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

February 28, 2011 updated by: Guangzhou General Hospital of Guangzhou Military Command

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

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

50

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510010
        • Recruiting
        • Guangzhou General Hospital of Guangzhou Military Command
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: MSC
Intravenous bone marrow derived mesenchymal stem cells infusion from related donor to patients with relapsed/refractory aplastic anemia.
Biological: bone marrow derived mesenchymal stem cells
Intravenous administration of up to 6x10^5 MSCs per kg,qw,for 4 weeks
Other Names:
  • Mesenchymal Stem Cells
  • Multipotent Mesenchymal Stem Cells
  • Multipotent Mesenchymal Stromal Cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Number of participants with adverse events
Time Frame: up to 30 days
up to 30 days

Secondary Outcome Measures

Outcome Measure
Time Frame
Hematologic response
Time Frame: up to 1 year
up to 1 year
Relapse
Time Frame: up to 1 year
up to 1 year
Clonal evolution to PNH, myelodysplasia or acute leukemia
Time Frame: up to 1 year
up to 1 year
Survival
Time Frame: up to 1 year
up to 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Guangzhou General Hospital of Guangzhou Military Command

Collaborators

Guangzhou Municipal Twelfth People's Hospital
Guangdong Prevention and Treatment Center for Occupational Diseases

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2011

Primary Completion (Anticipated)

June 1, 2012

Study Completion (Anticipated)

December 1, 2012

Study Registration Dates

First Submitted

February 28, 2011

First Submitted That Met QC Criteria

February 28, 2011

First Posted (Estimate)

March 1, 2011

Study Record Updates

Last Update Posted (Estimate)

March 1, 2011

Last Update Submitted That Met QC Criteria

February 28, 2011

Last Verified

February 1, 2011

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HM-2010-16

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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