Clinical trial NCT02083731: MSC for Treatment of CMV Infection
Official title: Mesenchymal Stem Cells for Treatment of CMV Infection After Hematopoietic Stem Cell Transplant
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Stem Cell Transplantation, Hematopoietic
CMV Infection
Hematological Diseases
Keywords: CMV infection
Mesenchymal Stem Cells
Allogeneic hematopoietic stem cell transplantation
Lead sponsor: Nanfang Hospital, Southern Medical University
Sponsor class: OTHER
Collaborators: name: Academy Military Medical Science, China
name: Peking University People's Hospital
name: Sun Yat-sen University
name: Guangdong Provincial People's Hospital
name: Guangzhou General Hospital of Guangzhou Military Command
name: Third Affiliated Hospital, Sun Yat-Sen University
name: Shanghai Zhongshan Hospital
First posted: 2014-03-11
Enrollment: 120
Sex: ALL
Minimum age (years): 14
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy of mesenchymal stem cells (MSC) in the treatment of refractory cytomegalovirus (CMV) infection after allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Detailed description: Viral infections are common complications after allo-HSCT. With wide use of HLA-mismatch, unrelated and cord blood donors as alternative sources of hematopoietic stem cells, and anti-thymocyte globulin (ATG) as the standard prophylaxis of graft versus host disease (GVHD) in HLA-mismatch and unrelated donor transplantation, allo-HSCT recipients are at increasing risk for viral infections.

Till now, CMV remains one of the most important viruses and causes of death in the recipients of allo-HSCT. Approximately 75% of CMV-seropositive recipients develop CMV reactivation, and 20-30% of these patients develop CMV disease without intervention. Ganciclovir is the first-line treatment of CMV diseases. However, bone marrow suppression, which is the main and common side effect, limits the utility of ganciclovir in allo-HSCT recipients. Besides, ganciclovir and other antiviral agents resistance has been reported up to 28%. Since it has been known that specific immune response to CMV is important to control reactivation, CMV-specific CTL has been used in prophylaxis and treatment of CMV viremia in several studies. However, the production of CTL requires time. Mesenchymal stem cells (MSC) are a form of multipotent adult stem cells that can be isolated from bone marrow (BM), adipose tissue, and cord blood. In vivo experiment showed that MSCs have antimicrobial activity.

In this trial, we will use MSCs in the recipients with refractory CMV infections.

Eligibility criteria: Inclusion Criteria:

* A patient age of 14-65 years
* Refractory CMV infection or CMV-associated diseases
* Subjects (or their legally acceptable representatives) must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study

Exclusion Criteria:

* Any abnormality in a vital sign (e.g., heart rate, respiratory rate, or blood pressure)
* Patients with any conditions not suitable for the trial (investigators' decision)

Primary outcomes:
measure: Percentage of Participants achieved complete remission of CMV infection
timeFrame: 1 year
Secondary outcomes:
measure: Number of Participants with Serious and Non-Serious Adverse Events
timeFrame: up to 1 year
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Department of Hematology,Nanfang Hospital, Southern Medical University
state: Guangdong
Study officials:
affiliation: Nanfang Hospital, Southern Medical University
name: Qifa Liu, MD.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Meisel R, Brockers S, Heseler K, Degistirici O, Bulle H, Woite C, Stuhlsatz S, Schwippert W, Jager M, Sorg R, Henschler R, Seissler J, Dilloo D, Daubener W. Human but not murine multipotent mesenchymal stromal cells exhibit broad-spectrum antimicrobial effector function mediated by indoleamine 2,3-dioxygenase. Leukemia. 2011 Apr;25(4):648-54. doi: 10.1038/leu.2010.310. Epub 2011 Jan 18.
citation: Ljungman P, de la Camara R, Cordonnier C, Einsele H, Engelhard D, Reusser P, Styczynski J, Ward K; European Conference on Infections in Leukemia. Management of CMV, HHV-6, HHV-7 and Kaposi-sarcoma herpesvirus (HHV-8) infections in patients with hematological malignancies and after SCT. Bone Marrow Transplant. 2008 Aug;42(4):227-40. doi: 10.1038/bmt.2008.162. Epub 2008 Jun 30.