Clinical Trial: Safety and Efficacy of Patient's Own AD-MSC and AD-HSC Transplantation in Patients With Severe Aplastic Anemia
Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional
Official Title: A Multicenter, Randomized, Controlled Study of the Efficacy and Safety of the Combination of Adipose Tissue-derived Hematopoietic Stem Cells (AD-HSCs) and ATG in the Treatment of Severe RATIONALE: It has been shown that about 30% of patients do not respond to immunosuppressive therapy or experience recurrence, and graft rejection and graft-versus-host-disease (GVHD) decrease event-free survival to 30% to 50% in the alternative donor (matched unrelated, partially matched family member) transplantation. Although an overall and disease free survival of 85% to 100%, can be obtained in allogeneic blood or bone marrow stem cell transplantation using an human leukocyte antigen (HLA) matched sibling donor, only about 25% of patients have such a donor.
PURPOSE: In an attempt to avoid GVHD, reduce earlier infection rate and decrease regimen-related toxicity while maintaining better engraftment, this study is to evaluate the effectiveness and safety of patient's own adipose-derived mesenchymal stem cell (AD-MSC) or AD-MSC transdifferentiated HSC (AD-HSC) transplant after an immunosuppressive regimen in treating patients who have severe aplastic anemia.
The patient will be in the study for one year for observation and active monitoring. After treatment and active monitoring are over, the patient's medical condition will be followed indefinitely. The principle measures of safety and efficacy will be :
- Patient survival probability at 3 months, 6 months and 1 year.
- Engraftment at 3 months, 6 months and 1 year
- Incidence of graft versus host disease (GVHD), incidence of acute and chronic GVHD and Incidence of earlier infection rate as well as other complications within 6 months and 1 years.
Detailed Summary:
Severe aplastic anemia is characterized by severe deficiencies in peripheral-blood platelets, white cells, and red cells. These defects in mature cells occur because aplastic bone marrow contains severely reduced numbers of hematopoietic stem cells. To date, Hematopoietic stem cell (HSC) transplants are routinely used to treat patients with many different diseases, including various cancers and blood disorders, such as aplastic anemia. The main sources of HSCs are bone marrow, cord blood and peripheral blood. However, challenges include obtaining enough functional HSCs to ensure optimal engraftment, and avoiding immune rejection and other complications associated with allogeneic transplantations. Novel abundant sources of clinical-grade HSCs are therefore being sought.
Our novel studies have demonstrated that adipose-derived mesenchymal stem cells (AD-MSCs) can be converted rapidly (in 4 days) into AD-HSCs on a large scale (2X108-9 cluster of differentiation 34（CD34）positive cells) by transfection of small RNAs to the the early region 1A (E1A)-like inhibitor of differentiation 1 (EID1) in the presence of specific cytokines. In vitro, AD-HSCs expanded efficiently and resembled cord-blood HSCs in phenotype, genotype, and colony-forming ability. In a mouse model, primary and secondary transplantation analysis and repopulating assays showed that AD-HSCs homed to the bone marrow, differentiated into functional blood cells, and showed a long-term ability to self-renew. we show that adipose-derived mesenchymal stem cells (AD-MSCs) can be converted into AD-HSCs by transfection of small RNAs to the E1A-like inhibitor of differentiation 1 (EID1) in the presence of specific cytokines. In vitro, AD-HSCs expanded efficiently and resembled cord-blood HSCs in phenotype, genotype, and colony-forming ability. In a mouse model, primary and secondary transplantation analysis a
Sponsor: Navy General Hospital, Beijing
Current Primary Outcome: Engraftment at 42 days post AD-HSC transplantation for patients with severe aplastic anemia. [ Time Frame: 42 days posttransplant ]
Original Primary Outcome: Same as current
Current Secondary Outcome:
- To estimate the overall survival (OS) at 1 year following AD-HSC transplantation for Patients with Severe Aplastic Anemia [ Time Frame: 1 year ]Number of Subjects Alive at 12 months Post Transplant
- Relapse [ Time Frame: 1 year post transplant ]Return of SAA during the specified post-transplantation period.
- Incidence of chronic graft-versus-host disease [ Time Frame: 6 months ]Number of patients with chronic graft-versus-host disease by 6 months and 1 year
- Evaluation of the occurrence of secondary malignancies [ Time Frame: 6 months post transplant ]Occurring of any tumors during the specified post-transplantation period.
- Hematology labs [ Time Frame: 12 weeks ]Association between AD-HSC transplantation and response in hemoglobin, platelet, total white blood cell count, and absolute neutrophil count to be evaluate by maximal hemoglobin, platelet, total white blood cell count, and absolute neutrophil counts achieved in patients with severe aplastic anemia
- Number of participants with adverse events as a measure of safety and tolerability of intravenous AD-HSC infusion in patients with severe aplastic anemia [ Time Frame: weekly untill 12 months ]Adverse events like allergic reactions, infectious diseases, organ dysfunction or other related to AD-HSC infusion will be assessed
- Transfusional requirements [ Time Frame: weekly untill 6 months ]Units of blood or platelets transfused after AD-HSC infusion will be measured and compared to previously.
- To assess treatment related mortality [ Time Frame: 12 months ]Number of death after transplantation during the specified post-transplantation period.
Original Secondary Outcome: Same as current
Information By: Navy General Hospital, Beijing
Dates:
Date Received: March 25, 2015
Date Started: January 2015
Date Completion: July 2017
Last Updated: April 2, 2015
Last Verified: March 2015
