Mesenchymal Stem Cells Co-transplantation in Alternative Donor Transplantation of Severe Aplastic Anemia.
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02247973|
Recruitment Status : Unknown
Verified September 2014 by Yang Xiao, Guangzhou General Hospital of Guangzhou Military Command.
Recruitment status was: Enrolling by invitation
First Posted : September 25, 2014
Last Update Posted : September 25, 2014
|Condition or disease||Intervention/treatment||Phase|
|Severe Aplastic Anemia||Biological: mesenchymal stem cells||Phase 2|
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 (Clinical Trial)|
|Estimated Enrollment :||100 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||PhaseⅡTrial of Co-transplantation With Bone Marrow Derived Mesenchymal Stem Cells From Related Donors in Alternative Donor Transplantation of Severe Aplastic Anemia.|
|Study Start Date :||February 2013|
|Estimated Primary Completion Date :||February 2017|
|Estimated Study Completion Date :||February 2018|
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 Name: Multipotent Mesenchymal Stromal Cells
Biological: mesenchymal stem cells
bone marrow derived mesenchymal stem cells from related donors.
- survival rate [ Time Frame: up to 2 years after HSCT ]The 2-year disease-free survival and overall survival.
- acute GVHD [ Time Frame: UP to 3 months after HSCT ]The incidence of acute GVHD after HSCT.
- chronic GVHD [ Time Frame: UP to 2 years after HSCT ]The incidence of chronic GVHD after HSCT.
- Transplant-related mortality [ Time Frame: UP to 1 months after HSCT ]
- Rates of relapse [ Time Frame: UP to 2 years after HSCT ]
- The implantation [ Time Frame: Up to 4 weeks after HSCT ]The implantation rate and implantation time.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02247973
|Guangzhou General Hospital of Guangzhou Military Command|
|Guangzhou, Guangdong, China, 510010|
|Study Chair:||Yang Xiao, MD||Guangzhou General Hospital of Guangzhou Military Command|