Pharmacokinetic Study of Fludarabine in Pediatric Hematopoietic Stem Cell Transplantation

Study Overview
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Brief Summary
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The purpose of this study is to analysis of the pharmacokinetics of fludarabine for hematopoietic stem cell transplantation in pediatric patients.

Detailed Description
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Fludarabine is a commonly used chemotherapeutic agent for hematopoietic stem cell transplantation in children. However, no pharmacokinetic study has thus far been conducted in pediatric patients. Fludarabine can cause adverse reactions which include neurotoxicity, damage to lungs. Pharmacokinetic study is critical to predict the safety of fludarabine in pediatric patients. Through an individualized pharmacokinetic study (which entails numerous samplings) of fludarabine in pediatric patients, this study aims to develop a sampling-minimized analysis method and study the population pharmacokinetics. Through a pharmacokinetic analysis, we aim to evaluate whether pediatric patients show similar population pharmacokinetics of adults, for whom fludarabine is authorized, and evaluate the safety (toxicity) and efficacy (event free survival).

Official Title
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Pharmacokinetic Study of Fludarabine in Pediatric Hematopoietic Stem Cell Transplantation

Conditions
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Acute Leukemia, Chronic Leukemia, Severe Aplastic Anemia

Intervention / Treatment
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* Drug: Fludarabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Conditioning regimen including fludarabine Age: < 19 years old Functional class: ECOG 0-2 No loss of function of major organs. Criteria may be individualized. Heart: shortening fraction > 30%, ejection fraction > 45%. Liver: total bilirubin < 2 ⅹ upper limit of normal; ALT < 3 ⅹ upper limit of normal. Kidney: creatinine < 2 ⅹ normal or a creatinine clearance (GFR) > 60 ml/min/1.73m2. No active viral or fungal infection Appropriate hematopoietic stem cell donor Informed consent from patients' parents Exclusion Criteria: Pregnant or breast feeding Disease progression due to clinical test Psychiatric disease may interfere with clinical test Whether attending physician consider the patient inappropriate for study enrollment

Ages Eligible for Study
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Maximum Age: 19 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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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fludarabine<br>Analysis of the pharmacokinetics of fludarabine for hematopoietic stem cell transplantation in pediatric patients | Drug: Fludarabine<br>* Fludarabine 40 mg/m^2 once a day intravenous administration over 30 min Development of sampling-minimized analysis method through individualized pharmacokinetics Sampling time: 0hr (pre-dose), 30 min (post-dose), 1hr, 3hr, 5hr, 8hr, 24hr Population pharmacokinetics analysis Comparative analysis of population pharmacokinetics in pediatric and adult patients Analysis of population pharmacokinetics, toxicity, engraftment rate, survival rate<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Analysis of the pharmacokinetics of fludarabine for hematopoietic stem cell transplantation in pediatric patients |  | 0hr (pre-dose), 30 min, 1, 3, 5, 8, 24hrs post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparative analysis of the pharmacokinetics of fludarabine in pediatric and adult patients |  | 3 years | 
| Evaluation of toxicity, event free survival according to the pharmacokinetics of fludarabine |  | 1, 3, 6 and 12 months after transplantation | 
| Evaluation of therapy related toxicity, significant adverse reaction |  | for 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hematopoietic stem cell transplantation with fludarabine based conditioning