Laboratory Study of Lymphoblasts in Young Patients With High-Risk Acute Lymphoblastic Leukemia

Childhood Cancer Therapeutically Applicable Research to Generate Effective Treatments (TARGET) Initiative High-Risk ALL Pilot Project: Application of Array-Based Methods and Gene Re-Sequencing to Identify Candidate Molecular Targets for High-Risk Pediatric Acute Lymphoblastic Leukemia

RATIONALE: Collecting and storing samples of bone marrow and blood from patients with cancer to study in the laboratory may help doctors learn more about changes that may occur in DNA and identify biomarkers related to cancer.

PURPOSE: This laboratory study is looking at lymphoblasts in young patients with high-risk acute lymphoblastic leukemia.

Study Overview

• Status: Completed
• Conditions: Leukemia
• Intervention / Treatment: Genetic: polymorphism analysis; Genetic: tumor replication error analysis; Genetic: loss of heterozygosity analysis; Genetic: microarray analysis

Detailed Description

OBJECTIVES:

• Identify regions of copy number abnormalities (CNA) and uniparental disomy in leukemic lymphoblasts from pediatric patients with high-risk acute lymphoblastic leukemia (ALL) using Affymetrix GeneChip Mapping 500K array sets. (Pilot project)
• Identify regions of CNA and loss-of-heterozygosity using Affymetrix SNP 6.0 microarrays. (Expansion project)
• Define gene expression profiles for leukemic lymphoblasts using Affymetrix U133 Plus 2.0 arrays.
• Assess the global expression of microRNAs in leukemic lymphoblasts using microRNA gene chips.
• Utilize array-generated gene expression data and data for CNAs and uniparental disomy to prioritize candidate genes and genomic regions for resequencing.
• Characterize epigenomic profiles using the HpaII tiny fragment Enrichment by Ligation-mediated PCR (HELP) assay. (Expansion project)
• Discover candidate therapeutic targets for these patients by identifying genes that are consistently mutated in leukemic lymphoblasts using high-throughput focused gene resequencing. (Pilot project)
• Discover candidate therapeutic targets for these patients by next generation sequencing technologies, including whole genome, whole transcriptome, and whole exome. (Expansion project)

OUTLINE: This is a multicenter study.

Banked biological samples (bone marrow and peripheral blood) are analyzed using gene expression profiling, single-nucleotide polymorphism and genotyping assays, DNA copy number and loss of heterozygosity estimates, epigenetic profiling, and gene resequencing.

PROJECTED ACCRUAL: A total of 150 patient samples will be accrued for this study.

• Study Type: Observational
• Enrollment (Anticipated): 150

Contacts and Locations

Study Locations

• United States
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Hollings Cancer Center at Medical University of South Carolina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Targets for High-Risk Pediatric Acute Lymphoblastic Leukemia

Description

DISEASE CHARACTERISTICS:

• Diagnosis of B-cell precursor acute lymphoblastic leukemia (ALL)

  • High-risk disease

• Participation in clinical trial COG-P9906 required (pilot project)

  • In complete remission
  • Consented to future studies using banked tissue specimens

• Participation in clinical trial and COG-AALL03B1 and linked therapeutic studies COG-AALL0232 and COG- AALL0331(expansion project)

  • Experienced a bone marrow relapse within 36 months of initial diagnosis
  • Consented to future studies using banked tissue specimens
  • Have matched ALL blast and germline specimens
  • Demographic, clinical and pathologic data elements for these biospecimens available

PATIENT CHARACTERISTICS:

• Not specified

PRIOR CONCURRENT THERAPY:

• Not specified

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Identification of regions of copy number abnormalities (CNA) and uniparental disomy in leukemic lymphoblasts using Affymetrix GeneChip Mapping 500K array sets
Identification of regions of CNA and loss-of-heterozygosity using Affymetrix SNP 6.0 microarrays. (Expansion project)
Gene expression profiles for leukemic lymphoblasts using Affymetrix U133 Plus 2.0 arrays
Global expression of microRNAs in leukemic lymphoblasts using microRNA gene chips
Epigenomic profiles using the HpaII tiny fragment Enrichment by Ligation-mediated PCR (HELP) assay. (Expansion project)
Prioritization of candidate genes and genomic regions for resequencing using array-generated gene expression data and data for CNAs
Identification of genes that are consistently mutated in leukemic lymphoblasts using high-throughput focused gene resequencing

Collaborators and Investigators

• Sponsor: Children's Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Stephen P. Hunger, MD, Children's Hospital Colorado Center for Cancer and Blood Disorders

Study record dates

Study Major Dates

• Study Start: May 1, 2006
• Primary Completion (Actual): May 1, 2016
• Study Completion (Actual): May 1, 2016

Study Registration Dates

• First Submitted: May 9, 2009
• First Submitted That Met QC Criteria: May 9, 2009
• First Posted (Estimate): May 12, 2009

Study Record Updates

• Last Update Posted (Estimate): May 17, 2016
• Last Update Submitted That Met QC Criteria: May 13, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: B-cell childhood acute lymphoblastic leukemia; childhood acute lymphoblastic leukemia in remission
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid
• Other Study ID Numbers: AALL06B1; COG-AALL06B1 (Other Identifier: Children's Oncology Group); CDR0000496763 (Other Identifier: Clinical Trials.gov); NCI-2009-00314 (Registry Identifier: CTRP (Clinical Trial Reporting Program))