- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03190733
A Optimal Anti-Thymoglobuline (ATG) Dose Decrease cGVHD But Not Increase Leukemia Relapse for Haplo-HSCT
A Randomized,Open,Multicenter and Prospective Study of the Optimized Dose of Anti-Thymoglobuline in Haploidentical Allogeneic Stem Cell Transplantation
Study Overview
Status
Intervention / Treatment
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 Type
Enrollment (Anticipated)
Phase
- Phase 4
Contacts and Locations
Study Contact
- Name: Jianghui xu, Dr
- Phone Number: 00862062782318
- Email: xiaoxu_75@sina.com
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: PREVENTION
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: SINGLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: ATG 10.0mg/kg
ATG 10.0mg/kg group refers to treatment with ATG in the total dose of 10.0mg/kg.
|
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.
Other Names:
|
ACTIVE_COMPARATOR: ATG 12.5mg/kg
ATG 12.5mg/kg group refers to treatment with ATG in the total dose of 12.5mg/kg.
|
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.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
from the day of stem cell transplantation to one year after stem cell transplantation
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
one year cumulative incidence of leukemia relapse
Time Frame: from the day of stem cell transplantation to one year after stem cell transplantation
|
leukemia relapse base on morphology criterion
|
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
|
acute GVHD diagnosis based on NIH criterion
|
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
|
no relapse death
|
from the day of stem cell transplantation to one year after stem cell transplantation
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Bingyi Wu, MD, Zhejiang Hospital of southern Medical Unversity
Publications and helpful links
General 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.
- Long 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.
- Chang 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. Erratum In: Cancer. 2018 Feb 15;124(4):868.
Study record dates
Study Major Dates
Study Start (ANTICIPATED)
Primary Completion (ANTICIPATED)
Study Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2016-XYNK-001
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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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