Clinical trial NCT01765634: Mesenchymal Stem Cells for Treatment of Refractory Acute Graft-versus-host Disease
Official title: Mesenchymal Stem Cells From Third-party Donors for Treatment of Refractory Acute Graft-versus-host Disease
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Acute Graft-versus-host Disease
Keywords: Hematopoietic Stem Cell Transplantation
Mesenchymal Stem Cells
Acute Graft-versus-host disease
Lead sponsor: Nanfang Hospital, Southern Medical University
Sponsor class: OTHER
Collaborators: name: Sun Yat-sen University
name: Peking University People's Hospital
name: Guangdong Provincial People's Hospital
name: Guangzhou General Hospital of Guangzhou Military Command
name: Southern Medical University, China
name: Third Affiliated Hospital, Sun Yat-Sen University
name: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
name: Guangzhou First People's Hospital
name: Zhongshan People's Hospital, Guangdong, China
First posted: 2013-01-10
Enrollment: 40
Sex: ALL
Minimum age (years): 12
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the utility of treating patients experiencing refractory acute graft-versus-host disease with ex-vivo-expanded BM-drived mesenchymal stem cells from third-party donors. The objective was to evaluate the effect and safety of such treatment on refractory acute graft-versus-host disease.

Detailed description: Allogeneic hematopoietic stem cell transplantation(allo-HSCT) can cure many hematologic diseases. Although great progress has been made in the prevention and treatment of side effects associated with transplantation,acute graft-versus-host disease(aGVHD) remains an important complication that occurs in 35-80% patients. The mortality of aGVHD is positively correlated with its severity. At present, glucocorticoids is still the first line treatment of aGVHD. If glucocorticoids treatment is ineffective, second line drugs would be taken, such as tacrolimus(FK506), mycophenolate mofetil (MMF)and antithymocyte globulin (ATG). However, no method could be continuously effective. The effective rates of second line treatment to aGVHD is only about 60%. The effective rates and prognosis of refractory aGVHD are even worse.

Mesenchymal stem cells (MSCs) are a form of multipotent adult stem cells that can be isolated from bone marrow (BM), adipose tissue, and cord blood. Clinical applications of human MSCs are evolving rapidly with goals of improving hematopoietic engraftment, preventing and treating GVHD after allo-HSCT and so on. However, the efficacy of treatment of refractory aGVHD using expanded BM-derived MSCs from a third-party donor is rarely reported. If such treatment could be shown to be effective and safe, BM-derived MSCs could potentially be used as an universal donor material. This would have a major impact because the generation of donor-specific MSCs is time-consuming, costly, and often impractical if the clinical status of a patient is urgent.

In the present study, the investigators will prospectively evaluate the efficacy and safety of ex-vivo-expanded BM-derived MSCs from third-party donors in treating patients with refractory aGVHD.

Eligibility criteria: Inclusion Criteria:

* A patient age of 12-65 years
* Recipients of allogeneic hematopoietic stem cell transplantation
* Patients with refractory aGVHD
* On a voluntary basis, patients are divided into MSCs and Non-MSCs group
* 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: The efficacy of treatment for refractory aGVHD
timeFrame: 1 year
Secondary outcomes:
measure: acute and late toxic side effects of MSCs treatment
timeFrame: 1 year
Other outcomes:
measure: infections
timeFrame: 1 year
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
role: PRINCIPAL_INVESTIGATOR
References:
citation: Le Blanc K, Frassoni F, Ball L, Locatelli F, Roelofs H, Lewis I, Lanino E, Sundberg B, Bernardo ME, Remberger M, Dini G, Egeler RM, Bacigalupo A, Fibbe W, Ringden O; Developmental Committee of the European Group for Blood and Marrow Transplantation. Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet. 2008 May 10;371(9624):1579-86. doi: 10.1016/S0140-6736(08)60690-X.
citation: von Bonin M, Stolzel F, Goedecke A, Richter K, Wuschek N, Holig K, Platzbecker U, Illmer T, Schaich M, Schetelig J, Kiani A, Ordemann R, Ehninger G, Schmitz M, Bornhauser M. Treatment of refractory acute GVHD with third-party MSC expanded in platelet lysate-containing medium. Bone Marrow Transplant. 2009 Feb;43(3):245-51. doi: 10.1038/bmt.2008.316. Epub 2008 Sep 29.