Learning Impairments Among Survivors of Childhood Cancer

NCT ID: NCT00576472

Last Updated: 2017-05-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 469 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2000-01-31
• Study Completion Date: 2010-03-31

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.

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.

Conditions

Acute Lymphoblastic Leukemia; Brain Tumors

Study Design

• Intervention Model: CROSSOVER
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: QUADRUPLE

Study Groups

Treatment

Group Type: EXPERIMENTAL

Methylphenidate

Intervention Type: DRUG

Please see detailed description for dosing information and study design.

Interventions

Methylphenidate

Please see detailed description for dosing information and study design.

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

St. Jude Children's Research Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Heather M Conklin

Role: PRINCIPAL_INVESTIGATOR

St. Jude Children's Research Hospital

Locations

Duke University Medical Center

Durham, North Carolina, United States

Medical University of South Carolina

Charleston, South Carolina, United States

St. Jude Children's Research Hospital

Memphis, Tennessee, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 15570081 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 16411228 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 17569711 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 17933846 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 19564304 (View on PubMed)

Related Links

http://www.stjude.org

St. Jude Children's Research Hospital

Other Identifiers

R01CA078957

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01CA081445

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA021765

Identifier Type: NIH

Identifier Source: secondary_id

View Link

MEMFX2

Identifier Type: -

Identifier Source: org_study_id