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CMV-CTL for the Treatment of CMV Infection After HSCT

Primary Purpose

Cytomegalovirus Infections, Hematological Disease

Status
Completed
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
donor derived cytomegalovirus specific T lymphocytes
Foscarnet
Ganciclovir
Sponsored by
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cytomegalovirus Infections focused on measuring cytomegalovirus infection, cytotoxic T lymphocyte, hematopoietic stem cell transplantation

Eligibility Criteria

14 Years - 60 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Any allogeneic stem cell transplant recipient ≥ 14 years of age and ≤ 60 years of age
  • Bilirubin/ SGOT/SGPT < 5 × upper normal limits.
  • Creatinine < 2 × upper normal limits.
  • Ejection fraction ≥ 50%, no severe arrhythmia.
  • Estimated life expectancy ≥ 6 months.
  • Patients' CMV-DNA ≥ 1000cp/ml in treatment group and being negative in prophylactic group.

Exclusion Criteria:

  • Patients receiving prednisone ≥ 1mg/kg/d for the treatment of acute GVHD or mild, severe chronic GVHD.
  • Recipient < 14years of age
  • Donor is sero-positive in HBV/HCV/HIV or RPR.

Sites / Locations

  • Shanghai Jiao Tong University Affilated Shanghai General Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CMV-CTL

Arm Description

The donor derived cytomegalovirus specific T lymphocytes (CMV-CTL) will be transfused to the patients. The patients will receive CMV-CTL cells when they are sero-positive for CMV-DNA 30 days after transplant. The CMV-DNA levels will be monitored weekly for at least 60 days after the transplant. If after the initial dose of CMV-CTL cells the patient develops a viral infection, then they may be eligible to receive one additional injection of CMV-CTLs. If the CMV levels in the blood continue to rise after the dose of T cells then the patient will receive treatment with Ganciclovir or Foscarnet.

Outcomes

Primary Outcome Measures

30-day response rate
The percentage of patient whose serum CMV-DNA becomes negative in 30 days.

Secondary Outcome Measures

1-year overall survival
The length of patients who are alive in 1 years.
100-day incidence of acute GVHD
the incidence of acute GVHD
1-year incidence of chronic GVHD
the incidence of chronic GVHD

Full Information

First Posted
December 18, 2016
Last Updated
April 24, 2023
Sponsor
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
Collaborators
Shanghai iCELL Biotechnology Co., Ltd, Shanghai, China
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1. Study Identification

Unique Protocol Identification Number
NCT03004261
Brief Title
CMV-CTL for the Treatment of CMV Infection After HSCT
Official Title
Cytomegalovirus Specific Cytotoxic T Lymphocyte for the Treatment of Cytomegalovirus Infection After Allogeneic Hematopoietic Stem Cell Transplantation
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Completed
Study Start Date
November 2016 (undefined)
Primary Completion Date
December 31, 2021 (Actual)
Study Completion Date
December 31, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
Collaborators
Shanghai iCELL Biotechnology Co., Ltd, Shanghai, China

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Human cytomegalovirus (CMV) infection is a major cause of morbidity and mortality for recipients of allogeneic hematopoietic stem cell transplantation(HSCT). we propose to study the immunologic and virologic effects of donor derived CMV specific cytotoxic T lymphocyte (CMV-CTL) given to transplant recipients CMV antigen peptides will be used to induce the CMV antigen specific T lymphocytes derived from donor peripheral blood mononuclear cells for a period of 18~21 days.The patients will receive CMV-CTL cells when they are sero-positive for CMV-DNA 30 days after transplant. The CMV-DNA level will be monitored weekly after transfusion.
Detailed Description
Allogeneic hematopoietic stem cell transplantation is widely used for the treatment of hematological malignancies and bone marrow failure diseases. Human cytomegalovirus (CMV) infection is a major cause of morbidity and mortality for recipients of allogeneic hematopoietic stem cell transplantation(HSCT). Approximately half of the recipients would develop CMV infection after transplant. Present treatment recommendation for CMV infection including ganciclovir and foscarnet. However, these medications have many side effects, the most serious is myelosuppression and renal injury, moreover, many patients do not response to these medications. Considering the risk associated with persistent infection and the potential for CMV specific cytotoxic T lymphocyte (CMV-CTL) to restore immunity, we propose to study the immunologic and virologic effects of donor derived CMV-CTL given to transplant recipients, levels of CMV-CTL and CMV DNA will be measured from CTL recipients. If the patient and their donor are eligible, we will take 80 ml of fresh blood from the donor or 5 ml peripheral blood stem cell from the donor.The peripheral blood mononuclear cells will be separated from peripheral blood or peripheral blood stem cell. CMV antigen peptides will be used to induce the CMV-CTL for a period of 18~21 days. The donor derived CMV-CTL cells will be transfused into the patients' intravenous line. The patients will receive the dose of CMV-CTL cells when they are sero-positive for CMV-DNA 30 days after transplant. The CMV-DNA levels will be monitored weekly for at least 60 days after the transplant. If after the initial dose of CMV-CTL cells the patient develops a viral infection, then they may be eligible to receive one additional injection of CTLs. If the CMV levels in the blood continue to rise after the dose of T cells then the patient will receive treatment with Ganciclovir, Foscarnet.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cytomegalovirus Infections, Hematological Disease
Keywords
cytomegalovirus infection, cytotoxic T lymphocyte, hematopoietic stem cell transplantation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
5 (Actual)

