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

NCT02745717 | Completed Phase 4 DMC

• 1 other identifier: Shanghai1st-48
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Severe Aplastic Anemia

Keywords

Severe aplastic anemia; immunosuppressive therapy; cord blood transfusion

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• overall response rate

  3 months to 24 months

• overall survival

  24month

Other Outcomes (1)

• Treatment related mortality

  3months, 24months

Study Arms (2)

cord blood and IST group

EXPERIMENTAL

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; Procedure: Cord blood; Drug: Cyclosporine Oral Product

IST group

ACTIVE COMPARATOR

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; Drug: Cyclosporine Oral Product

Interventions

Thymoglobulin DRUG

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

Also known as: Thymoglobuline

IST group; cord blood and IST group

Cord blood PROCEDURE

transfusion of one unit of at least 4/6 HLA loci matched cord blood.

cord blood and IST group

Cyclosporine Oral Product DRUG

administration of cyclosporine A 5mg/kg orally, and maintain the trough serum concentration between 200ng/ml to 300ng/ml.

Also known as: cyclosporine A

IST group; cord blood and IST group

Eligibility Criteria

• Age: Up to 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• ．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.
• \. Under 60 years old, male or female.
• \. No HLA matched siblings.
• \. No previous ATG treatment history.
• \. Performance status score no more than 2 (ECOG criteria).
• ．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.
• \. Adequate cardiac function without acute myocardial infarction, arrhythmia or atrioventricular block, heart failure, active rheumatic heart disease and cardiac dilatation.
• ．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.
• \. Willingness and ability to comly with scheduled visits, treatment plans, laboratory tests, and other study procedures.

You may not qualify if:

• Presence of any condition inappropriate for HSCT.
• Presence of any fatal disease, including respiratory failure, heart failure, liver or kidney function failure et al.
• ．Severely allergic to biologic products.
• ．Pregnancy or breastfeeding.
• ．Current treatment on another clinical trail.
• ．Any other condition the investigator judged the patient inappropriate for entry into this study.

Sponsors & Collaborators

• Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine: lead
• Ruijin Hospital: collaborator
• Xinhua Hospital, Shanghai Jiao Tong University School of Medicine: collaborator
• Shanghai Tongji Hospital, Tongji University School of Medicine: collaborator
• Zhejiang Provincial Hospital of TCM: collaborator

Study Sites (1)

Shanghai general hospital, Shanghai Jiaotong university school of medicine

Shanghai, Shanghai Municipality, 200080, China

Location

Related 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.

  PMID: 26568159 BACKGROUND

• 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.

  PMID: 22246086 BACKGROUND

MeSH Terms

Conditions

Anemia, Aplastic

Interventions

thymoglobulin; Antilymphocyte Serum; Cyclosporine

Condition Hierarchy (Ancestors)

Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Failure Disorders; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides

Study Officials

• Chun Wang, M.D., Ph. D.

  Shanghai General Hospital, Shanghai Jiaotong University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: director, department of hematology

Study Record Dates

• First Submitted: April 7, 2016
• First Posted: April 20, 2016
• Study Start: January 1, 2016
• Primary Completion: December 1, 2021
• Study Completion: December 1, 2021
• Last Updated: March 17, 2023

Record last verified: 2023-03

Locations

CN (1)