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for people ages 1–17
at San Francisco, California and other locations
study started



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.

Official Title

A Study of Neurocognitive Function in Children Treated for ALL



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.


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


For people ages 1–17

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


  • Children's Hospital Central California
    Madera, California, 93636-8762, United States
  • Lucile Packard Children's Hospital Stanford University
    Palo Alto, California, 94304, United States
  • Children's Hospital Los Angeles
    Los Angeles, California, 90027, United States
  • Cedars-Sinai Medical Center
    Los Angeles, California, 90048, United States
  • Southern California Permanente Medical Group
    Downey, California, 90242, United States
  • Miller Children's and Women's Hospital Long Beach
    Long Beach, California, 90806, United States
  • Children's Hospital of Orange County
    Orange, California, 92868, United States
  • Nevada Cancer Research Foundation CCOP
    Las Vegas, Nevada, 89106, United States


in progress, not accepting new patients
Start Date
Children's Oncology Group
Study Type
Last Updated
April 2016