Brain Function in Young Patients Receiving Methotrexate for Acute Lymphoblastic Leukemia

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00437060
First received: February 15, 2007
Last updated: August 20, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention
B-cell Childhood Acute Lymphoblastic Leukemia
Cognitive/Functional Effects
Long-term Effects Secondary to Cancer Therapy in Children
Neurotoxicity
Psychosocial Effects of Cancer and Its Treatment
T-cell Childhood Acute Lymphoblastic Leukemia
Untreated Childhood Acute Lymphoblastic Leukemia
Procedure: cognitive assessment
Procedure: psychosocial assessment and care
Procedure: diffusion tensor imaging
Other: laboratory biomarker analysis
Other: pharmacological study

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: A Study of Neurocognitive Function in Children Treated for ALL

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Change in neurocognitive function by the Pediatric Quality of Life (PedQL) battery, Full Scale Intelligence Quotient (FSIQ) score [ Time Frame: From baseline to up to 24 months ] [ Designated as safety issue: No ]
    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.

  • Polymorphisms as predictors of neurocognitive dysfunction or acute neurotoxicity [ Time Frame: Up to 24 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Correlation between neuropsychological outcomes and acute neurotoxicity [ Time Frame: Up to 24 months ] [ Designated as safety issue: Yes ]

Biospecimen Retention:   Samples With DNA

blood and cerebrospinal fluid


Enrollment: 249
Study Start Date: January 2007
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Ancillary/Correlative (neurocognitive assessment, biomarkers))

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
Ancillary studies
Procedure: psychosocial assessment and care
Ancillary studies
Other Names:
  • psychosocial assessment
  • psychosocial assessment/care
  • psychosocial care
  • psychosocial care/assessment
  • psychosocial studies
Procedure: diffusion tensor imaging
Correlative studies
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Detailed 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.

  Eligibility

Ages Eligible for Study:   1 Year to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Patients with a diagnosis of acute lymphoblastic leukemia meeting other criteria.

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00437060

  Show 112 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Principal Investigator: Naomi Winick, MD Children's Oncology Group
  More Information

No publications provided

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00437060     History of Changes
Other Study ID Numbers: AALL06N1, NCI-2009-00315, CDR0000528920, AALL06N1, AALL06N1, U10CA098543
Study First Received: February 15, 2007
Last Updated: August 20, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neurotoxicity Syndromes
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Nervous System Diseases
Poisoning
Chemically-Induced Disorders

ClinicalTrials.gov processed this record on August 26, 2014