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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 : December 28, 2016
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

Study Description
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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
Severe Aplastic Anemia Procedure: IST Biological: cord blood transfusion Drug: Thymoglobuline® and oral CSA 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.


Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated 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
Study Start Date : January 2016
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2018

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: cord blood transfusion group
patients 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.
 Procedure: IST
ATG 3.5mg/kg/d (Thymoglobuline®, Genzyme) is administrated for 5 days intravenously, and oral CSA is administrated from 5mg/kg/d and adjusted to maintain trough serum concentration of 200-300ng/ml
Other Name: ATG and CSA

Biological: cord blood transfusion
one unit of cord blood having no more than 2 HLA-A,B and DRB1 mismatches is transfused 24 hours after last dose of ATG administration

Drug: Thymoglobuline® and oral CSA
Active Comparator: IST group
patient receive standard IST only, which includes ATG 3.5mg/kg/d for 5 days plus oral CSA started from 5mg/kg/d and adjusted to maintain trough serum concentration of 200-300ng/ml
 Procedure: IST
ATG 3.5mg/kg/d (Thymoglobuline®, Genzyme) is administrated for 5 days intravenously, and oral CSA is administrated from 5mg/kg/d and adjusted to maintain trough serum concentration of 200-300ng/ml
Other Name: ATG and CSA

Drug: Thymoglobuline® and oral CSA


Outcome Measures
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Primary Outcome Measures :
  1. 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.



Secondary Outcome Measures :
  1. 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)

  2. disease free survival [ Time Frame: 24month ]
  3. overall survival [ Time Frame: 24month ]

Other Outcome Measures:
  1. Treatment related mortality [ Time Frame: 3months, 24months ]

Eligibility Criteria
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Ages Eligible for Study:   up to 60 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02745717


Contacts
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

Locations
China, Shanghai
Shanghai general hospital, Shanghai Jiaotong university school of medicine Recruiting
Shanghai, Shanghai, China, 200080
Contact: Xingpeng Wang, M.D., Ph.D.    86-21-63069298    sfph_edu2@163.com   
Contact: Yanhong Zhu, M.S    86-21-63240090 ext 6213    sfph_edu2@shumu.edu.cn   
Sub-Investigator: Jieling Jiang, M.D.         
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
More Information
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Publications:

Responsible Party: Chun Wang, director, department of hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
ClinicalTrials.gov Identifier: NCT02745717     History of Changes
Other Study ID Numbers: Shanghai1st-48
First Posted: April 20, 2016    Key Record Dates
Last Update Posted: December 28, 2016
Last Verified: December 2016

Keywords provided by Chun Wang, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine:
Severe aplastic anemia
immunosuppressive therapy
cord blood transfusion

Additional relevant MeSH terms:
Anemia
Anemia, Aplastic
Hematologic Diseases
Bone Marrow Diseases
 Immunosuppressive Agents
Thymoglobulin
Immunologic Factors
Physiological Effects of Drugs