The Efficacy of Immunosuppressive Therapy Combined With Cord Blood Transfusion in Treatment of Severe Aplastic Anemia

Sponsor
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine (Other)
Overall Status
Recruiting
CT.gov ID
NCT02745717
Collaborator
Ruijin Hospital (Other), Xinhua Hospital, Shanghai Jiao Tong University School of Medicine (Other), Shanghai Tongji Hospital, Tongji University School of Medicine (Other), Zhejiang Provincial Hospital of TCM (Other)
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Study Details

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.

Condition or Disease Intervention/Treatment Phase
Phase 4

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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Study Design

Study Type:
Interventional
Anticipated Enrollment :
120 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
The Efficacy of Immunosuppressive Therapy Combined With Cord Blood Transfusion in Treatment of Severe Aplastic Anemia
Actual Study Start Date :
Jan 1, 2016
Anticipated Primary Completion Date :
Dec 1, 2021
Anticipated Study Completion Date :
Dec 1, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: cord blood and IST group

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.

Drug: Thymoglobulin
administration of ATG 3.5mg/kg/d (Thymoglobuline®, Genzyme) intravenously for 5 days
Other Names:
  • Thymoglobuline
  • Procedure: Cord blood
    transfusion of one unit of at least 4/6 HLA loci matched cord blood.

    Drug: Cyclosporine Oral Product
    administration of cyclosporine A 5mg/kg orally, and maintain the trough serum concentration between 200ng/ml to 300ng/ml.
    Other Names:
  • cyclosporine A
  • Active Comparator: IST group

    Antithymocyte ( Thymoglobulin ) 3.5mg/kg/d for 5 days , Cyclosporine Oral Product 5mg/kg/d with trough serum concentration of 200-300ng/ml.

    Drug: Thymoglobulin
    administration of ATG 3.5mg/kg/d (Thymoglobuline®, Genzyme) intravenously for 5 days
    Other Names:
  • Thymoglobuline
  • Drug: Cyclosporine Oral Product
    administration of cyclosporine A 5mg/kg orally, and maintain the trough serum concentration between 200ng/ml to 300ng/ml.
    Other Names:
  • cyclosporine A
  • Outcome Measures

    Primary Outcome Measures

    1. 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 Outcome Measures

    1. 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).

    2. overall survival [24month]

      The length of time from the start of treatment for patients with SAA are still alive.

    Other Outcome Measures

    1. Treatment related mortality [3months, 24months]

      The death rate of patients because of treatment

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    N/A to 60 Years
    Sexes Eligible for Study:
    All
    Accepts 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.

    1. Under 60 years old, male or female.

    2. No HLA matched siblings.

    3. No previous ATG treatment history.

    4. 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.

    1. 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.

    1. 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Shanghai general hospital, Shanghai Jiaotong university school of medicine Shanghai Shanghai China 200080

    Sponsors and Collaborators

    • Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
    • Ruijin Hospital
    • Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
    • Shanghai Tongji Hospital, Tongji University School of Medicine
    • Zhejiang Provincial Hospital of TCM

    Investigators

    • Principal Investigator: Chun Wang, M.D., Ph. D., Shanghai General Hospital, Shanghai Jiaotong University School of Medicine

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Chun Wang, director, department of hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
    ClinicalTrials.gov Identifier:
    NCT02745717
    Other Study ID Numbers:
    • Shanghai1st-48
    First Posted:
    Apr 20, 2016
    Last Update Posted:
    Oct 12, 2021
    Last Verified:
    Oct 1, 2021
    Keywords provided by Chun Wang, director, department of hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Oct 12, 2021