Study of Fludarabine Drug Exposure in Pediatric Bone Marrow Transplantation (HCT)
Fludarabine is a chemotherapy drug used extensively in bone marrow transplantation. The goal of this study is to determine what causes some children to have different drug concentrations of fludarabine in their bodies and if drug levels are related to whether or not a child experiences severe side-effects during their bone marrow transplant. The hypothesis is that clinical and genetic factors cause changes in fludarabine drug levels in pediatric bone marrow transplant patients and that high levels may cause severe side-effects.
Genetic Inborn Errors of Metabolism
Sickle Cell Disease
|Study Design:||Time Perspective: Prospective|
|Official Title:||Population Pharmacokinetics of Fludarabine in Pediatric Patients Undergoing Hematopoietic Cell Transplantation|
- Identify specific clinical markers or characteristics that impact fludarabine PK exposure. [ Time Frame: up to 100 days post transplant ] [ Designated as safety issue: No ]
- Establish the relationship between fludarabine exposure and clinical outcomes. [ Time Frame: up to 100 days post transplant ] [ Designated as safety issue: No ]
Biospecimen Retention: Samples With DNA
whole blood, DNA
|Study Start Date:||September 2010|
|Estimated Primary Completion Date:||June 2015 (Final data collection date for primary outcome measure)|
Fludarabine is a nucleoside analog with potent antitumor and immunosuppressive properties used in conditioning regimens of pediatric allogeneic hematopoietic cell transplantation (alloHCT) to promote stem cell engraftment.
This is a single-center, pharmacokinetic-pharmacodynamic (PK-PD) study investigating the clinical pharmacology of fludarabine in 45 children undergoing alloHCT at UCSF Benioff Children's Hospital.
Patients would receive fludarabine regardless of whether or not they decide to consent to PK sampling.
Fludarabine doses will not be adjusted based on PK data.
We will apply the combination of a D-optimality-based limited sampling strategy and population PK methodologies to determine specific factors influencing fludarabine exposure in pediatric alloHCT recipients and identify exposure-response relationships.
Subjects will undergo PK sampling of plasma (f-ara-a) and intracellular (f-ara-ATP) drug concentrations over the duration of fludarabine therapy (3 to 5 days).
To evaluate sources of variability impacting fludarabine exposure clinical data will be obtained from the patient's medical chart on each day of PK sampling.
A single blood draw for the collection of DNA and genotyping of single nucleotide polymorphisms of genes involved in fludarabine activation, transport or elimination will occur in all patients.
To assess exposure-response relationships neutrophil engraftment, treatment-related toxicity, and survival data will be collected through day 100 post-transplant.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01316549
|Contact: Janel R Long-Boyle, PharmD, PhDfirstname.lastname@example.org|
|Contact: Chris Dvorak, MDemail@example.com|
|United States, California|
|University of California, San Francisco||Recruiting|
|San Francisco, California, United States, 94143|
|Contact: Janel R Long-Boyle, PharmD, PhD 415-514-2746 firstname.lastname@example.org|
|Principal Investigator: Janel R Long-Boyle, PharmD, PhD|
|Principal Investigator:||Janel R Long-Boyle, PharmD, PhD||University of California, San Francisco|