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

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ClinicalTrials.gov Identifier: NCT02745717
Recruitment Status : Recruiting
First Posted : April 20, 2016
Last Update Posted : September 11, 2018
Sponsor:
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
Information provided by (Responsible Party):
Chun Wang, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

Tracking Information
First Submitted Date  ICMJE April 7, 2016
First Posted Date  ICMJE April 20, 2016
Last Update Posted Date September 11, 2018
Actual Study Start Date  ICMJE January 2016
Estimated Primary Completion Date December 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 8, 2018)
neutrophil recovery day [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: April 19, 2016)
neutrophil recovery day [ Time Frame: from day 0 ]
the neutrophil recovery day is defined to have occurred on the first of 3 consecutive days during which the absolute neutrophil count (ANC) is >0.5×109/L, without G-CSF administration . The day of first dose of ATG administration is record as day 0.
Change History Complete list of historical versions of study NCT02745717 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 8, 2018)
  • overall response rate [ Time Frame: 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 [ Time Frame: 24month ]
    The length of time from the start of treatment for patients with SAA are still alive.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 19, 2016)
  • response rate [ Time Frame: every 3 months to 24 months ]
    response rate is the ratio of CR and PR patients to all evaluated patients at the time point. CR,PR,NR and relapse is evaluated according to the guidelines for the diagnosis and management of adult aplastic anaemia from British Committee for Standards in Haematology (BCSH)
  • disease free survival [ Time Frame: 24month ]
  • overall survival [ Time Frame: 24month ]
Current Other Pre-specified Outcome Measures
 (submitted: September 8, 2018)
Treatment related mortality [ Time Frame: 3months, 24months ]
The death rate of patients because of treatment
Original Other Pre-specified Outcome Measures
 (submitted: April 19, 2016)
Treatment related mortality [ Time Frame: 3months, 24months ]
 
Descriptive Information
Brief Title  ICMJE The Efficacy of Immunosuppressive Therapy Combined With Cord Blood Transfusion in Treatment of Severe Aplastic Anemia
Official Title  ICMJE 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Severe Aplastic Anemia
Intervention  ICMJE
  • Drug: Thymoglobulin
    administration of ATG 3.5mg/kg/d (Thymoglobuline®, Genzyme) intravenously for 5 days
    Other Name: 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 Name: cyclosporine A
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: Thymoglobulin
    • Procedure: Cord blood
    • Drug: Cyclosporine Oral Product
  • 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.
    Interventions:
    • Drug: Thymoglobulin
    • Drug: Cyclosporine Oral Product
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 19, 2016)
120
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2018
Estimated Primary Completion Date December 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 60 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jieling Jiang, M.D. 86-21-37798987 jiangjieling66@hotmail.com
Contact: Liping Wan, M.D.,Ph. D. 86-21-63240090 ext 3921 wanliping924@hotmail.com
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02745717
Other Study ID Numbers  ICMJE Shanghai1st-48
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Chun Wang, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
Study Sponsor  ICMJE Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
Collaborators  ICMJE
  • 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  ICMJE
Principal Investigator: Chun Wang, M.D., Ph. D. Shanghai General Hospital, Shanghai Jiaotong University School of Medicine
PRS Account Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
Verification Date September 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP