Clinical trial NCT00085176: Neurobehavioral Complications in Children Who Were Previously Treated With Steroids and Intrathecal Therapy for Acute Lymphoblastic Leukemia
Official title: Neurobehavioral Outcomes in Childhood Acute Lymphoblastic Leukemia. A Limited Non-Therapeutic Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Leukemia
Long-term Effects Secondary to Cancer Therapy in Children
Neurotoxicity
Psychosocial Effects of Cancer and Its Treatment
Keywords: long-term effects secondary to cancer therapy in children
neurotoxicity
psychosocial effects of cancer and its treatment
childhood acute lymphoblastic leukemia in remission
Lead sponsor: Children's Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-06-11
Enrollment: 286
Sex: ALL
Minimum age (years): 6
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Children previously randomized to (1) dexamethasone instead of prednisone on COG 1922 and (2) intrathecal methotrexate, cytarabine, and hydrocortisone (triple therapy) instead of intrathecal methotrexate alone on COG 1952

Brief summary: RATIONALE: Cancer therapies may affect the ability of a child's brain and central nervous system to function normally. Learning to identify which patients will develop complications may improve the ability of doctors to plan cancer treatment and improve patient quality of life.

PURPOSE: This clinical trial is studying neurobehavioral changes in children who have received steroid therapy or intrathecal therapy for acute lymphoblastic leukemia.

Detailed description: OBJECTIVES:

* Compare neurobehavioral functioning, specifically memory, attention, executive function, visual-motor integration, and processing speed, in children previously treated with steroids (prednisone vs dexamethasone) and intrathecal therapy (methotrexate alone vs methotrexate, cytarabine, and hydrocortisone) for childhood acute lymphoblastic leukemia.
* Correlate non-treatment risk factors, such as gender, age at diagnosis, and time since termination of prior therapy, with impaired neurobehavioral function in these patients.
* Correlate neurobehavioral complications with quality-of-life of these patients.

OUTLINE: This is a multicenter, cohort study. Patients are assigned to 1 of 2 cohorts (prior treatment per CCG-1922 \[prednisone vs dexamethasone\] vs prior treatment per CCG-1952 \[intrathecal (IT) methotrexate vs IT methotrexate, cytarabine, and hydrocortisone\]). Patients in each cohort are stratified according to age at diagnosis, gender, and time since prior treatment termination.

* Cohort A (CCG-1922): Patients undergo physical and neurological examination, neurobehavioral evaluation, and quality of life assessment. Neurobehavioral evaluations assess memory, attention, and executive function.
* Cohort B (CCG-1952): Patients undergo evaluation as above. Neurobehavioral evaluations assess visual-motor integration and processing speed.

PROJECTED ACCRUAL: A total of 448 patients (224 per cohort) will be accrued for this study within 4 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Diagnosis of standard-risk childhood acute lymphoblastic leukemia (ALL)

  * In continuous first remission
  * No history of CNS pathology requiring radiotherapy or surgery
* Prior enrollment on one of the following Children's Cancer Group (CCG) protocols AND terminated therapy at least 1 year ago:

  * CCG-1922 (prednisone vs dexamethasone)
  * CCG-1952 (intrathecal methotrexate vs triple intrathecal therapy)

    * No prior enrollment on CCG-1952 arm III
* No history of pre-existing neurodevelopmental disorder before diagnosis of ALL (e.g., mental retardation, Down syndrome, seizure disorder, or traumatic brain injury)
* No neuropsychological assessment within the past 6 months

PATIENT CHARACTERISTICS:

Age

* 6.5 to 16 years

Performance status

* Not specified

Life expectancy

* Not specified

Hematopoietic

* Not specified

Hepatic

* Not specified

Renal

* Not specified

Other

* Reading, speaking, and listening comprehension of English by patient required (English and/or Spanish by parent)
* No history of very low birth weight (\< 1,500 grams)

PRIOR CONCURRENT THERAPY:

Biologic therapy

* Not specified

Chemotherapy

* See Disease Characteristics

Endocrine therapy

* See Disease Characteristics

Radiotherapy

* See Disease Characteristics

Surgery

* See Disease Characteristics

Other

* Concurrent stimulants allowed

Primary outcomes:
measure: Two-sided comparisons of various mean neurobehavioral scores between the two treatment arms within each study
timeFrame: length of study
Secondary outcomes:
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Loma Linda
country: United States
facility: Loma Linda University Cancer Institute at Loma Linda University Medical Center
state: California
city: Long Beach
country: United States
facility: Jonathan Jaques Children's Cancer Center at Miller Children's Hospital
state: California
city: Los Angeles
country: United States
facility: Childrens Hospital Los Angeles
state: California
city: Los Angeles
country: United States
facility: Jonsson Comprehensive Cancer Center at UCLA
state: California
city: Oakland
country: United States
facility: Children's Hospital and Research Center Oakland
state: California
city: Aurora
country: United States
facility: Children's Hospital Center for Cancer and Blood Disorders
state: Colorado
city: Farmington
country: United States
facility: Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center
state: Connecticut
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Wilmington
country: United States
facility: Alfred I. duPont Hospital for Children
state: Delaware
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Indianapolis
country: United States
facility: Indiana University Melvin and Bren Simon Cancer Center
state: Indiana
city: Des Moines
country: United States
facility: Blank Children's Hospital
state: Iowa
city: Iowa City
country: United States
facility: Holden Comprehensive Cancer Center at University of Iowa
state: Iowa
city: Lexington
country: United States
facility: Lucille P. Markey Cancer Center at University of Kentucky
state: Kentucky
city: Ann Arbor
country: United States
facility: C.S. Mott Children's Hospital at University of Michigan Medical Center
state: Michigan
city: Grand Rapids
country: United States
facility: Butterworth Hospital at Spectrum Health
state: Michigan
city: Minneapolis
country: United States
facility: Children's Hospitals and Clinics of Minnesota - Minneapolis
state: Minnesota
city: Minneapolis
country: United States
facility: Masonic Cancer Center at University of Minnesota
state: Minnesota
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
city: New York
country: United States
facility: NYU Cancer Institute at New York University Medical Center
state: New York
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University Cancer Institute
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
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Houston
country: United States
facility: M. D. Anderson Cancer Center at University of Texas
state: Texas
city: Salt Lake City
country: United States
facility: Primary Children's Medical Center
state: Utah
city: Seattle
country: United States
facility: Children's Hospital and Regional Medical Center - Seattle
state: Washington
Study officials:
affiliation: Yale University
name: Nina S. Kadan-Lottick, MD, MSPH
role: STUDY_CHAIR
affiliation: Masonic Cancer Center, University of Minnesota
name: Joseph P. Neglia, MD, MPH
role: STUDY_CHAIR
References:
citation: Lindemulder SJ, Stork LC, Bostrom BC, et al.: Trends in body mass index (BMI) during and after treatment for standard risk (SR) acute lymphoblastic leukemia (ALL): A report from the Children's Oncology Group (COG). [Abstract] J Clin Oncol 30 (Suppl 15): A-9546, 2012.
citation: Kadan-Lottick NS, Brouwers P, Breiger D, Kaleita T, Dziura J, Liu H, Chen L, Nicoletti M, Stork L, Bostrom B, Neglia JP. A comparison of neurocognitive functioning in children previously randomized to dexamethasone or prednisone in the treatment of childhood acute lymphoblastic leukemia. Blood. 2009 Aug 27;114(9):1746-52. doi: 10.1182/blood-2008-12-186502. Epub 2009 Jun 22.
citation: Breiger D, Kaleita TA, Kadan-Lottick NS, et al.: Behavioral social adjustment in survivors of childhood acute lymphoblastic leukemia (ALL) treated without cranial radiation. [Abstract] Pediatr Blood Cancer 46 (6): A-3505.43, 690, 2006.
citation: Kadan-Lottick NS, Brouwers P, Kaleita TA, et al.: Preliminary findings of neurobehavioral outcomes in survivors of childhood acute lymphoblastic leukemia (ALL) treated without cranial radiation. [Abstract] Pediatr Blood Cancer 46 (6): A-3505.45, 691, 2006.
citation: Kadan-Lottick NS, Stork LC, Bostrom BC, et al.: Increased prevalence of overweight status in survivors of acute lymphoblastic leukemia (ALL) treated without cranial radiation . [Abstract] Pediatr Blood Cancer 46 (6): A-3505.44, 690, 2006.