Chronic Graft-versus-host-diseasePhase 4NCT03190733
A Optimal Anti-Thymoglobuline (ATG) Dose Decrease cGVHD But Not Increase Leukemia Relapse for Haplo-HSCT
A Phase 4 study testing ATG in people with Chronic Graft-versus-host-disease and Leukemia Relapse, run by Zhujiang Hospital.
Trial summary
In this study, a randomized, prospective, multicenter, open cohort study was conducted to investigate patients with acute leukemia (14～60-year-old) with different ATG doses (10 mg / kg and 12.5 mg / kg ) in fludarabine, busulfan, cyclophosphamide and antilymphocyte globulin (FBCA) pretreatment protocol of… Read more about this study
- Who is it for?
- Ages 14 to 60 years
- Conditions the study is for
- Chronic Graft-versus-host-disease, Leukemia Relapse
- What is being tested?
- ATG
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 192 participants
- Where
- No sites listed yet
- Study dates
- 30 Aug 2017to 30 Sep 2021
- 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 14 to 60 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- patients age between 14 yeas old and 60 years old
- patients with acute myeloid leukemia and acute lymphoblastic leukemia who needed stem cell transplantation without available HLA-identical related or unrelated donors
Who cannot join
- Patients with severe infections
- patients with major organ abnormal including renal, liver, lung or heart.
- Patients with any conditions not suitable for the trial (investigators' decision)
- patients age below 14 years old and more than 60 years old.
Trial locations and contacts
No sites are listed yet.
About this study
Official title: A Randomized,Open,Multicenter and Prospective Study of the Optimized Dose of Anti-Thymoglobuline in Haploidentical Allogeneic Stem Cell Transplantation
In this study, a randomized, prospective, multicenter, open cohort study was conducted to investigate patients with acute leukemia (14～60-year-old) with different ATG doses (10 mg / kg and 12.5 mg / kg ) in fludarabine, busulfan, cyclophosphamide and antilymphocyte globulin (FBCA) pretreatment protocol of Haploidentical hematopoietic stem cell transplantation (haplo-HSCT). The purpose is to compare the incidences of chronic graft vs host disease (cGVHD) in haplo-HSCT recipients receiving different dose ATG and one year leukemia relapse after transplantation. The main objective was to investigate the optimal dose of ATG for decrease cGVHD and not increase one year relapse leukemia after haplo-HSCT. Its significance is to provide evidence-based medical evidence to reduce the occurrence of cGVHD and to improve the quality of life of patients with haplo-HSCT.
Read the detailed description
Human leukocyte antigen (HLA) haploidentical hematopoietic stem cell transplantation is an effective method for the treatment of hematological malignancies. However, high incidence rate of graft-versus-host disease (GVHD) seriously affects the quality of life of patients.
Using ATG in vivo T cell transplantation regimens reduce the rate of acute GVHD (aGVHD) and cGVHD. However, the optimal dose of ATG is unknown, Huang's reported that a prospective, randomized trial, which compared the long-term outcomes of 2 ATG doses used in myeloablative conditioning before unmanipulated haplo-HSCT. Patients were received 10 mg/kg or 6 mg/kg of ATG in conditioning regimen. The 5-year cumulative incidence of cGVHD was found to be higher with ATG 6mg/kg (75.0% vs 56.3% [P = .007] and moderate-to-severe cGVHD: 56.3% vs 30.4% [P<.0001]. ATG 10mg/kg in conditioning regimen was found to be associated with a lower risk of cGVHD. But the moderate-to-severe cGVHD was as high as 35%. We established the FBCA pretreatment regimen which added ATG and achieve the goal of reducing GVHD. In this FBCA pretreatment regimen the ATG dose was 12.5mg/kg which higher than that of other protocol. The cumulative incidence of grades II-IV aGVHD and cGVHD was 21.9% and 14.3% with the 12.5mg/kg ATG in the FBCA conditioning regimen which was lower than that of ATG 10mg/kg reported by Huang. However, ATG may lead to immunosuppression and lead to slow recovery of immune function and increased infection rate and may increase leukemia relapse after transplantation. What is the optimal does of ATG in FBCA pretreatment regimen which could reduce cGVHD and not increase leukemia relapse after transplantation? Access to ClinicalTrials and other sites found that there was still no related international studies with the FBCA conditioning regimen. We hypothesize that total ATG dose 12.5mg/kg in FBCA pretreatment regimen will decrease cGVHD and not increase leukemia relapse post transplantation.
