Learning Impairments Among Survivors of Childhood Cancer - Full Text View

Sponsors and Collaborators:	St. Jude Children's Research Hospital National Cancer Institute (NCI)
Information provided by:	St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier:	NCT00576472

Purpose

Children surviving some types of cancer have a higher risk of developing learning problems after cancer treatment than do children who have not had cancer or its treatment. Cancer treatment may cause problems with learning, attention, and memory. The purpose of this study is to identify brain changes that may underlie learning problems in cancer survivors and investigate whether methylphenidate (a stimulant medication) may reduce these problems.

Subjects who have had treatment for acute lymphoblastic leukemia (ALL) or a brain tumor will be asked to take part in this research study. Siblings of some subjects will also be asked to take part, so that their results can be compared with those of children who have had cancer treatment. We hypothesize that children receiving more aggressive therapy will have lower white matter brain volumes and these volumes will be significantly lower than age-matched siblings. We also hypothesize that children who take methylphenidate will show improvements on teacher and parent report measures of attention and social skills.

Condition	Intervention	Phase
Acute Lymphoblastic Leukemia Brain Tumors	Drug: Methylphenidate	Phase IV

MedlinePlus related topics: Brain Cancer Cancer Childhood Brain Tumors Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood

Drug Information available for: Methylphenidate hydrochloride Methylphenidate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Supportive Care, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Crossover Assignment, Efficacy Study
Official Title:	Learning Impairments Among Survivors of Childhood Cancer

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

Primary Outcome Measures:

Child performance on a measure of academic skills (Wechsler Individual Achievement Test) [ Time Frame: Conducted at screening and at the end of the 12-month open-label trial ] [ Designated as safety issue: No ]
Cross sectional analysis of white matter brain volume based on structural neuroimaging [ Time Frame: Conducted at screening and the end of the 12-month open-label trial ] [ Designated as safety issue: No ]
Parent and teacher report on a measure of the child's attention abilities (Conners' Report Forms) and a measure of social skills (Social Skills Rating System) [ Time Frame: Conducted at 1, 3, 6 and 12 months during the open-label trial ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

A laboratory measure of sustained attention (Conners' Continuous Performance Test) and a measure of verbal learning (California Verbal Learning Test). [ Time Frame: Conducted during the two-day in the clinic trial. ] [ Designated as safety issue: No ]
Measure of stimulant medication side effects (Barkley's Side Effects Rating Scale). [ Time Frame: Conducted during the two-day in clinic trial. ] [ Designated as safety issue: Yes ]
Measure of stimulant medication side effects (Barkley's Side Effects Rating Scale). [ Time Frame: Gathered during the three-week home-crossover trial ] [ Designated as safety issue: Yes ]
Parent and teacher report on a measure of child attention abilities (Conners' Report Forms) and a measure of social skills (Social Skills Rating System) [ Time Frame: Gathered during the three-week home-crossover trial ] [ Designated as safety issue: No ]
Statistical correlations among white matter volumes on neuroimaging and measures of attention and learning [ Time Frame: After study completion ] [ Designated as safety issue: No ]
Statistical correlations among white matter volumes on neuroimaging and indicies of medication response [ Time Frame: After study completion ] [ Designated as safety issue: No ]

Estimated Enrollment:	600
Study Start Date:	January 2000
Estimated Study Completion Date:	June 2009
Estimated Primary Completion Date:	June 2009 (Final data collection date for primary outcome measure)

Intervention Details:

Please see detailed description for dosing information and study design.

Detailed Description:

This study is a multi-phase, multi-site methylphenidate (MPH) trial in childhood cancer survivors. Study participants that meet inclusion and exclusion criteria are screened to ensure that they have adequate global cognitive functioning (IQ > 50) and have academic and attention difficulties that might be managed with MPH. Following the screening phase, qualifying participants take part in a two-day, in-clinic, double-blind, cross-over trial during which they receive MPH (0.6 mg/kg; maximum dose, 20 mg) and placebo (inert substance) in a randomly assigned order. Patients who do not have a significant adverse reaction during the two-day trial go on to participate in a randomized, double-blind, placebo-controlled, three-week home cross-over trial consisting of placebo, low-dose MPH (0.3 mg/kg; maximum dose, 10 mg bid), and moderate-dose MPH (0.6 mg/kg; maximum dose, 20 mg bid). Patients are then selected for participation in a 12-month open-label MPH trial if they show improvement over placebo on a parent and/or teacher rating of attention during the three-week home cross-over trial. The 12-month open-label MPH trial includes individually titrated MPH dosing to maximize clinical benefit, monthly monitoring of side effects and regular acquisition of parent and teacher ratings of attention and behavior. Laboratory measures of intellectual function, attention and memory are conducted at the end of the 12-month trial.

