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

Phase 2

• Conditions: Acute Graft-versus-host Disease
• Interventions: Biological: Mesenchymal stem cells; Biological: Non-mesenchymal stem cells

• Registration Number: NCT01765634
• Lead Sponsor: Nanfang Hospital, Southern Medical University

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.

Study Timeline

• Status Verified: 2013-01
• Study Start: 2013-01
• Study First Submitted: 2013-01-05
• Study First Submitted QC: 2013-01-08
• Last Update Submitted: 2013-01-08
• Study First Posted: 2013-01-10
• Last Update Posted: 2013-01-10
• Primary Completion: 2015-12
• Study Completion: 2016-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 40

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Mesenchymal stem cells	Mesenchymal stem cells	Mesenchymal stem cell group refers to treatment with mesenchymal stem cells (1×10\^6 cells/kg, intravenously)each week, four times for a cycle
Non-mesenchymal stem cells	Non-mesenchymal stem cells	Non-mesenchymal stem cell group refers to treatment with other second line drugs

Primary Outcome Measures

Name	Time	Method
The efficacy of treatment for refractory aGVHD	1 year	The response criteria include complete response (CR), part response (PR), stable disease(SD) and progressive disease(PD). CR:aGVHD symptoms and signs disappear; PR:aGVHD symptoms and signs improve; SD:aGVHD symptoms and signs remain (without improvement or deterioration);PD: aGVHD symptoms and signs deteriorate.

Secondary Outcome Measures

Name	Time	Method
acute and late toxic side effects of MSCs treatment	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.

Trial Locations

Locations (1)

Department of Hematology,Nanfang Hospital, Southern Medical University; 🇨🇳 Guangzhou, Guangdong, China