PD-1 Antibody for Reactive EBV After BMT

Study Overview
=================
Brief Summary
-----------------
PD-1 antibody for reactivation of EBV after transplantation in patients with CAEBV/EBV-HLH

Detailed Description
-----------------
Transplantaion is recongnized as a cure for CAEBV and EBV associated HLH，however, many patients undergo the reactivation of EBV after transpaltion, patiens may at high risk for recurrence of the disease. PD-1 is a promising therapy to solve this problem. The present study was a one-arm clinical study, the main subject is to evaluate the effect of PD-1 antibody on the clearance of EBV

Official Title
-----------------
Reactivation of EBV for Patients With CAEBV and EBV Associated HLH After Transplantation

Conditions
-----------------
PD-1, EBV Infection, Transplant

Intervention / Treatment
-----------------
* Drug: toripalimab injection


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Meet hemophagocytic lymphohistiocytosis (HLH)-04 diagnostic criteria; EBV-DNA in peripheral blood or EBER in tissue were positive, patients were diagnosed with EBV associated HLH (EBV-HLH). Chronic active EBV infection (CAEBV) was diagnosed by WHO criteria. Undergo allo-HCT, have achieved full chimerism Age >18 years old, gender is not limited. After transplantation, EBV was reactivated and EBV-DNA was positive in blood No secondary graft failure. (After grafted, ANC <0.5*10^9/l,PLT <10*10^9/l) No uncontrollable infection Withdraw immunosuppressor, no graft-versus-host disease was observed. Before the start of the study, aminopherase (ALT/AST) and total bilirubin were normal. Serum creatinine ≤ 1.5 times the upper limit of Normal (ULN); No thyroid dysfunction. The left ventricular ejection fraction (LVEF) was normal. Informed consent. Exclusion Criteria: Allergic to toripalimab Serious immunoreaction: myocardial damage, hepatitis, pneumonia Central nervous system symptoms Serious mental illness; Active bleeding of the internal organs Pancreatitis history. Patients unable to comply during the trial and/or follow-up phase; Participate in other clinical research at the same time.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: one group<br>All patients encountered EBV reactivation after allo-HCT could be enrolled in this study, there was only one group of treatment. | Drug: toripalimab injection<br>* when EBV-DNA is positive after allo-HCT, and EBV infected T/NK cell, one dose of toripalimab 3mg/kg would be used, the same dose would be repeated 4 weeks later.<br>* Other names: EBV-DNA positive;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| EBV-DNA turn negative | after treatment, the EBV-DNA copies can not be detected in peripheral blood | 4 weeks after PD-1 antibody was used | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| treatment-related adverse events as assessed by CTCAE v5.0 | Adverse events including thyroid function，liver function damage, myelosuppression, infection, bleeding and so on | 4 weeks after PD-1 antibody was used |