8. Arms, Groups, and Interventions

Arm Title
CMV-CTL
Arm Type
Experimental
Arm Description
The donor derived cytomegalovirus specific T lymphocytes (CMV-CTL) will be transfused to the patients. The patients will receive CMV-CTL cells when they are sero-positive for CMV-DNA 30 days after transplant. The CMV-DNA levels will be monitored weekly for at least 60 days after the transplant. If after the initial dose of CMV-CTL cells the patient develops a viral infection, then they may be eligible to receive one additional injection of CMV-CTLs. If the CMV levels in the blood continue to rise after the dose of T cells then the patient will receive treatment with Ganciclovir or Foscarnet.
Intervention Type
Biological
Intervention Name(s)
donor derived cytomegalovirus specific T lymphocytes
Other Intervention Name(s)
cytomegalovirus specific T lymphocytes
Intervention Description
donor derived cytomegalovirus specific T lymphocytes will be transfused to recipients of hematopoietic stem cell transplant when they are sero-positive for CMV-DNA.
Intervention Type
Drug
Intervention Name(s)
Foscarnet
Intervention Description
Foscarnet may be used for the treatment of CMV infection before and after the CMV-CTL infusion.
Intervention Type
Drug
Intervention Name(s)
Ganciclovir
Intervention Description
Ganciclovir may be used for the treatment of CMV infection before and after CMV-CTL infusion.
Primary Outcome Measure Information:
Title
30-day response rate
Description
The percentage of patient whose serum CMV-DNA becomes negative in 30 days.
Time Frame
from the date of CMV-CTL infusion to 30 days after the infusion
Secondary Outcome Measure Information:
Title
1-year overall survival
Description
The length of patients who are alive in 1 years.
Time Frame
from the date of transplant to 1 year after transplant
Title
100-day incidence of acute GVHD
Description
the incidence of acute GVHD
Time Frame
from the date of transplant to 100 days after transplant
Title
1-year incidence of chronic GVHD
Description
the incidence of chronic GVHD
Time Frame
from the date of transplant to 1 year after transplant

10. Eligibility

Sex
All
Minimum Age & Unit of Time
14 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Any allogeneic stem cell transplant recipient ≥ 14 years of age and ≤ 60 years of age Bilirubin/ SGOT/SGPT < 5 × upper normal limits. Creatinine < 2 × upper normal limits. Ejection fraction ≥ 50%, no severe arrhythmia. Estimated life expectancy ≥ 6 months. Patients' CMV-DNA ≥ 1000cp/ml in treatment group and being negative in prophylactic group. Exclusion Criteria: Patients receiving prednisone ≥ 1mg/kg/d for the treatment of acute GVHD or mild, severe chronic GVHD. Recipient < 14years of age Donor is sero-positive in HBV/HCV/HIV or RPR.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Liping Wan, M.D.,Ph.D.
Organizational Affiliation
Shanghai Jiao Tong University Affiliated Shanghai General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Shanghai Jiao Tong University Affilated Shanghai General Hospital
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200080
Country
China

12. IPD Sharing Statement

Plan to Share IPD
No

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CMV-CTL for the Treatment of CMV Infection After HSCT

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