PD-1 Antibody Improve Mixed Chimerism

Study Overview
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Brief Summary
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PD-1/PD-L1 pathway play an important role in Inhibiting the function of antigen-specific CD8+T cells, thus matter a lot in immune escape. We intend to use PD-1 antibody to improve the function of lymhocyte and improve the chimerism in patients after allo-HCT.

Detailed Description
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Mixed chimerism is a trouble condition after allogeneic hematopoietic cell transplantation (Allo-HCT),all targeted treatment are aimed to improve the function of lymphocyte recipient. PD-1 antibody was reported to restored the function of impaired lymphocyte. Therefore, we want to use PD-1 antibody to improve the function of lymhocyte and improve the chimerism in HLH patients after allo-HCT.

Official Title
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PD-1 Antibody Improve Mixed Chimerism in Patients With Hemophagocytic Lymphohistiocytosis After Allo-HCT

Conditions
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PD-1 Antibody, Mixed Chimerism

Intervention / Treatment
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* Drug: Toripalimab Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: EBV-HLH according to the HLH-04 diagnostic criteria. After allo-HCT, have achieved engraftment and reconstitute of hematopoiesis. have achieved full donor chimerism. Withdraw immunosuppressive agent, chimeric rate was 80%-95% Age >18 years old, gender is not limited. no graft-versus-host disease was observed. No secondary graft failure (ANC <0.5*10^9/l,PLT <10*10^9/l) 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 the test drug ingredients or to a more severe allergic constitution. Chimeric rate continue to decline after 2 weeks of toripalimab Injection used. Serious immunoreaction: myocardial damage, hepatitis, pneumonia. Central nervous system symptoms. Serious mental illness. Active bleeding of the internal organs Uncontrollable infection； 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
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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: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: one group of HLH patients with mixed chimerism (80%-95%), PD-1 antibody will be used to improve the chimerism
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PD-1 antibody for mixed chimerism<br>PD-1 antibody (Toripalimab Injection) used for mixed chimerism in HLH patients after allo-HCT | Drug: Toripalimab Injection<br>* Toripalimab Injection used for mixed chimerism between 80%-95% in HLH patients. Dose: 240mg toripalimab Injection, two weeks later, the same dose will be repeated if patients have some improve in the chimeric rate.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Chimeric rate | Chimeric rate in bone marrow or peripheral blood of HLH patients | 4 weeks after toripalimab injection 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. | every 2 weeks after intervention, until 8 weeks after the use of PD-1 antibody | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chimerism, PD-1