Severe Aplastic Anemia
Conditions
Keywords
Severe aplastic anemia, immunosuppressive therapy, cord blood transfusion
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. .
Interventions
DRUGThymoglobulin
administration of ATG 3.5mg/kg/d (Thymoglobuline®, Genzyme) intravenously for 5 days
PROCEDURECord blood
transfusion of one unit of at least 4/6 HLA loci matched cord blood.
administration of cyclosporine A 5mg/kg orally, and maintain the trough serum concentration between 200ng/ml to 300ng/ml.
Sponsors
Ruijin Hospital
Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
Shanghai Tongji Hospital, Tongji University School of Medicine
Zhejiang Provincial Hospital of TCM
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 60 Years
Healthy volunteers
No
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
1. Presence of any condition inappropriate for HSCT. 2. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| neutrophil recovery day | 5 days to 365 days | 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
| Measure | Time frame | Description |
|---|---|---|
| overall response rate | 3 months to 24 months | 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 | 24month | The length of time from the start of treatment for patients with SAA are still alive. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Treatment related mortality | 3months, 24months | The death rate of patients because of treatment |
Countries
China
Outcome results
None listed