Administration of Virus Specific CTLs for the Prophylaxis and Treatment of EBV/CMV Infections After HSCT in China

February 18, 2016 updated by: Affiliated Hospital to Academy of Military Medical Sciences

Adoptive Transfer of Peptide Stimulated CMV/EBV Specific Cytotoxic T Lymphocytes to Prevent and Treat EBV/CMV Infections in Patients Post Allogeneic Stem Cell Transplantation in China

Cytomegalovirus (CMV) and Epstein Barr Virus (EBV) cause significant morbidity and mortality in hematopoietic stem cell transplantation (HSCT) patients in China. Antiviral drugs given either prophylactically or as early therapy for patients with detectable viral loads appear to be an effective strategy for reducing viral infections. However, long-term treatment with these drugs is associated with significant toxicity, expense and the appearance of drug resistant virus isolates ultimately resulting in treatment failure. CMV and EBV specific T cells infusion to immunocompromised patients following HSCT is able to induce a successful anti-viral response. The primary purpose of this study is to determine the safety and efficacy of the infusion of CMV and EBV specific cytotoxic T cells (CTLs) for patients with CMV and EBV reactivation or infection.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

To generate CMV/EBV specific CTLs, G-CSF mobilized hemopoietic progenitor cell (G-HPC) products or nonmobilized peripheral blood apheresis collectings were stimulated with CMV/EBV specific peptides covering most HLA alleles among Chinese populations. Once the investigators made sufficient numbers of T cells, they tested their ex vivo properties.Then a fraction of CTLs were separated for immediate infusion and the others were frozen for further infusion.

If the donor was available, the donor derived CTLs were started to produce when CMV reactivation was detected by qPCR in recipients peripheral blood. Otherwise, autologous CTLs were used. For patients at high risk of developing CMV/EBV infections after stem cell transplantation, a small part of G-HPC products was extracted for CTLs generation.

Study Type

Interventional

Enrollment (Anticipated)

30

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100071
        • Recruiting
        • Affiliated Hospital to Academy of Military Medical Sciences
        • Contact:
          • Zhang Bin, M.D., Ph.D.
          • Phone Number: +86-010-6694-7125
          • Email: zb307ctc@163.com
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients with any type of allogeneic HSCT
  • CMV, adenovirus or EBV activation or infection which is defined as below. EBV/CMV reactivation is defined as CMV/EBV DNA levels > 1000 IU/ml for a single test or > 500 IU/ml for two consecutive tests. EBV/CMV related disease were defined as the demonstration of CMV/EBV biopsy specimen or clinical diagnosis through symptoms, signs or radiography.
  • Written informed consent and/or signed assent line from patient, parent or guardian
  • Positive CMV or EBV serology of the donor
  • Absence of severe renal disease (Creatinine > 3x upper limit normal)
  • Absence of severe hepatic disease (Bilirubin > 3x upper limit normal, AST > 3x upper limit normal)
  • Life expectancy > 30 days

Exclusion Criteria:

  • Active acute GVHD grades II-IV
  • Received donor lymphocytes infusion(DLI) within 30 days
  • Received ATG or other immunosuppressive monoclonal antibodies within 30 days
  • Uncontrolled acute infections
  • Active and relapse of malignancy
  • Received steroids treatment more than 0.5 mg/kg/day prednisone

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Infusion of CMV/EBV specific CTLs
Repetitive CTLs infusion to treat CMV/EBV activation and infection
Biological: CMV/EBV specific CTLs
Patients will receive approximately 1x10e6 CTLs/kg as a single infusion via IV injection and may receive 1 to 8 additional infusions at intervals of one week.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Toxicity of adoptive transfer of CMV/EBV specific CTLs(The increase of temperature by 1℃ and/or the appearance of rash within 24h after infusion)
Time Frame: 24 hours
Assessment of acute transfusion toxicity within 24 hours after adoptive CTLs transfer
24 hours
Assessment of viral load response to the CTL infusion assessed by CMV/EBV specific PCR of peripheral blood
Time Frame: 3 months
Assess the effect of the CTL infusion on viral load
3 months

Secondary Outcome Measures

Outcome Measure
Time Frame
The incidence of Ⅱ~Ⅳ°aGVHD within 30 days after the last dose of CTL infusion
Time Frame: 3 months
3 months
Reconstitution of antiviral immunity monitored by flow cytometry
Time Frame: 6 months
6 months
Number of patients with chronic GVHD
Time Frame: 6 months
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Affiliated Hospital to Academy of Military Medical Sciences

Investigators

  • Principal Investigator: Chen Hu, M.D., Ph.D., Affiliated Hospital to Academy of Military Medical Sciences

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2015

Primary Completion (Anticipated)

July 1, 2016

Study Completion (Anticipated)

August 1, 2016

Study Registration Dates

First Submitted

May 21, 2015

First Submitted That Met QC Criteria

May 27, 2015

First Posted (Estimate)

May 28, 2015

Study Record Updates

Last Update Posted (Estimate)

February 22, 2016

Last Update Submitted That Met QC Criteria

February 18, 2016

Last Verified

February 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 307-CMV/EBV-CTL

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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