DNA Analysis of Tumor Tissue Samples From Young Patients With Acute Lymphoblastic Leukemia

Single Nucleotide Polymorphisms and Relapse Risk in Standard Risk ALL

This laboratory study is looking at DNA in tumor tissue samples from young patients with acute lymphoblastic leukemia. DNA analysis of tumor tissue may help doctors predict how well patients will respond to treatment

Study Overview

• Status: Completed
• Conditions: Childhood Acute Lymphoblastic Leukemia in Remission; Recurrent Childhood Acute Lymphoblastic Leukemia
• Intervention / Treatment: Other: Laboratory Biomarker Analysis

Detailed Description

PRIMARY OBJECTIVE:

I. To validate significant associations between SNPs and treatment outcome and toxicity on Children's Cancer Group (CCG)-1891 on an independent sample set from a successor CCG study for standard risk acute lymphoblastic leukemia (ALL), CCG-1952.

II. To evaluate the role of SNPs in drug metabolizing enzymes and the development of veno-occlusive disease in patients on CCG-1952.

III. To evaluate interactions among genotypes and other risk factors for treatment response in a combined data set of CCG-1891 and CCG-1952 with recently developed analytic tools for high dimensional data.

IV. To develop predictive models utilizing genetic information obtained in Aim 1.1 and clinical data to predict treatment response and toxicity.

OUTLINE:

Tumor tissue samples undergo genotype assessment on the Pyrosequencing platform. Contingency tables and X^2 test performs a univariate analysis of the risk of relapse and genotype, and multivariable analyses using logistic regression. Cox proportional hazards evaluate the risk of relapse given genotype and other confounders. Genotype patterning, classification and regression trees, and multifactor dimensionality reduction evaluates for patterns of single nucleotide polymorphisms associated with toxicity and relapse risk.

• Study Type: Observational
• Enrollment (Actual): 520

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Childrens Oncology Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Description

Inclusion Criteria:

• Enrolled in clinical trial CCG-1891 or CCG-1952 with pediatric ALL

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Ancillary-Correlative (genotype assessment); Tumor tissue samples undergo genotype assessment on the Pyrosequencing platform. Contingency tables and X^2 test performs a univariate analysis of the risk of relapse and genotype, and multivariable analyses using logistic regression. Cox proportional hazards evaluate the risk of relapse given genotype and other confounders. Genotype patterning, classification and regression trees, and multifactor dimensionality reduction evaluates for patterns of single nucleotide polymorphisms associated with toxicity and relapse risk.

Other: Laboratory Biomarker Analysis; Correlative studies

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Leukemia Relapse	Contingency tables will be used to tabulate the relationship between relapse and genotype, race, leukemia cytogenetics, day 7 bone marrow status, and treatment arm	Day 7
Development of veno-occlusive disease in patients on CCG-1952	Classification and Regression Trees (CART), genotype patterning, Multifactor Dimensionality Reduction (MDR) techniques will be used to identify SNP combinations associated with risk of relapse and VOD	Day 28
Development of a predictive model of leukemia relapse	Predictive models will be developed utilizing genetic information obtained in Aim 1.1 and clinical data to predict treatment response	Day 28
Development of a predictive model of leukemia toxicity	Predictive models will be developed utilizing genetic information obtained in Aim 1.1 and clinical data to predict treatment toxicity.	Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Development of grade III/IV toxicity as defined by the CCG toxicity criteria	Contingency tables will be used to tabulate categorical toxicities and toxicity severity grade.	Day 28

Collaborators and Investigators

• Sponsor: Children's Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Richard Aplenc, Children's Oncology Group

Study record dates

Study Major Dates

• Study Start (Actual): May 13, 2004
• Primary Completion (Actual): May 5, 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 (Actual): August 15, 2022
• Last Update Submitted That Met QC Criteria: August 12, 2022
• Last Verified: October 1, 2017

More Information

Terms related to this study

• 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: AALL04B2 (Other Identifier: CTEP); U10CA098543 (U.S. NIH Grant/Contract); NCI-2009-00309 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); CDR0000371580; COG-AALL04B2