ATG Combined With Cyclophosphamide And Cord Blood Transfusion in Treating Patients With Severe Aplastic Anemia

Phase 4

• Conditions: Aplastic Anemia
• Interventions: Drug: Rabbit ATG, (Genzyme); Drug: Cy; Drug: CsA; Biological: Cord blood

• Registration Number: NCT02838992
• Lead Sponsor: Jinan Military General Hospital

Brief Summary

To assess whether ATG Combined With Cyclophosphamide and cord blood infusion can accelerate hematopoietic reconstruction in severe aplastic anemia patients and improve clinical curative effect and safety

Detailed Description

Aplastic Anemia( AA), is a set of bone marrow hematopoietic dysfunction caused by a variety of causes, with hyperplasia of bone marrow hematopoietic cells to reduce whole blood cells and peripheral blood at the characteristics of clinical main performance for anemia, bleeding and infection. According to the severity of the bone marrow failure and the progress of the clinical course ,it is divided into Severe Aplastic Anemia (SAA) and the Non - Severe Aplastic Anemia (NSAA).Severe Aplastic Anemia can be divided into two categories: Very Severe Aplastic Anemia (VSAA) and Severe Aplastic Anemia (SAA), with the characteristics of rapid progress, refractory, poor prognosis, high mortality .The natural course is six months or so, and most patients die in a year . Hematopoietic stem cell transplantation and immunosuppressive therapy are two main treatment . The former is by far the only possible cure. It is recommended as first-line treatments, if patients have a matched sibling donor. The recommended age limit is 40 years old. But for those who have no sibling donor or patients older than 40 years old, it is recommend the immunosuppressive therapy.

The investigators have already summarized the effectiveness of rabbit antithymocyte immunoglobulin (ATG), cyclophosphamide (Cy) and cyclosporine, A (CsA) and the combination of the umbilical cord blood infusion for SAA/VSAA patients without suitable donor, with short duration, without long-term immunosuppressive therapy history. The total effectiveness rates has improved to 88%, with shorter immunosuppressive maintaining therapy , rapid hematopoietic reconstruction, fewer complications. The aim of this study is to further explore whether this solution can accelerate hematopoietic reconstruction of SAA/VSAA patients and its clinical curative effect and security. This study scheme has been approved by the Jinan military region general hospital medical ethics committee.

Study Timeline

• Study First Submitted: 2016-07-06
• Study First Submitted QC: 2016-07-19
• Study First Posted: 2016-07-20
• Status Verified: 2017-01
• Last Update Submitted: 2017-01-31
• Study Start: 2017-02
• Last Update Posted: 2017-02-01
• Primary Completion: 2018-12
• Study Completion: 2019-07

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 130

Inclusion Criteria

1. Male or female ,under the age of 60.
2. Diagnosis of SAA and VSAA in accordance with the <aplastic anemia, diagnosis and treatment expert consensus> Camitta standard (see appendix 1).
3. Confirmed of heavy and very heavy aplastic anemia within 6 months.
4. No obvious abnormal liver and kidney function: ALT, AST,≤2.5 times the upper limit of normal , serum Creatinine and BUN ≤1.25 times the upper limit of normal
5. Clear understanding, voluntary to participate in the study, and signed informed consent document by the patient or the legal guardian
6. Willingness and ability to comly with the treatment plan, follow-up and laboratory tests as required

Exclusion Criteria

1. Congenital aplastic anemia
2. Pregnancy or breastfeeding
3. Participated in other clinical trials within three months
4. Presence of Any fatal disease, including respiratory failure, heart failure, liver or kidney failure, et al
5. Aplastic anemia caused by the treatment of other malignant tumor treatment
6. With severe mental illness
7. With other malignant tumor
8. Severe infection or the infection difficult to be controlled
9. Received ATG or cyclosporine A within six months
10. Severely allergic to biological agents
11. Any other situation judged by the investigator that the patients inappropriate for entry into this study

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ATG, Cy and cord blood transfusion group	Rabbit ATG, (Genzyme)	ATG 3mg/kg/d for 5 days Cy 50mg/kg/d for 2 days CSA Started from 5mg/kg/d and adjusted to maintain trough serum concentration of 200-400ng/ml One unit of cord blood having no more than 3 HLA-A,B and DRB1 mismatches is transfused 24h after last dose of ATG administration. Intervention: Drug: Rabbit ATG, Thymoglobuline (Genzyme) plus Cyclophosphamide plus CSA Biological: Cord blood transfusion
ATG, Cy and cord blood transfusion group	Cord blood	ATG 3mg/kg/d for 5 days Cy 50mg/kg/d for 2 days CSA Started from 5mg/kg/d and adjusted to maintain trough serum concentration of 200-400ng/ml One unit of cord blood having no more than 3 HLA-A,B and DRB1 mismatches is transfused 24h after last dose of ATG administration. Intervention: Drug: Rabbit ATG, Thymoglobuline (Genzyme) plus Cyclophosphamide plus CSA Biological: Cord blood transfusion
ATG and CSA group	Rabbit ATG, (Genzyme)	ATG 3mg/kg/d for 5 days CSA started from 5mg/kg/d and adjusted to maintain trough serum concentration of 200-400ng/ml Intervention: Drug: Rabbit ATG, Thymoglobuline (Genzyme) plus CSA
ATG, Cy and cord blood transfusion group	Cy	ATG 3mg/kg/d for 5 days Cy 50mg/kg/d for 2 days CSA Started from 5mg/kg/d and adjusted to maintain trough serum concentration of 200-400ng/ml One unit of cord blood having no more than 3 HLA-A,B and DRB1 mismatches is transfused 24h after last dose of ATG administration. Intervention: Drug: Rabbit ATG, Thymoglobuline (Genzyme) plus Cyclophosphamide plus CSA Biological: Cord blood transfusion
ATG, Cy and cord blood transfusion group	CsA	ATG 3mg/kg/d for 5 days Cy 50mg/kg/d for 2 days CSA Started from 5mg/kg/d and adjusted to maintain trough serum concentration of 200-400ng/ml One unit of cord blood having no more than 3 HLA-A,B and DRB1 mismatches is transfused 24h after last dose of ATG administration. Intervention: Drug: Rabbit ATG, Thymoglobuline (Genzyme) plus Cyclophosphamide plus CSA Biological: Cord blood transfusion
ATG and CSA group	CsA	ATG 3mg/kg/d for 5 days CSA started from 5mg/kg/d and adjusted to maintain trough serum concentration of 200-400ng/ml Intervention: Drug: Rabbit ATG, Thymoglobuline (Genzyme) plus CSA

Primary Outcome Measures

Name	Time	Method
The total response rate	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)

Secondary Outcome Measures

Name	Time	Method
Infection rates	1 year
Treatment related mortality	2 years
Overall survival	2 years
Neutrophil recovery time	From day 0 until the first of 3 consecutive days	The neutrophil recovery day is defined from day "0" until the first of 3 consecutive days during which the absolute neutrophil count (ANC) is \>0.5×10\^9/L, without G-CSF administration .

Trial Locations

Locations (1)

The General Hospital Of Jinan Military Command; 🇨🇳 Jinan, Shandong, China