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

  Hide Study Locations
Locations
United States, Alabama
Children's Hospital of Alabama
Birmingham, Alabama, United States, 35233
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, California
Children's Oncology Group
Arcadia, California, United States, 91006-3776
Southern California Permanente Medical Group
Downey, California, United States, 90242
Miller Children's Hospital
Long Beach, California, United States, 90806
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027
Cedars-Sinai Medical Center
Los Angeles, California, United States, 90048
Children's Hospital Central California
Madera, California, United States, 93636-8762
Childrens Hospital of Orange County
Orange, California, United States, 92868-3874
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, United States, 94304
Rady Children's Hospital - San Diego
San Diego, California, United States, 92123
University of California San Francisco Medical Center-Parnassus
San Francisco, California, United States, 94143
United States, Colorado
Children's Hospital Colorado
Aurora, Colorado, United States, 80045
United States, Connecticut
Connecticut Children's Medical Center
Hartford, Connecticut, United States, 06106
Yale University
New Haven, Connecticut, United States, 06520
United States, Delaware
Alfred I duPont Hospital for Children
Wilmington, Delaware, United States, 19803
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010
Lombardi Comprehensive Cancer Center at Georgetown University
Washington, District of Columbia, United States, 20057
United States, Florida
Broward Health Medical Center
Fort Lauderdale, Florida, United States, 33316
Golisano Children's Hospital of Southwest Florida
Fort Myers, Florida, United States, 33908
Memorial Healthcare System - Joe DiMaggio Children's Hospital
Hollywood, Florida, United States, 33021
Nemours Children's Clinic - Jacksonville
Jacksonville, Florida, United States, 32207-8426
Miami Children's Hospital
Miami, Florida, United States, 33155
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, United States, 33136
Nemours Children's Hospital
Orlando, Florida, United States, 32827
Nemours Children's Clinic - Pensacola
Pensacola, Florida, United States, 32504
All Children's Hospital
Saint Petersburg, Florida, United States, 33701
Saint Joseph Children's Hospital of Tampa
Tampa, Florida, United States, 33607
Saint Mary's Hospital
West Palm Beach, Florida, United States, 33407
United States, Georgia
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia, United States, 30322
United States, Hawaii
University of Hawaii
Honolulu, Hawaii, United States, 96813
United States, Illinois
Lurie Children's Hospital-Chicago
Chicago, Illinois, United States, 60614
University of Illinois
Chicago, Illinois, United States, 60612
Advocate Children's Hospital-Oak Lawn
Oak Lawn, Illinois, United States, 60453
United States, Indiana
Riley Hospital for Children
Indianapolis, Indiana, United States, 46202
Saint Vincent Hospital and Health Services
Indianapolis, Indiana, United States, 46260
United States, Iowa
Blank Children's Hospital
Des Moines, Iowa, United States, 50309
United States, Kentucky
University of Kentucky
Lexington, Kentucky, United States, 40536
United States, Maryland
Sinai Hospital of Baltimore
Baltimore, Maryland, United States, 21215
United States, Massachusetts
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, United States, 02114
University of Massachusetts Medical School
Worcester, Massachusetts, United States, 01655
United States, Michigan
C S Mott Children's Hospital
Ann Arbor, Michigan, United States, 48109
Wayne State University-Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
Saint John Hospital and Medical Center
Detroit, Michigan, United States, 48236
Hurley Medical Center
Flint, Michigan, United States, 48502
Helen DeVos Children's Hospital at Spectrum Health
Grand Rapids, Michigan, United States, 49503
Kalamazoo Center for Medical Studies
Kalamazoo, Michigan, United States, 49008
Bronson Methodist Hospital
Kalamazoo, Michigan, United States, 49007
Michigan State University - Breslin Cancer Center
Lansing, Michigan, United States, 48910
United States, Minnesota
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, United States, 55404
University of Minnesota Medical Center-Fairview
Minneapolis, Minnesota, United States, 55455
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Mississippi
University of Mississippi Medical Center
Jackson, Mississippi, United States, 39216
United States, Missouri
University of Missouri-Columbia
Columbia, Missouri, United States, 65212
United States, Nevada
Nevada Cancer Research Foundation CCOP
Las Vegas, Nevada, United States, 89106
