Risk of Psychopathology and Neurocognitive Impairment in Leukemia Survivors

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by St. Jude Children's Research Hospital
Sponsor:
Collaborator:
Information provided by (Responsible Party):
St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier:
NCT01014195
First received: November 13, 2009
Last updated: August 8, 2014
Last verified: August 2014
  Purpose
  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.

Condition Intervention
Neurocognitive Impairment
Acute Lymphoblastic Leukemia
Other: Neurocognitive and behavioral evaluation

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Risk of Psychopathology and Neurocognitive Impairment in Leukemia Survivors

Resource links provided by NLM:


Further study details as provided by St. Jude Children's Research Hospital:

Primary Outcome Measures:
  • Neurocognitive assessment of attention, processing speed, and executive functions. [ Time Frame: Once, at least 5 years post ALL diagnosis and 2 years off treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • Family and parental stress as reported by primary caregiver. [ Time Frame: Once, at least 5 years post ALL diagnosis and 2 years off treatment ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 236
Study Start Date: January 2010
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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.
Other Name: Neurocognitive and behavioral evaluation

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 procedures during resting state and participation in attention and working memory tasks.

  Eligibility

Ages Eligible for Study:   8 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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).

Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01014195

Contacts
Contact: Kevin Krull, Ph.D 1-866-278-5833 info@stjude.org

Locations
United States, Tennessee
St. Jude Children's Research Hospital Recruiting
Memphis, Tennessee, United States, 38105
Contact: Kevin Krull, Ph.D    866-278-5833    info@stjude.org   
Sponsors and Collaborators
St. Jude Children's Research Hospital
Investigators
Principal Investigator: Kevin Krull, Ph.D St. Jude Children's Research Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT01014195     History of Changes
Other Study ID Numbers: NEULS, R01MH085849
Study First Received: November 13, 2009
Last Updated: August 8, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by St. Jude Children's Research Hospital:
Acute Lymphoblastic Leukemia
Neurocognitive function
ADHD
brain imaging
genetic polymorphisms
Psychopathology and neurocognitive Impairment in Leukemia Survivors

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on October 23, 2014