Haematological malignancy Cancer Other and unspecified malignant neoplasms of lymphoid, haematopoietic and related tissue
Conditions
Interventions
Cohort receives oral celecoxib 10 mg/kg 3 hours prior to first scheduled LP (LP 1) and then 5 mg/kg 12 hours after first dose and multiple blood samples to create blood PK profile. Randomisation into
Group 2: dose variation) prior to undergoing the remaining scheduled LPs (LPs 2-5).
Group 1: Oral celecoxib 10 mg/kg either 60, 120, 300 or 900 mins prior to remaining 4 LPs followed by 5 mg/kg post
Sponsors
Children's Hospital of Eastern Ontario Research Institute (Canada)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Both males and females, age 2-18 years with haematological malignancy expected to undergo five lumbar punctures.
Exclusion criteria
Exclusion criteria: 1. Serum creatinine >2 X upper normal limit (UNL) 2. Abnormal liver function; namely alanine aminotransferase (ALT) >1.5 X UNL, alkaline phosphatase (ALP) > 5X UNL, total bilirubin >2 X UNL 3. History of peptic ulcer disease 4. Allergy to celecoxib, sulfonamide compounds or non steroidal anti-inflammatory drugs (NSAIDs) 5. Patients receiving CYP2C9 inhibitors fluconazole, amiodarone and oxandrolone 6. Patients receiving CYP2C9 inducers rifampin and phenobarbitol 7. Extremes of body mass index (BMI) (age related below 10th or above 90th percentile) 8. Parents of any participants, irrespective of age, who are unable to read and understand instructions relayed in English or French 9. Participant and/or parents of any participants, irrespective of age, who suffer from dementia, psychosis, significant developmental delay or other impairment that would prohibit the understanding and giving of informed consent or assent or the participation in self-care or toxicity reporting
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. All patients and CSF dose timing cohort (Group 1: Oral celecoxib 10 mg/kg pharmacokinetic profile) 1.1. Mean total and unbound plasma concentration ug/L at approximately the following time intervals (mins): 30, 60, 90, 120, 180, 300, 900 1.2. Mean CSF concentration ug/L at approximately the following time intervals (mins): 60, 120, 180, 300, 900 1.3. Ratio CSF/unbound plasma concentration at approximately the following time intervals (mins): 60, 120, 180, 300, 900 1.4. This information will be used to determine plasma and CSF mean +/- SD values for maximum concentration (Cmax [ug/L]); area under concentration curve from time 0 to infinity; apparent oral volume of distribution (Vd/F [L/kg]); apparent oral clearance (CL/F [L·h-1·kg-1] and terminal elimination half-life (t1/2 [h]). A median value will be determined for time to maximum concentration (tmax[h]). 2. Dose escalation cohort (Group 2: Oral celecoxib 6 mg/kg and 14 mg/kg pharmacokinetic profile) 2.1. Mean total and unbound plasma concentration ug/L at approximately the following time intervals (mins): 60, 180, 300 2.2. Mean CSF concentration ug/L at approximately 180 min 2.3. Ratio CSF/unbound plasma concentration at approximately 180 min 2.4. This information in conjunction with the pharmacokinetic profile established in the dose timing cohort (10 mg/kg) will be used to predict plasma and CSF values for tmax, Cmax, AUC, Vd/F, CL/F and t1/2 for 6 and 14 mg/kg oral doses respectively. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Polymorphisms of genotypes CYP2C9 and CYP3A4 liver enzymes and correlations to drug levels 2. Pediatric Quality of life Inventory (PedsQL) version 4.0 scores before and 7 days after LP 2.1. Parent report for children aged 2-7, 8-12 and 13-18 2.2. Child report ages 8-12 and 13-18 3. PedsQL Cancer module version 3.0 scores before and 7 days after LP 3.1. Parent report for children aged 2-7, 8-12 and 13-18 3.2. Child report ages 8-12 and 13-18 4. PedsQL Multidimension Fatigue Scale version 1.0 scores before and 7 days after LP 4.1. Parent report for children aged 2-7, 8-12 and 13-18 4.2. Child report ages 8-12 and 13-18 5. PedsQL Pediatric Pain Questionnaire baseline and daily scores for 7 days after LP 5.1. Parent report for children aged 2-7, 8-12 and 13-18 5.2. Child report ages 5-7, 8-12 and 13-18 6. Demographics including professional identity of the individual performing the LP+/-BM, description of the LP and BM needles used, number of attempts and degree of difficulty 7. Adverse events recorded daily for 7 days after each dose ingested | — |
Countries
Canada
Outcome results
None listed