In this study, a randomized, prospective, multicenter, open cohort study was conducted to investigate patients (14～60-year-old) with different ATG doses (10 mg / kg and 12.5 mg / kg ) in the FBCA pretreatment protocol of haploidentical hematopoietic stem cell transplantation. The purpose of this study is to compare the incidences of cGVHD and one year leukemia relapse in haploidentical hematopoietic stem cell transplant recipients receiving different dose of antithymocyte globulin (ATG) for acute graft-versus-host disease(aGVHD) prophylaxis The first objective was to investigate the optimal dose of ATG for decrease cGVHD and not increase one year relapse leukemia after haplo-HSCT. Its significance is to provide evidence-based medical evidence to reduce the occurrence of cGVHD and to improve the quality of life of patients with HLA haploid hematopoietic stem cell transplantation.
- Being tested
- ATG
- Keywords
- Hematopoietic Stem Cell Transplantation, ATG, chronic GVHD, leukemia relapse
- Medical subject headings
- Bronchiolitis Obliterans Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ATGDrug
Also called fludarabine
ATG will be intravenously infused via a central venous catheter in 4 or 5 days, from day -4 or -3 until day 0. The other conditioning drugs administered before transplantation include fludarabine (Flu), busulfan (Bu),cyclophosphamide (Cy). All transplant recipients will receive cyclosporine A (CsA), mycophenolate mofetil(MMF) for aGVHD prevention.
| Study group | Role | What they receive |
|---|---|---|
| ATG 10.0mg/kg | Experimental | ATG 10.0mg/kg group refers to treatment with ATG in the total dose of 10.0mg/kg. Receives: Drug: ATG |
| ATG 12.5mg/kg | Active comparator | ATG 12.5mg/kg group refers to treatment with ATG in the total dose of 12.5mg/kg. Receives: Drug: ATG |
What is being measured
The primary outcome is the main question the study is designed to answer.
occurrence of chronic GVHD
chronic GVHD diagnosis based on National Institutes of Health (NIH) criterion
Measured: from the day of stem cell transplantation to one year after stem cell transplantation
Secondary outcomes (3)
one year cumulative incidence of leukemia relapse
leukemia relapse base on morphology criterion
Measured: from the day of stem cell transplantation to one year after stem cell transplantation
The cumulative incidence rate of acute GVHD
acute GVHD diagnosis based on NIH criterion
Measured: from the day of stem cell transplantation to one year after stem cell transplantation
no relapse mortality one year
no relapse death
Measured: from the day of stem cell transplantation to one year after stem cell transplantation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jun 2017
- Study start30 Aug 2017 (estimated)
- Primary completion30 Sep 2020 (estimated)
- Study completion30 Sep 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Chronic Graft-versus-host-diseaseStudies 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 192 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Zhujiang Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Nanfang Hospital, Southern Medical University, First Affiliated Hospital, Sun Yat-Sen University, Second Affiliated Hospital, Sun Yat-Sen University
- Responsible party
- Sponsor
- Investigators
- Bingyi Wu, MD, Principal investigator, Zhejiang Hospital of southern Medical Unversity
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03190733
- Sponsor's protocol ID
- 2016-XYNK-001
- Status last verified
- Dec 2016
- First submitted
- 15 Jun 2017
- Last updated
- 19 Jun 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: individual participant data are to be shared with other researchers, when it will be available and be obtained by web.
Publications
Lin X, Lu ZG, Song CY, Huang YX, Guo KY, Deng L, Tu SF, He YZ, Xu JH, Long H, Wu BY. Long-term outcome of HLA-haploidentical hematopoietic stem cell transplantation without in vitro T-cell depletion based on an FBCA conditioning regimen for hematologic malignancies. Bone Marrow Transplant. 2015 Aug;50(8):1092-7. doi: 10.1038/bmt.2015.108. Epub 2015 May 11.
PubMed 25961770Long H, Lu ZG, Song CY, Huang YX, Xu JH, Xu JX, Deng L, Tu SF, He YZ, Lin X, Guo KY, Wu BY. Long-term outcomes of HLA-haploidentical stem cell transplantation based on an FBCA conditioning regimen compared with those of HLA-identical sibling stem cell transplantation for haematologic malignancies. Bone Marrow Transplant. 2016 Nov;51(11):1470-1475. doi: 10.1038/bmt.2016.170. Epub 2016 Jun 20.
