Brain Function in Young Patients Receiving Methotrexate for Acute Lymphoblastic Leukemia
Trial Purpose and Description
RATIONALE: Learning about the long-term effects of methotrexate on brain function may help doctors plan cancer treatment.
PURPOSE: This clinical trial is looking at brain function in young patients receiving methotrexate for acute lymphoblastic leukemia.
- 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.
- Identify host polymorphisms that predict an increased risk of neurocognitive dysfunction or acute neurotoxicity in these patients.
- Correlate neuropsychological outcome measures and the occurrence of acute neurotoxicity with host polymorphisms in these patients.
- 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.
- 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.
PROJECTED ACCRUAL: A total of 450 patients will be accrued for this study.
- 1 Year - 17 Years
- Diagnosis of acute lymphoblastic leukemia
- Enrolled on COG-AALL0434 or COG-AALL0232
- 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
- Pervasive developmental disability
- Seizure disorder
- Attention-deficit hyperactivity disorder or specific learning disability (e.g.,
- No sensory impairment (e.g., pre-existing uncorrectable vision impairment or
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No cranial radiation therapy
- Children's Oncology Group
- National Cancer Institute (NCI)
- January 2007
- Last Updated:
- April 5, 2011
- Study HIC#:
Clinicaltrials.gov ID: NCT00437060