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Mesenchymal Stem Cells Transplantation to Patients With Relapsed/Refractory Aplastic Anemia. (MSC)

Primary Purpose

Aplastic Anemia

Status
Unknown status
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
bone marrow derived mesenchymal stem cells
Sponsored by
Guangzhou General Hospital of Guangzhou Military Command
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Aplastic Anemia

Eligibility Criteria

16 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients must fulfill definition of aplastic anaemia:

There must be at least two of the following:

haemoglobin < 100g/L; platelet count < 50 x 109/L; neutrophil count < 1.5 x 109/L, and a hypocellular bone marrow;

SAA as defined by a hypocellular bone marrow of <25% cellularity and two of the following:

neutrophil count < 0.5 x 109/L platelets < 20 x 109/L reticulocytes < 20 x 109/L nSAA as defined by a hypocellular bone marrow and cytopenia in at least two cell lines and neutrophil count > 0.5 x 109/L, and red cell and/or platelet transfusion dependence.

  • Patients belong to acquired aplastic anaemia.
  • Patients with a history SAA must have had an incomplete response at least 3 months following treatment with ATG/CsA, or they must have relapsed following an initial response to treatment, and they do not have a HLA-matched donor for bone marrow transplantation. Patients with a history nSAA must have red cell and/or platelet transfusion dependence.
  • Peripheral blood counts at the time of enrollment must include at least one of the following: haemoglobin < 90 g/L or red blood cell (RBC) transfusion dependence, PMN < 1 x 109/L, or platelet count < 50 x 109/L.
  • Patients must have organ function as defined below:

total bilirubin within normal institutional limits (NV: 0.0-20.5 umol/L) AST(SGOT)/ALT(SGPT) < 2.5 × institutional upper limit of normal AST (NV: 0-35 U/L); ALT (NV: 0-40 U/L) Creatinine within normal institutional limits (NV: 53-106 umol/L) or Creatinine clearance > 1.25 ml/s for patients with creatinine levels above institutional normal.

  • Age minimum 16 years old with no upper age limit.
  • Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  • Patients may not be receiving any other investigational agents within 4 weeks of study entry.
  • History of allergic reactions attributed to compounds of similar biologic composition to mesenchymal stem cells.
  • Current diagnosis of Fanconi's anemia, Dyskeratosis Congenita (DC) or other hereditary forms of AA.
  • Psychiatric, addictive or any other disorder that compromises ability to give a truly informed consent.
  • Age < 16 years old.
  • ECOG performance status > 2.
  • Malignancy within the last 5 years.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (defined as invasive fungal infection and progressive CMV viremia), symptomatic congestive heart failure (NYH class III and IV), unstable angina pectoris, or cardiac arrhythmia.
  • Pregnant or breastfeeding women.
  • HIV-positive patients.

Sites / Locations

  • Guangzhou General Hospital of Guangzhou Military CommandRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

MSC

Arm Description

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

Outcomes

Primary Outcome Measures

Number of participants with adverse events

Secondary Outcome Measures

Hematologic response
Relapse
Clonal evolution to PNH, myelodysplasia or acute leukemia
Survival

Full Information

First Posted
February 28, 2011
Last Updated
February 28, 2011
Sponsor
Guangzhou General Hospital of Guangzhou Military Command
Collaborators
Guangzhou Municipal Twelfth People's Hospital, Guangdong Prevention and Treatment Center for Occupational Diseases
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1. Study Identification

Unique Protocol Identification Number
NCT01305694
Brief Title
Mesenchymal Stem Cells Transplantation to Patients With Relapsed/Refractory Aplastic Anemia.
Acronym
MSC
Official Title
PhaseⅠ/ⅡTrial of Bone Marrow Derived Mesenchymal Stem Cell Transplantation From Related Donor to Patients With Relapsed/Refractory Aplastic Anemia.
Study Type
Interventional

2. Study Status

Record Verification Date
February 2011
Overall Recruitment Status
Unknown status
Study Start Date
February 2011 (undefined)
Primary Completion Date
June 2012 (Anticipated)
Study Completion Date
December 2012 (Anticipated)

3. Sponsor/Collaborators

Name of the Sponsor
Guangzhou General Hospital of Guangzhou Military Command
Collaborators
Guangzhou Municipal Twelfth People's Hospital, Guangdong Prevention and Treatment Center for Occupational Diseases