PubMed 27322852Chang YJ, Wang Y, Mo XD, Zhang XH, Xu LP, Yan CH, Chen H, Chen YH, Chen Y, Han W, Wang FR, Wang JZ, Liu KY, Huang XJ. Optimal dose of rabbit thymoglobulin in conditioning regimens for unmanipulated, haploidentical, hematopoietic stem cell transplantation: Long-term outcomes of a prospective randomized trial. Cancer. 2017 Aug 1;123(15):2881-2892. doi: 10.1002/cncr.30540. Epub 2017 Mar 16.
PubMed 28301690
Study at a glance
From the registry record, last updated by the sponsor on 19 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized,Open,Multicenter and Prospective Study of the Optimized Dose of Anti-Thymoglobuline in Haploidentical Allogeneic Stem Cell Transplantation
- ClinicalTrials.gov ID
- NCT03190733
- Acronym / sponsor ID
- 2016-XYNK-001
- Keywords
- Hematopoietic Stem Cell Transplantation, ATG, chronic GVHD, leukemia relapse
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 192 participants (estimated)
- Lead sponsor
- Zhujiang HospitalUniversity, hospital or other
- Collaborators
- Nanfang Hospital, Southern Medical University, First Affiliated Hospital, Sun Yat-Sen University, Second Affiliated Hospital, Sun Yat-Sen University
- Study start
- 30 Aug 2017 (estimated)
- Primary completion
- 30 Sep 2020 (estimated)
- Study completion
- 30 Sep 2021 (estimated)
- First posted
- 19 Jun 2017 (actual)
- 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.
In this study, a randomized, prospective, multicenter, open cohort study was conducted to investigate patients with acute leukemia (14～60-year-old) with different ATG doses (10 mg / kg and 12.5 mg / kg ) in fludarabine, busulfan, cyclophosphamide and antilymphocyte globulin (FBCA) pretreatment protocol of Haploidentical hematopoietic stem cell transplantation (haplo-HSCT). The purpose is to compare the incidences of chronic graft vs host disease (cGVHD) in haplo-HSCT recipients receiving different dose ATG and one year leukemia relapse after transplantation. The main objective was to investigate the optimal dose of ATG for decrease cGVHD and not increase one year relapse leukemia after haplo-HSCT. Its significance is to provide evidence-based medical evidence to reduce the occurrence of cGVHD and to improve the quality of life of patients with haplo-HSCT.
Detailed description
Human leukocyte antigen (HLA) haploidentical hematopoietic stem cell transplantation is an effective method for the treatment of hematological malignancies. However, high incidence rate of graft-versus-host disease (GVHD) seriously affects the quality of life of patients.
Using ATG in vivo T cell transplantation regimens reduce the rate of acute GVHD (aGVHD) and cGVHD. However, the optimal dose of ATG is unknown, Huang's reported that a prospective, randomized trial, which compared the long-term outcomes of 2 ATG doses used in myeloablative conditioning before unmanipulated haplo-HSCT. Patients were received 10 mg/kg or 6 mg/kg of ATG in conditioning regimen. The 5-year cumulative incidence of cGVHD was found to be higher with ATG 6mg/kg (75.0% vs 56.3% [P = .007] and moderate-to-severe cGVHD: 56.3% vs 30.4% [P<.0001]. ATG 10mg/kg in conditioning regimen was found to be associated with a lower risk of cGVHD. But the moderate-to-severe cGVHD was as high as 35%. We established the FBCA pretreatment regimen which added ATG and achieve the goal of reducing GVHD. In this FBCA pretreatment regimen the ATG dose was 12.5mg/kg which higher than that of other protocol. The cumulative incidence of grades II-IV aGVHD and cGVHD was 21.9% and 14.3% with the 12.5mg/kg ATG in the FBCA conditioning regimen which was lower than that of ATG 10mg/kg reported by Huang. However, ATG may lead to immunosuppression and lead to slow recovery of immune function and increased infection rate and may increase leukemia relapse after transplantation. What is the optimal does of ATG in FBCA pretreatment regimen which could reduce cGVHD and not increase leukemia relapse after transplantation? Access to ClinicalTrials and other sites found that there was still no related international studies with the FBCA conditioning regimen. We hypothesize that total ATG dose 12.5mg/kg in FBCA pretreatment regimen will decrease cGVHD and not increase leukemia relapse post transplantation.
