Brain Function in Young Patients Receiving Methotrexate for Acute Lymphoblastic Leukemia
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ClinicalTrials.gov Identifier: NCT00437060 |
Recruitment Status
:
Completed
First Posted
: February 19, 2007
Last Update Posted
: July 21, 2017
|
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Condition or disease | Intervention/treatment |
---|---|
Childhood B Acute Lymphoblastic Leukemia Childhood T Acute Lymphoblastic Leukemia Cognitive Side Effects of Cancer Therapy Long-Term Effects Secondary to Cancer Therapy in Children Neurotoxicity Syndrome Psychological Impact of Cancer Untreated Childhood Acute Lymphoblastic Leukemia | Procedure: Cognitive Assessment Procedure: Diffusion Tensor Imaging Other: Laboratory Biomarker Analysis Other: Pharmacological Study Procedure: Psychosocial Assessment and Care |
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.
Study Type : | Observational |
Actual Enrollment : | 233 participants |
Observational Model: | Cohort |
Time Perspective: | Prospective |
Official Title: | A Study of Neurocognitive Function in Children Treated for ALL |
Study Start Date : | January 2007 |
Actual Primary Completion Date : | September 2015 |

Group/Cohort | Intervention/treatment |
---|---|
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. |
Procedure: Cognitive Assessment
Ancillary studies
Procedure: Diffusion Tensor Imaging
Correlative studies
Other Name: DTI
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Pharmacological Study
Correlative studies
Procedure: Psychosocial Assessment and Care
Ancillary studies
Other Names:
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- 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 ]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 ]
- Correlation between neuropsychological outcomes and acute neurotoxicity [ Time Frame: Up to 24 months ]
Biospecimen Retention: Samples Without DNA

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Ages Eligible for Study: | 1 Year to 17 Years (Child) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Sampling Method: | Non-Probability Sample |
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
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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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00437060

Principal Investigator: | Naomi Winick | Children's Oncology Group |
Responsible Party: | Children's Oncology Group |
ClinicalTrials.gov Identifier: | NCT00437060 History of Changes |
Other Study ID Numbers: |
AALL06N1 NCI-2009-00315 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) CDR0000528920 AALL06N1 ( Other Identifier: Childrens Oncology Group ) AALL06N1 ( Other Identifier: CTEP ) U10CA098543 ( U.S. NIH Grant/Contract ) |
First Posted: | February 19, 2007 Key Record Dates |
Last Update Posted: | July 21, 2017 |
Last Verified: | July 2017 |
Additional relevant MeSH terms:
Neurotoxicity Syndromes Leukemia Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Lymphoid Precursor T-Cell Lymphoblastic Leukemia-Lymphoma Neoplasms by Histologic Type Neoplasms |
Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Nervous System Diseases Poisoning Chemically-Induced Disorders |