Eligibility

Ages Eligible for Study:	6 Years to 18 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Age: 6 to 18 years old.
Active subject at St. Jude Children's Research Hospital, or is an age-matched sibling control subject.
If a subject, received treatment for brain tumor or ALL with either radiation therapy and/or chemotherapy directed at the brain.
If a subject, at least 12 months post-completion of antineoplastic therapies
If a subject, no evidence of malignancy, or continuously stable disease since completion of therapy
English as a primary language
Informed consent

Exclusion Criteria:

Glaucoma
Patient or immediate family member with a history of Tourette's syndrome
Current antidepressant, anxiolytic, antipsychotic or stimulant therapy
History of substance abuse
Recent history of uncontrolled seizures
Uncorrected hypothyroidism
Previously or currently randomized on COGRM1 intervention arm
Previously diagnosed with ADHD, or, if a patient, diagnosed with ADHD prior to diagnosis of malignancy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00576472

Contacts

Contact: Heather M Conklin, PhD

1-866-278-5833

info@stjude.org

Locations

United States, North Carolina
Duke University Medical Center	Terminated
Durham, North Carolina, United States, 27710
United States, South Carolina
Medical University of South Carolina	Terminated
Charleston, South Carolina, United States, 29425
United States, Tennessee
St. Jude Children's Research Hospital	Recruiting
Memphis, Tennessee, United States, 38105
Contact: Heather M Conklin, PhD

Sponsors and Collaborators

St. Jude Children's Research Hospital

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Heather M Conklin

St. Jude Children's Research Hospital

More Information

St. Jude Children's Research Hospital This link exits the ClinicalTrials.gov site

Publications:

Mulhern RK, Khan RB, Kaplan S, Helton S, Christensen R, Bonner M, Brown R, Xiong X, Wu S, Gururangan S, Reddick WE. Short-term efficacy of methylphenidate: a randomized, double-blind, placebo-controlled trial among survivors of childhood cancer. J Clin Oncol. 2004 Dec 1;22(23):4795-803. Erratum in: J Clin Oncol. 2005 Jan 1;23(1):248.

Reddick WE, Shan ZY, Glass JO, Helton S, Xiong X, Wu S, Bonner MJ, Howard SC, Christensen R, Khan RB, Pui CH, Mulhern RK. Smaller white-matter volumes are associated with larger deficits in attention and learning among long-term survivors of acute lymphoblastic leukemia. Cancer. 2006 Feb 15;106(4):941-9.

Conklin HM, Khan RB, Reddick WE, Helton S, Brown R, Howard SC, Bonner M, Christensen R, Wu S, Xiong X, Mulhern RK. Acute neurocognitive response to methylphenidate among survivors of childhood cancer: a randomized, double-blind, cross-over trial. J Pediatr Psychol. 2007 Oct;32(9):1127-39. Epub 2007 Jun 14.

Reeves CB, Palmer S, Gross AM, Simonian SJ, Taylor L, Willingham E, Mulhern RK. Brief report: sluggish cognitive tempo among pediatric survivors of acute lymphoblastic leukemia. J Pediatr Psychol. 2007 Oct;32(9):1050-4. Epub 2007 Oct 12.

Responsible Party:	St. Jude Children's Research Hospital ( Heather M Conklin, PhD / Principal Investigator )
Study ID Numbers:	MEMFX2, RO1-CA078957, UO1-CA81445, P30-CA2Z1765
Study First Received:	December 17, 2007
Last Updated:	January 6, 2009
ClinicalTrials.gov Identifier:	NCT00576472
Health Authority:	United States: Institutional Review Board

Keywords provided by St. Jude Children's Research Hospital:

Brain Tumor, Acute Lymphoblastic Leukemia, Methylphenidate, Cognitive Late Effects

Study placed in the following topic categories:

Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immunoproliferative Disorders
Central Nervous System Diseases
Methylphenidate
Central Nervous System Neoplasms
Brain Diseases

Leukemia
Brain Neoplasms
Lymphatic Diseases
Dopamine
Lymphoproliferative Disorders
Lymphoma
Nervous System Neoplasms

Additional relevant MeSH terms:

Dopamine Uptake Inhibitors
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Neoplasms by Histologic Type
Immune System Diseases
Molecular Mechanisms of Pharmacological Action
Nervous System Diseases
Physiological Effects of Drugs

Central Nervous System Stimulants
Pharmacologic Actions
Neoplasms
Neoplasms by Site
Therapeutic Uses
Dopamine Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on January 16, 2009