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Study of Blood Samples From Newborns With Down Syndrome

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00959283
Recruitment Status : Active, not recruiting
First Posted : August 14, 2009
Last Update Posted : March 27, 2023
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Study Description
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Brief Summary:
This research study is looking at blood samples from newborns with Down syndrome. Studying the genes expressed in samples of blood from patients with Down syndrome may help doctors identify biomarkers related to cancer.

Condition or disease Intervention/treatment
Myeloid Proliferations Associated With Down Syndrome Other: Diagnostic Laboratory Biomarker Analysis Other: Pharmacological Study

Detailed Description:

PRIMARY OBJECTIVES:

I. To further our biological understanding of the natural history of transient myeloproliferative disorder (TMD) and its relationship to subsequent leukemia by facilitating the development of a TMD cell and protein bank, and repository of DNA/RNA from megakaryoblasts for future biological studies.

II. To investigate the biology of TMD molecular changes associated with resolution of TMD or its conversion to acute myeloid leukemia within each mortality-risk group by conducting GATA1 mutational analyses, hematopoiesis clonality studies, assessment of RAS mutations, and genomic instability studies using glycophorin A assays.

III. To determine if high-resolution microarray genomic analysis of TMD blasts (using Affymetrix SNP Genechip technology to assess gene expression, copy number variation, and loss of heterozygosity) can predict the development of subsequent leukemia.

IV. To determine the relationship of minimal residual disease (monitored by peripheral blood flow cytometry and GATA1 mutational studies) to clinical remission status and development of subsequent leukemia within each mortality-risk group of TMD patients.

V. To evaluate the relationship between karyotype (including FISH analysis) and subsequent leukemia in TMD patients.

VI. To examine pharmacogenetics and in vitro drug sensitivity to cytarabine (MTT assay) in blasts from TMD patients.

VII. To examine the relationship of functional polymorphisms in Phase I and Phase II drug detoxification genes, DNA repair, and DNA synthesis pathways that may modify susceptibility to leukemia and outcome in TMD patients.

VIII. To determine the relationship between fibrosis-associated serum factors (e.g., platelet-derived growth factor, transforming growth factor beta, N-terminal peptide of III procollagen, type IV collagen, and hyaluronic acid) and event-free survival.

OUTLINE: This is a multicenter study.

Patients undergo peripheral blood collection periodically for biomarker analysis. Samples are analyzed for GATA1 mutations by real-time PCR, polymorphisms, cytogenetics, and K-RAS mutations, gene expression, drug sensitivity patterns, and minimal residual disease by flow cytometry.

Patients are followed up periodically for 5 years.

Study Design
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Study Type : Observational
Actual Enrollment : 180 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Biology Study of Transient Myeloproliferative Disorder (TMD) in Children With Down Syndrome (DS)
Actual Study Start Date : February 23, 2009
Actual Primary Completion Date : December 30, 2011

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Down Syndrome

Groups and Cohorts
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Group/Cohort Intervention/treatment
Ancillary-correlative
Patients undergo peripheral blood collection periodically for biomarker analysis. Samples are analyzed for GATA1 mutations by real-time PCR, polymorphisms, cytogenetics, and K-RAS mutations, gene expression, drug sensitivity patterns, and minimal residual disease by flow cytometry.
 Other: Diagnostic Laboratory Biomarker Analysis
Correlative studies

Other: Pharmacological Study
Correlative studies


Outcome Measures
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Primary Outcome Measures :
  1. Event-free survival [ Time Frame: Up to 5 years ]

Secondary Outcome Measures :
  1. Overall survival [ Time Frame: Up to 5 years ]
  2. Incidence of TMD-related mortality [ Time Frame: Up to 5 years ]
  3. Incidence of subsequent leukemia for patients with resolved TMD [ Time Frame: Up to 5 years ]

Biospecimen Retention:   Samples With DNA
Blood

Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   up to 90 Days   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Newborns with transient myeloproliferative disorder (TMD)
Criteria

Inclusion Criteria:

  • Diagnosis of transient myeloproliferative disorder (TMD) at < 90 days of age and meeting 1 of the following criteria:

    • A diagnosis of Down syndrome or Down syndrome mosaicism AND non-erythroid and non-lymphoid blasts (any amount) in the peripheral blood verified with a second sample

      • Patients with typical physical characteristics of Down syndrome are allowed before cytogenetic or FISH confirmation of the diagnosis

    • Trisomy 21-positive leukemic blasts documented by biopsy of any organ (including > 5% non-erythroid/non-lymphoid blasts documented by bone marrow aspirate or biopsy)

      • Infants with isolated trisomy 21 positivity identified only in the leukemic blasts are allowed
  • Institutional immunophenotype characterization is required for study enrollment
Contacts and Locations
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Information from the National Library of Medicine

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): NCT00959283


Locations
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Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Investigators
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Principal Investigator: April D Sorrell Children's Oncology Group
More Information
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Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00959283    
Other Study ID Numbers: AAML08B1
NCI-2011-02193 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
COG-AAML08B1
CDR0000636115
AAML08B1
AAML08B1 ( Other Identifier: Childrens Oncology Group )
AAML08B1 ( Other Identifier: CTEP )
U10CA098543 ( U.S. NIH Grant/Contract )
UG1CA189958 ( U.S. NIH Grant/Contract )
First Posted: August 14, 2009    Key Record Dates
Last Update Posted: March 27, 2023
Last Verified: March 2023
Additional relevant MeSH terms:
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Down Syndrome
Syndrome
Disease
Pathologic Processes
Intellectual Disability
Neurobehavioral Manifestations
 Neurologic Manifestations
Nervous System Diseases
Abnormalities, Multiple
Congenital Abnormalities
Chromosome Disorders
Genetic Diseases, Inborn