Risk of Psychopathology and Neurocognitive Impairment in Leukemia Survivors

June 6, 2016 updated by: St. Jude Children's Research Hospital
  1. This study will evaluate the association between changes in basic cognitive and behavioral functioning by the end of chemotherapy treatment, and the later development of higher order executive functions in pediatric acute lymphoblastic leukemia (ALL).
  2. The association between acute treatment-related changes in brain integrity and subsequent brain maturation in long-term survivors of pediatric ALL will be evaluated.
  3. The association between patterns of behavioral and executive dysfunction and brain maturation in long-term survivors of pediatric ALL will be examined.
  4. The association between genetic polymorphisms in key enzyme pathways and higher order brain development in long-term survivors of pediatric ALL will be explored.
  5. The associations between biologic and behavioral indices of fatigue/sleep and higher order brain development in long-term survivors of pediatric ALL will be explored.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Survival rates for pediatric acute lymphoblastic leukemia (ALL) now exceed 80%. With this growing population of long-term survivors comes recognition that a considerable proportion experience one or more significant late effects. For children undergoing central nervous system (CNS) treatment, common late effects include neurocognitive impairment and neurobehavioral problems. Although these problems first manifest as subtle difficulties with attention and processing speed, they can evolve into deficits in higher order brain functions that significantly impact functional skills in a subset of long-term survivors. There currently is no method to accurately identify patients at greatest risk for these long-term behavioral and neurocognitive problems. Through this proposal, this study plans to utilize existing data collected during acute treatment to identify predictors of long-term neurocognitive and brain maturation outcomes. The study also proposes to collect data on attention-deficit/hyperactivity disorder (ADHD) and associated comorbidities, higher order executive functions, and structural and functional brain imaging in survivors who are at least 8 years of age and greater than 5 years from diagnosis.

All patients will undergo a single neurocognitive evaluation focused on assessment of higher order executive functions. Patients will be evaluated during their regularly scheduled annual follow-up visit, when health-related monitoring will also occur. Parents of participants will be asked to complete questionnaires designed to assess the family environment and the impact of cancer diagnosis on family functioning and parent stress.

Brain Imaging: To better demonstrate untoward treatment effects upon cortical brain development, quantitative MR imaging of myelin integrity using diffusion tensor imaging (DTI) and cortical thickness assessment using high resolution volumetric imaging will be utilized. All patients will also be evaluated using functional MRI (fMRI) procedures during resting state and participation in attention and working memory tasks. fMRI and DTI data will be de-identified then analyzed at MD Anderson Cancer Center in Houston, Texas.

Study Type

Observational

Enrollment (Actual)

237

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
    • Tennessee
      • Memphis, Tennessee, United States, 38105
        • St. Jude Children's Research Hospital

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

8 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Children originally enrolled and treated on the SJCRH TOTXV protocol. The study has reviewed TOTXV patient database and has identified 343 patients (189 males and 154 females) who will meet the inclusion criteria (assuming no additional deaths or relapse).

Description

Inclusion Criteria:

  • Enrolled on SJCRH TOTXV ALL protocol
  • ≥ 5 years post diagnosis of ALL
  • ≥ 8.0 years of age at time of follow-up evaluation

Exclusion Criteria:

  • History of cranial or total-body radiation therapy
  • History of bone marrow transplant
  • History of relapse
  • History of head injury, neurological condition unrelated to ALL treatment, or diagnosis of a genetic disorder associated with neurocognitive impairment (e.g. Down Syndrome)

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

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Group 1

Survivors of pediatric leukemia treated on Total Therapy Protocol XV (TOTXV) at St. Jude Children's Research Hospital (SJCRH), who are ≥ 8 years of age and ≥ 5 years from diagnosis.

Intervention: Neurocognitive and behavioral evaluation
Other: Neurocognitive and behavioral evaluation
The primary neurocognitive outcome will be performance on measures of cognitive flexibility and cognitive fluency. Functional behavior will be evaluated via the child or adult version of the Behavior Rating Inventory of Executive Function, using parent respondent for each version. The presence of ADHD and common comorbid conditions (i.e. depression, anxiety) will be determined with structured diagnostic interviews. Quality of life will be re-assessed with the PedQL.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Neurocognitive assessment of attention, processing speed, and executive functions.
Time Frame: Once, at least 5 years post ALL diagnosis and 2 years off treatment
Once, at least 5 years post ALL diagnosis and 2 years off treatment

Secondary Outcome Measures

Outcome Measure
Time Frame
Quantitative magnetic resonance imaging (MRI) and DTI and functional magnetic resonance imaging (fMRI) of brain structure and function.
Time Frame: Once, at least 5 years post ALL diagnosis and 2 years off treatment
Once, at least 5 years post ALL diagnosis and 2 years off treatment
Family and parental stress as reported by primary caregiver.
Time Frame: Once, at least 5 years post ALL diagnosis and 2 years off treatment
Once, at least 5 years post ALL diagnosis and 2 years off treatment
Associations between genetic polymorphisms in key enzyme pathways and higher order brain development in long-term survivors of pediatric ALL.
Time Frame: Once, at least 5 years post ALL diagnosis and 2 years off treatment
Once, at least 5 years post ALL diagnosis and 2 years off treatment
Associations between fatigue and neurocognitive performance and between sleep problems and neurocognitive performance.
Time Frame: Once, at least 5 years post ALL diagnosis and 2 years off treatment
Once, at least 5 years post ALL diagnosis and 2 years off treatment

Collaborators and Investigators

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

Sponsor

St. Jude Children's Research Hospital

Collaborators

M.D. Anderson Cancer Center
National Institute of Mental Health (NIMH)

Investigators

  • Principal Investigator: Kevin Krull, Ph.D, St. Jude Children's Research Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

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

January 1, 2010

Primary Completion (Actual)

October 1, 2014

Study Completion (Actual)

October 1, 2014

Study Registration Dates

First Submitted

November 13, 2009

First Submitted That Met QC Criteria

November 13, 2009

First Posted (Estimate)

November 16, 2009

Study Record Updates

Last Update Posted (Estimate)

June 7, 2016

Last Update Submitted That Met QC Criteria

June 6, 2016

Last Verified

June 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NEULS
  • R01MH085849 (U.S. NIH Grant/Contract)

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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