Natural History Study of GATA2 Deficiency and Related Disorders

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )
ClinicalTrials.gov Identifier:
NCT01905826
First received: July 18, 2013
Last updated: March 26, 2014
Last verified: March 2014
  Purpose

Background:

- GATA2 deficiency is a genetic disorder that can cause problems with a person s immune system and other body systems. Some people who have this disorder develop few problems from it. Others can have a wide range of health problems, from skin problems, to hearing loss, to cancer. These problems can happen at any age. Researchers want to study GATA2 deficiency to better understand what types of health problems it can cause, and why it causes problems in some people but not others, and at different ages.

Objectives:

- To improve understanding of GATA2 deficiency so there can be better diagnostic tests and treatments in the future.

Eligibility:

- People 2 years of age or older who have a GATA2 gene mutation or certain health conditions that are commonly seen in people with this mutation.

Design:

  • Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected to see whether participants have the GATA2 genetic mutation. Several other tests may be recommended, but participants can decline to take them.
  • Participants will be eligible to receive standard care for GATA2 deficiency through this protocol. They may be eligible for other clinical trials at the National Institutes of Health as well.
  • Participants will have regular study visits once a year to evaluate their GATA2 deficiency. Participants will take part in the study for at least 3 years and up to 15 years. At these follow-up visits, participants will fill out a questionnaire and take a physical exam and blood tests. Other tests may be performed as needed.

Condition
Myelodysplasia
Monocytopenia
B Cell Lymphopenia
NK Cell Deficiency
Warts

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: The Natural History of GATA2 Deficiency

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • This natural history protocol is designed to further characterize the clinical phenotype of GATA2 deficiency, [ Time Frame: yearly visits up to 15 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 600
Study Start Date: June 2013
Estimated Study Completion Date: March 2028
Estimated Primary Completion Date: March 2028 (Final data collection date for primary outcome measure)
Detailed Description:

Mutations in GATA2, a critical hematopoietic transcription factor, underlie a complex congenital disorder characterized by immunodeficiency, bone marrow failure, and lymphatic/vascular dysfunction. Patients with GATA2 deficiency may suffer from a striking variety of diseases including severe and recurrent infections, myelodysplasia/leukemia, pulmonary alveolar proteinosis, lymphedema, sensorineural hearing loss, and possibly susceptibility to other malignancies, autoimmune disorders, thrombotic events, and miscarriage. Mutations in GATA2 appear to be fully penetrant, but expressivity is remarkably variable, even among related individuals. Disease may also manifest at nearly any age ranging from early childhood to late adulthood, the reasons for which remain poorly understood.

While considerable progress has been made towards better understanding this complex congenital disorder, many important questions remain unanswered: What is the full spectrum of clinical disease and the associated pathophysiology? What accounts for the remarkable variability in age of onset and clinical phenotype? What are the optimal strategies for disease diagnosis and management? This natural history protocol is designed to further characterize the clinical phenotype of GATA2 deficiency, better understand the reasons for phenotypic variability, better understand disease progression over time, standardize the diagnostic evaluation, and facilitate the screening of at risk relatives. Up to 300 males and females greater than or equal to 2 years old with proven mutations in GATA2 or clinical and laboratory characteristics strongly consistent with GATA2 deficiency will initially undergo a series of baseline laboratory tests and diagnostic procedures at the NIH. Follow-up laboratory testing will be conducted at yearly visits for up to 15 years; additional follow-up diagnostic procedures will be conducted based on clinical need.

  Eligibility

Ages Eligible for Study:   2 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

Males and females greater than or equal to 2 years old must meet the following criteria to be eligible for participation in this study:

-Have a mutation in GATA2 proven by genetic testing (previous test results will be accepted) OR meet both of the following criteria:

a. Clinical characteristics strongly consistent with GATA2 deficiency per the following criteria and at the discretion of the principal investigator (PI). Individuals without a GATA2 mutation must have a past or present history of 1 or more of the following to be considered for study enrollment:

i. Disseminated NTM or invasive fungal infection.

ii. Severe or recurrent HPV or herpesvirus infection.

iii. MDS, AML, or CMML.

iiiv. Biopsy-proven PAP.

b. Laboratory characteristics strongly consistent with GATA2 deficiency per the following criteria. Individuals without a GATA2 mutation must have 1 or more of the following to be considered for study enrollment:

i. Absolute monocyte count < 240 cells/microL.

ii. Absolute B lymphocyte count < 60 cells/microL.

iii. Absolute NK lymphocyte count < 126 cells/microL.

  • Agree to undergo genetic testing.
  • Allow their samples to be stored for future research.

EXCLUSION CRITERIA:

-Individuals with any condition or who are taking any medications that, in the opinion of the investigator, contraindicates participation in the study will be excluded.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01905826

Contacts
Contact: Steven M Holland, M.D. (301) 402-7684 sholland@mail.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
Investigators
Principal Investigator: Steven M Holland, M.D. National Institute of Allergy and Infectious Diseases (NIAID)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )
ClinicalTrials.gov Identifier: NCT01905826     History of Changes
Other Study ID Numbers: 130157, 13-I-0157
Study First Received: July 18, 2013
Last Updated: March 26, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Hematopoiesis
Immunodeficiency
Myelodysplasia/Leukemia
Lymphedema
Pulmonary Alveolar Proteinosis

Additional relevant MeSH terms:
Lymphopenia
Myelodysplastic Syndromes
Preleukemia
Leukopenia
Leukocyte Disorders
Hematologic Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Bone Marrow Diseases
Precancerous Conditions
Neoplasms

ClinicalTrials.gov processed this record on July 23, 2014