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

January 31, 2017 updated by: Fang Zhou, Jinan Military General Hospital

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

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

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

130

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Shandong
      • Jinan, Shandong, China, 250031
        • The General Hospital Of Jinan Military Command

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

4 months to 58 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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
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
Other Names:
  • Thymoglobuline
  • Anti-thymoeyteGlobulin
Drug: Cy
Cyclophosphamide is a medication mainly used in chemotherapy. It is an alkylating agent of the nitrogen mustard type
Other Names:
  • Cytophosphane
  • Cyclophosphamide
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
Other Names:
  • Cyclosporine
  • Ciclosporin A
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
Other Names:
  • Umbilical cord blood
Active Comparator: 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
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
Other Names:
  • Thymoglobuline
  • Anti-thymoeyteGlobulin
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
Other Names:
  • Cyclosporine
  • Ciclosporin A

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The total response rate
Time Frame: 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)
Every 3 months to 24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: 2 years
2 years
Neutrophil recovery time
Time Frame: 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 .
From day 0 until the first of 3 consecutive days
Infection rates
Time Frame: 1 year
1 year
Treatment related mortality
Time Frame: 2 years
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Jinan Military General Hospital

Collaborators

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

Investigators

  • Study Chair: Fang Zhou, MD, The General Hospital Of Jinan Military Command

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

February 1, 2017

Primary Completion (Anticipated)

December 1, 2018

Study Completion (Anticipated)

July 1, 2019

Study Registration Dates

First Submitted

July 6, 2016

First Submitted That Met QC Criteria

July 19, 2016

First Posted (Estimate)

July 20, 2016

Study Record Updates

Last Update Posted (Estimate)

February 1, 2017

Last Update Submitted That Met QC Criteria

January 31, 2017

Last Verified

January 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • JinanMGH

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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