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

Aplastic Anemia Clinical Trial

Official title:

Multi-center Clinical Study of Immunosuppressants, Cyclophosphamide, And Cord Blood Transfusion in Treating Patients With Severe Aplastic Anemia

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02838992
• Other study ID #: JinanMGH
• Status: Not yet recruiting
• Phase: Phase 4
• First received: July 6, 2016
• Last updated: January 31, 2017
• Start date: February 2017
• Est. completion date: July 2019

Study information

• Verified date: January 2017
• Source: Jinan Military General Hospital
• Contact: Fang Zhou, MD
• Phone: 86-0531-51665316
• Email: zhoufang1[@]medmail.com.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 130
• Est. completion date: July 2019
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Anemia
• Anemia, Aplastic
• Aplastic Anemia

Intervention

Drug:
• Rabbit ATG, (Genzyme)
ATG is an infusion of rabbit-derived antibodies against human T cells, which is used in the prevention and treatment of acute rejection in organ transplantation and therapy of aplastic anemia
• Cy
Cyclophosphamide is a medication mainly used in chemotherapy. It is an alkylating agent of the nitrogen mustard type
• CsA
CsA is an immunosuppressant drug widely used in organ transplantation to prevent rejection. It reduces the activity of the immune system by interfering with the activity and growth of T cells

Biological:
• Cord blood
Cord blood is blood that remains in the placenta and in the attached umbilical cord after childbirth. Cord blood is collected because it contains stem cells, which can be used to treat hematopoietic and genetic disorders

Locations

Country	Name	City	State
China	The General Hospital Of Jinan Military Command	Jinan	Shandong

Sponsors (18)

Lead Sponsor

Collaborator

Jinan Military General Hospital

Affiliated Hospital of Weifang Medical University, Guangzhou First Municipal People’s Hospital, Harbin Institute of Hematology and Oncology, Institute of Hematology & Blood Diseases Hospital, JIANGXI Provincal People's Hospital, Jinhua Central Hospital, Jining Medical University, JINING No.1 People's Hospital, Linyi People's Hospital, Qingdao Center Medical Group, Qingdao University, Shandong Cord Blood Bank, Shandong University of Traditional Chinese Medicine, Shengjing Hospital, Taian City Central Hospital, Yantai Yuhuangding Hospital, Yishui Central Hospital of LINYI

Country where clinical trial is conducted

China, 

References & Publications (5)

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. Erratum in: Br J Haematol. 2016 Nov;175(3):546. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The total response rate	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)	Every 3 months to 24 months
Secondary	Neutrophil recovery time	The neutrophil recovery day is defined from day "0" until the ?rst of 3 consecutive days during which the absolute neutrophil count (ANC) is >0.5×10^9/L, without G-CSF administration .	From day 0 until the ?rst of 3 consecutive days
Secondary	Infection rates		1 year
Secondary	Overall survival		2 years
Secondary	Treatment related mortality		2 years