Efficacy and Safety Study of ATG for Prophylaxis of aGVHD in Matched Sibling Donor PBSCT

Study Overview
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Brief Summary
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The purpose of this study is to determine the efficacy and safety of combined ATG （antithymocyte globulin ） regimen for aGVHD(acute graft-versus-host disease ) prophylaxis in matched sibling donor peripheral blood stem cell transplantation (MSD-PBSCT).

Detailed Description
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Transplantation with G-CSF （Granulocyte colony stimulating factor ）mobilized peripheral blood stem cell (PBSCT) has been a stable transplant setting with matched sibling donor transplantation. Unmanipulated haploidentical donor PBSCT (haplo-PBSCT) has been applied in patients with hematologic malignancies. In our previous cohort study, haplo-PBSCT was associated with lower incidence of severe acute GVHD and extensive chronic GVHD compared with matched sibling donor PBSCT (MSD-PBSCT). Haplo-PBSCT has the same GVHD prophylaxis regimen with MSD-PBSCT, except ATG. It suggested the potential advantage of ATG in prophylaxis of GVHD and improvement of long-term quality of life of the transplant recipients, which motivate us to observe the efficacy of combined ATG regimen for GVHD prophylaxis in MSD-PBSCT.

Official Title
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Prospective Study of Combined ATG Regimen for Prophylaxis of aGVHD in Matched Sibling Donor PBSCT

Conditions
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aGVHD

Intervention / Treatment
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* Drug: ATG
* Drug: CsA
* Drug: mycophenolate mofetil
* Drug: Methotrexate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: acute myeloid leukemia (AML) in CR1 (complete remission 1) or CR2 (complete remission 2) phase regardless of cytogenetics; CML CP(chronic myelogenous leukemia , chronic phase); NHL (non-Hodgkin's lymphoma ) MDS-RAEB(myelodysplastic syndrome -refractory anemia with excess blasts ). All patients should aged 40 to 70 years Have matched sibling donor. Patients without any uncontrolled infections or without severe pulmonary, renal, hepatic or cardiac diseases . Exclusion Criteria: Patients aged less than 40 years old ; Patients with any uncontrolled infections or with severe pulmonary, renal, hepatic or cardiac diseases; AML patients with t (15;17);

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 70 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 |
| --- | --- |
| Experimental: ATG combined regimen<br>ATG combined regimen for prophylaxis of GVHD, includes ATG, MMF(Mycophenolate mofetil ),CsA (cyclosporin A) and MTX (methotrexate). All recipients in this arm received ATG, CsA, mycophenolate mofetil, and short-term methotrexate for GVHD prophylaxis. ATG (Thymoglobuline, rabbit) was used as 1.5 mg/kg/d on day -5 and 3.5 mg/kg/d on day -4. CsA (3 mg/kg, q12h, i.v.) was used from day -9, and the concentration was adjusted to 180-200 ng/mL. CsA was switched to oral administration when the patient's bowel function recovered. From day -9, 0.5 g of mycophenolate mofetil was administered orally from every 12 h, which was withdrawn on day +30. After graft infusion, MTX was given for all patients at 15 mg/m2 on day +1 and 10 mg/m2 on days +3, +6 and +11. | Drug: ATG<br>* rabbit ATG（Sanofi）<br>* Other names: Thymoglobuline;Drug: CsA<br>* cyclosporine (3 mg/kg, q12h, i.v.) was used from day -9, and the concentration was adjusted to 180-200 ng/mL. CsA was switched to oral administration when the patient's bowel function recovered.<br>* Other names: Neoral/Sandimmun;Drug: mycophenolate mofetil<br>* From day -9, 0.5 g of mycophenolate mofetil was administered orally from every 12 h, which was withdrawn on day +30 for MSD-PBSCT.<br>* Other names: MMF（Novartis）;Drug: Methotrexate<br>* short-term methotrexate<br>* Other names: MTX(Pfizer);|
| Active Comparator: no-ATG<br>regimen for prophylaxis of GVHD without ATG. The regimen includes MMF,CsA and MTX.CsA (3 mg/kg, q12h, i.v.) was used from day -9, and the concentration was adjusted to 180-200 ng/mL. CsA was switched to oral administration when the patient's bowel function recovered. From day -9, 0.5 g of mycophenolate mofetil was administered orally from every 12 h, which was withdrawn on day +30. After graft infusion, MTX was given for all patients at 15 mg/m2 on day +1 and 10 mg/m2 on days +3, +6 and +11. | Drug: CsA<br>* cyclosporine (3 mg/kg, q12h, i.v.) was used from day -9, and the concentration was adjusted to 180-200 ng/mL. CsA was switched to oral administration when the patient's bowel function recovered.<br>* Other names: Neoral/Sandimmun;Drug: mycophenolate mofetil<br>* From day -9, 0.5 g of mycophenolate mofetil was administered orally from every 12 h, which was withdrawn on day +30 for MSD-PBSCT.<br>* Other names: MMF（Novartis）;Drug: Methotrexate<br>* short-term methotrexate<br>* Other names: MTX(Pfizer);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with cGVHD as assessed by chronic graft versus host disease grading criteria (refer to NIH criteria) | Chronic graft versus host disease grading criteria (refer to NIH criteria) | three years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| all cause mortality |  | two years | 
| Number of participants relapse as assessed by NCCN (National Comprehensive Cancer Network )criteria |  | two years | 
| DFS(disease-free survival ) | disease-free survival | two years | 
| TRM(treatment-related mortality ) | treatment-related mortality | two years | 
| Number of participants with aGVHD as assessed by acute graft versus host disease grading criteria (refer to Glucksberg criteria) |  | three months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ATG, Matched sibling donor, peripheral blood stem cell transplantation