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

Sponsor

University of California, San Francisco (Other)

Overall Status

Completed

CT.gov ID

NCT03609814

Collaborator

(none)

Enrollment

Location

53.1

Actual Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Hematologic Malignancies Nonmalignant Diseases Immunodeficiencies Hemoglobinopathies Genetic Inborn Errors of Metabolism Fanconi's Anemia Thalassemia Sickle Cell Disease	Drug: Clofarabine Drug: Fludarabine Injection

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.

Study Design

Study Type:

Observational

Actual Enrollment :

30 participants

Observational Model:

Other

Time Perspective:

Prospective

Official Title:

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

Actual Study Start Date :

Jan 26, 2016

Actual Primary Completion Date :

Jun 30, 2020

Actual Study Completion Date :

Jun 30, 2020

Arms and Interventions

Arm	Intervention/Treatment
Pediatric Bone Marrow Transplantation Recipients Children undergoing alloHCT at UCSF Benioff Children's Hospital.	Drug: Clofarabine Given IV Drug: Fludarabine Injection Given IV

Arm

Intervention/Treatment

Pediatric Bone Marrow Transplantation Recipients

Children undergoing alloHCT at UCSF Benioff Children's Hospital.

Drug: Clofarabine

Given IV

Drug: Fludarabine Injection

Given IV

Outcome Measures

Primary Outcome Measures

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]
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]
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]
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 Outcome Measures

Evaluate the event free survival according to the AUC of fludarabine and clofarabine dual therapy [1month post transplant]
Evaluate the event free survival according to the AUC of fludarabine and clofarabine dual therapy [3 months post transplant]
Evaluate the event free survival according to the AUC of fludarabine and clofarabine dual therapy [1 year post transplant]