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

Study Overview
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Brief Summary
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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
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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.

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

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

Intervention / Treatment
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* Drug: Clofarabine
* Drug: Fludarabine Injection


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Pediatric Bone Marrow Transplantation Recipients<br>Children undergoing alloHCT at UCSF Benioff Children's Hospital. | Drug: Clofarabine<br>* Given IV<br>Drug: Fludarabine Injection<br>* Given IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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fludarabine, clofarabine, pharmacokinetics, pediatric, allogeneic