Studying Body Mass Index in Younger Patients Who Are Receiving Treatment for High-Risk Acute Lymphoblastic Leukemia

PRIMARY OBJECTIVES:

I. 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 lymphoblastic leukemia.

II. 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) (greater than or equal to 95th percentile [obese] vs 10th to 95th percentile [normal or
at risk for overweight] vs less than or equal to 10th 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
levels.

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.

Inclusion Criteria:

- Patients must be newly diagnosed with acute lymphoblastic leukemia and the intended
induction treatment must contain prednisone/prednisolone, vincristine and daunorubicin
in the doses and schedule as per the current COG AALL0232 protocol; prior registration
onto a COG protocol is not required

- Patients must be able to take either prednisone/prednisolone reliably by mouth on day
1 or 8 of induction (depending on sampling schedule chosen); patients who are being
sampled on Induction day 8 and who have received intravenous corticosteroid therapy in
the first week of induction must have received a minimum of six oral
prednisone/prednisolone doses prior to the morning prednisone/prednisolone dose on
induction day 8

Exclusion Criteria:

- Serum transaminase concentrations >= 5 X ULN for age

- Total serum bilirubin (conjugated + unconjugated) >= 1.5 mg/dl (>= 26 micromol/L)

- Serum creatinine > 1.5 X ULN for age

- With the exception of prednisone/prednisolone, receipt of medications or food known or
with the potential to alter the pharmacokinetics of the drugs under study within 14
days of diagnosis and throughout the period of pharmacokinetic sampling; such agents
include but are not limited to: grapefruit, tangelos or the juice of these fruits; St.
Johns wort; anticonvulsants: carbamazepine, oxcarbazepine, phenytoin, phenobarbital,
primidone; azole antifungal agents: ketoconazole, fluconazole, itraconazole,
voriconazole; macrolide antibiotics: erythromycin, clarithromycin; isoniazid;
rifampin; verapamil; and diltiazem

- Presence of known malabsorption syndrome

- Females with known pregnancy (pregnancy test must be negative to be eligible)