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

NCT ID: NCT02838992

Last Updated: 2017-02-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE4

Total Enrollment

130 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-02-28

Study Completion Date

2019-07-31

Brief Summary

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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

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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.

Conditions

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Aplastic Anemia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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ATG, Cy and cord blood transfusion group

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

Group Type EXPERIMENTAL

Rabbit ATG, (Genzyme)

Intervention Type DRUG

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

Intervention Type DRUG

Cyclophosphamide is a medication mainly used in chemotherapy. It is an alkylating agent of the nitrogen mustard type

CsA

Intervention Type DRUG

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

Cord blood

Intervention Type BIOLOGICAL

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

ATG and CSA group

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

Group Type ACTIVE_COMPARATOR

Rabbit ATG, (Genzyme)

Intervention Type DRUG

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

CsA

Intervention Type DRUG

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

Interventions

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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

Intervention Type DRUG

Cy

Cyclophosphamide is a medication mainly used in chemotherapy. It is an alkylating agent of the nitrogen mustard type

Intervention Type DRUG

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

Intervention Type DRUG

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

Intervention Type BIOLOGICAL

Other Intervention Names

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Thymoglobuline Anti-thymoeyteGlobulin Cyclophosphamide Cytophosphane Ciclosporin A Cyclosporine Umbilical cord blood

Eligibility Criteria

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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
Minimum Eligible Age

1 Year

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Shandong University of Traditional Chinese Medicine

OTHER

Sponsor Role collaborator

Jining Medical University

OTHER

Sponsor Role collaborator

Weifang Medical University

OTHER

Sponsor Role collaborator

Guangzhou First People's Hospital

OTHER

Sponsor Role collaborator

Harbin Hematology and Oncology Institute

OTHER

Sponsor Role collaborator

Jining First People's Hospital

OTHER

Sponsor Role collaborator

JIANGXI Provincal People's Hospital

UNKNOWN

Sponsor Role collaborator

Jinhua Central Hospital

OTHER

Sponsor Role collaborator

Linyi People's Hospital

OTHER

Sponsor Role collaborator

Shandong Cord Blood Bank

UNKNOWN

Sponsor Role collaborator

Qingdao Hiser Medical Group

OTHER

Sponsor Role collaborator

Qingdao University

OTHER

Sponsor Role collaborator

Taian City Central Hospital

OTHER

Sponsor Role collaborator

Yantai Yuhuangding Hospital

OTHER

Sponsor Role collaborator

Yishui Central Hospital of LINYI

UNKNOWN

Sponsor Role collaborator

Institute of Hematology & Blood Diseases Hospital, China

OTHER

Sponsor Role collaborator

Shengjing Hospital

OTHER

Sponsor Role collaborator

Jinan Military General Hospital

OTHER

Sponsor Role lead

Responsible Party

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Fang Zhou

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Fang Zhou, MD

Role: STUDY_CHAIR

The General Hospital Of Jinan Military Command

Locations

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The General Hospital Of Jinan Military Command

Jinan, Shandong, China

Site Status

Countries

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China

Central Contacts

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Fang Zhou, MD

Role: CONTACT

86-0531-51665316

Zhe Yu, MD

Role: CONTACT

86-0531-51665781

Facility Contacts

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Fang Zhou, MD

Role: primary

86-0531-51665316

Zhe Yu, MD

Role: backup

86-0531-51665781

References

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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.

Reference Type BACKGROUND
PMID: 26568159 (View on PubMed)

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.

Reference Type RESULT
PMID: 21663651 (View on PubMed)

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.

Reference Type RESULT
PMID: 24838091 (View on PubMed)

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.

Reference Type RESULT
PMID: 25932194 (View on PubMed)

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.

Reference Type RESULT
PMID: 26622526 (View on PubMed)

Other Identifiers

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JinanMGH

Identifier Type: -

Identifier Source: org_study_id

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