Clinical Study of Donor EBV-CTL Infusion in Patients With CAEBV and EBV-HLH After Allo-HSCT

Study Overview
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Brief Summary
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To evaluate the efficacy and safety of donor EBV-specific T lymphocytes (EBV-CTL) infusion in patients with chronic active Epstein-Barr virus infection (CAEBV) and EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH) after allogeneic hematopoietic stem cell transplantation (allo-HSCT)

Detailed Description
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Evaluate the efficacy and safety of donor EBV-specific T lymphocytes (EBV-CTL) infusion in patients with chronic active Epstein-Barr virus infection (CAEBV) and EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH) after allogeneic hematopoietic stem cell transplantation (allo-HSCT)

Official Title
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Clinical Study on the Efficacy and Safety of Donor EBV-CTL Infusion in Patients With CAEBV and EBV-associated Hemophagocytic Lymphohistiocytosis After Allogeneic Hematopoietic Stem Cell Transplantation

Conditions
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Chronic Active Epstein-Barr Virus Infection, Virus-Associated Hemophagocytic Syndrome

Intervention / Treatment
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* Other: donor EBV-specific T lymphocytes


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with CAEBV or EBV-HLH who were eligible for allogeneic hematopoietic stem cell transplantation agreed to regular monitoring of EBV-DNA after transplantation. Age ≤65 years old, ECOG score 0-2. Organ function: Cardiac EF≥40%, creatinine clearance ≥50%, aminotransferase (ALT/AST) < 200U/L. The estimated survival time is more than 3 months. 5) Have donors who meet the requirements of allogeneic hematopoietic stem cell transplantation donors， and the donor agreed to collect lymphocytes to prepare EBV-CTL Exclusion Criteria: The patient or donor had a New York Heart Association (NYHA) score of grade II or higher (including grade II). Or a definite diagnosis of cirrhosis. There are active infections other than EBV that have not yet been controlled. The donor has a blood-borne infectious disease (e.g. HIV, hepatitis B, hepatitis C, syphilis, etc.). The patient was positive for HBV-DNA or HCV-RNA. Active major hemorrhage of internal organs (including gastrointestinal hemorrhage, alveolar hemorrhage, intracranial hemorrhage, etc.). The donor refused to collect lymphocytes to prepare EBV-CTL cells, or the number of EBV-CTL cells prepared from the donor did not meet the infusion requirements. At the same time participate in other clinical studies.

Ages Eligible for Study
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Maximum Age: 65 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EBV-CTL infusion patients<br>Given donor EBV-CTL infusion after allo HSCT | Other: donor EBV-specific T lymphocytes<br>* EBV-DNA reactive after transplantation, or did not turn negative after +30 days, peripheral blood lymphocytes of the donor were collected to prepare EBV-CTL, and the first transfusion of EBV-CTL 6.0x105 was given at 48h to rapidly culture EBV-CTL, then EBV-CTL 6.0x105/kg was injected once a week untile EBV-DNA negative for 2 consecutive times or GVHD happened. After the second infusion, EBV-DNA did not decrease and there was no aGVHD patients, EBV-CTL infusion volume was increased to 1.2x106/kg, once a week. After 2 cycle infusion, EBV-DNA still did not decrease, and the reinfusion was terminated. Peripheral blood lymphocytes were collected from donors of high-risk patients at +14 days after allogeneic hematopoietic stem cell transplantation to prepare EBV-CTL, and EBV-CTL 6.0x105/kg was infused at +21d, +28d, +35d and + 42D for prevention. During treatment, if the patient develops GVHD, the infusion should be stopped.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| EBV-DNA | EBV-DNA negative conversion rate for patients with relapse/non-remission and EBV-DNA reactivation rate for high-risk patients | 1 year |