NCT03609814

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

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

• Status: Completed
• Phase: —
• Study type: Observational
• Enrollment: 30 (actual)
• Sponsor: University of California, San Francisco · Academic / Other
• Sex: All
• Age: 17 Years
• Healthy volunteers: Not accepted

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.

Detailed 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.

Conditions

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

Interventions

Type	Name	Description
DRUG	Clofarabine	Given IV
DRUG	Fludarabine Injection	Given IV

Timeline

• Start date: 2016-01-26
• Primary completion: 2020-06-30
• Completion: 2020-06-30
• First posted: 2018-08-01
• Last updated: 2021-10-04

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study