Targeted Busulfan, Fludarabine Conditioning Regimen for Hematopoietic Stem Cell Transplantation in Chronic Granulomatous Disease(CGD)

Study Overview
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Brief Summary
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In this study the investigators plan to use optimal busulfan dose through pharmacokinetic study in stem cell transplantation of CGD patients.

Detailed Description
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Chronic granulomatous disease is one of the rare congenital immunodeficiency which can be cured by hematopoietic stem cell transplantation. Previous myeloablative conditioning regimen has problems related to the severe toxicities, and non-myeloablative conditioning regimen has the risk of graft failure. Recently, reduced-intensity myeloablative conditioning regimen with busulfan and fludarabine was used usually in leukemia patients. Busulfan is a highly toxic drug with narrow therapeutic window. In this study we plan to use optimal busulfan dose through pharmacokinetic study in stem cell transplantation of CGD patients.

Conditions
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Chronic Granulomatous 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 CGD. Patients who need hematopoietic stem cell transplantation with busulfan based conditioning regimen. Age: No limit. 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. Heart: a shortening fraction > 30% and ejection fraction > 45%. Liver: total bilirubin < 2 × upper limit of normal; ALT < 3 × upper limit of normal. 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. Patients (or one of parents if patients age < 20) should sign informed consent.
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 |
| --- | --- | --- |
| Engraftment rate | To evaluate engraftment rate after hematopoietic stem cell transplantation. | 1 month after transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Transplantation-related mortality and toxicities | To evaluate 1-year event free survival after hematopoietic stem cell transplantation, toxicities associated with hematopoietic stem cell transplantation, acute and chronic GVHD, treatment related mortality and relapse rate. | 1, 3, 6 and 12 months after transplantation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic granulomatous disease, Hematopoietic Stem Cell Transplantation