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

NCT ID: NCT02247973

Last Updated: 2014-09-25

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-02-28
• Study Completion Date: 2018-02-28

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.

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.

Conditions

Severe Aplastic Anemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Mesenchymal stem cells

Intravenous bone marrow derived mesenchymal stem cells infusion from related donor to patients with severe aplastic anemia.

Group Type: EXPERIMENTAL

mesenchymal stem cells

Intervention Type: BIOLOGICAL

Intravenous administration of up to 1\~2x10\^6 MSCs per kg,for 2 times,d0 and d14

mesenchymal stem cells

Intervention Type: BIOLOGICAL

bone marrow derived mesenchymal stem cells from related donors.

Interventions

mesenchymal stem cells

Intravenous administration of up to 1\~2x10\^6 MSCs per kg,for 2 times,d0 and d14

Intervention Type: BIOLOGICAL

mesenchymal stem cells

bone marrow derived mesenchymal stem cells from related donors.

Intervention Type: BIOLOGICAL

Other Intervention Names

Multipotent Mesenchymal Stromal Cells

Eligibility 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.

• Minimum Eligible Age: 14 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Guangzhou First People's Hospital

OTHER

Sponsor Role: collaborator

Nanfang Hospital, Southern Medical University

OTHER

Sponsor Role: collaborator

Southern Medical University, China

OTHER

Sponsor Role: collaborator

First Affiliated Hospital, Sun Yat-Sen University

OTHER

Sponsor Role: collaborator

Second Affiliated Hospital, Sun Yat-Sen University

OTHER

Sponsor Role: collaborator

Third Affiliated Hospital, Sun Yat-Sen University

OTHER

Sponsor Role: collaborator

Fifth Affiliated Hospital, Sun Yat-Sen University

OTHER

Sponsor Role: collaborator

Guangdong Provincial People's Hospital

OTHER

Sponsor Role: collaborator

The Second People's Hospital of GuangDong Province

OTHER

Sponsor Role: collaborator

First Affiliated Hospital of Jinan University

OTHER

Sponsor Role: collaborator

The First Affiliated Hospital of Guangzhou Medical University

OTHER

Sponsor Role: collaborator

Second Affiliated Hospital of Guangzhou Medical University

OTHER

Sponsor Role: collaborator

Peking University Shenzhen Hospital

OTHER

Sponsor Role: collaborator

Shenzhen Second People's Hospital

OTHER

Sponsor Role: collaborator

Guangzhou General Hospital of Guangzhou Military Command

OTHER

Sponsor Role: lead

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.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Yang Xiao, MD

Role: STUDY_CHAIR

Guangzhou General Hospital of Guangzhou Military Command

Locations

Guangzhou General Hospital of Guangzhou Military Command

Guangzhou, Guangdong, China

Countries

China

References

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Other Identifiers

MSC-alternative donor SCT-SAA

Identifier Type: -

Identifier Source: org_study_id