Brain Function in Young Patients Receiving Methotrexate for Acute Lymphoblastic Leukemia

Study Description

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

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.

Condition or disease	Intervention/treatment
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	Procedure: Cognitive Assessment; Procedure: Diffusion Tensor Imaging; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Procedure: Psychosocial Assessment and Care

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 Design

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Study Type :	Observational
Actual Enrollment :	233 participants
Observational Model:	Cohort
Time Perspective:	Prospective
Official Title:	A Study of Neurocognitive Function in Children Treated for ALL
Study Start Date :	January 2007
Actual Primary Completion Date :	September 2015

Groups and Cohorts

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Group/Cohort

Intervention/treatment

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: Diffusion Tensor Imaging; Correlative studies; Other Name: DTI Other: Laboratory Biomarker Analysis; Correlative studies Other: Pharmacological Study; Correlative studies Procedure: Psychosocial Assessment and Care; Ancillary studies; Other Names: Psychosocial Assessment; Psychosocial Care; Psychosocial Care/Assessment; Psychosocial Studies; Psychosocial Support

Outcome Measures

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Primary Outcome Measures :

1. 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 ]
   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.
2. Polymorphisms as predictors of neurocognitive dysfunction or acute neurotoxicity [ Time Frame: Up to 24 months ]

Secondary Outcome Measures :

1. Correlation between neuropsychological outcomes and acute neurotoxicity [ Time Frame: Up to 24 months ]

Biospecimen Retention:   Samples Without DNA

blood and cerebrospinal fluid

Eligibility Criteria

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	1 Year to 17 Years (Child)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No
Sampling Method:	Non-Probability Sample

Study Population

Patients with newly diagnosed 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

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

  Show 112 Study Locations

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators

Principal Investigator:	Naomi Winick	Children's Oncology Group

More Information

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Children's Oncology Group
ClinicalTrials.gov Identifier:	NCT00437060 History of Changes
Other Study ID Numbers:	AALL06N1; NCI-2009-00315 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); CDR0000528920; AALL06N1 ( Other Identifier: Childrens Oncology Group ); AALL06N1 ( Other Identifier: CTEP ); U10CA098543 ( U.S. NIH Grant/Contract )
First Posted:	February 19, 2007
Last Update Posted:	July 21, 2017
Last Verified:	July 2017

Additional relevant MeSH terms:

Neurotoxicity Syndromes; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Precursor T-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