Study of Fludarabine + Cyclophosphamide + TBI Conditioning Regimen for Double Units Cord Blood Transplantation(CBT)in Severe Aplastic Anemia(SAA)

Study Overview
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Brief Summary
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Severe aplastic anemia is a fatal disease and patients without HLA matched siblings need alternative treatment option. Cord blood transplantation (CBT) has become an alternative treatment means in various diseases, but it has not been proved to be good for severe aplastic anemia. Double units CBT is proposed to have better engraftment potential and and we reported successful double units UCBT after engraftment failure with single unit with promising result. To increase the engraftment potential, fludarabine, cyclophosphamide plus TBI conditioning regimen for double units cord blood transplantation was proposed for the patient with severe aplastic anemia without HLA-matched donor.

Official Title
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Phase I/II Study of Fludarabine, Cyclophosphamide Plus TBI Conditioning Regimen for Double Units Cord Blood Transplantation in Severe Aplastic Anemia

Conditions
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Aplastic Anemia

Intervention / Treatment
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* Other: Cyclophosphosphamide, TBI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of severe aplastic anemia defined by any two or three peripheral blood criteria and either marrow criterion. Peripheral blood Neutrophils < 0.5 x 109/l Platelets < 20 x 109/l Corrected reticulocytes < 1% Bone marrow Severe hypocellularity (< 25%) Moderate hypocellularity (25-30%) with hematopoietic cells representing < 30% of residual cells No prior hematopoietic stem cell transplantation. Age: no limits. 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%, 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. No appropriate donor Appropriate cord blood is available: matched at least in 4/6 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. Congenital aplastic anemia including Fanconi anemia.

Ages Eligible for Study
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Minimum Age: 1 Year
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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fludarabine<br> | Other: Cyclophosphosphamide, TBI<br>* fludarabine (30 mg/m2 once daily i.v. on days -7, -6, -5, -4, -3, & -2) (if body weight < 10 kg or if age < 1 year: 1.33 mg/kg) cyclophosphamide (60 mg/kg once daily i.v. on days -9, & -8) total body irradiation (3G on days -1)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the engraftment potential of fludarabine, busulfan plus thymoglobulin conditioning regimen for cord blood transplantation (CBT) in severe aplastic anemia. |  | From Oct 2008. to Sep 2011 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the incidence and severity of toxicity and treatment related mortality |  | From Oct 2008. to Sep 2011 | 
| To evaluate overall and event free survival rate |  | From Oct 2008. to Sep 2011 | 
| To evaluate acute and chronic GVHD |  | From Oct 2008. to Sep 2011 | 
| To evaluate immunologic recovery after CBT |  | From Oct 2008. to Sep 2011 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fludarabine, Cyclophosphamide, TBI, severe aplastic anemia,, cord blood transplantation, pediatric