Genetic Analysis in Identifying Late-Occurring Complications in Childhood Cancer Survivors

Active, not recruiting

• Conditions: Childhood Malignant Neoplasm

• Registration Number: NCT00082745
• Lead Sponsor: Children's Oncology Group

Brief Summary

This clinical trial studies cancer survivors to identify those who are at increased risk of developing late-occurring complications after undergoing treatment for childhood cancer. A patient's genes may affect the risk of developing complications, such as congestive heart failure, avascular necrosis, stroke, and second cancer, years after undergoing cancer treatment. Genetic studies may help doctors identify survivors of childhood cancer who are more likely to develop late complications.

Detailed Description

PRIMARY OBJECTIVES:

I. To identify key adverse events developing in patients (cases) with a primary cancer diagnosed at age 21 or younger.

II. To characterize the key adverse events with respect to the nature of the primary malignancy (pathology, stage) and coded details of the therapeutic protocol.

III. To identify treatment-related and demographic risk factors through a direct comparison of the case-group and controls identified from the remaining patients with the same primary diagnosis.

IV. To compare the frequency of mutations or polymorphisms in specific candidate genes in cases and controls, using constitutional deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) from the cases and controls.

V. To explore the role and nature of gene-environment interaction in the development of key adverse events.

OUTLINE:

DNA and RNA from peripheral blood or saliva sample of patients is analyzed for the presence of polymorphisms in genes associated with an increased risk of late-occurring complications.

Study Timeline

• Study Start: 2004-03-25
• Study First Submitted: 2004-05-14
• Study First Submitted QC: 2004-05-18
• Study First Posted: 2004-05-19
• Primary Completion: 2004-12-31
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-06
• Last Update Posted: 2025-03-07

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 3885

Inclusion Criteria

• ELIGIBILITY CRITERIA - CASES

• Diagnosis of primary cancer at age 21 or younger, irrespective of current age

• No prior history of allogeneic (non-autologous) hematopoietic cell transplant

• Development of one of the following key adverse events at any time following initiation of cancer therapy:

  • Cardiac dysfunction; please note: case enrollment has been closed due to achievement of target accrual
  • Ischemic stroke (IS)
  • Subsequent malignant neoplasm (SMN)
  • Avascular necrosis (AVN); please note: case enrollment has been closed due to achievement of target accrual

• Submission of a blood specimen (or in certain cases a saliva specimen) to the Coordinating Center at the University of Alabama at Birmingham as per the requirements; please note: if a patient is currently receiving active cancer treatment, it is preferable to obtain the blood sample at a time when the patient's white blood cell (WBC) is > 2,000

• Written informed consent from the patient and/or the patient's legally authorized guardian

• In active follow up by a COG institution; active follow up will be defined as date of last visit or contact by a COG institution within the past 24 months; any type of contact, including contact specifically for participation in ALTE03N1, qualifies as active follow-up; please note: treatment on a COG (or legacy group) therapeutic protocol for the primary cancer is NOT required

• ELIGIBILITY CRITERIA - CONTROLS

• CONTROL: Diagnosis of primary cancer at age 21 or younger, irrespective of current age

• CONTROLS: No prior history of allogeneic (non-autologous) hematopoietic cell transplant

• CONTROLS: No clinical evidence of any of the following key adverse events:

  • Cardiac dysfunction (CD); please note: if a patient is currently receiving active cancer treatment, it is preferable to obtain the blood sample at a time when the patient's WBC is > 2,000
  • Ischemic stroke (IS)
  • Avascular necrosis (AVN)
  • Subsequent malignant neoplasm (SMN)

• CONTROLS: Submission of a blood specimen (or in certain cases a saliva specimen) to the Coordinating Center Laboratory at the University of Alabama at Birmingham as per the requirements

• CONTROLS: Written informed consent from the patient and/or the patient's legally authorized guardian

• CONTROLS: In active follow up by a COG institution; active follow up will be defined as date of last visit or contact by a COG institution within the past 24 months; any type of contact, including contact specifically for participation in ALTE03N1, qualifies as active follow-up; please note: treatment on a COG (or legacy group) therapeutic protocol for the primary cancer is NOT required

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Rate of adverse events (cardiac dysfunction, AVN, ischemic stroke, and SMN using a matched case-control)	Up to 1 year	Epidemiological, clinical and laboratory variables will be tested for their association with key adverse events. McNemar's test for paired data will be used to compare the unmatched general characteristics of cases and controls.
Frequency of mutations or polymorphisms in specific candidate genes in cases and controls	Up to 1 year	Allele frequencies will be estimated by the gene counting method, and the chi-square test will be used to check for departures from Hardy-Weinberg equilibrium.
Crude disease-exposure	Up to 1 year	The crude disease-exposure association will be determined by estimating the OR and its 95% confidence interval (CI). This will be done by univariate conditional logistic regression, to account for the matched design. The significance of the OR will be assessed by the Wald test. Backward stepwise regression procedures will be used to develop the final multivariate model and possible interactions will be examined. The fit of the model will be assessed by the logistic regression diagnostics procedure.

Trial Locations

Locations (156)

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

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

City of Hope Comprehensive Cancer Center; 🇺🇸 Duarte, California, United States

Children's Hospital Los Angeles; 🇺🇸 Los Angeles, California, United States

Cedars Sinai Medical Center; 🇺🇸 Los Angeles, California, United States

Mattel Children's Hospital UCLA; 🇺🇸 Los Angeles, California, United States

Valley Children's Hospital; 🇺🇸 Madera, California, United States

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