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

Down Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05702645
• Other study ID #: ALTE22C1
• Secondary ID: NCI-2022-09410AL
• Status: Recruiting
• Start date: June 12, 2023
• Est. completion date: December 16, 2028

Study information

• Verified date: May 2024
• Source: Children's Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 330
• Est. completion date: December 16, 2028
• Est. primary completion date: December 16, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 39 Years

Eligibility

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

Related Conditions & MeSH terms

• Down Syndrome
• Leukemia
• Myeloid Leukemia Associated With Down Syndrome
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Syndrome

Intervention

Procedure:
• Biospecimen Collection
Patients undergo saliva/buccal and blood sample collection

Other:
• Clinical Evaluation
Undergo a clinical assessment
• Questionnaire Administration
Ancillary studies
• Survey Administration
Ancillary studies

Locations

Country	Name	City	State
United States	Albany Medical Center	Albany	New York
United States	C S Mott Children's Hospital	Ann Arbor	Michigan
United States	Children's Healthcare of Atlanta - Egleston	Atlanta	Georgia
United States	Dell Children's Medical Center of Central Texas	Austin	Texas
United States	Montefiore Medical Center - Moses Campus	Bronx	New York
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas
United States	Dayton Children's Hospital	Dayton	Ohio
United States	Sanford Broadway Medical Center	Fargo	North Dakota
United States	Golisano Children's Hospital of Southwest Florida	Fort Myers	Florida
United States	Cook Children's Medical Center	Fort Worth	Texas
United States	BI-LO Charities Children's Cancer Center	Greenville	South Carolina
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	Nemours Children's Clinic-Jacksonville	Jacksonville	Florida
United States	Children's Mercy Hospitals and Clinics	Kansas City	Missouri
United States	East Tennessee Childrens Hospital	Knoxville	Tennessee
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	Sunrise Hospital and Medical Center	Las Vegas	Nevada
United States	University Medical Center of Southern Nevada	Las Vegas	Nevada
United States	Valley Children's Hospital	Madera	California
United States	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin
United States	UCSF Benioff Children's Hospital Oakland	Oakland	California
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Nemours Children's Hospital	Orlando	Florida
United States	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania
United States	Oregon Health and Science University	Portland	Oregon
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Renown Regional Medical Center	Reno	Nevada
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	UCSF Medical Center-Mission Bay	San Francisco	California
United States	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota
United States	Providence Sacred Heart Medical Center and Children's Hospital	Spokane	Washington
United States	Saint Joseph's Hospital/Children's Hospital-Tampa	Tampa	Florida
United States	Alfred I duPont Hospital for Children	Wilmington	Delaware
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Children's Oncology Group

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Structural birth defects and genetic associations with etiology extending to CHC for Down syndrome acute lymphoblastic leukemia (DS-ALL)	Will determine the association between structural birth defects and the number, organ system category, and severity of CHC in DS-PALS survivors. Will use Cox regression to estimate hazard ratio and 95% CI for number, severity, and type of CHC by number of birth defects. Will explore the role of DS-ALL susceptibility variants identified in our genome-wide assessment on DS-associated CHC in survivors. Will use Cox regression to estimate the association between four DS-ALL susceptibility loci (rs58923657 near IKZF1, rs3731249 in CDKN2A, rs7090445 in ARID5B, and rs3781093 in GATA3) and CHC.	Up to study completion
Other	Telomere length (TL) determined by polygenic risk score and telomere flow-fluorescence in situ hybridization (FISH) in association with outcomes from in-person NP assessment for DS-ALL	Will determine genetically-estimated TL. Will use a multivariable Cox proportional hazard model to estimate hazard ratio, 95% CI for the association between each of nine variants and risk for NP deficit =<1 standard deviation below the mean, and consider the weighted and unweighted risk score from the number of risk alleles present and previously-published beta estimates. For flow-FISH analyses, TL =< 1st percentile is considered 'very short,' as previously defined. Will determine objective responses for NP deficits =< 1.5 standard deviation below the mean for an age-normative sample in subjects with TL > or =< 1st percentile, adjusted for relevant covariates and treatment factors. Will report 95% CI, p values using a Chi square test (two-tailed p-value of 0.05 statistically significant).	Up to study completion
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Well-annotated cohort of Down syndrome phenotyping acute leukemia study (DS-PALS) survivors and associated biobank	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.	Up to study completion