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

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Brief Title

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

Official Title

PhaseⅡTrial of Co-transplantation With Bone Marrow Derived Mesenchymal Stem Cells From Related Donors in Alternative Donor Transplantation of Severe Aplastic Anemia.

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.
    

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).

      Allogeneic BMT from an HLA-identical sibling donor or matched-alternative donor is the
      treatment of choice for patients with aplastic anaemia.Transplantation for patients with
      severe aplastic anaemia from an HLA identical sibling donor is now very successful with a
      75-90% chance of long term cure and with overall survival of between 65% and 73% at 5 years
      for matched-alternative donor transplantation. However, these two approachs are limited by
      the availability of HLA-matched donors.

      Patients without HLA-identical sibling donor or matched-alternative donor can be offered
      immunosuppressive treatment (IST) involving injections of Anti-thymocyte globulin (ATG) in
      combination with cyclosporine (CsA). The treatment response with ATG is at best between
      60-80%, 30%-40% patients relapse following an initial response to treatment. Moreover, a
      recent study has shown that on multivariate analysis of response at 6 months, only younger
      age, absolute reticulocyte count (ARC) and absolute lymphocyte count (ALC), correlate with
      response to ATG. Patients with SAA or vSAA, with much lower ARC and ALC, were poor response
      to IST and have high risks of dying of infection and bleeding.

      Nowadays, with advances in transplant technology, HLA-mismatched related donors and unrelated
      donors transplantation has achieved good clinical results. Data from the XJ Huang indicated
      that patients with HLA-mismatched related donors achieved 100% donor myeloid engraftment and
      have a survival rate of 64.6±12.4%. Retrospectively analyzed results for 154 patients with
      acquired SAA who received BMT from unrelated donors identified through the Japan Marrow Donor
      Program showed the probability of OS at 5 years was 56% (95% confidence interval, 34%-78%).

      Compared with malignant disease, mismatched related donor or unrelated donor HSCT for SAA
      involves distinct challenges mainly associated with high graft failure and high GVHD. So, if
      we can find a way to promote implantation meanwhile prevent or reduce GVHD , the efficacy of
      HLA-mismatched related donors transplantation can improve.

      Mesenchymal stem cells (MSCs) are multi-potent non-hematopoietic progenitors mainly found in
      BM, cord blood, and adipose tissue. MSCs are attractive because of the ease with which they
      can be isolated and expanded ex vivo, their ability to undergo multilineage differentiation,
      and their lack of immunogenicity. These cells were shown to provide support for the growth
      and differentiation of hematopoietic progenitor cells in BM micro-environments. In additon,
      preliminary studies have shown clinical effectiveness of allogeneic MSC in the treatment of
      refractory graft-versus-host disease and an improvement in or resolution of severe aGVHD when
      co-transplantation with MSCs. Due to these properties, MSCs have become an interesting
      candidate for use in cellular therapy and are considered "theoretically perfect cells" for
      potential clinical use against AA mismatched related donors transplantation.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

survival rate

Secondary Outcome

 acute GVHD

Condition

Severe Aplastic Anemia

Intervention

mesenchymal stem cells

Study Arms / Comparison Groups

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

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Biological

Estimated Enrollment

100

Start Date

February 2013

Completion Date

February 2018

Primary Completion Date

February 2017

Eligibility Criteria

        Inclusion Criteria:

          1. In line with the 2009 Edition (United Kingdom) aplastic anemia diagnostic criteria for
             SAA or VSAA;

          2. Age less than 50 years old,willing to transplant;

          3. No HLA-identical sibling donor;

          4. Have HLA-mismatched related donors or unrelated donors ( ≥5/10 HLA matched loci in
             related donors; ≥8/10 HLA matched loci in unrelated donors )

          5. No serious infection or acute hemorrhage;

          6. Cardiac ultrasound examination showed left ventricular ejection fraction is greater
             than 50%;

          7. Both transaminase and serum creatinine level are no more than twice times the upper
             limit of normal value (ULN);

          8. No acute infectious disease;

          9. Ability to understand and the willingness to sign a written informed consent document.

         10. ECOG score of 0-2 points.

        Exclusion Criteria:

          1. Patients with severe infection or active bleeding;

          2. With severe cardiac insufficiency, left ventricular ejection fraction <50%;

          3. With severe liver dysfunction, liver function (ALT and the TBIL) is higher than the
             ULN 3 times;

          4. 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;

          5. Active tuberculosis, severe acute hepatitis and other infectious diseases in active
             period;

          6. ECOG score more than 3 points;

          7. Accompanied by malignant tumors and other clonal disease;

          8. Poor compliance and the researchers considered unsuitable for MSC infusion.
      

Gender

All

Ages

14 Years - 50 Years

Accepts Healthy Volunteers

No

Contacts

Yang Xiao, MD, , 

Location Countries

China

Location Countries

China

Administrative Informations


NCT ID

NCT02247973

Organization ID

MSC-alternative donor SCT-SAA


Responsible Party

Principal Investigator

Study Sponsor

Guangzhou General Hospital of Guangzhou Military Command

Collaborators

 Guangzhou First People's Hospital

Study Sponsor

Yang Xiao, MD, Study Chair, Guangzhou General Hospital of Guangzhou Military Command


Verification Date

September 2014