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

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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
Sponsor:
Collaborators:
Guangzhou First People's Hospital
Nanfang Hospital of Southern Medical University
Southern Medical University, China
First Affiliated Hospital, Sun Yat-Sen University
Second Affiliated Hospital, Sun Yat-Sen University
Third Affiliated Hospital, Sun Yat-Sen University
Fifth Affiliated Hospital, Sun Yat-Sen University
Guangdong General Hospital
The Second People's Hospital of GuangDong Province
First Affiliated Hospital of Jinan University
The First Affiliated Hospital of Guangzhou Medical University
Second Affiliated Hospital of Guangzhou Medical University
Peking University Shenzhen Hospital
Shenzhen Second People's Hospital
Information provided by (Responsible Party):
Yang Xiao, Guangzhou General Hospital of Guangzhou Military Command

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.

Condition or disease Intervention/treatment Phase
Severe Aplastic Anemia Biological: mesenchymal stem cells Phase 2

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  (Clinical Trial)
Estimated Enrollment : 100 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine


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 Name: Multipotent Mesenchymal Stromal Cells

Biological: mesenchymal stem cells
bone marrow derived mesenchymal stem cells from related donors.




Primary Outcome Measures :
  1. survival rate [ Time Frame: up to 2 years after HSCT ]
    The 2-year disease-free survival and overall survival.


Secondary Outcome Measures :
  1. acute GVHD [ Time Frame: UP to 3 months after HSCT ]
    The incidence of acute GVHD after HSCT.

  2. chronic GVHD [ Time Frame: UP to 2 years after HSCT ]
    The incidence of chronic GVHD after HSCT.

  3. Transplant-related mortality [ Time Frame: UP to 1 months after HSCT ]
  4. Rates of relapse [ Time Frame: UP to 2 years after HSCT ]
  5. The implantation [ Time Frame: Up to 4 weeks after HSCT ]
    The implantation rate and implantation time.



Information from the National Library of Medicine

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Ages Eligible for Study:   14 Years to 50 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

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


Locations
China, Guangdong
Guangzhou General Hospital of Guangzhou Military Command
Guangzhou, Guangdong, China, 510010
Sponsors and Collaborators
Guangzhou General Hospital of Guangzhou Military Command
Guangzhou First People's Hospital
Nanfang Hospital of Southern Medical University
Southern Medical University, China
First Affiliated Hospital, Sun Yat-Sen University
Second Affiliated Hospital, Sun Yat-Sen University
Third Affiliated Hospital, Sun Yat-Sen University
Fifth Affiliated Hospital, Sun Yat-Sen University
Guangdong General Hospital
The Second People's Hospital of GuangDong Province
First Affiliated Hospital of Jinan University
The First Affiliated Hospital of Guangzhou Medical University
Second Affiliated Hospital of Guangzhou Medical University
Peking University Shenzhen Hospital
Shenzhen Second People's Hospital
Investigators
Study Chair: Yang Xiao, MD Guangzhou General Hospital of Guangzhou Military Command

Publications:

Responsible Party: Yang Xiao, PhaseⅡtrial of co-transplantation with bone marrow derived mesenchymal stem cells from related donors in alternative donor transplantation of severe aplastic anemia., Guangzhou General Hospital of Guangzhou Military Command
ClinicalTrials.gov Identifier: NCT02247973     History of Changes
Other Study ID Numbers: MSC-alternative donor SCT-SAA
First Posted: September 25, 2014    Key Record Dates
Last Update Posted: September 25, 2014
Last Verified: September 2014

Additional relevant MeSH terms:
Anemia
Anemia, Aplastic
Hematologic Diseases
Bone Marrow Diseases