Clinical trial NCT02838992: ATG Combined With Cyclophosphamide And Cord Blood Transfusion in Treating Patients With Severe Aplastic Anemia
Official title: Multi-center Clinical Study of Immunosuppressants, Cyclophosphamide, And Cord Blood Transfusion in Treating Patients With Severe Aplastic Anemia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Aplastic Anemia
Keywords: Cyclophosphamide
Umbilical Cord Blood
ATG
Lead sponsor: Jinan Military General Hospital
Sponsor class: OTHER
Collaborators: name: Shandong University of Traditional Chinese Medicine
name: Jining Medical University
name: Weifang Medical University
name: Guangzhou First People's Hospital
name: Harbin Hematology and Oncology Institute
name: Jining First People's Hospital
name: JIANGXI Provincal People's Hospital
name: Jinhua Central Hospital
name: Linyi People's Hospital
name: Shandong Cord Blood Bank
name: Qingdao Hiser Medical Group
name: Qingdao University
name: Taian City Central Hospital
name: Yantai Yuhuangding Hospital
name: Yishui Central Hospital of LINYI
name: Institute of Hematology & Blood Diseases Hospital, China
name: Shengjing Hospital
First posted: 2016-07-20
Enrollment: 130
Sex: ALL
Minimum age (years): 1
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: The total response rate
timeFrame: Every 3 months to 24 months
Secondary outcomes:
measure: Neutrophil recovery time
timeFrame: From day 0 until the ﬁrst of 3 consecutive days
measure: Infection rates
timeFrame: 1 year
measure: Overall survival
timeFrame: 2 years
measure: Treatment related mortality
timeFrame: 2 years
Other outcomes:
Locations:
city: Jinan
country: China
facility: The General Hospital Of Jinan Military Command
state: Shandong
Study officials:
affiliation: The General Hospital Of Jinan Military Command
name: Fang Zhou, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: Zhou F, Ge L, Yu Z, Fang Y, Kong F. Clinical observations on intensive immunosuppressive therapy combined with umbilical cord blood support for the treatment of severe aplastic anemia. J Hematol Oncol. 2011 Jun 10;4:27. doi: 10.1186/1756-8722-4-27.
citation: Xie LN, Fang Y, Yu Z, Song NX, Kong FS, Liu XM, Zhou F. Increased immunosuppressive treatment combined with unrelated umbilical cord blood infusion in children with severe aplastic anemia. Cell Immunol. 2014 May-Jun;289(1-2):150-4. doi: 10.1016/j.cellimm.2014.03.014. Epub 2014 Apr 3.
citation: Yu Z, Zhou F, Ge LF, Liu XM, Fang Y, Xie LN, Kong FS, Song NX, Yu QQ. Mechanism of immunosuppressants combined with cord blood for severe aplastic anemia. Int J Clin Exp Med. 2015 Feb 15;8(2):2484-94. eCollection 2015.
citation: Xie LN, Zhou F. Unexpected unrelated umbilical cord blood stem cell engraft in two patients with severe aplastic anemia that received immunosuppressive treatment: A case report and literature review. Exp Ther Med. 2015 Oct;10(4):1563-1565. doi: 10.3892/etm.2015.2698. Epub 2015 Aug 21.