In this study, a randomized, prospective, multicenter, open cohort study was conducted to investigate patients (14～60-year-old) with different ATG doses (10 mg / kg and 12.5 mg / kg ) in the FBCA pretreatment protocol of haploidentical hematopoietic stem cell transplantation. The purpose of this study is to compare the incidences of cGVHD and one year leukemia relapse in haploidentical hematopoietic stem cell transplant recipients receiving different dose of antithymocyte globulin (ATG) for acute graft-versus-host disease(aGVHD) prophylaxis The first objective was to investigate the optimal dose of ATG for decrease cGVHD and not increase one year relapse leukemia after haplo-HSCT. Its significance is to provide evidence-based medical evidence to reduce the occurrence of cGVHD and to improve the quality of life of patients with HLA haploid hematopoietic stem cell transplantation.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ATG 10.0mg/kg | Experimental | Drug: ATGATG 10.0mg/kg group refers to treatment with ATG in the total dose of 10.0mg/kg. |
| ATG 12.5mg/kg | Active comparator | Drug: ATGATG 12.5mg/kg group refers to treatment with ATG in the total dose of 12.5mg/kg. |
Who may qualify
- Ages
- 14 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (2 listed)
- patients age between 14 yeas old and 60 years old
- patients with acute myeloid leukemia and acute lymphoblastic leukemia who needed stem cell transplantation without available HLA-identical related or unrelated donors
Key exclusion criteria (4 listed)
- Patients with severe infections
- patients with major organ abnormal including renal, liver, lung or heart.
- Patients with any conditions not suitable for the trial (investigators' decision)
- patients age below 14 years old and more than 60 years old.
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 |
|---|---|---|
| ATGAlso: fludarabineATG will be intravenously infused via a central venous catheter in 4 or 5 days, from day -4 or -3 until day 0. The other conditioning drugs administered before transplantation include fludarabine (Flu), busulfan (Bu),cyclophosphamide (Cy). All transplant recipients will receive cyclosporine A (CsA), mycophenolate mofetil(MMF) for aGVHD prevention. | Drug | ATG 10.0mg/kg, ATG 12.5mg/kg |
Primary outcome
occurrence of chronic GVHD
Time frame: from the day of stem cell transplantation to one year after stem cell transplantation
chronic GVHD diagnosis based on National Institutes of Health (NIH) criterion
3 secondary outcomes
one year cumulative incidence of leukemia relapse
Time frame: from the day of stem cell transplantation to one year after stem cell transplantation
The cumulative incidence rate of acute GVHD
Time frame: from the day of stem cell transplantation to one year after stem cell transplantation
no relapse mortality one year
Time frame: from the day of stem cell transplantation to one year after stem cell transplantation
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jun 2017.
- Background: PubMed 25961770Lin X, Lu ZG, Song CY, Huang YX, Guo KY, Deng L, Tu SF, He YZ, Xu JH, Long H, Wu BY. Long-term outcome of HLA-haploidentical hematopoietic stem cell transplantation without in vitro T-cell depletion based on an FBCA conditioning regimen for hematologic malignancies. Bone Marrow Transplant. 2015 Aug;50(8):1092-7. doi: 10.1038/bmt.2015.108. Epub 2015 May 11.
- Background: PubMed 27322852Long H, Lu ZG, Song CY, Huang YX, Xu JH, Xu JX, Deng L, Tu SF, He YZ, Lin X, Guo KY, Wu BY. Long-term outcomes of HLA-haploidentical stem cell transplantation based on an FBCA conditioning regimen compared with those of HLA-identical sibling stem cell transplantation for haematologic malignancies. Bone Marrow Transplant. 2016 Nov;51(11):1470-1475. doi: 10.1038/bmt.2016.170. Epub 2016 Jun 20.
- Background: PubMed 28301690Chang YJ, Wang Y, Mo XD, Zhang XH, Xu LP, Yan CH, Chen H, Chen YH, Chen Y, Han W, Wang FR, Wang JZ, Liu KY, Huang XJ. Optimal dose of rabbit thymoglobulin in conditioning regimens for unmanipulated, haploidentical, hematopoietic stem cell transplantation: Long-term outcomes of a prospective randomized trial. Cancer. 2017 Aug 1;123(15):2881-2892. doi: 10.1002/cncr.30540. Epub 2017 Mar 16.
- Individual participant dataSharing planned: Yes. individual participant data are to be shared with other researchers, when it will be available and be obtained by web.
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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.
Bingyi Wu, MD principal investigator
Zhejiang Hospital of southern Medical Unversity
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing ATG in people with Chronic Graft-versus-host-disease and Leukemia Relapse, run by Zhujiang Hospital.
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 2 inclusion and 4 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 19 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
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 Jianghui xu, Dr (00862062782318, xiaoxu_75@sina.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
occurrence of chronic GVHD (time frame: from the day of stem cell transplantation to one year after stem cell transplantation). 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 NCT03190733, which also lists 3 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 19 Jun 2017.