A Study to Learn More About the Health of Persons With Down Syndrome After Treatment for Acute Leukemia

Study Overview
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Brief Summary
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This study attempts to learn more about the health of persons with Down syndrome after treatment for acute leukemia. Children with Down syndrome are at increased risk for side effects during treatment for acute leukemia, but it is unclear of their risk for long-term effects of cancer treatment. By learning more about the factors that may contribute to chronic health conditions and long-term effects after treatment for leukemia in persons with Down syndrome, clinical practice guidelines for survivorship care can be developed to help improve their quality-of-life.

Detailed Description
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PRIMARY OBJECTIVE: I. To determine the prevalence, type, and severity of chronic health conditions (CHC) in survivors of Down syndrome-associated acute leukemia (DS-AL), and to compare CHC with frequency-matched DS individuals that have no cancer history. SECONDARY OBJECTIVES: I. To characterize post-treatment clinical outcomes of DS-AL by prospective, in-person assessment. II. To determine the prevalence and severity of parent-reported neuropsychological (NP) in survivors of DS-AL, compared with frequency-matched DS individuals with no cancer history. III. To determine health-related quality of life (HRQOL) in survivors of DS-AL, compared with frequency-matched DS individuals with no cancer history. IV. To identify clinical risk determinants of CHC, NP, and clinical outcomes in survivors of DS-AL. V. To establish a well-annotated cohort of survivors of DS-AL and associated biobank as a resource for future investigations. EXPLORATORY OBJECTIVES: I. For DS-acute lymphoblastic leukemia (DS-ALL), test if structural birth defects and genetic associations with etiology extend to CHC. II. For DS-ALL, test if telomere length determined by polygenic risk score and telomere flow-fluorescence in situ hybridization (FISH) are associated with outcomes from in-person NP assessment. OUTLINE: Patients undergo an optional saliva/buccal swab in part 1 and clinical assessment in part 2 of the study. Patients may then undergo blood sample collection in part 3 of the study.

Official Title
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Chronic Health Conditions in Down Syndrome-Associated Acute Leukemia: The Down Syndrome Phenotyping Acute Leukemia Study in Survivors (DS-PALS Survivors)

Conditions
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B Acute Lymphoblastic Leukemia Associated With Down Syndrome, Down Syndrome, Myeloid Leukemia Associated With Down Syndrome

Intervention / Treatment
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* Procedure: Biospecimen Collection
* Other: Clinical Evaluation
* Other: Questionnaire Administration
* Other: Survey Administration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients age >= 6 and < 40 years at the time of enrollment A diagnosis of Down syndrome is required, and may include any of the three recognized types: trisomy 21 resulting from chromosomal nondisjunction (most common), translocation (the patient has 46 chromosomes, but all or part of an additional copy of chromosome 21 is attached to another chromosome), or mosaicism (trisomy 21 that is present in only a fraction of cells) All patients must be DS-AL survivors (acute lymphoblastic leukemia [ALL] or acute myeloid leukemia [AML]) Note: Myeloid leukemia of Down syndrome (ML-DS) would be included under AML category above. Also note that survivors of relapsed disease are eligible, so long as the patient otherwise meets eligibility criteria, i.e., treatment for relapse was completed at least 36 calendar months prior to enrollment and did not include stem cell transplant Patients must have been treated for ALL or AML Note: History of COG therapeutic trial participation is not required. As a reminder ML-DS would be included under the AML category here above All cancer treatment (oral or intravenous) must have been completed at least 36 calendar months prior to enrollment Patients must have a life expectancy of > 1 year Patient and parent of subject must be either English or Spanish speaking. At least one parent or guardian must be able to read and write in English or Spanish Note: Parents or guardians are responsible for completing all forms, even in the case of subjects that are >= 18 years old All patients and/or their parents or legal guardians must sign a written informed consent All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met Exclusion Criteria: Patients with history of hematopoietic stem cell transplant (HSCT) are excluded Note: Patients with previous chimeric antigen receptor T-cell (CAR T-cell) therapy, and other cellular cancer therapies can participate, as long as all other eligibility criteria are satisfied Patients with a history of cancers prior to their ALL or AML diagnosis are excluded. Patients that developed a subsequent malignant neoplasm following their ALL or AML diagnosis are also excluded Note: Prior history of transient abnormal myelopoiesis is allowed, but is not sufficient for eligibility Patients whose parents or guardians are unable to complete the required forms are excluded

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Observational (biospecimen collection, clinical evaluation)<br>Patients undergo an optional saliva/buccal swab in part 1 and clinical assessment in part 2 of the study. Patients may then undergo blood sample collection in part 3 of the study. | Procedure: Biospecimen Collection<br>* Patients undergo saliva/buccal and blood sample collection<br>* Other names: Specimen Collection;Other: Clinical Evaluation<br>* Undergo a clinical assessment<br>* Other names: Clinical Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>Other: Survey Administration<br>* Ancillary studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalence, type, and severity of chronic health conditions (CHC) | Summary statistics will be used to characterize the study populations on CHC outcomes. Quantitative data (number of comorbidities) will be summarized using descriptive statistics and correlational techniques. Will use pooled logistic regression to estimate overall response, 95% confidence interval (CI), and p-values for association of acute leukemia (AL) diagnosis with medical record-verified CHC, agnostic of time to CHC. Will use stratified Cox models to refine associations of AL diagnosis with CHC based on time to CHC incidence. Within each age interval, we will estimate the hazard ratio, 95% CI, and p-values to report time-dependent effects of AL diagnosis on CHC. | Up to study completion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post-treatment clinical outcomes | Summary statistics will be used to characterize the study population on clinical outcomes, by AL subtype and, for each test, the proportion of normal, abnormal, and missing tests. | Up to study completion | 
| Prevalence and severity of parent-proxy neuropsychological (NP) outcomes | NP outcomes (measured by both parent proxy and direct assessment) will be reported by both raw and normalized scores, and quantitative data summarized using descriptive statistics and correlational techniques. The mean score for each test will be compared between the cohorts using a student t-test (2-sided significance level of 0.05 and equal variance). | Up to study completion | 
| Health-related quality of life (HRQOL) | HRQOL will be assessed using the Pediatric Quality of Life Inventory. Parents will be asked to scale 23 items comprising four dimensions (Physical, Emotional, Social, and School functioning) on a 5 point unweighted Likert scale. Will use a t-test (or Wilcoxon rank sum test if appropriate) to compare the mean (or median) HRQOL score. | Up to study completion | 
| Clinical risk determinants of CHC, NP, and clinical outcomes | Will use Cox regression to estimate the hazard ratio and 95% CI for (1) number, severity, and type of CHC, and (2) NP deficits dichotomized as clinically significant impairment yes/no (=< 1.5 standard deviation outside of the mean for the age-normative sample) according to age at diagnosis, years off therapy, sex, race/ethnicity, diagnosis, and treatment exposures. | Up to study completion | 
| Well-annotated cohort of Down syndrome phenotyping acute leukemia study (DS-PALS) survivors and associated biobank |  | Up to study completion |