Learning Impairments Among Survivors of Childhood Cancer

NCT00576472 | Completed Phase 4 Results

• 4 other identifiers: MEMFX2R01CA078957U01CA081445P30CA021765
• Study Type: interventional
• Target: 469
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Acute Lymphoblastic Leukemia; Brain Tumors

Keywords

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

Outcome Measures

Primary Outcomes (11)

• Brain White Matter Volume for Patients Versus Sibling Controls

  To compare the white matter volume of patients with those of sibling controls using MRI results captured between -1.8 and 42.36 months from study enrollment. Existing MRIs very close to enrollment were permissable for inclusion in this study.

  Enrollment to evaluation of MRI, on average 12.8 months.

• Brain White Matter Volume for Patients With Acute Lymphoblastic Leukemia Versus Brain Tumors

  To compare the white matter volume of Acute Lymphoblastic Leukemia (ALL) patients with those of patients with malignant brain tumors using MRI results captured between -1.8 and 42.36 months from study enrollment. Existing MRIs very close to enrollment were permissable for inclusion in this study.

  Enrollment to evaluation of MRI, on average 12.8 months.

• Brain White Matter Volume for Treatment Intensity Groups and Sibling Controls

  To compare the white matter volume of patients by treatment intensity groups (mild, moderate, and high) and sibling controls using MRI results captured between -1.8 and 42.36 months from study enrollment. Existing MRIs very close to enrollment were permissable for inclusion in this study.

  Enrollment to evaluation of MRI, on average 12.8 months.

• Change From Methylphenidate (MPH) Home Maintenance Phase Baseline to Completion of Phase as Measured by Conners' Teacher Rating Scale (CTRS: ADHD T Score)

  The Conners' Teacher Rating Scale- Revised (S) is a measure of the observed frequency of behaviors associated with ADHD. Twenty-eight questions are rated on a scale from 0 (not true at all) to 3 (very much true). Raw scores are converted to T scores using age and gender normative data. T scores have a mean of 50 ± 10 where higher scores are indicative of greater problems. Assessments were performed prior to beginning the Methylphenidate (MPH) Home Maintenance Phase(baseline) and upon completion of the phase. Phase completion ranged between 11.44 and 24.36 months.

  From beginning and at completion of Methylphenidate (MPH) Home Maintenance Phase, on average 16.3 months.

• Change From Maintenance Phase Baseline to Completion of Phase as Measured by Conners' Teacher Rating Scale (CTRS: Cognitive Problem T Score)

  The Conners' Teacher Rating Scale- Revised (S) is a measure of the observed frequency of behaviors associated with ADHD. Twenty-eight questions are rated on a scale from 0 (not true at all) to 3 (very much true). Raw scores are converted to T scores using age and gender normative data. T scores have a mean of 50 ± 10 where higher scores are indicative of greater problems. Assessments were performed prior to beginning the Home Therapy Phase (baseline) and upon completion of the phase. Phase completion ranged between 11.44 to 24.36 months

  From beginning and at completion of home maintenance phase, on average 16.3 months.

• Change From Maintenance Phase Baseline to Completion of Phase as Measured by Conners' Parent Rating Scale (CPRS: ADHD T Score)

  The Conners' Teacher Rating Scale- Revised (S) is a measure of the observed frequency of behaviors associated with ADHD. Twenty-seven questions are rated on a scale from 0 (not true at all) to 3 (very much true). Raw scores are converted to T scores using age and gender normative data. T scores have a mean of 50 ± 10 where higher scores are indicative of greater problems. Assessments were performed prior to beginning the Home Therapy Phase (baseline) and upon completion of the phase. Phase completion ranged between 11.44 and 24.36 months.

  From beginning and at completion of home maintenance phase, on average 16.3 months.

• Change From Maintenance Phase Baseline to Completion of Phase as Measured by Conner's Parent Rating Scale (CPRS: Cognitive Problem T Score)

  The Conners' Teacher Rating Scale- Revised (S) is a measure of the observed frequency of behaviors associated with ADHD. Twenty-seven questions are rated on a scale from 0 (not true at all) to 3 (very much true). Raw scores are converted to T scores using age and gender normative data. T scores have a mean of 50 ± 10 where higher scores are indicative of greater problems. Assessments were performed prior to beginning the Home Therapy Phase (baseline) and upon completion of the phase. Phase completion ranged between 11.44 to 24.36 months

  From beginning and at completion of home maintenance phase, on average 16.3 months.

• Change From Maintenance Phase Baseline to Completion of Phase as Measured by Social Skill Rating System (SSRS-P)

  The Social Skills Rating System- Parent Version (SSRS-P) is a parent rating scale of social behaviors in reference to typically developing children. Thirty eight questions are rated 0 (Never) to 3 (very often). The social skills score is norm-referenced with a mean of 100±15 where a higher score is indicative of better skills. Assessments were performed prior to beginning the Home Therapy Phase (baseline) and upon completion of the phase. Phase completion ranged between 11.44 to 24.36 months

  From beginning and at completion of home maintenance phase, on average 16.3 months.

