and those who don't
- Risk of Cancer with Specific Mutations [ Time Frame: Ongoing ]Determine risk of cancer in IBMFS patients with specific gene mutations

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Ages Eligible for Study: | Child, Adult, Older Adult |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | Yes |
Sampling Method: | Non-Probability Sample |
- INCLUSION CRITERIA:
The participants will be affected by an IBMFS, or be members of a family with an IBMFS, and be at risk of being affected or carriers of the syndrome. Except for the rare X-linked recessive disorder (e.g. some dyskeratosis congenita patients), there should be equal numbers of male and female probands and family members. These IBMFS have been reported in most racial and ethnic groups, and thus all such groups will be included. The age range will be from birth to old age (grandparents of probands). The majority of the probands will be children (10-20% will be adults), and their parents and grandparents will be adults. All racial/ethnic groups are eligible.
INCLUSION CRITERIA - PATIENTS:
- Fanconi s anemia.
- Diamond Blackfan anemia.
- Dyskeratosis congenita.
- Shwachman Diamond Syndrome.
- Amegakaryocytic thrombocytopenia.
- Thrombocytopenia absent radii.
- Severe congenital neutropenia.
- Pearson Syndrome.
- Other bone marrow failure syndromes.
Family Members of IBMFS - Affected Subjects:
-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:
-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:
- Evidence that the hematologic disorder is acquired rather than genetic. Such evidence includes temporal relation of the aplastic anemia to known marrow suppressant drugs, chemicals, toxins, or viruses (in the absence of evidence indicative of an inherited marrow failure disorder).
- Known causes of cytopenias such as autoantibodies to red cells, platelets, or neutrophils, viruses (especially hepatitis), micronutrient deficiencies, transient erythroblastopenia of childhood, and cyclic neutropenia.
- Assignment of the patient s physical findings to other syndromes or causes that are not part of the IBMFS disease spectrum.
- Inability of the participant or LAR to understand and be willing to sign a written informed consent document.
- Unwillingness to permit access to medical records and pathology specimens.
There are no other exclusion parameters not related to the primary disease.
-Unaffected/Family Members: An individual who meets any of the following criteria will be excluded from participation in this study:
- If there is no affected individual in the family who meets the inclusion criteria
- Inability of the participant or LAR to understand and be willing to sign a written informed consent document.
- Unwillingness to permit access to medical records and pathology specimens.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00027274
Contact: Stephanie M Steinbart, R.N. | (800) 518-8474 | stephanie.steinbart@nih.gov | |
Contact: Neelam Giri, M.D. | (240) 276-7256 | girin@mail.nih.gov |
United States, Maryland | |
National Institutes of Health Clinical Center | Recruiting |
Bethesda, Maryland, United States, 20892 | |
National Cancer Institute - Shady Grove | Recruiting |
Rockville, Maryland, United States, 20850 |
Principal Investigator: | Neelam Giri, M.D. | National Cancer Institute (NCI) |
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | National Cancer Institute (NCI) |
ClinicalTrials.gov Identifier: | NCT00027274 |
Obsolete Identifiers: | NCT00056121 |
Other Study ID Numbers: |
020052 02-C-0052 |
First Posted: | November 30, 2001 Key Record Dates |
Last Update Posted: | January 25, 2023 |
Last Verified: | January 23, 2023 |
Studies a U.S. FDA-regulated Drug Product: | No |
Studies a U.S. FDA-regulated Device Product: | No |
Fanconi Anemia Diamond Blackfan Anemia Dyskeratosis Congenita Shwachman Diamond Syndrome Hereditary Natural History |
Fanconi's Anemia Bone Marrow Inherited Bone Marrow Failure Syndromes IBMFS Familial Cancer |
Shwachman-Diamond Syndrome Fanconi Syndrome Anemia Anemia, Aplastic Fanconi Anemia Bone Marrow Failure Disorders Pancytopenia Hemoglobinuria, Paroxysmal Anemia, Diamond-Blackfan Dyskeratosis Congenita Congenital Bone Marrow Failure Syndromes Syndrome Disease Pathologic Processes Hematologic Diseases |
Bone Marrow Diseases Anemia, Hypoplastic, Congenital Genetic Diseases, Inborn DNA Repair-Deficiency Disorders Metabolic Diseases Renal Tubular Transport, Inborn Errors Kidney Diseases Urologic Diseases Anemia, Hemolytic Myelodysplastic Syndromes Red-Cell Aplasia, Pure Skin Abnormalities Congenital Abnormalities Genetic Diseases, X-Linked Skin Diseases, Genetic |