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

Phase 2
Conditions
Chronic Graft-versus-host Disease
Interventions
Biological: Non-mesenchymal stem cells
Biological: Mesenchymal stem cells
Registration Number
NCT01765660
Lead Sponsor
Nanfang Hospital, Southern Medical University
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.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
60
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

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Non-mesenchymal stem cellsNon-mesenchymal stem cellsNon-mesenchymal stem cell group refers to treatment with other second line drugs
Mesenchymal stem cellsMesenchymal stem cellsMesenchymal stem cell group refers to treatment with mesenchymal stem cells (1×10\^6 cells/kg, intravenously)every two weeks, four times for a cycle
Primary Outcome Measures
NameTimeMethod
The efficacy of treatment for refractory cGVHD1 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.

Secondary Outcome Measures
NameTimeMethod
acute and late toxic side effects of MSCs treatment1 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

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