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.
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
Primary outcome:
1. Rate of adverse events (cardiac dysfunction, AVN, ischemic stroke, and SMN using a matched case-control) (Time Frame - 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.
2. Frequency of mutations or polymorphisms in specific candidate genes in cases and controls (Time Frame - 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.
3. Crude disease-exposure (Time Frame - 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.
- Laboratory Biomarker Analysis:
Correlative studies - Questionnaire Administration:
Ancillary studies
Quelle: ClinicalTrials.gov