United States, New Hampshire
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756
United States, New Jersey
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
Morristown Memorial Hospital
Morristown, New Jersey, United States, 07962
Overlook Hospital
Summit, New Jersey, United States, 07902
United States, New Mexico
University of New Mexico Cancer Center
Albuquerque, New Mexico, United States, 87106
United States, New York
Montefiore Medical Center
Bronx, New York, United States, 10467-2490
Winthrop University Hospital
Mineola, New York, United States, 11501
State University of New York Upstate Medical University
Syracuse, New York, United States, 13210
Ny Cancer%
Valhalla, New York, United States, 10595
United States, North Carolina
Mission Hospitals
Asheville, North Carolina, United States, 28801
Presbyterian Hospital
Charlotte, North Carolina, United States, 28204
Duke University Medical Center
Durham, North Carolina, United States, 27710
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States, 27157
United States, Ohio
Children's Hospital Medical Center of Akron
Akron, Ohio, United States, 44308
Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195
Rainbow Babies and Childrens Hospital
Cleveland, Ohio, United States, 44106
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
The Children's Medical Center of Dayton
Dayton, Ohio, United States, 45404
The Toledo Hospital/Toledo Children's Hospital
Toledo, Ohio, United States, 43606
United States, Oregon
Legacy Emanuel Children's Hospital
Portland, Oregon, United States, 97227
Legacy Emanuel Hospital and Health Center
Portland, Oregon, United States, 97227
Oregon Health and Science University
Portland, Oregon, United States, 97239
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States, 15224
United States, South Carolina
BI-LO Charities Children's Cancer Center
Greenville, South Carolina, United States, 29605
Greenville Cancer Treatment Center
Greenville, South Carolina, United States, 29605
United States, South Dakota
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota, United States, 57117-5134
United States, Tennessee
T C Thompson Children's Hospital
Chattanooga, Tennessee, United States, 37403
East Tennessee Childrens Hospital
Knoxville, Tennessee, United States, 37916
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232
United States, Texas
Dell Children's Medical Center of Central Texas
Austin, Texas, United States, 78723
Driscoll Children's Hospital
Corpus Christi, Texas, United States, 78411
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75390
Cook Children's Medical Center
Fort Worth, Texas, United States, 76104
Baylor College of Medicine
Houston, Texas, United States, 77030
Covenant Children's Hospital
Lubbock, Texas, United States, 79410
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States, 78229-3900
Methodist Children's Hospital of South Texas
San Antonio, Texas, United States, 78229
United States, Utah
Primary Children's Hospital
Salt Lake City, Utah, United States, 84113
United States, Virginia
Virginia Commonwealth University
Richmond, Virginia, United States, 23298
United States, Washington
Seattle Children's Hospital
Seattle, Washington, United States, 98105
Providence Sacred Heart Medical Center and Children's Hospital
Spokane, Washington, United States, 99204
Madigan Army Medical Center
Tacoma, Washington, United States, 98431
Mary Bridge Children's Hospital and Health Center
Tacoma, Washington, United States, 98405
United States, Wisconsin
Saint Vincent Hospital
Green Bay, Wisconsin, United States, 54301
Marshfield Clinic
Marshfield, Wisconsin, United States, 54449
Midwest Children's Cancer Center
Milwaukee, Wisconsin, United States, 53226
Australia, Queensland
Royal Brisbane and Women's Hospital
Herston, Queensland, Australia, 4029
Royal Childrens Hospital
Herston, Queensland, Australia, 4029
Australia, Western Australia
Princess Margaret Hospital for Children
Perth, Western Australia, Australia, 6008
Canada, Alberta
University of Alberta Hospital
Edmonton, Alberta, Canada, T6G 2B7
Canada, British Columbia
British Columbia Children's Hospital
Vancouver, British Columbia, Canada, V6H 3V4
Canada, Manitoba
CancerCare Manitoba
Winnipeg, Manitoba, Canada, R3E 0V9
Canada, Ontario
Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
Canada, Saskatchewan
Saskatoon Cancer Centre
Saskatoon, Saskatchewan, Canada, S7N 4H4
New Zealand
Starship Children's Hospital
Grafton, Auckland, New Zealand, 1145
Christchurch Hospital
Christchurch, New Zealand, 8011
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:
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Leukemia
Neurotoxicity Syndromes
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 September 30, 2014