Comparison of Different Dose of Post-transplantation Cyclophosphamide as Graft Versus Host Disease Prophylaxis

Study Overview
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Brief Summary
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Post-transplantation cyclophosphamide (PTCY) is considered as major graft versus host disease (GVHD) prophylaxis. In our previous study, the investigators demonstrated that the standard dose PTCY of 50mg/kg with tacrolimus and post-engrafted low-dose anti-thymoglobulin (ATG) achieved low incidence of acute GVHD. More recently, it has been shown that reduced dose of PTCY of 40mg/kg is considered with similar efficacy as GVHD prophylaxis, In this study, a multi-center randomized comparison is planned to evaluate the clinical outcome of GVHD prophylaxis of PTCy 40 versus 50.

Detailed Description
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Post-transplantation cyclophosphamide (PTCY) is considered as major graft versus host disease (GVHD) prophylaxis. In our previous study, the investigators demonstrated that the standard dose PTCY of 50mg/kg with tacrolimus and post-engrafted low-dose anti-thymoglobulin (ATG) achieved low incidence of acute GVHD. In the clinical setting, reduced dose of PTCY (40mg/kg) was used for patients over 60 or with high HCT-CI and the overall incidence of acute GVHD was similar to PTCY 50mg/kg but chronic GVHD was slightly increased. To confirmed our observation, in this study, a prospective multiple-center randomized comparison is planned to evaluate the clinical outcomes of reduced dose of PTCY (40mg/kg) versus 50mg/kg as GVHD prophylaxis.

Official Title
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A Comparison Study of Reduced Dose of Post-transplantation Cyclophosphamide (PTCy 40mg/kg) Versus Standard (PTCY 50mg/kg): a Multi-center Study for Halo-identical Donor Transplantation

Conditions
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GVHD

Intervention / Treatment
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* Drug: PTCY


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with hematological malignancies Patients undergo allogeneic stem cell transplantation from haplo-identical donors Patents with informed consent provided Exclusion Criteria: Patients with active infection ()bacteria, fungal or viral) Patients with liver, renal and cardiac dysfunction not suitable for undergoing allogeneic stem cell transplantation.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: PTCy-40<br>Patients receive 40mg/kg PTCY (day+3 and +4) with tacrolimus from day+5 and low-dose ATG of 2,5mg/kg 72 hours after documentation neutrophil engraftment. | Drug: PTCY<br>* PTCY as 40mg/kg or 50mg/kg at day +3 and +4 for GVHD prophylaxis<br>|
| Active Comparator: PTCy-50<br>Patients receive 50mg/kg PTCY (day+3 and +4) with tacrolimus from day+5 and low-dose ATG of 2,5mg/kg 72 hours after documentation neutrophil engraftment. | Drug: PTCY<br>* PTCY as 40mg/kg or 50mg/kg at day +3 and +4 for GVHD prophylaxis<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| acute GVHD (grade II-IV) | clinical documentation of grade II-IV aGVHD | day 100 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Non-relapse mortality | Death without documentation of disease relapse or progression (bone marrow >5% or with extra medullary diseases) | 1 year | 
| chronic GVHD | incidence of patients with clinical documentation of chronic GVHD | 1 year | 
| overall survival | Event defined as death of any causes | 1 year | 
| Disease-free survival | Event defined as death of any causes and disease relapse or progression | 1 year | 
| Survival without relapse and moderate to severe GVHD | Rate of patients remain alive without disease relapse or progression (bone marrow blast >5% or extra medullary diseases) and without documentation of grade III-IV acute GVHD and moderate to severe chronic GVHD | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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graft versus host disease (GVHD), post-transplantation cyclophosphamide (PTCy), allogeneic stem cell transplantation, haplo-identical donor