Aplastic AnemiaPhase 4NCT02838992
ATG Combined With Cyclophosphamide And Cord Blood Transfusion in Treating Patients With Severe Aplastic Anemia
A Phase 4 study testing Rabbit ATG, (Genzyme), Cy and CsA in people with Aplastic Anemia, run by Jinan Military General Hospital at 1 site in China.
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 Read more about this study
- Who is it for?
- Ages 1 year to 60 years
- Conditions the study is for
- Aplastic Anemia
- What is being tested?
- Rabbit ATG, (Genzyme), Cy and CsA
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 130 participants
- Where
- 1 siteChina
- Study dates
- Feb 2017to Jul 2019
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 60 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Male or female ,under the age of 60.
- Diagnosis of SAA and VSAA in accordance with the <aplastic anemia, diagnosis and treatment expert consensus> Camitta standard (see appendix 1).
- Confirmed of heavy and very heavy aplastic anemia within 6 months.
- 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
- Clear understanding, voluntary to participate in the study, and signed informed consent document by the patient or the legal guardian
- Willingness and ability to comly with the treatment plan, follow-up and laboratory tests as required
Who cannot join
- Congenital aplastic anemia
- Pregnancy or breastfeeding
- Participated in other clinical trials within three months
- Presence of Any fatal disease, including respiratory failure, heart failure, liver or kidney failure, et al
- Aplastic anemia caused by the treatment of other malignant tumor treatment
- With severe mental illness
Show all 11Show fewer
- With other malignant tumor
- Severe infection or the infection difficult to be controlled
- Received ATG or cyclosporine A within six months
- Severely allergic to biological agents
- Any other situation judged by the investigator that the patients inappropriate for entry into this study
Trial locations and contacts
1 site in 1 country.
China1 site
The General Hospital Of Jinan Military Command
Jinan, Shandong, 250031
Fang Zhou, MD, 86-0531-51665316, zhoufang1@medmail.com.cn
Zhe Yu, MD, 86-0531-51665781, doctoryu1120@163.com
About this study
Official title: 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
Read the 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.
- Conditions
- Aplastic Anemia
- Being tested
- Rabbit ATG, (Genzyme), Cy, CsA, Cord blood
- Keywords
- Cyclophosphamide, Umbilical Cord Blood, ATG
- Medical subject headings
- Anemia, Aplastic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rabbit ATG, (Genzyme)Drug
Also called Thymoglobuline, Anti-thymoeyteGlobulin
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
CyDrug
Also called Cyclophosphamide, Cytophosphane
Cyclophosphamide is a medication mainly used in chemotherapy. It is an alkylating agent of the nitrogen mustard type
CsADrug
Also called Ciclosporin A, Cyclosporine
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 bloodBiological
Also called Umbilical 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
| Study group | Role | What they receive |
|---|---|---|
| ATG, Cy and cord blood transfusion group | Experimental | 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 Receives: Drug: Rabbit ATG, (Genzyme); Drug: Cy; Drug: CsA; Biological: Cord blood |
| ATG and CSA group | Active comparator | 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 Receives: Drug: Rabbit ATG, (Genzyme); Drug: CsA |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: Every 3 months to 24 months
Secondary outcomes (4)
Neutrophil recovery time
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 .
Measured: From day 0 until the first of 3 consecutive days
Infection rates
Measured: 1 year
Overall survival
Measured: 2 years
Treatment related mortality
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jul 2016 (estimated)
- Study startFeb 2017 (estimated)
- Primary completionDec 2018 (estimated)
- Study completionJul 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Aplastic AnemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 130 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Jinan Military General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Shandong University of Traditional Chinese Medicine, Jining Medical University, Weifang Medical University, Guangzhou First People's Hospital, Harbin Hematology and Oncology Institute, Jining First People's Hospital, Jiangxi Provincial People's Hopital, Jinhua Central Hospital, Linyi People's Hospital, Shandong Cord Blood Bank, Qingdao Hiser Medical Group, Qingdao University, Taian City Central Hospital, Yantai Yuhuangding Hospital, Yishui Central Hospital of LINYI, Institute of Hematology & Blood Diseases Hospital, China, Shengjing Hospital
- Responsible party
- Principal investigator, Fang Zhou, Jinan Military General Hospital
- Investigators
- Fang Zhou, MD, Study chair, The General Hospital Of Jinan Military Command
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02838992
- Sponsor's protocol ID
- JinanMGH
- Status last verified
- Jan 2017
- First submitted
- 6 Jul 2016
- Last updated
- 1 Feb 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 26568159Zhou 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.
