Mesenchymal Stem Cells Co-transplantation in Alternative Donor Transplantation of Severe Aplastic Anemia.

NCT02247973 | Unknown Phase 2 DMC

• 1 other identifier: MSC-alternative donor SCT-SAA
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

The study is a phase II trial designed to evaluate the efficacy and safety of co-transplantation with bone marrow derived mesenchymal stem cells from related donors in alternative donor transplantation of severe aplastic anemia.

Conditions

Severe Aplastic Anemia

Outcome Measures

Primary Outcomes (1)

• survival rate

  The 2-year disease-free survival and overall survival.

  up to 2 years after HSCT

Secondary Outcomes (5)

• acute GVHD

  UP to 3 months after HSCT

• chronic GVHD

  UP to 2 years after HSCT

• Transplant-related mortality

  UP to 1 months after HSCT

• Rates of relapse

  UP to 2 years after HSCT

• The implantation

  Up to 4 weeks after HSCT

Study Arms (1)

Mesenchymal stem cells

EXPERIMENTAL

Intravenous bone marrow derived mesenchymal stem cells infusion from related donor to patients with severe aplastic anemia.

Biological: mesenchymal stem cells

Interventions

mesenchymal stem cells BIOLOGICAL

Intravenous administration of up to 1\~2x10\^6 MSCs per kg,for 2 times,d0 and d14

Also known as: Multipotent Mesenchymal Stromal Cells

Mesenchymal stem cells

Eligibility Criteria

• Age: 14 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• In line with the 2009 Edition (United Kingdom) aplastic anemia diagnostic criteria for SAA or VSAA;
• Age less than 50 years old,willing to transplant；
• No HLA-identical sibling donor；
• Have HLA-mismatched related donors or unrelated donors ( ≥5/10 HLA matched loci in related donors; ≥8/10 HLA matched loci in unrelated donors )
• No serious infection or acute hemorrhage;
• Cardiac ultrasound examination showed left ventricular ejection fraction is greater than 50%;
• Both transaminase and serum creatinine level are no more than twice times the upper limit of normal value (ULN);
• No acute infectious disease;
• Ability to understand and the willingness to sign a written informed consent document.
• ECOG score of 0-2 points.

You may not qualify if:

• Patients with severe infection or active bleeding;
• With severe cardiac insufficiency, left ventricular ejection fraction \<50%;
• With severe liver dysfunction, liver function (ALT and the TBIL) is higher than the ULN 3 times;
• With severe renal insufficiency, renal function (Cr) is twice higher than the ULN; or 24-hour urine creatinine clearance rate (Ccr) lower than 50ml/min;
• Active tuberculosis, severe acute hepatitis and other infectious diseases in active period;
• ECOG score more than 3 points;
• Accompanied by malignant tumors and other clonal disease;
• Poor compliance and the researchers considered unsuitable for MSC infusion.

Sponsors & Collaborators

• Guangzhou General Hospital of Guangzhou Military Command: lead
• Guangzhou First People's Hospital: collaborator
• Nanfang Hospital, Southern Medical University: collaborator
• Southern Medical University, China: collaborator
• First Affiliated Hospital, Sun Yat-Sen University: collaborator
• Second Affiliated Hospital, Sun Yat-Sen University: collaborator
• Third Affiliated Hospital, Sun Yat-Sen University: collaborator
• Fifth Affiliated Hospital, Sun Yat-Sen University: collaborator
• Guangdong Provincial People's Hospital: collaborator
• The Second People's Hospital of GuangDong Province: collaborator
• First Affiliated Hospital of Jinan University: collaborator
• The First Affiliated Hospital of Guangzhou Medical University: collaborator
• Second Affiliated Hospital of Guangzhou Medical University: collaborator
• Peking University Shenzhen Hospital: collaborator
• Shenzhen Second People's Hospital: collaborator

Study Sites (1)

Guangzhou General Hospital of Guangzhou Military Command

Guangzhou, Guangdong, 510010, China

Location

Related Publications (15)

• Marsh JC, Ball SE, Cavenagh J, Darbyshire P, Dokal I, Gordon-Smith EC, Keidan J, Laurie A, Martin A, Mercieca J, Killick SB, Stewart R, Yin JA; British Committee for Standards in Haematology. Guidelines for the diagnosis and management of aplastic anaemia. Br J Haematol. 2009 Oct;147(1):43-70. doi: 10.1111/j.1365-2141.2009.07842.x. Epub 2009 Aug 10. No abstract available.

  PMID: 19673883 BACKGROUND

• Bacigalupo A, Locatelli F, Lanino E, Marsh J, Socie G, Maury S, Prete A, Locasciulli A, Cesaro S, Passweg J; Severe Aplastic Anemia Working Party of the European Group for Blood and Marrow Transplantation. Fludarabine, cyclophosphamide and anti-thymocyte globulin for alternative donor transplants in acquired severe aplastic anemia: a report from the EBMT-SAA Working Party. Bone Marrow Transplant. 2005 Dec;36(11):947-50. doi: 10.1038/sj.bmt.1705165.

  PMID: 16205733 BACKGROUND

• Deeg HJ, O'Donnell M, Tolar J, Agarwal R, Harris RE, Feig SA, Territo MC, Collins RH, McSweeney PA, Copelan EA, Khan SP, Woolfrey A, Storer B. Optimization of conditioning for marrow transplantation from unrelated donors for patients with aplastic anemia after failure of immunosuppressive therapy. Blood. 2006 Sep 1;108(5):1485-91. doi: 10.1182/blood-2006-03-005041. Epub 2006 May 9.

