Efficacy and Safety Study of Allogenic Mesenchymal Stem Cells for Patients With Chronic Graft Versus Host Disease

Chronic Graft Versus Host Disease Clinical Trial

— MSCsTcGVHD  

Official title:

Phase Ⅱ/Ⅲ Clinical Trial, Multicenter, Randomized, Controlled, for the Evaluation of Efficacy and Safety of Therapy With Allogenic Mesenchymal Stem Cells in Patients With Chronic Graft Versus Host Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01526850
• Other study ID #: D07050701350701
• Status: Recruiting
• Phase: Phase 2/Phase 3
• First received: February 1, 2012
• Last updated: August 1, 2012
• Start date: February 2012
• Est. completion date: June 2014

Study information

• Verified date: February 2012
• Source: Chinese Academy of Medical Sciences
• Contact: He Huang, MD
• Phone: 86-0571-87236706
• Email: hehuangyu[@]126.com
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The primary purpose of the study is to evaluate the safety and efficacy of mesenchymal stem cells (MSC) for the treatment of patients who have developed an extensive chronic graft versus host disease (with skin and/or liver damage) after HSCs transplantation and do not respond to first-line therapy.

The secondary purpose of the study is to evaluate the effect of mesenchymal stem cells (MSC) on one-year survival rate, long-term survival rate, life quality and recurrence of patients who have developed an extensive chronic graft versus host disease (with skin and/or liver damage) after HSCs transplantation and do not respond to hormone treatment.

Description:

Chronic Graft-versus-host disease (GVHD)， with the incidence of 30%-60%, is a serious late complication of allogeneic hematopoietic stem cell transplantation (HSCT) and is the major cause of death in the late stage of transplantation. According to targeted organs, cGVHD is divided into two types, limited cGVHD and extensive cGVHD. Extensive cGVHD needs systemic immunosuppressant treatment. However, currently standard first-line regimen including cyclophosphamide and prednisolone is only effective for some patients. Novel treatment is urgently needed. Our previous study has shown that mesenchymal stem cells (MSCs) are effective for cGVHD patients with multiple skin damage. To further explore the therapeutic effect of MSCs for extensive cGVHD, we plan to conduct a multi-center clinical trial. Patients who developed an extensive cGVHD (with skin and/or liver damage) after HSCs transplantation and do not respond to first-line therapy are enrolled. They will be randomly divided into two groups which will receive MSCs and routine second-line drugs respectively. We will evaluate the efficacy and safety of MSCs for extensive cGVHD by comparison of symptom improvement, survival rate, recurrence as well as side effects in the two groups.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: June 2014
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years to 60 Years

Eligibility

Inclusion Criteria:

• Extensive cGVHD with skin and/or liver damage developed after allogeneic hematopoietic stem cell transplantation

• cGVHD that do not response to conventional immunosuppressant treatment for two months

• KPS>= 30

• informed consent from the patient

Exclusion Criteria:

• Extensive cGVHD without skin or liver damage

• With other acute severe complications

• In pregnancy or lactation

• Disease relapses

• With non-hematological malignancy

• Have a history of mental disorder, drug or alcohol abuse over the past five years

• Allergic

• Participate in other clinical trial within three months before the start of this trial

• With bone marrow fibrosis

• Have undergone hematopoietic stem cell transplantation to treat solid tumor

Study Design

Allocation: 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:
• Biological: mesenchymal stem cell
Mesenchymal stem cells, 1-2×107, bone marrow injection, once a week for the first four weeks; whether to continue after four weeks depends on patients' symptoms.

Drug:
• Cyclosporine and Glucocorticoid
Calmodulin inhibitors such as cyclosporine, combined with Glucocorticoid 0.5-1mg/kg/d ,to the end of the study.

Locations

Country	Name	City	State
China	Zhejiang University	Hangzhou	Zhejiang

Sponsors (5)

Lead Sponsor	Collaborator
Chinese Academy of Medical Sciences	307 Hospital of PLA, Chinese PLA General Hospital, Peking Union Medical College, Zhejiang University

Country where clinical trial is conducted

China, 

References & Publications (14)

Chen L, Zhang W, Yue H, Han Q, Chen B, Shi M, Li J, Li B, You S, Shi Y, Zhao RC. Effects of human mesenchymal stem cells on the differentiation of dendritic cells from CD34+ cells. Stem Cells Dev. 2007 Oct;16(5):719-31. — View Citation

Deng W, Han Q, Liao L, Li C, Ge W, Zhao Z, You S, Deng H, Zhao RC. Allogeneic bone marrow-derived flk-1+Sca-1- mesenchymal stem cells leads to stable mixed chimerism and donor-specific tolerance. Exp Hematol. 2004 Sep;32(9):861-7. — View Citation

