Trial Information

A Study of Neurocognitive Function in Children Treated for ALL

OBJECTIVES:

- 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.