Study of Clofarabine and Fludarabine Drug Exposure in Pediatric Bone Marrow Transplantation (HCT)

Sickle Cell Disease Clinical Trial

Official title:

Population Pharmacokinetics of the Nucleoside Analogues Clofarabine and Fludarabine in Pediatric Patients Undergoing Hematopoietic Cell Transplantation (alloHCT)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03609814
• Other study ID #: P1518454
• Secondary ID: 19081
• Status: Completed
• Start date: January 26, 2016
• Est. completion date: June 30, 2020

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 and clofarabine are chemotherapy drugs used extensively in bone marrow transplantation. The goal of this study is to determine what causes some children to have different drug concentrations of clofarabine and 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 individual factors cause changes in clofarabine and fludarabine drug levels in pediatric bone marrow transplant patients and that high levels may cause severe side-effects.

Description:

Fludarabine and clofarabine are nucleoside analogs 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, prospective, non-interventional pharmacokinetic (PK) study investigating the clinical pharmacology of combination nucleoside analogue therapy in 24 children undergoing alloHCT at University of California, San Francisco Benioff Children's Hospital. Patients would receive clofarabine and fludarabine regardless of whether or not they decide to consent to PK sampling. Clofarabine and fludarabine doses will not be adjusted based on PK data. The investigators will apply the combination of a limited sampling strategy and population PK methodologies to determine specific factors influencing clofarabine and fludarabine exposure in pediatric alloHCT recipients and identify exposure-response relationships. Subjects will undergo PK sampling of clofarabine and fludarabine drug concentrations over the duration of combination therapy (3 to 5 days). To evaluate sources of variability impacting clofarabine and fludarabine exposure clinical data will be obtained from the patient's medical chart on each day of PK sampling. 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: 30
• Est. completion date: June 30, 2020
• Est. primary completion date: June 30, 2020
• 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 clofarabine and fludarabine-based preparative regimen

Exclusion Criteria:

• Any child 7-17 years of age unwilling to provide assent

Related Conditions & MeSH terms

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

Intervention

Drug:
• Clofarabine
Given IV
• Fludarabine Injection
Given IV

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
University of California, San Francisco

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 and clofarabine dual therapy for HCT in pediatric patients.		2hours post start on infusion
Primary	Analysis of the Area under the Plasma Concentration versus Time Curve (AUC) of fludarabine and clofarabine dual therapy 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 and clofarabine dual therapy 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 and clofarabine dual therapy for HCT in pediatric patients.		24hours post start of infusion
Secondary	Evaluate the event free survival according to the AUC of fludarabine and clofarabine dual therapy		1month post transplant
Secondary	Evaluate the event free survival according to the AUC of fludarabine and clofarabine dual therapy		3 months post transplant
Secondary	Evaluate the event free survival according to the AUC of fludarabine and clofarabine dual therapy		1 year post transplant