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

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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

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.

      .
    

Study Phase

Phase 4

Study Type

Interventional


Primary Outcome

neutrophil recovery day

Secondary Outcome

 overall response rate

Condition

Severe Aplastic Anemia

Intervention

Thymoglobulin

Study Arms / Comparison Groups

 cord blood and IST group
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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

120

Start Date

January 2016

Completion Date

December 2021

Primary Completion Date

December 2021

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:

          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.
      

Gender

All

Ages

N/A - 60 Years

Accepts Healthy Volunteers

No

Contacts

Chun Wang, M.D., Ph. D., 86-21-37798987, [email protected]

Location Countries

China

Location Countries

China

Administrative Informations


NCT ID

NCT02745717

Organization ID

Shanghai1st-48


Responsible Party

Principal Investigator

Study Sponsor

Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

Collaborators

 Ruijin Hospital

Study Sponsor

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


Verification Date

April 2020