PTCy-ATG vs ATG in Haploidentical HSCT for Acute Graft-versus-host Disease Prophylaxis

Study Overview
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Brief Summary
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The granulocyte colony-stimulating factor (G-CSF)+antithymocyte globulin (ATG)-based protocols and posttransplantation cyclophosphamide (PTCy) protocols have been widely used for graft-versus-host disease (GVHD) prophylaxis in haploidentical related donor transplantation (haplo-HSCT). Nevertheless, severe acute GVHD remains an obstacle for haplo-HSCT. This study is aim to evaluate the efficacy of a modified protocol that includes PTCY and ATG in recipients of haplo-HSCT.

Detailed Description
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Haploidentical related donor transplantation is now considered an important alternative to allogeneic hematopoietic stem cell transplantation (allo-HSCT). Currently, the strategies for graft-versus-host disease (GVHD) prophylaxis mainly include ex vivo and in vivo T-cell depletion (TCD) in haploidentical HSCT (haplo-HSCT). In vivo TCD modalities have become mainstream including granulocyte colony-stimulating factor (G-CSF)+antithymocyte globulin (ATG)-based protocols and posttransplantation cyclophosphamide (PTCy) protocols. The ATG strategy has been widely used. Nevertheless, severe acute GVHD remains an obstacle for haplo-HSCT. In addition, infections, especially viral infections, remain an important drawback of this strategy. This study is aim to evaluate the efficacy of a modified protocol that includes PTCY and ATG in recipients of haplo-HSCT.

Official Title
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A Comparison of PTCy-ATG and ATG Strategy in Haploidentical HSCT for Acute Graft-versus-host Disease Prophylaxis

Conditions
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Hematopoietic Stem Cell Transplantation

Intervention / Treatment
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* Drug: ATG
* Drug: CTX
* Drug: Mycophenolate Mofetil
* Drug: Ciclosporin A (CsA)
* Drug: methotrexate (MTX)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A patient age of 18-65 years Haploidentical hematopoietic stem cell transplant recipient Subjects (or their legally acceptable representatives) must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study Exclusion Criteria: Any abnormality in a vital sign (e.g., heart rate, respiratory rate, or blood pressure) Patients with any conditions not suitable for the trial (investigators' decision)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: PTCy-ATG group<br>PTCy-ATG group refers to treatment with PTCy-ATG protocol as GVHD prophylaxis at a total dose of 4.5mg/kg ATG, a dose of 50mg/kg/d cyclophosphamide (CTX), a dose of 2.5mg/kg/d Ciclosporin A （CsA）, and a dose of 1.0g/d Mycophenolate Mofetil(MMF). | Drug: ATG<br>* In PTCy-ATG group, ATG will be intravenously infused via a central venous catheter from day -3 until day -1 at a total dose of 4.5mg/kg. In ATG group, ATG will be intravenously infused via a central venous catheter from day -5 until day -2 at a total dose of 7.5mg/kg.<br>Drug: CTX<br>* In PTCy-ATG group, CTX will be intravenously infused via a central venous catheter on day +4 at a dose of 50mg/kg/d.<br>Drug: Mycophenolate Mofetil<br>* In PTCy-ATG group, Mycophenolate Mofetil will be taken orally from day +5 with the dosage of 0.5g twice a day. The dosage will be halved from day +30. In ATG group, Mycophenolate Mofetil will be taken orally from day -9 with the dosage of 0.5g twice a day. The dosage will be halved from day +30.<br>Drug: Ciclosporin A (CsA)<br>* In PTCy-ATG group, Ciclosporin A (CsA) will be intravenously infused from day +5 at a dose of 2.5mg/kg/d. In ATG group, Ciclosporin A (CsA) will be intravenously infused from day -9 at a dose of 2.5mg/kg/d.<br>|
| Active Comparator: ATG group<br>ATG group refers to treatment with ATG protocol as GVHD prophylaxis at a total dose of 7.5mg/kg ATG, a dose of 2.5mg/kg/d Ciclosporin A （CsA）, a dose of 1.0g/d Mycophenolate Mofetil(MMF) and methotrexate (MTX, on days +1, +3 and +6). | Drug: ATG<br>* In PTCy-ATG group, ATG will be intravenously infused via a central venous catheter from day -3 until day -1 at a total dose of 4.5mg/kg. In ATG group, ATG will be intravenously infused via a central venous catheter from day -5 until day -2 at a total dose of 7.5mg/kg.<br>Drug: Mycophenolate Mofetil<br>* In PTCy-ATG group, Mycophenolate Mofetil will be taken orally from day +5 with the dosage of 0.5g twice a day. The dosage will be halved from day +30. In ATG group, Mycophenolate Mofetil will be taken orally from day -9 with the dosage of 0.5g twice a day. The dosage will be halved from day +30.<br>Drug: Ciclosporin A (CsA)<br>* In PTCy-ATG group, Ciclosporin A (CsA) will be intravenously infused from day +5 at a dose of 2.5mg/kg/d. In ATG group, Ciclosporin A (CsA) will be intravenously infused from day -9 at a dose of 2.5mg/kg/d.<br>Drug: methotrexate (MTX)<br>* In ATG group, methotrexate (MTX) will be intravenously on days +1, +3 and +6.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CMV DNAemia | CMV DNAemia was defined as positive CMV-DNA in the blood when the copies exceeded 500 copies/ml. | 1 year posttransplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| aGVHD | aGVHD (acute GVHD) was defined according to the 1994 Consensus Conference on Acute GVHD Grading and graded from I to IV. | 100 days 1 year posttransplantation | 
| cGVHD | Chronic GVHD (cGVHD) was graded as limited or extensive. | 2 year posttransplantation | 
| EBV DNAemia | EBV DNAemia was defined as positive EBV-DNA in the blood when the copies exceeded 500 copies/ml. | 1 year posttransplantation | 
| Leukemia relapse | primary disease relapse | 2 year posttransplantation | 
| OS | overall survival | 2 year posttransplantation | 
| DFS | disease-free survival | 2 year posttransplantation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hematopoietic Stem Cell Transplantation, posttransplantation cyclophosphamide, antithymocyte globulin, viral infection, graft-versus-host disease