Mesenchymal Stem Cells for Treatment of Refractory Chronic Graft-versus-host Disease

Tracking Information
First Submitted Date ICMJE	January 5, 2013
First Posted Date ICMJE	January 10, 2013
Last Update Posted Date	January 10, 2013
Study Start Date ICMJE	January 2013
Estimated Primary Completion Date	December 2015 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: January 8, 2013)	The efficacy of treatment for refractory cGVHD [ Time Frame: 1 year ]; The response criteria include complete response (CR), part response (PR), stable disease(SD) and progressive disease(PD). CR:cGVHD symptoms and signs disappear; PR:cGVHD symptoms and signs improve; SD:cGVHD symptoms and signs remain (without improvement or deterioration);PD: cGVHD symptoms and signs deteriorate.
Original Primary Outcome Measures ICMJE	Same as current
Change History	No Changes Posted
Current Secondary Outcome Measures ICMJE; (submitted: January 8, 2013)	acute and late toxic side effects of MSCs treatment [ Time Frame: 1 year ]; Toxic side effects of treatment includes acute toxicity and late side effects. Acute toxicity principally involves the heart,live and kidney. Late toxic side effects involves principally the development of secondary tumors and relapse of the primary disease.
Original Secondary Outcome Measures ICMJE	Same as current
Current Other Outcome Measures ICMJE; (submitted: January 8, 2013)	infections [ Time Frame: 1 year ]; Infections will be mainly focused within the first 100 days after MSCs treatment.
Original Other Outcome Measures ICMJE	Same as current
Descriptive Information
Brief Title ICMJE	Mesenchymal Stem Cells for Treatment of Refractory Chronic Graft-versus-host Disease
Official Title ICMJE	Mesenchymal Stem Cells From Third-party Donors for Treatment of Refractory Chronic Graft-versus-host Disease
Brief Summary	The purpose of this study is to evaluate the utility of treating patients experiencing refractory chronic 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 chronic 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,chronic graft-versus-host disease(cGVHD) remains an important complication that occurs in about 50% patients. The mortality of cGVHD and its complication could reach up to 50%,and cGVHD seriously influence the quality of life. At present, glucocorticoids and cyclosporine (CsA) are the first line treatment of cGVHD, but their effective rates are only 50%. If first line treatment is ineffective, second line drugs would be taken, such as mycophenolate mofetil(MMF)and rituximab. The effective rates of second line drugs are 30%-61%. The effective rates and prognosis of refractory cGVHD 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 cGVHD 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 cGVHD.
Study Type ICMJE	Interventional
Study Phase	Phase 2
Study Design ICMJE	Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Chronic Graft-versus-host Disease
Intervention ICMJE	Biological: Mesenchymal stem cells Mesenchymal stem cells will be intravenously infused via a central venous catheter(at a dose of 1×10^6 cells/kg, over 15 mins) every two weeks, four times for a cycle. Other Name: MSCs; Biological: Non-mesenchymal stem cells Other second line drugs are taken. Other Name: Non-MSCs
Study Arms	Experimental: Non-mesenchymal stem cells Non-mesenchymal stem cell group refers to treatment with other second line drugs Intervention: Biological: Non-mesenchymal stem cells; Experimental: Mesenchymal stem cells Mesenchymal stem cell group refers to treatment with mesenchymal stem cells (1×10^6 cells/kg, intravenously)every two weeks, four times for a cycle Intervention: Biological: Mesenchymal stem cells
Publications *	Pérez-Simon JA, López-Villar O, Andreu EJ, Rifón J, Muntion S, Diez Campelo M, Sánchez-Guijo FM, Martinez C, Valcarcel D, Cañizo CD. Mesenchymal stem cells expanded in vitro with human serum for the treatment of acute and chronic graft-versus-host disease: results of a phase I/II clinical trial. Haematologica. 2011 Jul;96(7):1072-6. doi: 10.3324/haematol.2010.038356. Epub 2011 Mar 10.; Ringdén O, Uzunel M, Rasmusson I, Remberger M, Sundberg B, Lönnies H, Marschall HU, Dlugosz A, Szakos A, Hassan Z, Omazic B, Aschan J, Barkholt L, Le Blanc K. Mesenchymal stem cells for treatment of therapy-resistant graft-versus-host disease. Transplantation. 2006 May 27;81(10):1390-7.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Unknown status
Estimated Enrollment ICMJE; (submitted: January 8, 2013)	60
Original Estimated Enrollment ICMJE	Same as current
Estimated Study Completion Date	December 2016
Estimated Primary Completion Date	December 2015 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: A patient age of 12-65 years; Recipients of allogeneic hematopoietic stem cell transplantation; Patients with refractory cGVHD; 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)
Sex/Gender	Sexes Eligible for Study: All
Ages	12 Years to 65 Years (Child, Adult, Older Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	China
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01765660
Other Study ID Numbers ICMJE	NFH-MSCs-cGVHD-2013
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Nanfang Hospital of Southern Medical University
Study Sponsor ICMJE	Nanfang Hospital of Southern Medical University
Collaborators ICMJE	Sun Yat-sen University; Peking University People's Hospital; Guangdong General Hospital; Guangzhou General Hospital of Guangzhou Military Command; Southern Medical University, China; Third Affiliated Hospital, Sun Yat-Sen University; Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University; Guangzhou First People's Hospital; Zhongshan People's Hospital, Guangdong, China
Investigators ICMJE	Principal Investigator: Qifa Liu Nanfang Hospital of Southern Medical University
PRS Account	Nanfang Hospital of Southern Medical University
Verification Date	January 2013
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP