Brain Function in Young Patients Receiving Methotrexate for Acute Lymphoblastic Leukemia

Children's Oncology Group

Status: Completed

Conditions: Untreated Childhood Acute Lymphoblastic Leukemia; Psychological Impact of Cancer; Long-Term Effects Secondary to Cancer Therapy in Children; Cognitive Side Effects of Cancer Therapy; Childhood B Acute Lymphoblastic Leukemia; Neurotoxicity Syndrome; Childhood T Acute Lymphoblastic Leukemia

Treatments: Procedure: Psychosocial Assessment and Care; Procedure: Diffusion Tensor Imaging; Procedure: Cognitive Assessment; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study

Study type: Observational

Funder types: NETWORK; NIH

Identifiers

NCT00437060

AALL06N1 (Other Identifier)

U10CA098543 (U.S. NIH Grant/Contract)

NCI-2009-00315 (Registry Identifier)

CDR0000528920

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 233 patients

Sex: All

Ages: 1 to 17 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

233 participants in 1 patient group

Ancillary/Correlative (neurocognitive assessment, biomarkers))

Description:

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.

Treatment:

Other: Laboratory Biomarker Analysis

Procedure: Psychosocial Assessment and Care

Procedure: Diffusion Tensor Imaging

Procedure: Cognitive Assessment

Other: Pharmacological Study