Clinical trial NCT03004261: 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
Overall status: COMPLETED
Phase: PHASE4
Conditions: Cytomegalovirus Infections
Hematological Disease
Keywords: cytomegalovirus infection
cytotoxic T lymphocyte
hematopoietic stem cell transplantation
Lead sponsor: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
Sponsor class: OTHER
Collaborators: name: Shanghai iCELL Biotechnology Co., Ltd, Shanghai, China
First posted: 2016-12-28
Enrollment: 5
Sex: ALL
Minimum age (years): 14
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: 30-day response rate
timeFrame: from the date of CMV-CTL infusion to 30 days after the infusion
Secondary outcomes:
measure: 1-year overall survival
timeFrame: from the date of transplant to 1 year after transplant
measure: 100-day incidence of acute GVHD
timeFrame: from the date of transplant to 100 days after transplant
measure: 1-year incidence of chronic GVHD
timeFrame: from the date of transplant to 1 year after transplant
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Jiao Tong University Affilated Shanghai General Hospital
state: Shanghai
Study officials:
affiliation: Shanghai Jiao Tong University Affiliated Shanghai General Hospital
name: Liping Wan, M.D.，Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: