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

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Brief Title

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

Official Title

PhaseⅠ/ⅡTrial of Bone Marrow Derived Mesenchymal Stem Cell Transplantation From Related Donor to Patients With Relapsed/Refractory Aplastic Anemia.

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.
    

Study Phase

Phase 1/Phase 2

Study Type

Interventional


Primary Outcome

Number of participants with adverse events

Secondary Outcome

 Hematologic response

Condition

Aplastic Anemia

Intervention

bone marrow derived mesenchymal stem cells

Study Arms / Comparison Groups

 MSC
Description:  Intravenous bone marrow derived mesenchymal stem cells infusion from related donor to patients with relapsed/refractory 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

50

Start Date

February 2011

Completion Date

December 2012

Primary Completion Date

June 2012

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.
      

Gender

All

Ages

16 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Yang Xiao, MD, 86-20-36653562, [email protected]

Location Countries

China

Location Countries

China

Administrative Informations


NCT ID

NCT01305694

Organization ID

HM-2010-16



Study Sponsor

Guangzhou General Hospital of Guangzhou Military Command

Collaborators

 Guangzhou Municipal Twelfth People's Hospital

Study Sponsor

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


Verification Date

February 2011