Clinical trial NCT00437060: Brain Function in Young Patients Receiving Methotrexate for Acute Lymphoblastic Leukemia
Official title: A Study of Neurocognitive Function in Children Treated for ALL
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: 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
Lead sponsor: Children's Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-02-19
Enrollment: 233
Sex: ALL
Minimum age (years): 1
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with newly diagnosed acute lymphoblastic leukemia meeting other criteria.

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.

Eligibility 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

Primary outcomes:
measure: Change in neurocognitive function by the Pediatric Quality of Life (PedQL) battery, Full Scale Intelligence Quotient (FSIQ) score
timeFrame: From baseline to up to 24 months
measure: Polymorphisms as predictors of neurocognitive dysfunction or acute neurotoxicity
timeFrame: Up to 24 months
Secondary outcomes:
measure: Correlation between neuropsychological outcomes and acute neurotoxicity
timeFrame: Up to 24 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Children's Hospital of Alabama
state: Alabama
city: Birmingham
country: United States
facility: University of Alabama at Birmingham Cancer Center
state: Alabama
city: Downey
country: United States
facility: Southern California Permanente Medical Group
state: California
city: Long Beach
country: United States
facility: Miller Children's and Women's Hospital Long Beach
state: California
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Madera
country: United States
facility: Children's Hospital Central California
state: California
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: Palo Alto
country: United States
facility: Lucile Packard Children's Hospital Stanford University
state: California
city: San Diego
country: United States
facility: Rady Children's Hospital - San Diego
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center-Parnassus
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Hartford
country: United States
facility: Connecticut Children's Medical Center
state: Connecticut
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Wilmington
country: United States
facility: Alfred I duPont Hospital for Children
state: Delaware
city: Washington, D.C.
country: United States
facility: MedStar Georgetown University Hospital
state: District of Columbia
city: Washington, D.C.
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Broward Health Medical Center
state: Florida
city: Fort Myers
country: United States
facility: Golisano Children's Hospital of Southwest Florida
state: Florida
city: Hollywood
country: United States
facility: Memorial Regional Hospital/Joe DiMaggio Children's Hospital
state: Florida
city: Jacksonville
country: United States
facility: Nemours Children's Clinic-Jacksonville
state: Florida
city: Miami
country: United States
facility: University of Miami Miller School of Medicine-Sylvester Cancer Center
state: Florida
city: Miami
country: United States
facility: Nicklaus Children's Hospital
state: Florida
city: Orlando
country: United States
facility: Nemours Children's Hospital
state: Florida
city: Pensacola
country: United States
facility: Nemours Children's Clinic - Pensacola
state: Florida
city: Saint Petersburg
country: United States
facility: All Children's Hospital
state: Florida
city: Tampa
country: United States
facility: Saint Joseph's Hospital/Children's Hospital-Tampa
state: Florida
city: West Palm Beach
country: United States
facility: Saint Mary's Hospital
state: Florida
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta - Egleston
state: Georgia
city: Honolulu
country: United States
facility: University of Hawaii Cancer Center
state: Hawaii
city: Chicago
country: United States
facility: Lurie Children's Hospital-Chicago
state: Illinois
city: Chicago
country: United States
facility: University of Illinois
state: Illinois
city: Oak Lawn
country: United States
facility: Advocate Children's Hospital-Oak Lawn
state: Illinois
city: Indianapolis
country: United States
facility: Riley Hospital for Children
state: Indiana
city: Indianapolis
country: United States
facility: Saint Vincent Hospital and Health Care Center
state: Indiana
city: Des Moines
country: United States
facility: Blank Children's Hospital
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky/Markey Cancer Center
state: Kentucky
city: Baltimore
country: United States
facility: Sinai Hospital of Baltimore
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Medical School
state: Massachusetts
city: Ann Arbor
country: United States
facility: C S Mott Children's Hospital
state: Michigan
city: Detroit
country: United States
facility: Wayne State University/Karmanos Cancer Institute
state: Michigan
city: Detroit
country: United States
facility: Saint John Hospital and Medical Center
state: Michigan
city: East Lansing
country: United States
facility: Michigan State University Clinical Center
state: Michigan
city: Flint
country: United States
facility: Hurley Medical Center
state: Michigan
city: Grand Rapids
country: United States
facility: Helen DeVos Children's Hospital at Spectrum Health
state: Michigan
