Targeted Busulfan, Fludarabine Conditioning Regimen for Hematopoietic Stem Cell Transplantation in GRD

Study Overview
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Brief Summary
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To evaluate the outcome of hematopoietic stem cell transplantation using targeted busulfan, fludarabine conditioning regimen in genetic rare disease

Detailed Description
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Busulfan is a highly toxic drug with narrow therapeutic window used for the conditioning of hematopoietic stem cell transplantation. High exposure is associated with systemic toxicity such as veno-occlusive disease (VOD) and underexposure is associated with graft failure or relapse. In this study the investigators plan to improve the outcome of hematopoietic stem cell transplantation by using optimal busulfan dose through pharmacokinetic study.

Official Title
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Targeted Busulfan, Fludarabine Conditioning Regimen for Hematopoietic Stem Cell Transplantation in Genetic Rare Disease

Conditions
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Genetic Rare Disease

Intervention / Treatment
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* Drug: Busulfan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who are diagnosed as genetic rare disease. Patients who need hematopoietic stem cell transplantation Age: up to 21 years Performance status: ECOG 0-2. Patients must be free of significant functional deficits in major organs, but the following eligibility criteria may be modified in individual cases. 1. Heart: a shortening fraction > 30% and ejection fraction > 45%. 2. Liver: total bilirubin < 2 × upper limit of normal; ALT < 3 × upper limit of normal. 3. Kidney: creatinine <2 × normal or a creatinine clearance (GFR) > 60 ml/min/1.73m2. Patients must lack any active viral infections or active fungal infection. Appropriate donor is available: Matched in 6/6 of A, B, DR loci. Patients (or one of parents if patients age < 19) should sign informed consent. Exclusion Criteria: Pregnant or nursing women. Malignant or nonmalignant illness that is uncontrolled or whose control may be jeopardized by complications of study therapy. Psychiatric disorder that would preclude compliance.

Ages Eligible for Study
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Maximum Age: 21 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: Busulfan<br>First dose: busulfan (120 mg/m2 ivs once daily) (if age<1 yr: 80 mg/ m2) Second to forth dose: according to the daily pharmacokinetic study | Drug: Busulfan<br>* First dose: busulfan (120 mg/m2 ivs once daily) (if age<1 yr: 80 mg/ m2) Second to forth dose: according to the daily pharmacokinetic study<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate engraftment rate | To evaluate engraftment rate | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate treatment related mortality | To evaluate treatment related mortality | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hematopoietic stem cell transplantation