Clinical trial NCT00900445: Studying Body Mass Index in Younger Patients Who Are Receiving Treatment for High-Risk Acute Lymphoblastic Leukemia
Official title: Impact of Obesity on the Pharmacokinetics of Anticancer Therapy in Children With High Risk Acute Lymphoblastic Leukemia (ALL)
Study type: OBSERVATIONAL
Overall status: WITHDRAWN
Conditions: Acute Lymphoblastic Leukemia
Untreated Childhood Acute Lymphoblastic Leukemia
Lead sponsor: Children's Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2009-05-12
Enrollment: 0
Sex: ALL
Minimum age (years): 10
Maximum age (years): 19
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Sampling method: NON_PROBABILITY_SAMPLE

Brief summary: This clinical trial is studying body mass index in younger patients receiving prednisone/prednisolone, vincristine, daunorubicin, and pegaspargase for high-risk acute lymphoblastic leukemia. Studying samples of blood from patients with cancer in the laboratory may help doctors learn more about the affect of body mass index on the way anticancer drugs work in the body. It may also help doctors predict how patients will respond to treatment

Detailed description: 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Pharmacokinetic parameters of prednisone/prednisolone
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 4, 6 to 8, 10 and 12 hours
measure: Pharmacokinetic parameters of daunorubicin hydrochloride
timeFrame: Pre-dose, 0.5, 0.75, 1, 2, 4, 8, 12, 24 to 36 hours, and 48 to 72 hours
measure: Pharmacokinetic parameters of vincristine sulfate
timeFrame: Pre-dose, 0.5, 1, 2, 4, 8, 24 to 36 hours, and 48 to 72 hours
Secondary outcomes:
measure: RER and SER status
timeFrame: Up to 1.5 years
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Childrens Oncology Group
state: Pennsylvania
Study officials:
affiliation: Children's Oncology Group
name: Ian Pollack
role: PRINCIPAL_INVESTIGATOR
References: