A Study to Learn More About the Health of Persons With Down Syndrome After Treatment for Acute Leukemia
- Conditions
- Myeloid Leukemia Associated With Down SyndromeB Acute Lymphoblastic Leukemia Associated With Down SyndromeDown Syndrome
- Interventions
- Procedure: Biospecimen CollectionOther: Clinical EvaluationOther: Questionnaire AdministrationOther: Survey Administration
- Registration Number
- NCT05702645
- Lead Sponsor
- Children's Oncology Group
- Brief Summary
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
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 adverse neuropsychological (NP) outcomes 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 with DS-ALL may then undergo blood sample collection and neurocognitive assessment in part 3 of the study.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 330
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Patients age >= 6 and < 40 years at the time of enrollment
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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)
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All patients must be DS-AL survivors (acute lymphoblastic leukemia [ALL] or acute myeloid leukemia [AML])
- Note 1: Myeloid leukemia of Down syndrome (ML-DS) is included in the AML category above. Per the World Health Organization (WHO) definition of ML-DS, this diagnosis encompasses both myelodysplastic syndrome (MDS) and overt AML. 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
- Note 2: A diagnosis of transient abnormal myelopoiesis (TAM), also known as transient myeloproliferative disease (TMD), is not alone sufficient for inclusion in this study
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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
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All cancer treatment (oral or intravenous) must have been completed at least 36 calendar months prior to enrollment
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Patients must have a life expectancy of > 1 year
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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 questionnaires, even in the case of subjects that are >= 18 years old
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All patients and/or their parents or legal guardians must sign a written informed consent
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All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
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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
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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
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Observational (biospecimen collection, clinical evaluation) Survey Administration 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. Observational (biospecimen collection, clinical evaluation) Biospecimen Collection 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. Observational (biospecimen collection, clinical evaluation) Questionnaire Administration 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. Observational (biospecimen collection, clinical evaluation) Clinical Evaluation 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.
- Primary Outcome Measures
Name Time Method Prevalence, type, and severity of chronic health conditions (CHC) Up to study completion 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, will estimate the hazard ratio, 95% CI, and p-values to report time-dependent effects of AL diagnosis on CHC.
- Secondary Outcome Measures
Name Time Method Prevalence and severity of parent-proxy neuropsychological (NP) outcomes Up to study completion 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).
Health-related quality of life (HRQOL) Up to study completion 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.
Post-treatment clinical outcomes Up to study completion 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.
Clinical risk determinants of CHC, NP, and clinical outcomes Up to study completion 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.
Well-annotated cohort of Down syndrome phenotyping acute leukemia study (DS-PALS) survivors and associated biobank Up to study completion The number of patients who agree to be in the Biobanking part of the study and have leftover tumor tissue and some normal blood, bone marrow, or other tissue saved for future research.
Trial Locations
- Locations (54)
Valley Children's Hospital
🇺🇸Madera, California, United States
UCSF Benioff Children's Hospital Oakland
🇺🇸Oakland, California, United States
UCSF Medical Center-Mission Bay
🇺🇸San Francisco, California, United States
Yale University
🇺🇸New Haven, Connecticut, United States
Alfred I duPont Hospital for Children
🇺🇸Wilmington, Delaware, United States
Golisano Children's Hospital of Southwest Florida
🇺🇸Fort Myers, Florida, United States
Memorial Regional Hospital/Joe DiMaggio Children's Hospital
🇺🇸Hollywood, Florida, United States
Nemours Children's Clinic-Jacksonville
🇺🇸Jacksonville, Florida, United States
Nemours Children's Hospital
🇺🇸Orlando, Florida, United States
Saint Joseph's Hospital/Children's Hospital-Tampa
🇺🇸Tampa, Florida, United States
Children's Healthcare of Atlanta - Arthur M Blank Hospital
🇺🇸Atlanta, Georgia, United States
Augusta University Medical Center
🇺🇸Augusta, Georgia, United States
Sinai Hospital of Baltimore
🇺🇸Baltimore, Maryland, United States
C S Mott Children's Hospital
🇺🇸Ann Arbor, Michigan, United States
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
Children's Mercy Hospitals and Clinics
🇺🇸Kansas City, Missouri, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Children's Hospital and Medical Center of Omaha
🇺🇸Omaha, Nebraska, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
University Medical Center of Southern Nevada
🇺🇸Las Vegas, Nevada, United States
Sunrise Hospital and Medical Center
🇺🇸Las Vegas, Nevada, United States
Alliance for Childhood Diseases/Cure 4 the Kids Foundation
🇺🇸Las Vegas, Nevada, United States
Summerlin Hospital Medical Center
🇺🇸Las Vegas, Nevada, United States
Renown Regional Medical Center
🇺🇸Reno, Nevada, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Albany Medical Center
🇺🇸Albany, New York, United States
Montefiore Medical Center - Moses Campus
🇺🇸Bronx, New York, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
UNC Lineberger Comprehensive Cancer Center
🇺🇸Chapel Hill, North Carolina, United States
Wake Forest University Health Sciences
🇺🇸Winston-Salem, North Carolina, United States
Sanford Broadway Medical Center
🇺🇸Fargo, North Dakota, United States
Children's Hospital Medical Center of Akron
🇺🇸Akron, Ohio, United States
Rainbow Babies and Childrens Hospital
🇺🇸Cleveland, Ohio, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Dayton Children's Hospital
🇺🇸Dayton, Ohio, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Children's Hospital of Pittsburgh of UPMC
🇺🇸Pittsburgh, Pennsylvania, United States
Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States
Prisma Health Richland Hospital
🇺🇸Columbia, South Carolina, United States
BI-LO Charities Children's Cancer Center
🇺🇸Greenville, South Carolina, United States
Sanford USD Medical Center - Sioux Falls
🇺🇸Sioux Falls, South Dakota, United States
East Tennessee Childrens Hospital
🇺🇸Knoxville, Tennessee, United States
Vanderbilt University/Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
Dell Children's Medical Center of Central Texas
🇺🇸Austin, Texas, United States
UT Southwestern/Simmons Cancer Center-Dallas
🇺🇸Dallas, Texas, United States
Cook Children's Medical Center
🇺🇸Fort Worth, Texas, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
🇺🇸Houston, Texas, United States
M D Anderson Cancer Center
🇺🇸Houston, Texas, United States
University of Texas Health Science Center at San Antonio
🇺🇸San Antonio, Texas, United States
Seattle Children's Hospital
🇺🇸Seattle, Washington, United States
Providence Sacred Heart Medical Center and Children's Hospital
🇺🇸Spokane, Washington, United States
Marshfield Medical Center-Marshfield
🇺🇸Marshfield, Wisconsin, United States