Brain Function in Young Patients Receiving Methotrexate for Acute Lymphoblastic Leukemia

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Study of Neurocognitive Function in Children Treated for ALL

Conditions
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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

Intervention / Treatment
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* Procedure: Cognitive Assessment
* Procedure: Diffusion Tensor Imaging
* Other: Laboratory Biomarker Analysis
* Other: Pharmacological Study
* Procedure: Psychosocial Assessment and Care


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Ancillary/Correlative (neurocognitive assessment, biomarkers))<br>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<br>* Ancillary studies<br>Procedure: Diffusion Tensor Imaging<br>* Correlative studies<br>* Other names: DTI;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Other: Pharmacological Study<br>* Correlative studies<br>Procedure: Psychosocial Assessment and Care<br>* Ancillary studies<br>* Other names: Psychosocial Support;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in neurocognitive function by the Pediatric Quality of Life (PedQL) battery, Full Scale Intelligence Quotient (FSIQ) score | 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. | From baseline to up to 24 months | 
| Polymorphisms as predictors of neurocognitive dysfunction or acute neurotoxicity |  | Up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between neuropsychological outcomes and acute neurotoxicity |  | Up to 24 months |