Population Pharmacokinetics and Safety of Oral Posaconazole in Children With Leukemia

Study Overview
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Brief Summary
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This study is designed to evaluate the safety, efficacy and Population Pharmacokinetics of Oral Posaconazole in Children with leukemia.

Detailed Description
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Posaconazole as a new triazole antifungal agent with broad spectrum coverage, was recommended for prophylaxis of invasive fungal disease in adults. Some studies have demonstrated the relationship between posaconazole plasma concentration and efficacy and few data have been published in children with leukemia.The purpose of this study is to describe the off-label use of posaconazole oral suspensions in children;to figure out the relationship between concentration and clinical outcomes/ adverse events;to identify factors that influence plasma concentration.

Official Title
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Population Pharmacokinetics and Safety of Oral Posaconazole in Children With Leukemia

Conditions
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Leukemia, Acute

Intervention / Treatment
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* Drug: posaconazole oral suspensions


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1、Patients age 2-14 years with acute leukemia (AML, ALL) undergoing chemotherapy and neutropenia expected to last at least 7 days. 2、Karnofsky/Lansky score of 60% or greater. 3、defined as alanine transaminase (ALT) <3 x upper limit of normal (ULN),aspartate aminotransferase (AST) <3 x ULN; serum bilirubin and alkaline phosphatase <2 x ULN. 4、No other treatment and combination of triazoles antifungals and drugs like vincristine, sirolimus, cyclosporine etc. 5、Able to take oral medication or take medication via enteral feeding tube. 6、Ability to give informed consent. 7、No history of anaphylaxis attributed to the azole class of antifungal agents. Exclusion Criteria: 1、Existing severe illness (e.g. significant cardiac, pulmonary, hepatic diseases, etc.) or major organ dysfunction. 2、Subject is not considered eligible for this clinical research program with posaconazole. 3、Use of medications that are known to interact with posaconazole and that may lead to life-threatening side to effects.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 14 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: posaconazole as antifungal prophylaxis<br> | Drug: posaconazole oral suspensions<br>* posaconazole oral suspensions（5mg/kg/d,tid) will be administered specially febrile neutropenia patients four times a day and blood samples will be taken any hours after the first dose at least Day 7.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number, type and grade of adverse events of posaconazole assessed by CTCAE v4.0 | Number, type and grade of adverse events of posaconazole oral suspensions to children with leukemia assessed by CTCAE v4.0. | 1 year | 
| Plasma posaconazole concentration monitoring and its pharmacokinetic | Blood samples for determination of plasma posaconazole concentration will be collected predoses (just prior to a daily dose) on days 3, 7, 14 and 21. Anther concentration (include peak concentraton) will also be collected at least 7days after the first dose. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serious Adverse events and drug-related adverse events monitoring |  | 2 years |