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

Study Overview
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Brief Summary
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The purpose of this study is to compare the incidences of GVHD and viral infections in haploidentical hematopoietic stem cell transplant recipients receiving different dose of antithymocyte globulin (ATG) for acute graft-versus-host disease(aGVHD) prophylaxis. Our first objective was to investigate the optimal dose of ATG for aGVHD and second object was to evaluate the effect of different dose of ATG on post-transplant viral infection.

Detailed Description
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Allogeneic hematopoietic stem cell transplantation (allo-HSCT)is the only therapeutic option for many hematological malignancies. Unfortunately, about 75% of patients who require allo-HSCT lack human leukocyte antigen (HLA)-matched donors. The alternative is hematopoietic stem cells from an HLA-mismatched family donor. However, this strategy, which is called haploidentical HSCT, may be associated with high risk of early death and severe GVHD. Opportunistic infections are common complications after allo-HSCT. Due to the absence of effective preventive and therapeutic drugs for most viruses, viral infections has become one of the most important causes of death. The immunosuppression regimen including ATG has been shown effective to prevent severe GVHD in haploidentical HSCT. But this strategy delays immune reconstitution, and therefore increase the risk of viral infection. The optimal dose of the different ATG preparations with respect to prevention of GvHD is not fully understood today. The total doses between 6 mg/kg to 15 mg/kg are effective for prevention of GVHD, but the dose above 10 mg/kg may increase the development of viral infection. In this trial, we will focus on the incidence of aGVHD and viral infections in patients treated with 7.5mg/kg or 10mg/kg of ATG. The incidence of GVHD and viral infections will be compared between different dose arms.

Official Title
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Dose Study of Antithymocyteglobulin in Haploidentical Hematopoietic Stem Cell Transplantation for Acute Graft-versus-host Disease Prophylaxis

Conditions
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Hematopoietic Stem Cell Transplantation, Antithymocyte Globulin, Viral Infection

Intervention / Treatment
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* Drug: ATG


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A patient age of 14-65 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: 14 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ATG 7.5mg/kg<br>ATG 7.5mg/kg group refers to treatment with ATG in the total dose of 7.5mg/kg. | Drug: ATG<br>* ATG will be intravenously infused via a central venous catheter in 3 or 4 days, from day -4 or -3 until day -1. The other conditioning drugs administered before transplantation include cytosine arabinoside (Ara-C), busulfan (Bu),cyclophosphamide (Cy), Semustine(Me-CCNU), and ATG. All transplant recipients will receive cyclosporine A (CsA), mycophenolate mofetil(MMF), and short-term methotrexate for aGVHD prevention.<br>|
| Experimental: ATG 10mg/kg<br>ATG 10mg/kg group refers to treatment with ATG in the total dose of 10mg/kg. | Drug: ATG<br>* ATG will be intravenously infused via a central venous catheter in 3 or 4 days, from day -4 or -3 until day -1. The other conditioning drugs administered before transplantation include cytosine arabinoside (Ara-C), busulfan (Bu),cyclophosphamide (Cy), Semustine(Me-CCNU), and ATG. All transplant recipients will receive cyclosporine A (CsA), mycophenolate mofetil(MMF), and short-term methotrexate for aGVHD prevention.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Epstein-Barr virus(EBV) viremia | Incidence of EBV viremia within 1 year | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of acute GVHD | Acute GVHD was graded according to standard criteria. | 100 days | 
| Incidence of EBV-associated diseases | the Incidence of EBV-associated end-organ diseases | 2 years | 
| Immune reconstitution | Immune reconstitution is performed every 3 months after transplantation. | 1 year | 
| Survival | Survival includes overall and disease-free survival within 2 years after transplantation. | 3 years | 
| Incidence of chronic GVHD | Chronic GVHD was assessed in patients alive after day 100. | 2 years | 
| Incidence of cytomegalovirus(CMV) viremia | Incidence of CMV viremia within 1 year | 1 year | 
| Incidence of CMV-associated diseases | the Incidence of CMV-associated end-organ diseases | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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haploidentical hematopoietic Stem Cell Transplantation, Antithymocyte globulin, viral infection