CMV-CTL for the Treatment of CMV Infection After HSCT

Cytomegalovirus Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03004261
• Other study ID #: CMV-CTL-201609
• Status: Completed
• Phase: Phase 4
• Start date: November 2016
• Est. completion date: December 31, 2021

Study information

• Verified date: April 2023
• Source: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5
• Est. completion date: December 31, 2021
• Est. primary completion date: December 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 14 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Communicable Diseases
• Cytomegalovirus Infections
• Hematologic Diseases
• Hematological Disease
• Infections

Intervention

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.

Drug:
• Foscarnet
Foscarnet may be used for the treatment of CMV infection before and after the CMV-CTL infusion.
• Ganciclovir
Ganciclovir may be used for the treatment of CMV infection before and after CMV-CTL infusion.

Locations

Country	Name	City	State
China	Shanghai Jiao Tong University Affilated Shanghai General Hospital	Shanghai	Shanghai

Sponsors (2)

Lead Sponsor	Collaborator
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine	Shanghai iCELL Biotechnology Co., Ltd, Shanghai, China

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	1-year overall survival	The length of patients who are alive in 1 years.	from the date of transplant to 1 year after transplant
Secondary	100-day incidence of acute GVHD	the incidence of acute GVHD	from the date of transplant to 100 days after transplant
Secondary	1-year incidence of chronic GVHD	the incidence of chronic GVHD	from the date of transplant to 1 year after transplant