PubMed 21663651Xie 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.
PubMed 24838091Yu 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.
PubMed 25932194Xie 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.
PubMed 26622526
Study at a glance
From the registry record, last updated by the sponsor on 1 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multi-center Clinical Study of Immunosuppressants, Cyclophosphamide, And Cord Blood Transfusion in Treating Patients With Severe Aplastic Anemia
- ClinicalTrials.gov ID
- NCT02838992
- Acronym / sponsor ID
- JinanMGH
- Conditions
- Aplastic Anemia
- Keywords
- Cyclophosphamide, Umbilical Cord Blood, ATG
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 130 participants (estimated)
- Lead sponsor
- Jinan Military General HospitalUniversity, hospital or other
- Collaborators
- Shandong University of Traditional Chinese Medicine, Jining Medical University, Weifang Medical University, Guangzhou First People's Hospital, Harbin Hematology and Oncology Institute, Jining First People's Hospital, Jiangxi Provincial People's Hopital, Jinhua Central Hospital, Linyi People's Hospital, Shandong Cord Blood Bank, Qingdao Hiser Medical Group, Qingdao University, Taian City Central Hospital, Yantai Yuhuangding Hospital, Yishui Central Hospital of LINYI, Institute of Hematology & Blood Diseases Hospital, China, Shengjing Hospital
- Study start
- Feb 2017 (estimated)
- Primary completion
- Dec 2018 (estimated)
- Study completion
- Jul 2019 (estimated)
- First posted
- 20 Jul 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ATG, Cy and cord blood transfusion group | Experimental | Drug: Rabbit ATG, (Genzyme), Drug: Cy, Drug: CsA, Biological: Cord bloodATG 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 |
| ATG and CSA group | Active comparator | Drug: Rabbit ATG, (Genzyme), Drug: CsAATG 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 |
Who may qualify
- Ages
- 1 year to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- Male or female ,under the age of 60.
- Diagnosis of SAA and VSAA in accordance with the <aplastic anemia, diagnosis and treatment expert consensus> Camitta standard (see appendix 1).
- Confirmed of heavy and very heavy aplastic anemia within 6 months.
- 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
- Clear understanding, voluntary to participate in the study, and signed informed consent document by the patient or the legal guardian
Key exclusion criteria (11 listed)
- Congenital aplastic anemia
- Pregnancy or breastfeeding
- Participated in other clinical trials within three months
- Presence of Any fatal disease, including respiratory failure, heart failure, liver or kidney failure, et al
- Aplastic anemia caused by the treatment of other malignant tumor treatment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Rabbit ATG, (Genzyme)Also: Thymoglobuline, Anti-thymoeyteGlobulinATG 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 | Drug | ATG and CSA group, ATG, Cy and cord blood transfusion group |
| CyAlso: Cyclophosphamide, CytophosphaneCyclophosphamide is a medication mainly used in chemotherapy. It is an alkylating agent of the nitrogen mustard type | Drug | ATG, Cy and cord blood transfusion group |
| CsAAlso: Ciclosporin A, CyclosporineCsA 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 | Drug | ATG and CSA group, ATG, Cy and cord blood transfusion group |
| Cord bloodAlso: Umbilical cord bloodCord 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 | Biological | ATG, Cy and cord blood transfusion group |
Primary outcome
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)
4 secondary outcomes
Neutrophil recovery time
Time frame: From day 0 until the first of 3 consecutive days
Infection rates
Time frame: 1 year
Overall survival
Time frame: 2 years
Treatment related mortality
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Feb 2017.
- Background: PubMed 26568159Killick 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.
- Results publication: PubMed 21663651Zhou 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.
- Results publication: PubMed 24838091Xie 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.
- Results publication: PubMed 25932194Yu 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.
- Results publication: PubMed 26622526Xie 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Fang Zhou, MD study chair
The General Hospital Of Jinan Military Command
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Rabbit ATG, (Genzyme), Cy and CsA in people with Aplastic Anemia, run by Jinan Military General Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 1 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Fang Zhou, MD (86-0531-51665316, zhoufang1@medmail.com.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The total response rate (time frame: Every 3 months to 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02838992, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Feb 2017.