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Cancer in Inherited Bone Marrow Failure Syndromes

This study is currently recruiting participants.
Verified July 14, 2017 by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
Sponsor:
ClinicalTrials.gov Identifier:
NCT00027274
First Posted: November 30, 2001
Last Update Posted: October 19, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
November 29, 2001
November 30, 2001
October 19, 2017
January 1, 2002
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  • Establish a cohort of families with IBMFS [ Time Frame: Ongoing ]
  • Compare biology of IBMFS patients with general populations [ Time Frame: Ongoing ]
  • Identify differences between patients with IBMFS who develop cancer and those who don't [ Time Frame: Ongoing ]
  • Determine risk of cancer in IBMFS patients with specific gene mutations [ Time Frame: Ongoing ]
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Complete list of historical versions of study NCT00027274 on ClinicalTrials.gov Archive Site
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Cancer in Inherited Bone Marrow Failure Syndromes
Etiologic Investigation of Cancer Susceptibility in Inherited Bone Marrow Failure Syndromes: A Natural History Study

Background:

A prospective cohort of Inherited Bone Marrow Failure Syndrome (IBMFS) will provide new information regarding cancer rates and types in these disorders.

Mutations 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 gene mutations 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 gene mutations 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 mutations.

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 mutation 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..

Background:

A prospective cohort of Inherited Bone Marrow Failure Syndrome (IBMFS) will provide new information regarding cancer rates and types in these disorders.

Mutations 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 gene mutations 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 gene mutations 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 mutations.

To determine the risk of cancer in IBMFS carriers.

Eligibility:

North American families (or other eligible families) with a proband with an IBMFS.

IBMFS suspected by phenotype, confirmed by mutation 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.

Observational
Observational Model: Family-Based
Time Perspective: Other
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  • Aplastic Anemia
  • Head and Neck Neoplasms
  • Bone Marrow Failure
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*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
4000
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  • INCLUSION CRITERIA - PATIENTS:
  • Fanconi s anemia.
  • Diamond Blackfan anemia.
  • Dyskeratosis congenita.
  • Shwachman Diamond Syndrome.
  • Amegakaryocytic thrombocytopenia.
  • Thrombocytopenia absent radii.
  • Severe congenital neutropenia.
  • Pearson s Syndrome.
  • Other bone marrow failure syndromes.
  • 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, specifically for Hypothesis 4.
  • 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).
  • Adult patients and family members who are unable to provide consent.

EXCLUSION CRITERIA - PARENT PROTOCOL:

  • 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.
  • Unwillingness to permit access to medical records and pathology specimens.

There are no other exclusion parameters not related to the primary disease.

Sexes Eligible for Study: All
up to 120 Years   (Child, Adult, Senior)
Yes
Contact: Blanche P Alter, M.D. (240) 276-7239 alterb@mail.nih.gov
United States
 
 
NCT00027274
020052
02-C-0052
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National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
National Cancer Institute (NCI)
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Principal Investigator: Blanche P Alter, M.D. National Cancer Institute (NCI)
National Institutes of Health Clinical Center (CC)
July 14, 2017