Deng W, Han Q, Liao L, You S, Deng H, Zhao RC. Effects of allogeneic bone marrow-derived mesenchymal stem cells on T and B lymphocytes from BXSB mice. DNA Cell Biol. 2005 Jul;24(7):458-63. — View Citation

Guo M, Sun Z, Sun QY, Han Q, Yu CL, Wang DH, Qiao JH, Chen B, Sun WJ, Hu KX, Liu GX, Liu B, Zhao RC, Ai H. A modified haploidentical nonmyeloablative transplantation without T cell depletion for high-risk acute leukemia: successful engraftment and mild GVHD. Biol Blood Marrow Transplant. 2009 Aug;15(8):930-7. doi: 10.1016/j.bbmt.2009.04.006. — View Citation

Liao L, Zhao RC. An overview of stem cell-based clinical trials in China. Stem Cells Dev. 2008 Aug;17(4):613-8. doi: 10.1089/scd.2008.0183. Review. — View Citation

Liu K, Chen Y, Zeng Y, Xu L, Liu D, Chen H, Zhang X, Han W, Wang Y, Zhao T, Wang J, Wang J, Han Q, Zhao C, Huang X. Coinfusion of mesenchymal stromal cells facilitates platelet recovery without increasing leukemia recurrence in haploidentical hematopoietic stem cell transplantation: a randomized, controlled clinical study. Stem Cells Dev. 2011 Oct;20(10):1679-85. doi: 10.1089/scd.2010.0447. Epub 2011 Feb 5. — View Citation

Ren G, Zhang L, Zhao X, Xu G, Zhang Y, Roberts AI, Zhao RC, Shi Y. Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric oxide. Cell Stem Cell. 2008 Feb 7;2(2):141-50. doi: 10.1016/j.stem.2007.11.014. — View Citation

Shi D, Liao L, Zhang B, Liu R, Dou X, Li J, Zhu X, Yu L, Chen D, Zhao RC. Human adipose tissue-derived mesenchymal stem cells facilitate the immunosuppressive effect of cyclosporin A on T lymphocytes through Jagged-1-mediated inhibition of NF-?B signaling. Exp Hematol. 2011 Feb;39(2):214-224.e1. doi: 10.1016/j.exphem.2010.10.009. Epub 2010 Nov 13. — View Citation

Sun Z, Han Q, Zhu Y, Li Z, Chen B, Liao L, Bian C, Li J, Shao C, Zhao RC. NANOG has a role in mesenchymal stem cells' immunomodulatory effect. Stem Cells Dev. 2011 Sep;20(9):1521-8. doi: 10.1089/scd.2010.0366. Epub 2011 Feb 26. — View Citation

Wu Y, Zhao RC, Tredget EE. Concise review: bone marrow-derived stem/progenitor cells in cutaneous repair and regeneration. Stem Cells. 2010 May;28(5):905-15. doi: 10.1002/stem.420. Review. — View Citation

Zhang B, Liu R, Shi D, Liu X, Chen Y, Dou X, Zhu X, Lu C, Liang W, Liao L, Zenke M, Zhao RC. Mesenchymal stem cells induce mature dendritic cells into a novel Jagged-2-dependent regulatory dendritic cell population. Blood. 2009 Jan 1;113(1):46-57. doi: 10.1182/blood-2008-04-154138. Epub 2008 Oct 2. — View Citation

Zhang W, Ge W, Li C, You S, Liao L, Han Q, Deng W, Zhao RC. Effects of mesenchymal stem cells on differentiation, maturation, and function of human monocyte-derived dendritic cells. Stem Cells Dev. 2004 Jun;13(3):263-71. — View Citation

Zhou H, Guo M, Bian C, Sun Z, Yang Z, Zeng Y, Ai H, Zhao RC. Efficacy of bone marrow-derived mesenchymal stem cells in the treatment of sclerodermatous chronic graft-versus-host disease: clinical report. Biol Blood Marrow Transplant. 2010 Mar;16(3):403-12. doi: 10.1016/j.bbmt.2009.11.006. Epub 2009 Nov 17. — View Citation

Zhu Y, Sun Z, Han Q, Liao L, Wang J, Bian C, Li J, Yan X, Liu Y, Shao C, Zhao RC. Human mesenchymal stem cells inhibit cancer cell proliferation by secreting DKK-1. Leukemia. 2009 May;23(5):925-33. doi: 10.1038/leu.2008.384. Epub 2009 Jan 15. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The total Response rate defined as patients with complete and partial response		1 year after MSCs administration.	Yes
Secondary	one-year survival rate		1 year after MSCs administration	Yes
Secondary	disease relapse		2 years after MSCs administration	Yes
Secondary	quality of life		2 years after MSCs administration	Yes