Hematopoietic Stem Cell Transplantation for Patients With Thalassemia Major: A Multicenter, Prospective Clinical Study

Study Overview
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Brief Summary
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The only curative therapy for thalassemia major remains the replacement of the defective erythropoiesis by allogeneic hematopoietic stem cell transplantation(allo-HSCT). We conduct a prospective multicenter study to evaluate the efficacy of allo-HSCT in the treatment of thalassemia major.

Detailed Description
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Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is one of the established curative option for thalassemia major (TM). Previous study has predicted that more than 90% of TM patients can survive after allo-HSCT with a thalassemia-free survival (TFS) in around 80% of them.The purpose of this study is to evaluate the efficacy of allo-HSCT in the treatment of thalassemia major.

Official Title
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Hematopoietic Stem Cell Transplantation for Patients With Thalassemia Major: A Multicenter, Prospective Clinical Study

Conditions
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Thalassemia Major

Intervention / Treatment
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* Drug: Busulfan
* Drug: Cyclophosphamide
* Drug: Fludarabine
* Drug: Thymoglobulin
* Drug: cyclosporine A
* Drug: Mycophenolate mofetil
* Drug: Tacrolimus
* Drug: Methotrexate
* Drug: Basiliximab
* Drug: Ruxolitinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with thalassemia major. Indication of hematopoietic stem cell transplantation. A cardiac ejection fraction of >50%; normal pulmonary function tests and pulmonary examination results; and normal kidney function. Exclusion Criteria: Aspartate aminotransferase levels > 4-fold the upper limit of the normal range for our institution's lab criteria; Uncontrolled bacterial, viral or fungal infections; Any other restriction for transplantation.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 20 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
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MSD-HSCT<br>matched sibling donors hematopoietic stem cell transplantation | Drug: Busulfan<br>* Busulfan（4 mg/kg/day,4 days）<br>* Other names: Bu;Drug: Cyclophosphamide<br>* Cyclophosphamide（50 mg/kg/day,4 days）<br>* Other names: Cy;Drug: Fludarabine<br>* Fludarabine（50 mg/m2/day,3 days）<br>* Other names: Flu;Drug: Thymoglobulin<br>* Thymoglobulin（2.5 mg/kg/day,4 days）<br>* Other names: ATG;Drug: cyclosporine A<br>* cyclosporine A<br>* Other names: CsA;Drug: Mycophenolate mofetil<br>* Mycophenolate mofetil（0.25g/day）<br>* Other names: MMF;Drug: Methotrexate<br>* Methotrexate<br>* Other names: MTX;|
| Experimental: URD-HSCT<br>unrelated donor hematopoietic stem cell transplantation | Drug: Busulfan<br>* Busulfan（4 mg/kg/day,4 days）<br>* Other names: Bu;Drug: Cyclophosphamide<br>* Cyclophosphamide（50 mg/kg/day,4 days）<br>* Other names: Cy;Drug: Fludarabine<br>* Fludarabine（50 mg/m2/day,3 days）<br>* Other names: Flu;Drug: Thymoglobulin<br>* Thymoglobulin（2.5 mg/kg/day,4 days）<br>* Other names: ATG;Drug: Mycophenolate mofetil<br>* Mycophenolate mofetil（0.25g/day）<br>* Other names: MMF;Drug: Tacrolimus<br>* Tacrolimus<br>* Other names: FK506;Drug: Methotrexate<br>* Methotrexate<br>* Other names: MTX;Drug: Ruxolitinib<br>* Ruxolitinib<br>|
| Experimental: haplo-HSCT<br>haplo-identical hematopoietic stem cell transplantation | Drug: Busulfan<br>* Busulfan（4 mg/kg/day,4 days）<br>* Other names: Bu;Drug: Cyclophosphamide<br>* Cyclophosphamide（50 mg/kg/day,4 days）<br>* Other names: Cy;Drug: Fludarabine<br>* Fludarabine（50 mg/m2/day,3 days）<br>* Other names: Flu;Drug: Thymoglobulin<br>* Thymoglobulin（2.5 mg/kg/day,4 days）<br>* Other names: ATG;Drug: Mycophenolate mofetil<br>* Mycophenolate mofetil（0.25g/day）<br>* Other names: MMF;Drug: Tacrolimus<br>* Tacrolimus<br>* Other names: FK506;Drug: Methotrexate<br>* Methotrexate<br>* Other names: MTX;Drug: Basiliximab<br>* Basiliximab<br>* Other names: Simulect;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | 2-years overall survival | 2 years | 
| Thalassemia-free survival | 2-years thalassemia-free survival | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Engraftment | Myeloid engraftment at day +30 | 30 days | 
| Transplant Related Mortality | Transplant-related mortality by 1 year | 1 year | 
| Cumulative Incidence of acute Graft Versus Host Disease | Acute graft versus host disease at day +180 | 180 days | 
| Cumulative Incidence of chronic Graft Versus Host Disease | Chronic graft versus host disease by 2 years | 2 years | 
| Cumulative Incidence of Infectious Complications | Cumulative incidence of bacterial, fungal and viral infections by 2 years | 2 years | 

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