  PMID: 16684959 BACKGROUND

• George B, Mathews V, Viswabandya A, Lakshmi KM, Srivastava A, Chandy M. Allogeneic hematopoietic stem cell transplantation is superior to immunosuppressive therapy in Indian children with aplastic anemia--a single-center analysis of 100 patients. Pediatr Hematol Oncol. 2010 Mar;27(2):122-31. doi: 10.3109/08880010903540542.

  PMID: 20201693 BACKGROUND

• Kojima S, Matsuyama T, Kato S, Kigasawa H, Kobayashi R, Kikuta A, Sakamaki H, Ikuta K, Tsuchida M, Hoshi Y, Morishima Y, Kodera Y. Outcome of 154 patients with severe aplastic anemia who received transplants from unrelated donors: the Japan Marrow Donor Program. Blood. 2002 Aug 1;100(3):799-803. doi: 10.1182/blood.v100.3.799.

  PMID: 12130489 BACKGROUND

• Noort WA, Kruisselbrink AB, in't Anker PS, Kruger M, van Bezooijen RL, de Paus RA, Heemskerk MH, Lowik CW, Falkenburg JH, Willemze R, Fibbe WE. Mesenchymal stem cells promote engraftment of human umbilical cord blood-derived CD34(+) cells in NOD/SCID mice. Exp Hematol. 2002 Aug;30(8):870-8. doi: 10.1016/s0301-472x(02)00820-2.

  PMID: 12160838 BACKGROUND

• Le Blanc K, Rasmusson I, Sundberg B, Gotherstrom C, Hassan M, Uzunel M, Ringden O. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet. 2004 May 1;363(9419):1439-41. doi: 10.1016/S0140-6736(04)16104-7.

  PMID: 15121408 BACKGROUND

• Ringden O, Uzunel M, Rasmusson I, Remberger M, Sundberg B, Lonnies 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. doi: 10.1097/01.tp.0000214462.63943.14.

  PMID: 16732175 BACKGROUND

• Le Blanc K, Frassoni F, Ball L, Locatelli F, Roelofs H, Lewis I, Lanino E, Sundberg B, Bernardo ME, Remberger M, Dini G, Egeler RM, Bacigalupo A, Fibbe W, Ringden O; Developmental Committee of the European Group for Blood and Marrow Transplantation. Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet. 2008 May 10;371(9624):1579-86. doi: 10.1016/S0140-6736(08)60690-X.

  PMID: 18468541 BACKGROUND

• Ball LM, Bernardo ME, Roelofs H, Lankester A, Cometa A, Egeler RM, Locatelli F, Fibbe WE. Cotransplantation of ex vivo expanded mesenchymal stem cells accelerates lymphocyte recovery and may reduce the risk of graft failure in haploidentical hematopoietic stem-cell transplantation. Blood. 2007 Oct 1;110(7):2764-7. doi: 10.1182/blood-2007-04-087056. Epub 2007 Jul 16.

  PMID: 17638847 BACKGROUND

• Fang B, Li N, Song Y, Li J, Zhao RC, Ma Y. Cotransplantation of haploidentical mesenchymal stem cells to enhance engraftment of hematopoietic stem cells and to reduce the risk of graft failure in two children with severe aplastic anemia. Pediatr Transplant. 2009 Jun;13(4):499-502. doi: 10.1111/j.1399-3046.2008.01002.x. Epub 2008 Jul 30.

  PMID: 18673358 BACKGROUND

• Wang H, Wang Z, Xue M, Liu J, Yan H, Guo Z. Co-transfusion of haplo-identical hematopoietic and mesenchymal stromal cells to treat a patient with severe aplastic. Cytotherapy. 2010 Jul;12(4):563-5. doi: 10.3109/14653241003695059.

  PMID: 20380540 BACKGROUND

• Jaganathan BG, Tisato V, Vulliamy T, Dokal I, Marsh J, Dazzi F, Bonnet D. Effects of MSC co-injection on the reconstitution of aplastic anemia patient following hematopoietic stem cell transplantation. Leukemia. 2010 Oct;24(10):1791-5. doi: 10.1038/leu.2010.164. Epub 2010 Aug 19. No abstract available.

  PMID: 20724985 BACKGROUND

• Fang B, Song Y, Li N, Li J, Han Q, Zhao RC. Mesenchymal stem cells for the treatment of refractory pure red cell aplasia after major ABO-incompatible hematopoietic stem cell transplantation. Ann Hematol. 2009 Mar;88(3):261-6. doi: 10.1007/s00277-008-0599-0. Epub 2008 Sep 4.

  PMID: 18769919 BACKGROUND

• Xiao Y, Jiang ZJ, Pang Y, Li L, Gao Y, Xiao HW, Li YH, Zhang H, Liu Q. Efficacy and safety of mesenchymal stromal cell treatment from related donors for patients with refractory aplastic anemia. Cytotherapy. 2013 Jul;15(7):760-6. doi: 10.1016/j.jcyt.2013.03.007.

  PMID: 23731760 BACKGROUND

MeSH Terms

Conditions

Anemia, Aplastic

Condition Hierarchy (Ancestors)

Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Failure Disorders; Bone Marrow Diseases

Study Officials

• Yang Xiao, MD

  Guangzhou General Hospital of Guangzhou Military Command

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhaseⅡtrial of co-transplantation with bone marrow derived mesenchymal stem cells from related donors in alternative donor transplantation of severe aplastic anemia.

Study Record Dates

• First Submitted: September 17, 2014
• First Posted: September 25, 2014
• Study Start: February 1, 2013
• Primary Completion: February 1, 2017
• Study Completion: February 1, 2018
• Last Updated: September 25, 2014

Record last verified: 2014-09

Locations

CN (1)