Brain Function in Young Patients Receiving Methotrexate for Acute Lymphoblastic Leukemia

Completed

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

• Registration Number: NCT00437060
• Lead Sponsor: Children's Oncology Group

Brief Summary

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.

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.

Study Timeline

• Study Start: 2007-01
• Study First Submitted: 2007-02-15
• Study First Submitted QC: 2007-02-15
• Study First Posted: 2007-02-19
• Primary Completion: 2015-09
• Status Verified: 2017-07
• Last Update Submitted: 2017-07-19
• Last Update Posted: 2017-07-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 233

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Polymorphisms as predictors of neurocognitive dysfunction or acute neurotoxicity	Up to 24 months
Change in neurocognitive function by the Pediatric Quality of Life (PedQL) battery, Full Scale Intelligence Quotient (FSIQ) score	From baseline to up to 24 months	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.

Secondary Outcome Measures

Name	Time	Method
Correlation between neuropsychological outcomes and acute neurotoxicity	Up to 24 months

Trial Locations

Locations (111)

Children's Hospital of Alabama; 🇺🇸 Birmingham, Alabama, United States

University of Alabama at Birmingham Cancer Center; 🇺🇸 Birmingham, Alabama, United States

Southern California Permanente Medical Group; 🇺🇸 Downey, California, United States

Miller Children's and Women's Hospital Long Beach; 🇺🇸 Long Beach, California, United States

Children's Hospital Los Angeles; 🇺🇸 Los Angeles, California, United States

Cedars-Sinai Medical Center; 🇺🇸 Los Angeles, California, United States

Children's Hospital Central California; 🇺🇸 Madera, California, United States

Children's Hospital of Orange County; 🇺🇸 Orange, California, United States

Lucile Packard Children's Hospital Stanford University; 🇺🇸 Palo Alto, California, United States

Rady Children's Hospital - San Diego; 🇺🇸 San Diego, California, United States

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