Abatacept s.c. for aGVHD Prevention in Haplo-HCT

Study Overview
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Brief Summary
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Acute graft-versus-host disease (aGVHD) is a potentially fatal complication after allogeneic hematopoietic cell transplantation (HCT), particularly for that with a HLA-mismatched donor. Abatacept has been demonstrated as a potent drug to reduce the risk of aGVHD, but the efficacy of subcutaneous form has yet been investigated. This trial is designed to preliminarily determin the efficacy and saftey of subcutaneous abatacept in the prevention of aGVHD after haplo-identical HCT.

Official Title
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The Efficacy and Safety of Subcutaneous Abatacept in the Prevention of Acute Graft-versus-host Disease After Haplo-identical Donor Hematopoietic Cell Transplantation

Conditions
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Abatacept, Acute-graft-versus-host Disease, Haplo-identical HCT, Prevention

Intervention / Treatment
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* Drug: Abatacept s.c.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age≧18 years ECOG score 0-2 / Karnofsky score≧80 haplo-HCT is proposed Conditioning with motified Bu/Cy+ATG regimen Having the following hematologic malignancies with transplant indications: Acute leukemia Myelodysplastic syndrome Aggressive lymphoma Expected survival ≥ 3 months Written informed Consent can be acquired Agree to use effective contraception Exclusion Criteria: With a history of allo-HCT previously Allergic/intolerant to Abatacept Contraindications to the use of Abatacept HIV infection, or active HBV infection or HCV infection Uncontrolled active infection Vital organ function intolerated to transplantation Other malignancies except for the following diseases: malignant tumors that have been cured for at least 3 years without active lesions; adequete treated non-melanoma skin cancer, malignant amygdala, and carcinoma in situ without active lesions Evidence of complications or medical conditions that may interfere with research or put the subjects at serious risk, including but not limited to severe cardiovascular disease (e.g. New York Heart Association grade III or IV heart disease, myocardial infarction in the past 6 months, unstable arrhythmia or unstable angina) and/or severe lung disease (e.g. history of severe obstructive lung disease and symptomatic bronchospasm) Pregnant and lactational women Any life-threatening disease, medical condition, or organ dysfunction unfit for participants, or may interfere with the absorption or metabolism of Abatacept

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>The participants in Cohort 1 will receive abatacept s.c | Drug: Abatacept s.c.<br>* subcutaneous abatacept: 250mg (d-1) , 125mg (d+5, +14, +21, +28, +35, +42, +49, +56) combined with CsA, MTX, MMF.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of overt aGVHD | The incidence of grade II-IV aGVHD post-transplantation | 100 days post-HCT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of aGVHD | The incidence of grade I-IV aGVHD post-transplantation | 100 days post-HCT | 
| Incidence of severe aGVHD | The incidence of grade III-IV aGVHD post-transplantation | 100 days post-HCT | 
| Early transplant-related mortality | The incidence of early transplant-related mortality | 100 days post-HCT | 
| Relapse | The incidence of relapse/progression of underlying disease | 100 days post-HCT |