Back to resultsThe Efficacy of Immunosuppressive Therapy Combined With Cord Blood Transfusion in Treatment of Severe Aplastic Anemia
Primary Purpose
Severe Aplastic Anemia
Status
Completed
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
Thymoglobulin
Cord blood
Cyclosporine Oral Product
Sponsored by
About this trial
This is an interventional treatment trial for Severe Aplastic Anemia focused on measuring Severe aplastic anemia, immunosuppressive therapy, cord blood transfusion
Eligibility Criteria
Inclusion Criteria:
1．Diagnosis of AA confirmed by bone marrow aspirate and biopsy, myelodysplastic syndrome and paroxysmal nocturnal hemoglobinuria were excluded. To confirm severe AA, the patient must fulfill at least two of the criteria: i) ANC<0.5×109/L,ii)PLT<20×109/L and iii) Ret<20×109/L ,in addition, ANC<0.5×109/L must be included.
2. Under 60 years old, male or female.
3. No HLA matched siblings.
4. No previous ATG treatment history.
5. Performance status score no more than 2 (ECOG criteria).
6．Adequate organ function as defined by the following criteria:ALT, AST and total serum bilirubin <2×ULN (upper limit of normal) Serum creatinine and BUN <1.25×ULN.
7. Adequate cardiac function without acute myocardial infarction, arrhythmia or atrioventricular block, heart failure, active rheumatic heart disease and cardiac dilatation.
8．Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to enrollment.
9. Willingness and ability to comly with scheduled visits, treatment plans, laboratory tests, and other study procedures.
Exclusion Criteria:
- Presence of any condition inappropriate for HSCT.
- Presence of any fatal disease, including respiratory failure, heart failure, liver or kidney function failure et al.
3．Severely allergic to biologic products.
4．Pregnancy or breastfeeding.
5．Current treatment on another clinical trail.
6．Any other condition the investigator judged the patient inappropriate for entry into this study.
Sites / Locations
- Shanghai general hospital, Shanghai Jiaotong university school of medicine
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
cord blood and IST group
IST group
Arm Description
Administration of antithymocyte ( Thymoglobulin ) 3.5mg/kg/d for 5 days, Cyclosporine Oral Product 5mg/kg/d with trough serum concentration of 200-300ng/ml, plus one unit of at least 4/6 HLA loci matched cord blood transfusion 24 hours after last dose of ATG.
Antithymocyte ( Thymoglobulin ) 3.5mg/kg/d for 5 days , Cyclosporine Oral Product 5mg/kg/d with trough serum concentration of 200-300ng/ml.
Outcomes
Primary Outcome Measures
neutrophil recovery day
the first day of 3 consecutive days when the absolute neutrophil count (ANC) reaches 0.5×10^9/L, without G-CSF administration .
The day of first dose of ATG administration is record as day 0.
Secondary Outcome Measures
overall response rate
overall response rate is the percentage of patients who acquire complete remission and partial remission according to the criteria of British Committee for Standards in Haematology (BCSH).
overall survival
The length of time from the start of treatment for patients with SAA are still alive.
Full Information
NCT ID
NCT02745717
First Posted
April 7, 2016
Last Updated
March 15, 2023
Sponsor
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
Collaborators
Ruijin Hospital, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Tongji Hospital, Tongji University School of Medicine, Zhejiang Provincial Hospital of TCM
1. Study Identification
Unique Protocol Identification Number
NCT02745717
Brief Title
The Efficacy of Immunosuppressive Therapy Combined With Cord Blood Transfusion in Treatment of Severe Aplastic Anemia
Official Title
The Efficacy of Immunosuppressive Therapy Combined With Cord Blood Transfusion in Treatment of Severe Aplastic Anemia
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Completed
Study Start Date
January 2016 (Actual)
Primary Completion Date
December 2021 (Actual)
Study Completion Date
December 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
Collaborators
Ruijin Hospital, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Tongji Hospital, Tongji University School of Medicine, Zhejiang Provincial Hospital of TCM
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Aim: To evaluate if additional cord blood transfusion could accelerate the hematopoietic reconstitution in severe aplastic anemia(SAA) patients receiving immunosuppressive therapy (IST).
Study design: open-labed, prospective, multicenter, randomized control study Number of subjects: 60 each group
Treatment:
IST group: ATG (Thymoglobuline®, Genzyme) 3.5mg/kg/d×5d plus oral cyclosporine A (CSA) Cord blood transfusion group: In addition to the same dose and course of ATG and CSA , one unit of cord blood having no more than 2 HLA-A, B or DRB1 mismatches is transfused 24h after last dose of ATG administration.
Detailed Description
Eligible patients should be under 60 years old with confirmed SAA, without HLA matched siblings and previous ATG treatment history. Patients will be excluded if they present any fatal disease, including respiratory failure, heart failure, liver or kidney function failure et al or severely allergic to biologic products.
To evaluate if additional cord blood transfusion could accelerate the hematopoietic reconstitution in severe aplastic anemia(SAA) patients receiving IST therapy, 120 eligible patients will be randomized to two groups, the IST group and the cord blood transfusion group. Patients in the IST group receive standard IST which including ATG (Thymoglobuline®, Genzyme) 3.5mg/kg/d×5d plus oral cyclosporine A（CSA ) started from 5mg/kg/d and adjusted to maintain trough serum concentration of 200-300ng/ml. While patients in the cord blood transfusion group receive the same dose and course of ATG and CSA as the control group and one unit of cord blood having no more than 2 HLA-A, B and DRB1 mismatches is transfused 24h after last dose of ATG administration.
