Study of Fludarabine Drug Exposure in Pediatric Bone Marrow Transplantation

Sickle Cell Disease Clinical Trial

— HCT  

Official title:

Population Pharmacokinetics of Fludarabine in Pediatric Patients Undergoing Hematopoietic Cell Transplantation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01316549
• Other study ID #: P0037192
• Secondary ID: 10081
• Status: Completed
• Start date: January 1, 2011
• Est. completion date: April 30, 2016

Study information

• Verified date: September 2021
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Description:

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 University of California, San Francisco 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 67
• Est. completion date: April 30, 2016
• Est. primary completion date: April 30, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 17 Years

Eligibility

Inclusion Criteria:

• Children 0-17 years of age
• Undergoing alloHCT for the treatment of malignant or nonmalignant disorder
• Receiving fludarabine-based preparative regimen

Exclusion Criteria:

• Any child 7-17 years of age unwilling to provide assent
• Parent or guardian unwilling to provide written consent

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Fanconi Anemia
• Genetic Inborn Errors of Metabolism
• Hematologic Malignancies
• Hematologic Neoplasms
• Hemoglobinopathies
• Immunodeficiencies
• Metabolism, Inborn Errors
• Nonmalignant Diseases
• Sickle Cell Disease
• Thalassemia

Intervention

Drug:
• Fludarabine
Given as injection

Locations

Country	Name	City	State
United States	University of California, San Francisco	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, San Francisco	Thrasher Research Fund

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Analysis of the Area under the Plasma Concentration versus Time Curve (AUC) of fludarabine for HCT in pediatric patients.		2hours post start of infusion
Primary	Analysis of the Area under the Plasma Concentration versus Time Curve (AUC) of fludarabine for HCT in pediatric patients.		3hours post start of infusion
Primary	Analysis of the Area under the Plasma Concentration versus Time Curve (AUC) of fludarabine for HCT in pediatric patients.		6hours post start of infusion
Primary	Analysis of the Area under the Plasma Concentration versus Time Curve (AUC) of fludarabine for HCT in pediatric patients.		24hours post start of infusion
Secondary	Event free survival according to the AUC of fludarabine		1month post transplant
Secondary	Event free survival according to the AUC of fludarabine		3months post transplant
Secondary	Event free survival according to the AUC of fludarabine		1 year post transplant