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

Chronic Graft-versus-host Disease Clinical Trial

Official title:

Mesenchymal Stem Cells From Third-party Donors for Treatment of Refractory Chronic Graft-versus-host Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01765660
• Other study ID #: NFH-MSCs-cGVHD-2013
• Status: Recruiting
• Phase: Phase 2
• First received: January 5, 2013
• Last updated: January 8, 2013
• Start date: January 2013
• Est. completion date: December 2016

Study information

• Verified date: January 2013
• Source: Nanfang Hospital of Southern Medical University
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: December 2016
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 12 Years to 65 Years

Eligibility

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)

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Graft-versus-host Disease
• Graft vs Host Disease

Intervention

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.
• Non-mesenchymal stem cells
Other second line drugs are taken.

Locations

Country	Name	City	State
China	Department of Hematology,Nanfang Hospital, Southern Medical University	Guangzhou	Guangdong

Sponsors (10)

Lead Sponsor	Collaborator
Nanfang Hospital of Southern Medical University	Guangdong General Hospital, Guangzhou First Municipal People’s Hospital, Guangzhou General Hospital of Guangzhou Military Command, Peking University People's Hospital, Southern Medical University, China, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Sun Yat-sen University, Third Affiliated Hospital, Sun Yat-Sen University, Zhongshan People's Hospital, Guangdong, China

Country where clinical trial is conducted

China, 

References & Publications (2)

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	infections	Infections will be mainly focused within the first 100 days after MSCs treatment.	1 year	Yes
Primary	The efficacy of treatment for refractory cGVHD	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.	1 year	No
Secondary	acute and late toxic side effects of MSCs treatment	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.	1 year	Yes