Impact of Obesity on the Pharmacokinetics of Anticancer Therapy in Children With High Risk Acute Lymphoblastic Leukemia (ALL)
- To compare the pharmacokinetics of prednisone/prednisolone, vincristine, and
daunorubicin hydrochloride among obese, middle-weight, and underweight children aged 10
to less than 20 years of age undergoing induction therapy for high-risk acute
- To examine the relationship between the above parameters and response status as defined
by early response and induction failure.
OUTLINE: This is a multicenter study. Patients are stratified according to body mass index
(BMI) (≥ 95^th percentile [obese] vs 10^th to 95^th percentile [normal or at risk for
overweight] vs ≤ 10^th percentile [underweight]).
Patients receive anticancer therapy as prescribed by their treating clinicians. Patients
receive prednisone/prednisolone orally twice on either day 1 or day 8. Patients also receive
daunorubicin hydrochloride IV over 30 minutes and vincristine IV once on the same day.
Blood samples are obtained on either day 1 or day 8** of induction therapy for
pharmacokinetic analysis of prednisone, daunorubicin hydrochloride, and vincristine activity
Blood samples are analyzed via high-performance liquid chromatography (HPLC),
ultrafiltration, a Nessler reaction, ELISA, and liquid chromatography using reverse-phase
chromatography, fluorescent detection, and solid-phase extraction.
Demographic information, including ethnicity, is also collected. Weight and height is
recorded at diagnosis and on the day pharmacokinetic assessment of vincristine, prednisone,
and daunorubicin hydrochloride begins.
NOTE: **Patients who are being sampled on day 8 of induction therapy and who have received
intravenous corticosteroid therapy in the first week of induction must have received at
least six oral prednisone/prednisolone doses prior to the morning prednisone/prednisolone
dose on day 8.
Time Perspective: Prospective
Pharmacokinetic parameters of prednisone/prednisolone
Two multiple comparisons (normal weight versus obese and normal weight versus underweight groups) will be conducted with a priori planned contrasts using the Bonferroni adjustment method.
Pre-dose, 0.5, 1, 1.5, 2, 4, 6 to 8, 10 and 12 hours
Lillian Sung, MD, PhD
The Hospital for Sick Children
United States: Federal Government
|Cancer Research Center of Hawaii||Honolulu, Hawaii 96813|
|Children's Hospital of Pittsburgh||Pittsburgh, Pennsylvania 15213|
|Nemours Children's Clinic||Jacksonville, Florida 32207|
|St. Christopher's Hospital for Children||Philadelphia, Pennsylvania 19134-1095|
|Driscoll Children's Hospital||Corpus Christi, Texas 78466|
|East Tennessee Children's Hospital||Knoxville, Tennessee 37901|
|Overlook Hospital||Summit, New Jersey 07902-0220|
|Jonathan Jaques Children's Cancer Center at Miller Children's Hospital||Long Beach, California 90801|
|Nemours Children's Clinic - Orlando||Orlando, Florida 32806|
|Sacred Heart Cancer Center at Sacred Heart Hospital||Pensacola, Florida 32504|
|St. Joseph's Cancer Institute at St. Joseph's Hospital||Tampa, Florida 33607|
|Kaplan Cancer Center at St. Mary's Medical Center||West Palm Beach, Florida 33407|
|Alvin and Lois Lapidus Cancer Institute at Sinai Hospital||Baltimore, Maryland 21215|
|Wake Forest University Comprehensive Cancer Center||Winston-Salem, North Carolina 27157-1096|
|Methodist Children's Hospital of South Texas||San Antonio, Texas 78229-3993|
|Alfred I. duPont Hospital for Children||Wilmington, Delaware 19803|
|Lucille P. Markey Cancer Center at University of Kentucky||Lexington, Kentucky 40536-0093|
|Akron Children's Hospital||Akron, Ohio 44308-1062|
|Oklahoma University Cancer Institute||Oklahoma City, Oklahoma 73104|
|Greenville Hospital Cancer Center||Greenville, South Carolina 29605|