city: Kalamazoo
country: United States
facility: Bronson Methodist Hospital
state: Michigan
city: Kalamazoo
country: United States
facility: Kalamazoo Center for Medical Studies
state: Michigan
city: Minneapolis
country: United States
facility: Children's Hospitals and Clinics of Minnesota - Minneapolis
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota/Masonic Cancer Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Columbia
country: United States
facility: University of Missouri - Ellis Fischel
state: Missouri
city: Las Vegas
country: United States
facility: Nevada Cancer Research Foundation CCOP
state: Nevada
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Morristown
country: United States
facility: Morristown Medical Center
state: New Jersey
city: Summit
country: United States
facility: Overlook Hospital
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Center
state: New Mexico
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Center
state: New Mexico
city: Mineola
country: United States
facility: Winthrop University Hospital
state: New York
city: Syracuse
country: United States
facility: State University of New York Upstate Medical University
state: New York
city: Valhalla
country: United States
facility: New York Medical College
state: New York
city: Asheville
country: United States
facility: Mission Hospital-Memorial Campus
state: North Carolina
city: Charlotte
country: United States
facility: Novant Health Presbyterian Medical Center
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Akron
country: United States
facility: Children's Hospital Medical Center of Akron
state: Ohio
city: Cleveland
country: United States
facility: Rainbow Babies and Childrens Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Dayton
country: United States
facility: Dayton Children's Hospital
state: Ohio
city: Toledo
country: United States
facility: The Toledo Hospital/Toledo Children's Hospital
state: Ohio
city: Portland
country: United States
facility: Legacy Emanuel Children's Hospital
state: Oregon
city: Portland
country: United States
facility: Legacy Emanuel Hospital and Health Center
state: Oregon
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Greenville
country: United States
facility: BI-LO Charities Children's Cancer Center
state: South Carolina
city: Greenville
country: United States
facility: Greenville Cancer Treatment Center
state: South Carolina
city: Sioux Falls
country: United States
facility: Sanford USD Medical Center - Sioux Falls
state: South Dakota
city: Chattanooga
country: United States
facility: T C Thompson Children's Hospital
state: Tennessee
city: Knoxville
country: United States
facility: East Tennessee Childrens Hospital
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University/Ingram Cancer Center
state: Tennessee
city: Austin
country: United States
facility: Dell Children's Medical Center of Central Texas
state: Texas
city: Corpus Christi
country: United States
facility: Driscoll Children's Hospital
state: Texas
city: Dallas
country: United States
facility: UT Southwestern/Simmons Cancer Center-Dallas
state: Texas
city: Fort Worth
country: United States
facility: Cook Children's Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Lubbock
country: United States
facility: Covenant Children's Hospital
state: Texas
city: San Antonio
country: United States
facility: Methodist Children's Hospital of South Texas
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Salt Lake City
country: United States
facility: Primary Children's Hospital
state: Utah
city: Richmond
country: United States
facility: Virginia Commonwealth University/Massey Cancer Center
state: Virginia
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Spokane
country: United States
facility: Providence Sacred Heart Medical Center and Children's Hospital
state: Washington
city: Tacoma
country: United States
facility: Mary Bridge Children's Hospital and Health Center
state: Washington
city: Tacoma
country: United States
facility: Madigan Army Medical Center
state: Washington
city: Green Bay
country: United States
facility: Saint Vincent Hospital
state: Wisconsin
city: Marshfield
country: United States
facility: Marshfield Clinic
state: Wisconsin
city: Milwaukee
country: United States
facility: Midwest Children's Cancer Center
state: Wisconsin
city: Herston
country: Australia
facility: Royal Brisbane and Women's Hospital
state: Queensland
city: Herston
country: Australia
facility: Royal Children's Hospital-Brisbane
state: Queensland
city: Perth
country: Australia
facility: Princess Margaret Hospital for Children
state: Western Australia
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Vancouver
country: Canada
facility: British Columbia Children's Hospital
state: British Columbia
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
city: Toronto
country: Canada
facility: Hospital for Sick Children
state: Ontario
city: Saskatoon
country: Canada
facility: Saskatoon Cancer Centre
state: Saskatchewan
city: Grafton
country: New Zealand
facility: Starship Children's Hospital
state: Auckland
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
Study officials:
affiliation: Children's Oncology Group
name: Naomi Winick
role: PRINCIPAL_INVESTIGATOR
References: