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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

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 Drug: Thymoglobulin Procedure: Cord blood Drug: Cyclosporine Oral Product 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 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
Actual Study Start Date : January 2016
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2018


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 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

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 Name: 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 Name: cyclosporine A




Primary Outcome Measures :
  1. 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.



Secondary Outcome Measures :
  1. 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).

  2. overall survival [ Time Frame: 24month ]
    The length of time from the start of treatment for patients with SAA are still alive.


Other Outcome Measures:
  1. Treatment related mortality [ Time Frame: 3months, 24months ]
    The death rate of patients because of treatment



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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.


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

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: September 11, 2018
Last Verified: September 2018

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
Cyclosporins
Cyclosporine
Immunosuppressive Agents
Thymoglobulin
Antilymphocyte Serum
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Dermatologic Agents
Antirheumatic Agents
Calcineurin Inhibitors