A Study on Efficacy and Safety of iNK Cells for CAEBV /EBV-HLH After Allo-HSCT

A Study on Efficacy and Safety of iNK Cell Infusion in Patients With Chronic Active Epstein-Barr Virus Infection (CAEBV) and Epstein Barr Virus-induced Haemophagocytic Lymphohistiocytosis (EBV-HLH) After Allogeneic Hematopoietic Stem Cell Transplantation

To evaluate the efficacy and safety of iNK cells 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: Not yet recruiting
• Conditions: EBV; Hemophagocytic Lymphohistiocytoses; CAEBV (Chronic Active Epstein-Barr Virus Infection) Syndrome
• Intervention / Treatment: Other: NCR300（Allogenic Ipsc-derived Natural Killer cells ）

Detailed Description

It is a prospective, open-lable study to evaluate the efficacy and safety of iNK cell infusion in CAEBV/EBV-HLH patients after allo-HSCT. The study will enroll fifteen subjects who will receive ongoing least 4 doses of iNK cells intravenously infusion after allogeneic hematopoietic stem cell transplantation. All subjects will assess the incidence of disease relapse and EBV-DNA reactivation up to one year.

• 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, China
    • Beijing Friendship Hospital, Capital Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients with CAEBV or EBV-HLH who are eligible for allogeneic hematopoietic stem cell transplantation meet one of the following criteria:

   ①EBV-DNA (PBMC or plasma) was still more than 103 before transplantation；②Positive for Cerebrospinal fluid EBV-DNA；

   ③Abnormal phenotypic lymphocytes could still be detected in bone marrow immunotyping；

   ④Measurable EBV-related lesions on imaging；

2. ≤65 years，ECOG :0-2；
3. Cardiac EF≥40%, creatinine clearance ≥50%; aminotransferase（ALT/AST）<200U/L。；
4. In patients with HLH, HLH efficacy ≥Partial Response after prior treatment is required；
5. Estimated survival time is longer than three months；
6. Agree to sign the Informed Consent Form。

Exclusion Criteria:

1. Patients with evidence of grade II or more serious heart disease according to the New York Heart Association (NYHA) score (including Grade II) ; Clear diagnosis of cirrhosis；
2. Active infections other than EBV that have not yet been controlled；
3. Positive for hepatitis B virus or hepatitis C virus；
4. Active massive hemorrhage of internal organs (including gastrointestinal hemorrhage, alveolar hemorrhage, intracranial hemorrhage, etc.)；
5. Also participation in other interventional clinical studies within 4 weeks

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: iNK cells infusion patients; Given iNK cell infusion after allo HSCT	Other: NCR300（Allogenic Ipsc-derived Natural Killer cells ）; Patients will receive iNK cells i.V. infusion at 1.0x10^8/kg on days +14d, +21d, +28d, and +35d post-transplant. Continuation of the infusion after +35d post-transplant is at the discretion of the physician based on the patient's benefit.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-free survival time (DFS)	Assessment of CAEBV, EBV-HLH systemic disease status and peripheral blood EBV-DNA levels	1 year
complete remission rate (CR)	EBV-DNA negative rate in relapsed/non-remitting patients	1 year
Recurrence rate (RT)	EBV-DNA reactivation rate for high-risk patients	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Event（AE）	Assess the frequency and extent of adverse events	1 year
cytomegalovirus DNA	Incidence of post-transplant infection-related comorbidities	1 year

Collaborators and Investigators

• Sponsor: Beijing Friendship Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): July 15, 2024
• Primary Completion (Estimated): July 15, 2025
• Study Completion (Estimated): July 15, 2026

Study Registration Dates

• First Submitted: July 1, 2024
• First Submitted That Met QC Criteria: July 1, 2024
• First Posted (Actual): July 9, 2024

Study Record Updates

• Last Update Posted (Actual): July 11, 2024
• Last Update Submitted That Met QC Criteria: July 9, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Lymphatic Diseases; DNA Virus Infections; Tumor Virus Infections; Herpesviridae Infections; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Infections; Virus Diseases; Epstein-Barr Virus Infections; Lymphohistiocytosis, Hemophagocytic
• Other Study ID Numbers: 2024-P2-053-02

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