ATG Plus Low-dose PT-Cy for GVHD Prevention

Study Overview
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Brief Summary
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During the past decades, the wider application of easily available haploidentical donor hematopoietic cell transplant (haplo-HCT) has been made possible through the T cell-replete (TCR) regimens including T cell regulation with anti-thymocyte globulin (ATG)/granulocyte colony-stimulating factor (GCSF) and post-transplant cyclophosphamide (PTCy). To achieve decreased non-relapse mortality (NRM) and improved long-term outcomes in haploidentical transplant, the joint use of ATG and PTCy might effectively reduce graft versus host disease (GVHD) and mortality associated with severe forms of GVHD. Recently, investigators established a regimen using low-dose PTCy in conjunction with standard-dose ATG in order to lower the risk of GVHD without compromising engraftment and disease relapse.

Official Title
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Randomized Trial of Anti-thymocyte Globulin Plus Low-dose Post-transplant Cyclophosphamide for GVHD Prevention in Haploidentical Donor HCT

Conditions
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Hematologic Malignancy

Intervention / Treatment
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* Drug: Cyclophosphamid
* Drug: ATG


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with acute leukemia and/or myelodysplastic syndrome undergoing their first allogeneic hematopoietic stem cell transplantation; Male or female , aged 12-55 years; Haploidentical donor transplantation; ECOG score ≤3; The basic organ function tests met the following standards; 1) Cardiac ejection index >55% 2) Creatinine ≤1.5 times the highest normal value (ULN) Exclusion Criteria: Severe brain, heart, kidney or liver dysfunction; Refractory malignant state; Patients with other malignant tumors requiring treatment; Clinically uncontrolled severe active infection; The expected survival time was less than 3 months. A history of severe anaphylaxis. Pregnant or lactating women; Any condition considered by the investigators to be unsuitable for enrollment.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 55 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-PTCy cohort<br>The conditioning regimen is ATG/G-CSF based protocol (the so-called Beijing protocol). The rabbit ATG (Sangstat-Genzyme) 2.5mg/kg/day i.v., on days from - 5 to - 2 were administered.Two doses of 14.5 mg/kg Cy were given on days 3 and 4 post-HCT in ATG-PTCy cohort. | Drug: Cyclophosphamid<br>* A total of 10mg/kg ATG was administered, and two doses of 14.5 mg/kg Cy were given on days 3 and 4 post-HCT in ATG-PTCy cohort.<br>Drug: ATG<br>* A total of 10mg/kg ATG was administered.<br>|
| Active Comparator: ATG cohort<br>The conditioning regimen is ATG/G-CSF based protocol (the so-called Beijing protocol). The rabbit ATG (Sangstat-Genzyme) 2.5mg/kg/day i.v., on days from - 5 to - 2 were administered. | Drug: ATG<br>* A total of 10mg/kg ATG was administered.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of acute graft versus host disease. | The incidence of acute graft versus host disease. The severity of acute GVHD was evaluated according to standard international criteria. | 100 days post HSCT. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Engraftment | Myeloid engraftment was defined as the first of three consecutive days with an ANC X0.5≥10^9/L. | 30 days post HSCT. | 
| The incidence of chronic GvHD | The incidence of chronic GvHD. | 1 year post HSCT. | 
| The incidence of non-relapse mortality | The incidence of non-relapse mortality | 1 year post HSCT. | 
| The incidence of infection | The incidence of infection | 1 year post HSCT. | 
| The incidence of relapse | The incidence of relapse | 1 year post HSCT. | 
| Overall survival | Overall survival | 1 year post HSCT. | 
| Disease free survival | Disease free survival | 1 year post HSCT. | 
| GvHD relapse free survival | GvHD relapse free survival | 1 year post HSCT. | 
| Immune reconstitution | Immune reconstitution was evaluated at 1, 2, 3, 6, 9 and 12 months by analysis of peripheral blood MNCs detecting CD3, CD4, CD19 and immunoglobulin (Ig) A, G and M levels. | 1 year post HSCT. |