Study of Blood Samples From Newborns With Down Syndrome

Completed

• Conditions: Myeloid Proliferations Associated With Down Syndrome
• Interventions: Other: Diagnostic Laboratory Biomarker Analysis; Other: Pharmacological Study

• Registration Number: NCT00959283
• Lead Sponsor: Children's Oncology Group

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.

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 Timeline

• Study Start: 2009-02-23
• Study First Submitted: 2009-08-13
• Study First Submitted QC: 2009-08-13
• Study First Posted: 2009-08-14
• Primary Completion: 2011-12-30
• Study Completion: 2023-09-30
• Status Verified: 2023-10
• Last Update Submitted: 2023-10-02
• Last Update Posted: 2023-10-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 180

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Ancillary-correlative	Diagnostic Laboratory Biomarker Analysis	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.
Ancillary-correlative	Pharmacological 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.

Primary Outcome Measures

Name	Time	Method
Event-free survival	Up to 5 years

Secondary Outcome Measures

Name	Time	Method
Overall survival	Up to 5 years
Incidence of TMD-related mortality	Up to 5 years
Incidence of subsequent leukemia for patients with resolved TMD	Up to 5 years

Trial Locations

Locations (189)

Children's Hospital of Alabama; 🇺🇸 Birmingham, Alabama, United States

University of Alabama at Birmingham Cancer Center; 🇺🇸 Birmingham, Alabama, United States

USA Health Strada Patient Care Center; 🇺🇸 Mobile, Alabama, United States

Providence Alaska Medical Center; 🇺🇸 Anchorage, Alaska, United States

Phoenix Childrens Hospital; 🇺🇸 Phoenix, Arizona, United States

Arkansas Children's Hospital; 🇺🇸 Little Rock, Arkansas, United States

University of Arkansas for Medical Sciences; 🇺🇸 Little Rock, Arkansas, United States

Kaiser Permanente Downey Medical Center; 🇺🇸 Downey, California, United States

Loma Linda University Medical Center; 🇺🇸 Loma Linda, California, United States

Miller Children's and Women's Hospital Long Beach; 🇺🇸 Long Beach, California, United States

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