Brain Function in Young Patients Receiving Methotrexate for Acute Lymphoblastic Leukemia

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Children's Oncology Group
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00437060
First received: February 15, 2007
Last updated: February 21, 2014
Last verified: February 2014

February 15, 2007
February 21, 2014
January 2007
June 2015   (final data collection date for primary outcome measure)
  • Change in neurocognitive function by the Pediatric Quality of Life (PedQL) battery, Full Scale Intelligence Quotient (FSIQ) score [ Time Frame: From baseline to up to 24 months ] [ Designated as safety issue: No ]
    Vocabulary and Block Design, subtests of the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III), Wechsler Children Intelligence Scale (WISC-IV) and Wechsler Adult Intelligence Scale (WAIS-III) (based on age) will be used to estimate FSIQ, using the tables provided by Sattler.
  • Polymorphisms as predictors of neurocognitive dysfunction or acute neurotoxicity [ Time Frame: Up to 24 months ] [ Designated as safety issue: No ]
Not Provided
Complete list of historical versions of study NCT00437060 on ClinicalTrials.gov Archive Site
Correlation between neuropsychological outcomes and acute neurotoxicity [ Time Frame: Up to 24 months ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
Not Provided
 
Brain Function in Young Patients Receiving Methotrexate for Acute Lymphoblastic Leukemia
A Study of Neurocognitive Function in Children Treated for ALL

This clinical trial is looking at brain function in young patients receiving methotrexate for acute lymphoblastic leukemia. Learning about the long-term effects of methotrexate on brain function may help doctors plan cancer treatment.

OBJECTIVES:

I. Determine the neuropsychological function in children with acute lymphoblastic leukemia treated with either high-dose methotrexate or escalating-dose methotrexate in the absence of cranial radiation and nelarabine.

II. Identify host polymorphisms that predict an increased risk of neurocognitive dysfunction or acute neurotoxicity in these patients.

III. Correlate neuropsychological outcome measures and the occurrence of acute neurotoxicity with host polymorphisms in these patients.

IV. Measure concentrations of 5-methyltetrahydrofolate, homocysteine, Ado, S-adenosylmethionine, S-adenosylhomocysteine, and other potentially relevant compounds in serum and cerebrospinal fluid during interim maintenance therapy with low- or high-dose methotrexate regimens, respectively, and correlate these endpoints with the occurrence of acute neurologic toxicity and long-term neurocognitive dysfunction in these patients.

V. Determine whether or not diffusion tensor imaging will identify areas of selective vulnerability in CNS and provide an imaging modality that predicts and/or correlates with neuropsychological outcome.

OUTLINE: This is a prospective, cohort, multicenter study.

Patients complete neurocognitive tests to assess thinking, memory, attention, and concentration. The baseline test is administered during the consolidation phase of chemotherapy and further tests are done at 1 year from baseline and 1 year after* the completion of study therapy.

Patients undergo blood and cerebrospinal fluid collection periodically for biomarker, genotypic polymorphisms, and pharmacokinetic analysis. Patients undergo MRI diffusion-tensor imaging to correlate imaging with neuropsychological outcomes.

NOTE: * Within 8 months to 24 months after the completion of study therapy for patients on AALL0232.

Observational
Observational Model: Cohort
Time Perspective: Prospective
Not Provided
Retention:   Samples With DNA
Description:

blood and cerebrospinal fluid

Non-Probability Sample

Patients with a diagnosis of acute lymphoblastic leukemia meeting other criteria.

  • B-cell Childhood Acute Lymphoblastic Leukemia
  • Cognitive/Functional Effects
  • Long-term Effects Secondary to Cancer Therapy in Children
  • Neurotoxicity
  • Psychosocial Effects of Cancer and Its Treatment
  • T-cell Childhood Acute Lymphoblastic Leukemia
  • Untreated Childhood Acute Lymphoblastic Leukemia
  • Procedure: cognitive assessment
    Ancillary studies
  • Procedure: psychosocial assessment and care
    Ancillary studies
    Other Names:
    • psychosocial assessment
    • psychosocial assessment/care
    • psychosocial care
    • psychosocial care/assessment
    • psychosocial studies
  • Procedure: diffusion tensor imaging
    Correlative studies
  • Other: laboratory biomarker analysis
    Correlative studies
  • Other: pharmacological study
    Correlative studies
    Other Name: pharmacological studies
Ancillary/Correlative (neurocognitive assessment, biomarkers))

Patients complete neurocognitive tests to assess thinking, memory, attention, and concentration. The baseline test is administered during the consolidation phase of chemotherapy and further tests are done at 1 year from baseline and 1 year after* the completion of study therapy.

Patients undergo blood and cerebrospinal fluid collection periodically for biomarker, genotypic polymorphisms, and pharmacokinetic analysis. Patients undergo MRI diffusion-tensor imaging to correlate imaging with neuropsychological outcomes.

Interventions:
  • Procedure: cognitive assessment
  • Procedure: psychosocial assessment and care
  • Procedure: diffusion tensor imaging
  • Other: laboratory biomarker analysis
  • Other: pharmacological study
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
225
Not Provided
June 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Diagnosis of acute lymphoblastic leukemia
  • Enrolled on COG-AALL0434 (Cohort #1 only) or COG-AALL0232 (Cohorts #1 and #2)

    • Patients must have received either high-dose methotrexate or escalating-dose methotrexate during interim maintenance.
  • No CNS-3 disease
  • Patients must enroll within 8-24 months after completion of therapy on COG-AALL0232 and no evidence of relapsed or secondary malignancy
  • No known significant neurodevelopmental disability unrelated to cancer diagnosis including, but not limited to, any of the following:

    • Down syndrome
    • Fragile X mental retardation
    • Autism
    • Pervasive developmental disability
    • Seizure disorder
  • Attention-deficit hyperactivity disorder or specific learning disability (e.g., dyslexia) allowed
  • No sensory impairment (e.g., pre-existing uncorrectable vision impairment or deafness)
  • No cranial radiation therapy
Both
1 Year to 17 Years
No
United States,   Australia,   Canada,   New Zealand
 
NCT00437060
AALL06N1, NCI-2009-00315, CDR0000528920, AALL06N1, AALL06N1, U10CA098543
Yes
Children's Oncology Group
Children's Oncology Group
National Cancer Institute (NCI)
Principal Investigator: Naomi Winick, MD Children's Oncology Group
Children's Oncology Group
February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP