Safety and Efficacy of Patient's Own AD-MSC and AD-HSC Transplantation in Patients With Severe Aplastic Anemia
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 Aplastic Anemia
1 other identifier
interventional
90
1 country
1
Brief Summary
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 :
- 1.Patient survival probability at 3 months, 6 months and 1 year.
- 2.Engraftment at 3 months, 6 months and 1 year
- 3.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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Jan 2015
Typical duration for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
January 1, 2015
CompletedFirst Submitted
Initial submission to the registry
March 25, 2015
CompletedFirst Posted
Study publicly available on registry
April 3, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
July 1, 2017
CompletedApril 3, 2015
March 1, 2015
2 years
March 25, 2015
April 2, 2015
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Engraftment at 42 days post AD-HSC transplantation for patients with severe aplastic anemia.
Absolute neutrophil count \> 0.5 X 109/l and Platelet count \> 20 X 109 /l without infusion of platelet for 7 days.
42 days posttransplant
Secondary Outcomes (8)
To estimate the overall survival (OS) at 1 year following AD-HSC transplantation for Patients with Severe Aplastic Anemia
1 year
Relapse
1 year post transplant
Incidence of chronic graft-versus-host disease
6 months
Evaluation of the occurrence of secondary malignancies
6 months post transplant
Hematology labs
12 weeks
- +3 more secondary outcomes
Study Arms (3)
Rabbit antithymoglobulin （ATG）
ACTIVE COMPARATORPatient in this arm will receive rabbit ATG at 3.5 mg/kg/dose IV from day -6 to -2 with the goals of ablating host repressive T cells.
Rabbit ATG & AD-MSCs
EXPERIMENTALPatient in this arm will receive rabbit ATG at 3.5 mg/kg/dose IV from day -6 to -2 and then patient's own adipose derived mesenchymal stem cells (AD-MSCs) at a dose of 3000000/kg/d on day 1 to 3.
Rabbit ATG & AD-HSCs
EXPERIMENTALPatient in this arm will receive rabbit ATG at 3.5 mg/kg/dose IV from day -6 to -2 and then patient's own AD-MSC transdifferentiated HSCs (AD-HSCs) at a dose of 3000000/kg/d from day 1 to 4.
Interventions
Rabbit ATG at 3.5 mg/kg/dose IV is given from day -6 to -2.
Participants will receive rabbit ATG at 3.5 mg/kg/dose IV from day -6 to -2, and then patient's own AD-MSCs at a dose of 3000000 cells/kg/d on day 1-3.
Participants will receive rabbit anti-thymocyte globulin at 3.5 mg/kg/dose IV from day -6 to -2, and then patient's own AD-HSCs at a dose of 3000000 cells/kg/d from day 1 to 4.
Eligibility Criteria
You may qualify if:
- Male or female recipients must have histopathologically confirmed diagnosis of SAA-I without or with more than 6 months after less than one treatment with ATG. Diagnostic Criteria for Server Aplastic Anemia will be based on the definitions set forth by the international Aplastic Anemia Study Group.
- At least two of the following:
- Absolute neutrophil count ≤ 0.5 X 109/l, Platelet count ≤ 20 X 109 /l, Anemia with corrected reticulocyte count ≤ 1%, and Bone marrow cellularity ≤ 25%, or bone marrow cellularity ≤ 50% with fewer than 30% hematopoietic cell, Hepatic: alanine aminotransferase (ALT)/ aspartate aminotransferase (AST) no greater than 4 times normal, Bilirubin: no greater than 2 mg/dl, Renal: Creatinine clearance at least 50 ml/min, Cardiovascular: Shortening fraction or ejection fraction at least 40% of normal for age by echocardiogram or radionuclide scan.
- No clinically significant comorbid illnesses (e.g., myocardial infarction or cerebrovascular accident).
You may not qualify if:
- Active and uncontrolled infection, Active bleeding, Severe allergic history of ATG, HIV-1 infection, Pregnancy or breastfeeding, Carbon monoxide lung diffusion capacity (DLCO) \<40% predicted, SAA-II, Patients with severe psychological disorders, Recipients of other clinical trials.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Navy General Hospital, Beijinglead
- Peking Union Medical College Hospitalcollaborator
- General Hospital of Beijing PLA Military Regioncollaborator
- Chinese Academy of Medical Sciencescollaborator
Study Sites (1)
Navy General Hospital
Beijing, Beijing Municipality, 100048, China
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
james Q Yin, M.D.,Ph.D.
The military general hospital of Beijing
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Professor
Study Record Dates
First Submitted
March 25, 2015
First Posted
April 3, 2015
Study Start
January 1, 2015
Primary Completion
January 1, 2017
Study Completion
July 1, 2017
Last Updated
April 3, 2015
Record last verified: 2015-03