CMV-CTL for the Treatment of CMV Infection After HSCT

Cytomegalovirus Specific Cytotoxic T Lymphocyte for the Treatment of Cytomegalovirus Infection After Allogeneic Hematopoietic Stem Cell Transplantation

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.

Study Overview

• Status: Completed
• Conditions: Cytomegalovirus Infections; Hematological Disease
• Intervention / Treatment: Biological: donor derived cytomegalovirus specific T lymphocytes; Drug: Foscarnet; Drug: Ganciclovir

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.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200080
      • Shanghai Jiao Tong University Affilated Shanghai General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 60 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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.

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: CMV-CTL; 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.

Biological: donor derived cytomegalovirus specific T lymphocytes; donor derived cytomegalovirus specific T lymphocytes will be transfused to recipients of hematopoietic stem cell transplant when they are sero-positive for CMV-DNA.; Other Names: cytomegalovirus specific T lymphocytes; Drug: Foscarnet; Foscarnet may be used for the treatment of CMV infection before and after the CMV-CTL infusion.; Drug: Ganciclovir; Ganciclovir may be used for the treatment of CMV infection before and after CMV-CTL infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
30-day response rate	The percentage of patient whose serum CMV-DNA becomes negative in 30 days.	from the date of CMV-CTL infusion to 30 days after the infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1-year overall survival	The length of patients who are alive in 1 years.	from the date of transplant to 1 year after transplant
100-day incidence of acute GVHD	the incidence of acute GVHD	from the date of transplant to 100 days after transplant
1-year incidence of chronic GVHD	the incidence of chronic GVHD	from the date of transplant to 1 year after transplant

Collaborators and Investigators

• Sponsor: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
• Collaborators: Shanghai iCELL Biotechnology Co., Ltd, Shanghai, China
• Investigators: Principal Investigator: Liping Wan, M.D.，Ph.D., Shanghai Jiao Tong University Affiliated Shanghai General Hospital

Study record dates

Study Major Dates

• Study Start: November 1, 2016
• Primary Completion (Actual): December 31, 2021
• Study Completion (Actual): December 31, 2021

Study Registration Dates

• First Submitted: December 18, 2016
• First Submitted That Met QC Criteria: December 22, 2016
• First Posted (Estimate): December 28, 2016

Study Record Updates

• Last Update Posted (Actual): April 25, 2023
• Last Update Submitted That Met QC Criteria: April 24, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: hematopoietic stem cell transplantation; cytomegalovirus infection; cytotoxic T lymphocyte
• Additional Relevant MeSH Terms: Pathologic Processes; Virus Diseases; Disease Attributes; DNA Virus Infections; Herpesviridae Infections; Infections; Communicable Diseases; Hematologic Diseases; Cytomegalovirus Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Ganciclovir; Ganciclovir triphosphate; Foscarnet
• Other Study ID Numbers: CMV-CTL-201609

Plan for Individual participant data (IPD)

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