Administration of Virus Specific CTLs for the Prophylaxis and Treatment of EBV/CMV Infections After HSCT in China
Primary Purpose
Viral Infection
Status
Unknown status
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
CMV/EBV specific CTLs
Sponsored by
About this trial
This is an interventional treatment trial for Viral Infection
Eligibility Criteria
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
Sites / Locations
- Affiliated Hospital to Academy of Military Medical SciencesRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Infusion of CMV/EBV specific CTLs
Arm Description
Repetitive CTLs infusion to treat CMV/EBV activation and infection
Outcomes
Primary Outcome Measures
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)
Assessment of acute transfusion toxicity within 24 hours after adoptive CTLs transfer
Assessment of viral load response to the CTL infusion assessed by CMV/EBV specific PCR of peripheral blood
Assess the effect of the CTL infusion on viral load
Secondary Outcome Measures
The incidence of Ⅱ~Ⅳ°aGVHD within 30 days after the last dose of CTL infusion
Reconstitution of antiviral immunity monitored by flow cytometry
Number of patients with chronic GVHD
Full Information
NCT ID
NCT02456610
First Posted
May 21, 2015
Last Updated
February 18, 2016
Sponsor
Affiliated Hospital to Academy of Military Medical Sciences
1. Study Identification
Unique Protocol Identification Number
NCT02456610
Brief Title
Administration of Virus Specific CTLs for the Prophylaxis and Treatment of EBV/CMV Infections After HSCT in China
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
February 2016
Overall Recruitment Status
Unknown status
Study Start Date
May 2015 (undefined)
Primary Completion Date
July 2016 (Anticipated)
Study Completion Date
August 2016 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Affiliated Hospital to Academy of Military Medical Sciences
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Viral Infection
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Infusion of CMV/EBV specific CTLs
Arm Type
Experimental
Arm Description
Repetitive CTLs infusion to treat CMV/EBV activation and infection
Intervention Type
Biological
Intervention Name(s)
CMV/EBV specific CTLs
Intervention Description
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.
Primary Outcome Measure Information:
Title
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)
Description
Assessment of acute transfusion toxicity within 24 hours after adoptive CTLs transfer
Time Frame
24 hours
Title
Assessment of viral load response to the CTL infusion assessed by CMV/EBV specific PCR of peripheral blood
Description
Assess the effect of the CTL infusion on viral load
Time Frame
3 months
Secondary Outcome Measure Information:
Title
The incidence of Ⅱ~Ⅳ°aGVHD within 30 days after the last dose of CTL infusion
Time Frame
3 months
Title
Reconstitution of antiviral immunity monitored by flow cytometry
Time Frame
6 months
Title
Number of patients with chronic GVHD
Time Frame
6 months
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Zhang Bin, M.D., Ph.D.
Phone
+86-010-6694-7125
Email
zb307ctc@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Chen Hu, M.D., Ph.D.
Phone
+86-010-6694-7108
Email
chenhu217@aliyun.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Chen Hu, M.D., Ph.D.
Organizational Affiliation
Affiliated Hospital to Academy of Military Medical Sciences
Official's Role
Principal Investigator
Facility Information:
Facility Name
Affiliated Hospital to Academy of Military Medical Sciences
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100071
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zhang Bin, M.D., Ph.D.
Phone
+86-010-6694-7125
Email
zb307ctc@163.com
First Name & Middle Initial & Last Name & Degree
Chen Hu, M.D., Ph.D.
Phone
+86-010-6694-7108
Email
chenhu217@aliyun.com
12. IPD Sharing Statement
Learn more about this trial
Administration of Virus Specific CTLs for the Prophylaxis and Treatment of EBV/CMV Infections After HSCT in China
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