Risk of Psychopathology and Neurocognitive Impairment in Leukemia Survivors

Acute Lymphoblastic Leukemia Clinical Trial

Official title:

Risk of Psychopathology and Neurocognitive Impairment in Leukemia Survivors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01014195
• Other study ID #: NEULS
• Secondary ID: R01MH085849
• Status: Completed
• Phase: N/A
• First received: November 13, 2009
• Last updated: June 6, 2016
• Start date: January 2010
• Est. completion date: October 2014

Study information

• Verified date: June 2016
• Source: St. Jude Children's Research Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 237
• Est. completion date: October 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 8 Years and older

Eligibility

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 Design

Observational Model: Case-Only, Time Perspective: Prospective

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Leukemia
• Leukemia, Lymphoid
• Neurocognitive Impairment
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

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.

Locations

Country	Name	City	State
United States	St. Jude Children's Research Hospital	Memphis	Tennessee

Sponsors (3)

Lead Sponsor	Collaborator
St. Jude Children's Research Hospital	M.D. Anderson Cancer Center, National Institute of Mental Health (NIMH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Neurocognitive assessment of attention, processing speed, and executive functions.		Once, at least 5 years post ALL diagnosis and 2 years off treatment	No
Secondary	Quantitative magnetic resonance imaging (MRI) and DTI and functional magnetic resonance imaging (fMRI) of brain structure and function.		Once, at least 5 years post ALL diagnosis and 2 years off treatment	No
Secondary	Family and parental stress as reported by primary caregiver.		Once, at least 5 years post ALL diagnosis and 2 years off treatment	No
Secondary	Associations between genetic polymorphisms in key enzyme pathways and higher order brain development in long-term survivors of pediatric ALL.		Once, at least 5 years post ALL diagnosis and 2 years off treatment	No
Secondary	Associations between fatigue and neurocognitive performance and between sleep problems and neurocognitive performance.		Once, at least 5 years post ALL diagnosis and 2 years off treatment	No

External Links

•   Clinical Trials Open at St. Jude
•   St. Jude Children's Research Hospital