CMV-CTL for the Treatment of CMV Infection After HSCT

NCT ID: NCT03004261

Last Updated: 2023-04-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-30
• Study Completion Date: 2021-12-31

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.

Conditions

Cytomegalovirus Infections; Hematological Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

donor derived cytomegalovirus specific T lymphocytes

Intervention Type: BIOLOGICAL

donor derived cytomegalovirus specific T lymphocytes will be transfused to recipients of hematopoietic stem cell transplant when they are sero-positive for CMV-DNA.

Foscarnet

Intervention Type: DRUG

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

Ganciclovir

Intervention Type: DRUG

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

Interventions

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.

Intervention Type: BIOLOGICAL

Foscarnet

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

Intervention Type: DRUG

Ganciclovir

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

Intervention Type: DRUG

Other Intervention Names

cytomegalovirus specific T lymphocytes

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.

• Minimum Eligible Age: 14 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shanghai iCELL Biotechnology Co., Ltd, Shanghai, China

INDUSTRY

Sponsor Role: collaborator

Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Liping Wan

Chief Physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Liping Wan, M.D.，Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Shanghai Jiao Tong University Affiliated Shanghai General Hospital

Locations

Shanghai Jiao Tong University Affilated Shanghai General Hospital

Shanghai, Shanghai Municipality, China

Countries

China

Other Identifiers

CMV-CTL-201609

Identifier Type: -

Identifier Source: org_study_id