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The study is a phase I/II trial designed to establish the safety and efficacy of intravenous administration of bone marrow derived mesenchymal stem cells from related donor to patients with relapsed/refractory aplastic anemia.
Detailed Description
Aplastic anemia (AA) is an autoimmune hematologic stem cell disease mediated by activated T-lymphocytes that leads to bone marrow dysfunction. In the presence of an empty marrow, pancytopenia, and transfusion dependence, the severity of the disease is based on neutrophil (PMN) count: nonsevere AA (nSAA; PMN > 0.5 × 109/L), severe AA (SAA;PMN 0.2- 0.5 × 109/L), and very severe AA (vSAA; PMN< 0.2 × 109/L). Patients with nSAA can be offered supportive care, anabolic steroids, and/or low-dose steroids or cyclosporine (CsA).Patients with SAA and vSAA can be offered immunosuppressive treatment involving injections of Anti-thymocyte globulin (ATG) in combination with cyclosporine (CsA). However, some nSAA patients remains dependent to transfusion, the treatment response with ATG for SAA is at best between 50-60%,30%-40% patients relapse following an initial response to treatment, they also do not have a HLA-matched donor for bone marrow transplantation. These patients have a high risk of dying without additional treatment. Since the prognosis of these refractory and relapsed AA patients remains poor, there is a need for more safe and effective therapy that can improve response rates and remission duration in refractory and relapsed AA. Mesenchymal stem cells (MSCs) are part of the bone marrow stem cells repertoire. The main role of MSCs is to support hematopoiesis. Recently, significant interactions between MSCs and cells from the immune system have been demonstrated:MSCs were found to downregulate T and B lymphocytes, natural killer cells (NK) and antigen presenting cells through various mechanisms, including cell-to-cell interaction and soluble factor production. MSCs can fully suppress T cell function which involves some degree of MSC activation or 'licensing' thought to involve interferon (IFN)-γ in conjunction with IL-1α, IL-1β or tumour necrosis factor-a. Non-specific suppression of T cell proliferation is mediated by soluble factors such as transforming growth factor (TGF)-β, kynurenine, prostaglandin E2 (PGE2), nitric oxide, haem oxygenase products and insulin-like growth factor binding protein. Since the haematopoietic support and immunomodulatory effects, bone marrow-derived human MSCs transplantation maybe a safe novel therapeutic approach for patients with refractory and relapsed AA.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Aplastic Anemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
MSC
Arm Type
Experimental
Arm Description
Intravenous bone marrow derived mesenchymal stem cells infusion from related donor to patients with relapsed/refractory aplastic anemia.
Intervention Type
Biological
Intervention Name(s)
bone marrow derived mesenchymal stem cells
Other Intervention Name(s)
Mesenchymal Stem Cells, Multipotent Mesenchymal Stem Cells, Multipotent Mesenchymal Stromal Cells
Intervention Description
Intravenous administration of up to 6x10^5 MSCs per kg,qw,for 4 weeks
Primary Outcome Measure Information:
Title
Number of participants with adverse events
Time Frame
up to 30 days
Secondary Outcome Measure Information:
Title
Hematologic response
Time Frame
up to 1 year
Title
Relapse
Time Frame
up to 1 year
Title
Clonal evolution to PNH, myelodysplasia or acute leukemia
Time Frame
up to 1 year
Title
Survival
Time Frame
up to 1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients must fulfill definition of aplastic anaemia: There must be at least two of the following: haemoglobin < 100g/L; platelet count < 50 x 109/L; neutrophil count < 1.5 x 109/L, and a hypocellular bone marrow; SAA as defined by a hypocellular bone marrow of <25% cellularity and two of the following: neutrophil count < 0.5 x 109/L platelets < 20 x 109/L reticulocytes < 20 x 109/L nSAA as defined by a hypocellular bone marrow and cytopenia in at least two cell lines and neutrophil count > 0.5 x 109/L, and red cell and/or platelet transfusion dependence. Patients belong to acquired aplastic anaemia. Patients with a history SAA must have had an incomplete response at least 3 months following treatment with ATG/CsA, or they must have relapsed following an initial response to treatment, and they do not have a HLA-matched donor for bone marrow transplantation. Patients with a history nSAA must have red cell and/or platelet transfusion dependence. Peripheral blood counts at the time of enrollment must include at least one of the following: haemoglobin < 90 g/L or red blood cell (RBC) transfusion dependence, PMN < 1 x 109/L, or platelet count < 50 x 109/L. Patients must have organ function as defined below: total bilirubin within normal institutional limits (NV: 0.0-20.5 umol/L) AST(SGOT)/ALT(SGPT) < 2.5 × institutional upper limit of normal AST (NV: 0-35 U/L); ALT (NV: 0-40 U/L) Creatinine within normal institutional limits (NV: 53-106 umol/L) or Creatinine clearance > 1.25 ml/s for patients with creatinine levels above institutional normal. Age minimum 16 years old with no upper age limit. Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: Patients may not be receiving any other investigational agents within 4 weeks of study entry. History of allergic reactions attributed to compounds of similar biologic composition to mesenchymal stem cells. Current diagnosis of Fanconi's anemia, Dyskeratosis Congenita (DC) or other hereditary forms of AA. Psychiatric, addictive or any other disorder that compromises ability to give a truly informed consent. Age < 16 years old. ECOG performance status > 2. Malignancy within the last 5 years. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (defined as invasive fungal infection and progressive CMV viremia), symptomatic congestive heart failure (NYH class III and IV), unstable angina pectoris, or cardiac arrhythmia. Pregnant or breastfeeding women. HIV-positive patients.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yang Xiao, MD
Phone
86-20-36653562
Email
jdxiao111@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Li Li, MD
Phone
86-20-36652062
Email
Lily17155@yahoo.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yang Xiao, MD
Organizational Affiliation
Guangzhou General Hospital of Guangzhou Military Command
Official's Role
Study Director
Facility Information:
Facility Name
Guangzhou General Hospital of Guangzhou Military Command
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510010
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yang Xiao, MD
Phone
86-20-36653562
Email
jdxiao111@163.com
First Name & Middle Initial & Last Name & Degree
Li Li, MD
Phone
86-20-36654678
Email
Lily17155@yahoo.com.cn