• Change From Maintenance Phase Baseline to Completion of Phase as Measured by Wechsler Individual Achievement Test (WIAT) Reading: Composite Standard Score

  The Wechsler Individual Achievement Test is an examiner administered measure of academic skills. The Reading Composite consists of Basic Reading (single word reading) and Reading Comprehension. Raw scores are converted to standard scores with a mean of 100±15 where higher scores indicate better performance. Assessments were performed prior to beginning the Home Therapy Phase (baseline) and upon completion of the phase. Phase completion ranged between 11.44 to 24.36 months

  From beginning and at completion of home maintenance phase, on average 16.3 months.

• Change From Maintenance Phase Baseline to Completion of Phase as Measured by Wechsler Individual Achievement Test (WIAT) Spelling: Standard Score

  The Wechsler Individual Achievement Test is an examiner administered measure of academic skills. The Spelling score assesses the child's ability to spell words to dictation. Raw scores are converted to standard scores with a mean of 100±15 where higher scores indicate better performance. Assessments were performed prior to beginning the Home Therapy Phase (baseline) and upon completion of the phase. Phase completion ranged between 11.44 to 24.36 months

  From beginning and after completion of home maintenance phase, on average 16.3 months.

• Change From Maintenance Phase Baseline to Completion of Phase as Measured by Wechsler Individual Achievement Test (WIAT) Math: Composite Standard Score

  The Wechsler Individual Achievement Test is an examiner administered measure of academic skills. The Math Composite score assesses the child's ability to solve calculation problems (Numerical Operations) and solve applied, word problems (Math Reasoning). Raw scores are converted to standard scores with a mean of 100±15 where higher scores indicate better performance. Assessments were performed prior to beginning the Home Therapy Phase (baseline) and upon completion of the phase. Phase completion ranged between 11.44 to 24.36 months

  From beginning and after completion of home maintenance phase, on average 16.3 months.

Secondary Outcomes (23)

• Best Weekly Score Measured by Conners' Parent Rating Scale (CPRS: ADHD T Score) During the 3-week Home Crossover Phase.

  weekly during 3-week home crossover phase

• Effectiveness of MPH in Enhancing Classroom Attentiveness, Academic Productivity, and Social Behavior Measured by The Conners' Parent Rating Scale (CPRS) Cognitive Problem/Inattention Scale.

  Evaluated at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks.

• Effectiveness of MPH in Enhancing Classroom Attentiveness, Academic Productivity, and Social Behavior Measured by The Conners' Parent Rating Scale (CPRS) Hyperactivity Scale.

  Evaluated at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks.

• Effectiveness of MPH in Enhancing Classroom Attentiveness, Academic Productivity, and Social Behavior Measured by The Conners' Parent Rating Scale (CPRS) ADHD Index.

  Evaluated at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks.

• Effectiveness of MPH in Enhancing Classroom Attentiveness, Academic Productivity, and Social Behavior Measured by The Conners' Teacher Rating Scale (CTRS) Cognitive Problem/Inattention Scale.

  Evaluated at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks.

Study Arms (1)

Treatment

EXPERIMENTAL

Drug: Methylphenidate

Interventions

Methylphenidate DRUG

Please see detailed description for dosing information and study design.

Treatment

Eligibility Criteria

• Age: 6 Years - 18 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Related Publications (5)

• 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. doi: 10.1200/JCO.2004.04.128.

  PMID: 15570081 BACKGROUND

• 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. doi: 10.1002/cncr.21679.

  PMID: 16411228 BACKGROUND

• 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. doi: 10.1093/jpepsy/jsm045. Epub 2007 Jun 14.

  PMID: 17569711 BACKGROUND

• 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. doi: 10.1093/jpepsy/jsm063. Epub 2007 Oct 12.

  PMID: 17933846 BACKGROUND

• Conklin HM, Lawford J, Jasper BW, Morris EB, Howard SC, Ogg SW, Wu S, Xiong X, Khan RB. Side effects of methylphenidate in childhood cancer survivors: a randomized placebo-controlled trial. Pediatrics. 2009 Jul;124(1):226-33. doi: 10.1542/peds.2008-1855.

  PMID: 19564304 DERIVED

Related Links

• St. Jude Children's Research Hospital

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Brain Neoplasms

Interventions

Methylphenidate

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Heather Conklin PhD
• Organization: St. Jude Children's Research Hospital

info@stjude.org

1-866-278-5833

Study Officials

• Heather M Conklin

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2007
• First Posted: December 19, 2007
• Study Start: January 1, 2000
• Primary Completion: March 1, 2010
• Study Completion: March 1, 2010
• Last Updated: May 30, 2017
• Results First Posted: April 16, 2012

Record last verified: 2013-02

Locations

US (3)