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

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

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)

Study Overview

• Status: Recruiting
• Conditions: Chronic Active Epstein-Barr Virus Infection; Virus-Associated Hemophagocytic Syndrome
• Intervention / Treatment: Other: donor EBV-specific T lymphocytes

Detailed Description

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)

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: zhao wang, MD; Phone Number: 86010631383803; Email: wangzhao@ccmu.edu.cn

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100050
      • Recruiting
      • Zhao Wang
      • Contact: zhao wang, MD; Phone Number: 8601063138303; Email: wangzhao@ccmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients with CAEBV or EBV-HLH who were eligible for allogeneic hematopoietic stem cell transplantation agreed to regular monitoring of EBV-DNA after transplantation.
2. Age ≤65 years old, ECOG score 0-2.
3. Organ function: Cardiac EF≥40%, creatinine clearance ≥50%, aminotransferase (ALT/AST) < 200U/L.
4. 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:

1. 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.
2. There are active infections other than EBV that have not yet been controlled.
3. 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.
4. Active major hemorrhage of internal organs (including gastrointestinal hemorrhage, alveolar hemorrhage, intracranial hemorrhage, etc.).
5. 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.
6. At the same time participate in other clinical studies.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: EBV-CTL infusion patients; Given donor EBV-CTL infusion after allo HSCT

Other: donor EBV-specific T lymphocytes; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Beijing Friendship Hospital
• Investigators: Principal Investigator: Zhao Wang, MD, Beijing Friendship Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 8, 2022
• Primary Completion (Estimated): September 15, 2023
• Study Completion (Estimated): September 15, 2024

Study Registration Dates

• First Submitted: September 6, 2022
• First Submitted That Met QC Criteria: September 6, 2022
• First Posted (Actual): September 8, 2022

Study Record Updates

• Last Update Posted (Actual): June 27, 2023
• Last Update Submitted That Met QC Criteria: June 24, 2023
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Virus Diseases; Infections; Lymphatic Diseases; DNA Virus Infections; Tumor Virus Infections; Herpesviridae Infections; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Epstein-Barr Virus Infections; Lymphohistiocytosis, Hemophagocytic
• Other Study ID Numbers: EBV-CTL，CAEBV/EBV-HLH

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No