12. IPD Sharing Statement

Citations:
PubMed Identifier
18024605
Citation
Bacigalupo A. Aplastic anemia: pathogenesis and treatment. Hematology Am Soc Hematol Educ Program. 2007:23-8. doi: 10.1182/asheducation-2007.1.23.
Results Reference
background
PubMed Identifier
11986244
Citation
Di Nicola M, Carlo-Stella C, Magni M, Milanesi M, Longoni PD, Matteucci P, Grisanti S, Gianni AM. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood. 2002 May 15;99(10):3838-43. doi: 10.1182/blood.v99.10.3838.
Results Reference
background
PubMed Identifier
18493986
Citation
Polchert D, Sobinsky J, Douglas G, Kidd M, Moadsiri A, Reina E, Genrich K, Mehrotra S, Setty S, Smith B, Bartholomew A. IFN-gamma activation of mesenchymal stem cells for treatment and prevention of graft versus host disease. Eur J Immunol. 2008 Jun;38(6):1745-55. doi: 10.1002/eji.200738129.
Results Reference
background
PubMed Identifier
17507101
Citation
English K, Barry FP, Field-Corbett CP, Mahon BP. IFN-gamma and TNF-alpha differentially regulate immunomodulation by murine mesenchymal stem cells. Immunol Lett. 2007 Jun 15;110(2):91-100. doi: 10.1016/j.imlet.2007.04.001. Epub 2007 Apr 26.
Results Reference
background
PubMed Identifier
17521318
Citation
Ryan JM, Barry F, Murphy JM, Mahon BP. Interferon-gamma does not break, but promotes the immunosuppressive capacity of adult human mesenchymal stem cells. Clin Exp Immunol. 2007 Aug;149(2):353-63. doi: 10.1111/j.1365-2249.2007.03422.x. Epub 2007 May 22.
Results Reference
background
PubMed Identifier
15494428
Citation
Aggarwal S, Pittenger MF. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood. 2005 Feb 15;105(4):1815-22. doi: 10.1182/blood-2004-04-1559. Epub 2004 Oct 19.
Results Reference
background
PubMed Identifier
16985180
Citation
Sato K, Ozaki K, Oh I, Meguro A, Hatanaka K, Nagai T, Muroi K, Ozawa K. Nitric oxide plays a critical role in suppression of T-cell proliferation by mesenchymal stem cells. Blood. 2007 Jan 1;109(1):228-34. doi: 10.1182/blood-2006-02-002246. Epub 2006 Sep 19.
Results Reference
background
PubMed Identifier
17684157
Citation
Chabannes D, Hill M, Merieau E, Rossignol J, Brion R, Soulillou JP, Anegon I, Cuturi MC. A role for heme oxygenase-1 in the immunosuppressive effect of adult rat and human mesenchymal stem cells. Blood. 2007 Nov 15;110(10):3691-4. doi: 10.1182/blood-2007-02-075481. Epub 2007 Aug 7.
Results Reference
background
PubMed Identifier
17522338
Citation
Gieseke F, Schutt B, Viebahn S, Koscielniak E, Friedrich W, Handgretinger R, Muller I. Human multipotent mesenchymal stromal cells inhibit proliferation of PBMCs independently of IFNgammaR1 signaling and IDO expression. Blood. 2007 Sep 15;110(6):2197-200. doi: 10.1182/blood-2007-04-083162. Epub 2007 May 23.
Results Reference
background
PubMed Identifier
20955154
Citation
Kassis I, Vaknin-Dembinsky A, Karussis D. Bone marrow mesenchymal stem cells: agents of immunomodulation and neuroprotection. Curr Stem Cell Res Ther. 2011 Mar;6(1):63-8. doi: 10.2174/157488811794480762.
Results Reference
background
PubMed Identifier
23731760
Citation
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.
Results Reference
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Mesenchymal Stem Cells Transplantation to Patients With Relapsed/Refractory Aplastic Anemia.

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