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

Severe Aplastic Anemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02745717
• Other study ID #: Shanghai1st-48
• Status: Completed
• Phase: Phase 4
• Start date: January 2016
• Est. completion date: December 2021

Study information

• Verified date: March 2023
• Source: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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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Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: December 2021
• Est. primary completion date: December 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Anemia
• Anemia, Aplastic
• Severe Aplastic Anemia

Intervention

Drug:
• Thymoglobulin
administration of ATG 3.5mg/kg/d (Thymoglobuline®, Genzyme) intravenously for 5 days

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.

Locations

Country	Name	City	State
China	Shanghai general hospital, Shanghai Jiaotong university school of medicine	Shanghai	Shanghai

Sponsors (5)

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

Country where clinical trial is conducted

China, 

References & Publications (2)

Killick SB, Bown N, Cavenagh J, Dokal I, Foukaneli T, Hill A, Hillmen P, Ireland R, Kulasekararaj A, Mufti G, Snowden JA, Samarasinghe S, Wood A, Marsh JC; British Society for Standards in Haematology. Guidelines for the diagnosis and management of adult aplastic anaemia. Br J Haematol. 2016 Jan;172(2):187-207. doi: 10.1111/bjh.13853. Epub 2015 Nov 16. No abstract available. Erratum In: Br J Haematol. 2016 Nov;175(3):546. — View Citation

Liu HL, Sun ZM, Geng LQ, Wang XB, Ding KY, Tang BI, Tong J, Wang ZY. Unrelated cord blood transplantation for newly diagnosed patients with severe acquired aplastic anemia using a reduced-intensity conditioning: high graft rejection, but good survival. Bone Marrow Transplant. 2012 Sep;47(9):1186-90. doi: 10.1038/bmt.2011.251. Epub 2012 Jan 16. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Treatment related mortality	The death rate of patients because of treatment	3months, 24months
Primary	neutrophil recovery day	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.	5 days to 365 days
Secondary	overall response rate	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).	3 months to 24 months
Secondary	overall survival	The length of time from the start of treatment for patients with SAA are still alive.	24month