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

September 19, 2014 updated by: Yang Xiao, Guangzhou General Hospital of Guangzhou Military Command

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

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.

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).

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 Type

Interventional

Enrollment (Anticipated)

100

Phase

  • Phase 2

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
        • Guangzhou General Hospital of Guangzhou Military Command

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 to 48 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

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
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Mesenchymal stem cells
Intravenous bone marrow derived mesenchymal stem cells infusion from related donor to patients with severe aplastic anemia.
Biological: mesenchymal stem cells
Intravenous administration of up to 1~2x10^6 MSCs per kg,for 2 times,d0 and d14
Other Names:
  • Multipotent Mesenchymal Stromal Cells
Biological: mesenchymal stem cells
bone marrow derived mesenchymal stem cells from related donors.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
survival rate
Time Frame: up to 2 years after HSCT
The 2-year disease-free survival and overall survival.
up to 2 years after HSCT

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
acute GVHD
Time Frame: UP to 3 months after HSCT
The incidence of acute GVHD after HSCT.
UP to 3 months after HSCT
chronic GVHD
Time Frame: UP to 2 years after HSCT
The incidence of chronic GVHD after HSCT.
UP to 2 years after HSCT
Transplant-related mortality
Time Frame: UP to 1 months after HSCT
UP to 1 months after HSCT
Rates of relapse
Time Frame: UP to 2 years after HSCT
UP to 2 years after HSCT
The implantation
Time Frame: Up to 4 weeks after HSCT
The implantation rate and implantation time.
Up to 4 weeks after HSCT

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

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

Investigators

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

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, 2013

Primary Completion (Anticipated)

February 1, 2017

Study Completion (Anticipated)

February 1, 2018

Study Registration Dates

First Submitted

September 17, 2014

First Submitted That Met QC Criteria

September 19, 2014

First Posted (Estimate)

September 25, 2014

Study Record Updates

Last Update Posted (Estimate)

September 25, 2014

Last Update Submitted That Met QC Criteria

September 19, 2014

Last Verified

September 1, 2014

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MSC-alternative donor SCT-SAA

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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