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

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ClinicalTrials.gov Identifier: NCT02838992
Recruitment Status : Not yet recruiting
First Posted : July 20, 2016
Last Update Posted : February 1, 2017
Sponsor:
Collaborators:
Shandong University of Traditional Chinese Medicine
Jining Medical University
Weifang Medical University
Guangzhou First People's Hospital
Harbin Hematology and Oncology Institute
Shandong Jining No.1 People's Hospital
JIANGXI Provincal People's Hospital
Jinhua Central Hospital
Linyi People's Hospital
Shandong Cord Blood Bank
Qingdao Center Medical Group
Qingdao University
Taian City Central Hospital
Yantai Yuhuangding Hospital
Yishui Central Hospital of LINYI
Institute of Hematology & Blood Diseases Hospital
Shengjing Hospital
Information provided by (Responsible Party):
Fang Zhou, 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

Condition or disease Intervention/treatment Phase
Aplastic Anemia Drug: Rabbit ATG, (Genzyme) Drug: Cy Drug: CsA Biological: Cord blood Phase 4

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  (Clinical Trial)
Estimated Enrollment : 130 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Multi-center Clinical Study of Immunosuppressants, Cyclophosphamide, And Cord Blood Transfusion in Treating Patients With Severe Aplastic Anemia
Estimated Study Start Date : February 2017
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : July 2019


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:
  • Cyclophosphamide
  • Cytophosphane

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:
  • Ciclosporin A
  • Cyclosporine

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 Name: 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:
  • Ciclosporin A
  • Cyclosporine




Primary Outcome Measures :
  1. 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)


Secondary Outcome Measures :
  1. 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 .

  2. Infection rates [ Time Frame: 1 year ]
  3. Overall survival [ Time Frame: 2 years ]
  4. Treatment related mortality [ Time Frame: 2 years ]


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Ages Eligible for Study:   1 Year to 60 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02838992


Contacts
Contact: Fang Zhou, MD 86-0531-51665316 zhoufang1@medmail.com.cn
Contact: Zhe Yu, MD 86-0531-51665781 doctoryu1120@163.com

Locations
China, Shandong
The General Hospital Of Jinan Military Command Not yet recruiting
Jinan, Shandong, China, 250031
Contact: Fang Zhou, MD    86-0531-51665316    zhoufang1@medmail.com.cn   
Contact: Zhe Yu, MD    86-0531-51665781    doctoryu1120@163.com   
Sponsors and Collaborators
Jinan Military General Hospital
Shandong University of Traditional Chinese Medicine
Jining Medical University
Weifang Medical University
Guangzhou First People's Hospital
Harbin Hematology and Oncology Institute
Shandong Jining No.1 People's Hospital
JIANGXI Provincal People's Hospital
Jinhua Central Hospital
Linyi People's Hospital
Shandong Cord Blood Bank
Qingdao Center Medical Group
Qingdao University
Taian City Central Hospital
Yantai Yuhuangding Hospital
Yishui Central Hospital of LINYI
Institute of Hematology & Blood Diseases Hospital
Shengjing Hospital
Investigators
Study Chair: Fang Zhou, MD The General Hospital Of Jinan Military Command

Publications of Results:
Other Publications:
Responsible Party: Fang Zhou, Principal Investigator, Jinan Military General Hospital
ClinicalTrials.gov Identifier: NCT02838992     History of Changes
Other Study ID Numbers: JinanMGH
First Posted: July 20, 2016    Key Record Dates
Last Update Posted: February 1, 2017
Last Verified: January 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Fang Zhou, Jinan Military General Hospital:
Cyclophosphamide
Umbilical Cord Blood
ATG

Additional relevant MeSH terms:
Anemia
Anemia, Aplastic
Hematologic Diseases
Bone Marrow Diseases
Cyclophosphamide
Cyclosporins
Cyclosporine
Thymoglobulin
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Enzyme Inhibitors
Antifungal Agents
Anti-Infective Agents
Dermatologic Agents
Calcineurin Inhibitors