Celecoxib: In Phase I twenty (20) children will receive either celecoxib 14 or 7 mg/kg 120-180 minutes prior to lumbar puncture (LP). In Phase II forty-five (45) children will receive celecoxib 14 mg/kg, 7 mg/kg or placebo in one of 5 time intervals, 1-24 hours prior to LP.
Placebo: In Phase II forty-five (45) children will receive celecoxib 14 mg/kg, 7 mg/kg or placebo in one of 5 time intervals, 1-24 hours prior to LP.
Study summary
Celecoxib is effective for reducing postoperative pain in adults. Children use celecoxib more rapidly than adults and require higher doses. Celecoxib is partially metabolized in the liver by a certain enzyme. A person's genetic variation of this enzyme can influence how well their body uses Celecoxib. Furthermore, Celecoxib down-regulates P-glycoprotein (P-gp), a drug efflux transporter located at the blood brain barrier responsible for central nervous system (CNS) extrusion of ondansetron and possibly fentanyl; therefore celecoxib may augment the CNS effects of these drugs.
Understanding the blood and cerebrospinal fluid (CSF) profile of celecoxib in children and the influence of genetics on metabolism would help to develop appropriate celecoxib dosing in children for various treatment options.
Eligibility
Sex
ALL
Min age
2 Years
Max age
12 Years
Healthy volunteers
No
Inclusion Criteria:
Children aged 2-12 years, undergoing Maintenance phase chemotherapy for hematological malignancies and lymphomas (i.e. acute lymphoblastic leukemia \[ALL\] and lymphoblastic lymphomas \[LLy\] at CHEO. At this point, all patients would have achieved remission an average of 6 months earlier.
Exclusion Criteria:
1. Age \< 2yrs and \>12yrs old
2. Children with non-hematologic malignancies
3. AML
4. Children undergoing a bone marrow aspiration (BMA) only
5. Serum creatinine \> 2 X UNL (upper normal limit) within 30 days
6. Abnormal liver function; alanine aminotransferase (ALT) \> 2 X UNL, Aspartate aminotransferase (AST) \> 2 X UNL, total \& direct bilirubin \> 2 X UNL within 30 days
7. History of peptic ulcer disease
8. Allergy to celecoxib or NSAIDs (note: sulpha allergy does not exclude celecoxib)
9. Recent (within 7 days) celecoxib ingestion
10. Patients receiving CYP2C9 inhibitors fluconazole, amiodarone, oxandrolone
11. Patients receiving CYP2C9 inducers rifampin and phenobarbitol
12. Patients receiving high (≥ 5 gm/m2) and/ or escalating doses of methotrexate.
13. Extremes of body mass index (BMI) (BMI \<5th percentile or \>95th percentile)
14. Parents of any participants, irrespective of age, who are unable to read and understand instructions relayed in English or French
15. Participant and/or parents of any participants, irrespective of age, who suffer from dementia, psychosis or any impairment that would prohibit the understanding and giving of informed consent or study-related reporting
16. Patient enrolled in another trial
17. Pregnancy.
Primary outcome measure(s)
Mean celecoxib CSF concentration (ug/L) within 121-180 minutes post ingestion of 7 or 14 mg/kg celecoxib. — Day 0, the day of the procedure, after taking study medication. Compare mean celecoxib CSF concentration (ug/L) within 121-180 minutes post ingestion of 7 or 14 mg/kg celecoxib
Mean celecoxib total and unbound plasma concentration (ug/L) in the following time intervals (mins): 0-30, 31- 60, 61- 90, 91- 120, 121-180, 181-300, 301-900 and 901-1440. — Day 0, the day of the procedure, after taking study medication. Compare mean celecoxib total and unbound plasma concentration (ug/L) post ingestion of 7 or 14 mg/kg celecoxib
Mean celecoxib CSF concentration (ug/L) at the following time intervals (mins): 0-60, 61-120,121-180,181-300, 301-900 and 901-1440. — Day 0, the day of the procedure, after taking study medication. Compare mean celecoxib CSF concentration (ug/L) post ingestion of 7 or 14 mg/kg celecoxib
Develop a PK model that explores the relationship between plasma and CSF celecoxib concentrations and the impact of covariates including age, weight and genetics using nonlinear mixed effects models. — Day 0, the day of the procedure, after taking study medication. The PK model will be used to see if there is a correlation between plasma and CSF celecoxib concentrations and various factors such as age, weight and genetics.
Trial sites (1)
Facility
City
Region
Status
Children's Hospital of Eastern Ontario
Ottawa
Ontario
Recruiting
More Children's Hospital of Eastern Ontario trials in Canada
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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