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

April 18, 2024 updated by: Children's Oncology Group

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 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.

Study Type

Observational

Enrollment (Estimated)

330

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Madera, California, United States, 93636
        • Recruiting
        • Valley Children's Hospital
        • Contact:
        • Principal Investigator:
          • Karen S. Fernandez
      • Oakland, California, United States, 94609
        • Recruiting
        • UCSF Benioff Children's Hospital Oakland
        • Principal Investigator:
          • Jennifer G. Michlitsch
        • Contact:
      • San Francisco, California, United States, 94158
        • Recruiting
        • UCSF Medical Center-Mission Bay
        • Principal Investigator:
          • Anya Levinson
        • Contact:
    • Delaware
      • Wilmington, Delaware, United States, 19803
        • Recruiting
        • Alfred I duPont Hospital for Children
        • Contact:
        • Principal Investigator:
          • Ramamoorthy Nagasubramanian
    • Florida
      • Fort Myers, Florida, United States, 33908
        • Recruiting
        • Golisano Children's Hospital of Southwest Florida
        • Contact:
        • Principal Investigator:
          • Emad K. Salman
      • Jacksonville, Florida, United States, 32207
        • Recruiting
        • Nemours Children's Clinic-Jacksonville
        • Contact:
        • Principal Investigator:
          • Ramamoorthy Nagasubramanian
      • Orlando, Florida, United States, 32827
        • Recruiting
        • Nemours Children's Hospital
        • Contact:
        • Principal Investigator:
          • Ramamoorthy Nagasubramanian
      • Tampa, Florida, United States, 33607
        • Recruiting
        • Saint Joseph's Hospital/Children's Hospital-Tampa
        • Contact:
        • Principal Investigator:
          • Don E. Eslin
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Recruiting
        • Children's Healthcare of Atlanta - Egleston
        • Contact:
        • Principal Investigator:
          • Karen E. Effinger
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Recruiting
        • C S Mott Children's Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 800-865-1125
        • Principal Investigator:
          • Joshua W. Goldman
    • Missouri
      • Kansas City, Missouri, United States, 64108
        • Recruiting
        • Children's Mercy Hospitals and Clinics
        • Contact:
          • Site Public Contact
          • Phone Number: 816-302-6808
          • Email: rryan@cmh.edu
        • Principal Investigator:
          • Keith J. August
      • Saint Louis, Missouri, United States, 63110
        • Not yet recruiting
        • Washington University School of Medicine
        • Contact:
        • Principal Investigator:
          • Robert J. Hayashi
    • Nevada
      • Las Vegas, Nevada, United States, 89102
        • Recruiting
        • University Medical Center of Southern Nevada
        • Contact:
        • Principal Investigator:
          • Alan K. Ikeda
      • Las Vegas, Nevada, United States, 89109
        • Recruiting
        • Sunrise Hospital and Medical Center
        • Contact:
        • Principal Investigator:
          • Alan K. Ikeda
      • Las Vegas, Nevada, United States, 89135
        • Recruiting
        • Alliance for Childhood Diseases/Cure 4 the Kids Foundation
        • Contact:
        • Principal Investigator:
          • Alan K. Ikeda
      • Las Vegas, Nevada, United States, 89144
        • Recruiting
        • Summerlin Hospital Medical Center
        • Contact:
        • Principal Investigator:
          • Alan K. Ikeda
      • Reno, Nevada, United States, 89502
        • Recruiting
        • Renown Regional Medical Center
        • Contact:
        • Principal Investigator:
          • Alan K. Ikeda
    • New York
      • Albany, New York, United States, 12208
        • Recruiting
        • Albany Medical Center
        • Contact:
          • Site Public Contact
          • Phone Number: 518-262-5513
        • Principal Investigator:
          • Lauren R. Weintraub
      • Bronx, New York, United States, 10467
        • Recruiting
        • Montefiore Medical Center - Moses Campus
        • Contact:
        • Principal Investigator:
          • Alice Lee
      • Buffalo, New York, United States, 14263
        • Recruiting
        • Roswell Park Cancer Institute
        • Contact:
        • Principal Investigator:
          • Denise A. Rokitka
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27157
        • Recruiting
        • Wake Forest University Health Sciences
        • Contact:
          • Site Public Contact
          • Phone Number: 336-713-6771
        • Principal Investigator:
          • Thomas W. McLean
    • North Dakota
      • Fargo, North Dakota, United States, 58122
    • Ohio
      • Dayton, Ohio, United States, 45404
        • Recruiting
        • Dayton Children's Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 800-228-4055
        • Principal Investigator:
          • Mukund G. Dole
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Not yet recruiting
        • University of Oklahoma Health Sciences Center
        • Contact:
        • Principal Investigator:
          • Rene Y. McNall-Knapp
    • Oregon
      • Portland, Oregon, United States, 97239
        • Recruiting
        • Oregon Health and Science University
        • Contact:
        • Principal Investigator:
          • Susan J. Lindemulder
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15224
        • Recruiting
        • Children's Hospital of Pittsburgh of UPMC
        • Contact:
        • Principal Investigator:
          • Jean M. Tersak
    • Rhode Island
      • Providence, Rhode Island, United States, 02903
        • Recruiting
        • Rhode Island Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 401-444-1488
        • Principal Investigator:
          • Jennifer J. Welch
    • South Carolina
      • Greenville, South Carolina, United States, 29605
        • Recruiting
        • BI-LO Charities Children's Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 864-241-6251
        • Principal Investigator:
          • Aniket Saha
    • South Dakota
      • Sioux Falls, South Dakota, United States, 57117-5134
    • Tennessee
      • Knoxville, Tennessee, United States, 37916
        • Recruiting
        • East Tennessee Childrens Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 865-541-8266
        • Principal Investigator:
          • Susan E. Spiller
    • Texas
      • Austin, Texas, United States, 78723
        • Recruiting
        • Dell Children's Medical Center of Central Texas
        • Contact:
        • Principal Investigator:
          • Shannon M. Cohn
      • Dallas, Texas, United States, 75390
        • Recruiting
        • UT Southwestern/Simmons Cancer Center-Dallas
        • Principal Investigator:
          • Ksenya Shliakhtsitsava
        • Contact:
      • Fort Worth, Texas, United States, 76104
      • Houston, Texas, United States, 77030
        • Recruiting
        • M D Anderson Cancer Center
        • Contact:
        • Principal Investigator:
          • Najat C. Daw
      • Houston, Texas, United States, 77030
        • Recruiting
        • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 713-798-1354
          • Email: burton@bcm.edu
        • Principal Investigator:
          • Maria M. Gramatges
      • San Antonio, Texas, United States, 78229
        • Recruiting
        • University of Texas Health Science Center at San Antonio
        • Contact:
        • Principal Investigator:
          • Shafqat Shah
    • Washington
      • Spokane, Washington, United States, 99204
        • Recruiting
        • Providence Sacred Heart Medical Center and Children's Hospital
        • Contact:
        • Principal Investigator:
          • Judy L. Felgenhauer
    • Wisconsin
      • Marshfield, Wisconsin, United States, 54449

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 years to 40 years (Child, Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

DS-AL survivors from the Children's Oncology Group (COG) Registry and Epidemiology protocols or locally from participating institutions.

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Only
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Observational (biospecimen collection, 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.
Other: Questionnaire Administration
Ancillary studies
Other: Survey Administration
Ancillary studies
Procedure: Biospecimen Collection
Patients undergo saliva/buccal and blood sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Other: Clinical Evaluation
Undergo a clinical assessment
Other Names:
  • Clinical Assessment

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Prevalence, type, and severity of chronic health conditions (CHC)
Time Frame: 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, 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
Time Frame: 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.
Up to study completion
Prevalence and severity of parent-proxy neuropsychological (NP) outcomes
Time Frame: 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).
Up to study completion
Health-related quality of life (HRQOL)
Time Frame: 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.
Up to study completion
Clinical risk determinants of CHC, NP, and clinical outcomes
Time Frame: 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.
Up to study completion
Well-annotated cohort of Down syndrome phenotyping acute leukemia study (DS-PALS) survivors and associated biobank
Time Frame: Up to study completion
Up to study completion

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Structural birth defects and genetic associations with etiology extending to CHC for Down syndrome acute lymphoblastic leukemia (DS-ALL)
Time Frame: Up to study completion
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
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
Time Frame: Up to study completion
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Children's Oncology Group

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Maria M Gramatges, Children's Oncology Group

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 12, 2023

Primary Completion (Estimated)

December 16, 2028

Study Completion (Estimated)

December 16, 2028

Study Registration Dates

First Submitted

January 9, 2023

First Submitted That Met QC Criteria

January 18, 2023

First Posted (Actual)

January 27, 2023

Study Record Updates

Last Update Posted (Actual)

April 22, 2024

Last Update Submitted That Met QC Criteria

April 18, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ALTE22C1 (Other Identifier: CTEP)
  • UG1CA189955 (U.S. NIH Grant/Contract)
  • NCI-2022-09410 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • R01CA263000 (U.S. NIH Grant/Contract)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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