The neutrophil recovery day is defined as the first day of 3 consecutive days during which the absolute neutrophil count (ANC) is >0.5×109/L, without G-CSF adminstration. Platelet recovery day is defined to have occurred on the first of 7 consecutive days with a blood platelet count (BPC) of >20×109/L, without transfusion support. Response (CR, PR or NR) is evaluated on 3, 4, 6,9, 12, 18 and 24months after treatment.
The primary end point is the neutrophil recovery day and second end points are response rate (CR+PR), treatment related mortality, disease free survival and overall survival.
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6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Severe Aplastic Anemia
Keywords
Severe aplastic anemia, immunosuppressive therapy, cord blood transfusion
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
60 (Actual)
8. Arms, Groups, and Interventions
Arm Title
cord blood and IST group
Arm Type
Experimental
Arm Description
Administration of antithymocyte ( Thymoglobulin ) 3.5mg/kg/d for 5 days, Cyclosporine Oral Product 5mg/kg/d with trough serum concentration of 200-300ng/ml, plus one unit of at least 4/6 HLA loci matched cord blood transfusion 24 hours after last dose of ATG.
Arm Title
IST group
Arm Type
Active Comparator
Arm Description
Antithymocyte ( Thymoglobulin ) 3.5mg/kg/d for 5 days , Cyclosporine Oral Product 5mg/kg/d with trough serum concentration of 200-300ng/ml.
Intervention Type
Drug
Intervention Name(s)
Thymoglobulin
Other Intervention Name(s)
Thymoglobuline
Intervention Description
administration of ATG 3.5mg/kg/d (Thymoglobuline®, Genzyme) intravenously for 5 days
Intervention Type
Procedure
Intervention Name(s)
Cord blood
Intervention Description
transfusion of one unit of at least 4/6 HLA loci matched cord blood.
Intervention Type
Drug
Intervention Name(s)
Cyclosporine Oral Product
Other Intervention Name(s)
cyclosporine A
Intervention Description
administration of cyclosporine A 5mg/kg orally, and maintain the trough serum concentration between 200ng/ml to 300ng/ml.
Primary Outcome Measure Information:
Title
neutrophil recovery day
Description
the first day of 3 consecutive days when the absolute neutrophil count (ANC) reaches 0.5×10^9/L, without G-CSF administration .
The day of first dose of ATG administration is record as day 0.
Time Frame
5 days to 365 days
Secondary Outcome Measure Information:
Title
overall response rate
Description
overall response rate is the percentage of patients who acquire complete remission and partial remission according to the criteria of British Committee for Standards in Haematology (BCSH).
Time Frame
3 months to 24 months
Title
overall survival
Description
The length of time from the start of treatment for patients with SAA are still alive.
Time Frame
24month
Other Pre-specified Outcome Measures:
Title
Treatment related mortality
Description
The death rate of patients because of treatment
Time Frame
3months, 24months
10. Eligibility
Sex
All
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
1．Diagnosis of AA confirmed by bone marrow aspirate and biopsy, myelodysplastic syndrome and paroxysmal nocturnal hemoglobinuria were excluded. To confirm severe AA, the patient must fulfill at least two of the criteria: i) ANC<0.5×109/L,ii)PLT<20×109/L and iii) Ret<20×109/L ,in addition, ANC<0.5×109/L must be included.
2. Under 60 years old, male or female.
3. No HLA matched siblings.
4. No previous ATG treatment history.
5. Performance status score no more than 2 (ECOG criteria).
6．Adequate organ function as defined by the following criteria:ALT, AST and total serum bilirubin <2×ULN (upper limit of normal) Serum creatinine and BUN <1.25×ULN.
7. Adequate cardiac function without acute myocardial infarction, arrhythmia or atrioventricular block, heart failure, active rheumatic heart disease and cardiac dilatation.
8．Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to enrollment.
9. Willingness and ability to comly with scheduled visits, treatment plans, laboratory tests, and other study procedures.
Exclusion Criteria:
Presence of any condition inappropriate for HSCT.
Presence of any fatal disease, including respiratory failure, heart failure, liver or kidney function failure et al.
3．Severely allergic to biologic products.
4．Pregnancy or breastfeeding.
5．Current treatment on another clinical trail.
6．Any other condition the investigator judged the patient inappropriate for entry into this study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Chun Wang, M.D., Ph. D.
Organizational Affiliation
Shanghai General Hospital, Shanghai Jiaotong University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Shanghai general hospital, Shanghai Jiaotong university school of medicine
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200080
Country
China
12. IPD Sharing Statement
Citations:
PubMed Identifier
26568159
Citation
Killick SB, Bown N, Cavenagh J, Dokal I, Foukaneli T, Hill A, Hillmen P, Ireland R, Kulasekararaj A, Mufti G, Snowden JA, Samarasinghe S, Wood A, Marsh JC; British Society for Standards in Haematology. Guidelines for the diagnosis and management of adult aplastic anaemia. Br J Haematol. 2016 Jan;172(2):187-207. doi: 10.1111/bjh.13853. Epub 2015 Nov 16. No abstract available. Erratum In: Br J Haematol. 2016 Nov;175(3):546.
Results Reference
background
PubMed Identifier
22246086
Citation
Liu HL, Sun ZM, Geng LQ, Wang XB, Ding KY, Tang BI, Tong J, Wang ZY. Unrelated cord blood transplantation for newly diagnosed patients with severe acquired aplastic anemia using a reduced-intensity conditioning: high graft rejection, but good survival. Bone Marrow Transplant. 2012 Sep;47(9):1186-90. doi: 10.1038/bmt.2011.251. Epub 2012 Jan 16.
Results Reference
background
Learn more about this trial
The Efficacy of Immunosuppressive Therapy Combined With Cord Blood Transfusion in Treatment of Severe Aplastic Anemia
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