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

NCT01526850 | Unknown Phase 2 DMC

• 1 other identifier: D07050701350701
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Chronic Graft Versus Host Disease

Keywords

cGVHD

Outcome Measures

Primary Outcomes (1)

• The total Response rate defined as patients with complete and partial response

  1 year after MSCs administration.

Secondary Outcomes (3)

• one-year survival rate

  1 year after MSCs administration

• disease relapse

  2 years after MSCs administration

• quality of life

  2 years after MSCs administration

Study Arms (2)

allogenic mesenchymal stem cells (MSCs)

EXPERIMENTAL

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 standard first-line regimen including cyclophosphamide and prednisolone.

Biological: Biological: mesenchymal stem cell

Control group

ACTIVE COMPARATOR

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 standard first-line regimen including cyclophosphamide and prednisolone.

Drug: Cyclosporine and Glucocorticoid

Interventions

Biological: mesenchymal stem cell BIOLOGICAL

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.

Also known as: Regenerative medicine: MSCs

allogenic mesenchymal stem cells (MSCs)

Cyclosporine and Glucocorticoid DRUG

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

Also known as: Calmodulin inhibitors combined with Glucocorticoid

Control group

Eligibility Criteria

• Age: 2 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Chinese Academy of Medical Sciences: lead
• Zhejiang University: collaborator
• Chinese PLA General Hospital: collaborator
• 307 Hospital of PLA: collaborator
• Peking Union Medical College: collaborator

Study Sites (1)

Zhejiang University

Hangzhou, Zhejiang, China

RECRUITING

Related Publications (14)

• 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.

  PMID: 21235326 BACKGROUND

• 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-kappaB signaling. Exp Hematol. 2011 Feb;39(2):214-224.e1. doi: 10.1016/j.exphem.2010.10.009. Epub 2010 Nov 13.

  PMID: 21078360 BACKGROUND

• 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.

  PMID: 21142788 BACKGROUND

• 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.

  PMID: 20474078 BACKGROUND

• 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.

  PMID: 19925878 BACKGROUND

• 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.

  PMID: 19589482 BACKGROUND

• 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.

  PMID: 19148141 BACKGROUND

• 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.

  PMID: 18832657 BACKGROUND

• 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.

  PMID: 18673001 BACKGROUND

• 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.

  PMID: 18371435 BACKGROUND

• 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. doi: 10.1089/scd.2007.0065.

  PMID: 17999594 BACKGROUND

• 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. doi: 10.1089/dna.2005.24.458.

  PMID: 16008514 BACKGROUND

• 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. doi: 10.1016/j.exphem.2004.06.009.

  PMID: 15345288 BACKGROUND

• 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. doi: 10.1089/154732804323099190.

  PMID: 15186722 BACKGROUND

MeSH Terms

Conditions

Bronchiolitis Obliterans Syndrome

Interventions

Cyclosporine; Glucocorticoids

Condition Hierarchy (Ancestors)

Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases

Intervention Hierarchy (Ancestors)

Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• He Huang, MD

  Zhejiang University

  PRINCIPAL INVESTIGATOR

• Chunhua Zhao, MD,PHD

  Peking Union Medical College

  PRINCIPAL INVESTIGATOR

Central Study Contacts

He Huang, MD

CONTACT

86-0571-87236706; hehuangyu@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD，Professor of medicine

Study Record Dates

• First Submitted: February 1, 2012
• First Posted: February 6, 2012
• Study Start: February 1, 2012
• Primary Completion: December 1, 2013
• Study Completion: June 1, 2014
• Last Updated: August 3, 2012

Record last verified: 2012-02

Locations

CN (1)