Hematopoietic Stem Cell TransplantationPhase 4NCT05634915
Clinical Study of rATG Individualized Administration in Haploidentical Hematopoietic Stem Cell Transplantation
A Phase 4 study testing Individual ATG and ATG in people with Hematopoietic Stem Cell Transplantation and Acute Leukemia, run by The First Affiliated Hospital of Soochow University at 1 site in China.
Trial summary
The purpose of this prospective, open-label, pairing design, single-center study is to evaluate the effect of individualized rATG dosing vs traditional weight-based rATG dosing regimen（10mg/kg）for patients with acute leukemia undergoing a myeloablative conditioning regimen and haploidentical hematopoietic stem cell… Read more about this study
- Who is it for?
- Ages 16 to 60 years
- Conditions the study is for
- Hematopoietic Stem Cell Transplantation, Acute Leukemia
- What is being tested?
- Individual ATG and ATG
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 1 siteChina
- Study dates
- 20 Dec 2022to 1 May 2025
- 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 16 to 60 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- All patients were diagnosed with acute leukemia.
- All patients should have the indication of Haploidentical hematopoietic stem cell transplant and receive the myeloablative conditioning regimen.
- All patients should sign an informed consent document indicating that they understand the purpose of and procedures required for the study and be willing to participate in the study.
Who cannot join
- Patients with any conditions not suitable for the trial (investigators' decision).
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
The First Affiliated Hospital of Soochow University
Suzhou, Jiangsu, 215006
Xiaowen Tang, PhD, 67781525, xwtang1020@163.com
About this study
Official title: Clinical Study of rATG Individualized Administration for Prevention of GVHD and Maintenance of GVL in Haploidentical Hematopoietic Stem Cell Transplantation.
The purpose of this prospective, open-label, pairing design, single-center study is to evaluate the effect of individualized rATG dosing vs traditional weight-based rATG dosing regimen（10mg/kg）for patients with acute leukemia undergoing a myeloablative conditioning regimen and haploidentical hematopoietic stem cell transplantation (haplo-HSCT).
Read the detailed description
Allogeneic hematopoietic stem-cell transplantation (HSCT) is a potentially curative treatment option for acute leukemia. Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) has become the main choice for acute leukemia in China. Major difficulties of the procedure include graft-versus-host disease (GVHD), graft failure, and relapse. As an important role of haplo-HSCT, Rabbit anti-thymocyte globulin (rATG), a polyclonal rabbit-derived antibody that depletes lymphocytes, including T cells, was introduced to prevent GVHD and transplant rejection.
The recommended dose of rATG in haplo-HSCT is 10 mg/kg. However, while the traditional weight-based rATG dosing regimen (10mg/kg) reduces the incidence of GVHD, it increases the risk of delayed immune reconstitution, viral reactivation, and relapse in patients. Our previous retrospective study showed that active ATG exposure (area under the curve, AUC)) post-transplantation is associated with immune reconstitution, GVHD, relapse, survival, and viral reactivation in HSCT of acute leukemia patients. Identifying the optimal dose of ATG to achieve the optimal exposure range of active ATG is a pressing clinical issue.
The pharmacokinetics of ATG varies significantly in both pediatric and adult populations, especially the active ATG levels, and clarifying the relationship between the pharmacokinetics of ATG and the prognosis of patient outcomes can help in precise treatment. By constructing a population pharmacokinetic model of ATG, we can provide an individualized optimal dose of ATG based on factors prior to transplantation. ATG individualized administration may improve the survival and quality of life of patients undergoing haplo-HSCT. A prospective pairing design trial is required to evaluate the effect of individualized rATG dosing vs traditional weight-based rATG dosing regimen (10mg/kg) for patients with acute leukemia undergoing haplo-HSCT.
- Being tested
- Individual ATG, ATG
- Keywords
- Antithymocyte Globulin, Population pharmacokinetic model, Haploidentical Hematopoietic Stem Cell Transplantation, Acute Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Individual ATGDrug
Individual dose of ATG: Individual dose of ATG was Intravenous infused every day from day -5 to day -2 (total ATG dose was calculated based on population pharmacokinetic modeling). Prophylaxis against graft-versus-host disease (GVHD) was performed with cyclosporine A, mycophenolate mofetil, and low-dose methotrexate.
ATGDrug
ATG 10mg/kg: The total ATG dose was 10mg/kg. ATG was intravenously infused every day from day -5 to day -2. Prophylaxis against graft-versus-host disease (GVHD) was performed with cyclosporine A, mycophenolate mofetil, and low-dose methotrexate.
| Study group | Role | What they receive |
|---|---|---|
| Individual dose of ATG | Experimental | The total individual ATG dose was calculated based on population pharmacokinetic modeling. ATG was intravenously infused every day from day -5 to day -2. Receives: Drug: Individual ATG |
| ATG 10mg/kg | Active comparator | The total ATG dose was 10mg/kg. ATG was intravenously infused every day from day -5 to day -2. Receives: Drug: ATG |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cumulative incidences of aGVHD
The diagnosis and grading of aGVHD are based on the modified Glucksberg grading standard.
Measured: 100 days after transplantation
CD4+ immune reconstitution
CD4+ T-cells >0·05 × 10⁹/L twice within 3 months after transplantation
Measured: 3 months after transplantation
Leukemia-free survival (LFS)
Leukemia-free survival (LFS) is defined as the time from enrollment to relapse of primary disease or death from any cause, whichever occurred first.
Measured: 1 years after transplantation
Secondary outcomes (9)
Cumulative incidences of cGVHD
Chronic GVHD can be classified as "limited" or "extensive" according to the Seattle criteria, and also be classified as "mild" or "moderate" or "severe" according to the National Institutes of Health (NIH) criteria.
Measured: 1 years after transplantation
Cumulative incidences of EBV reactivation
The cumulative incidences of EBV reactivation after transplantation
Measured: 1 years after transplantation
Cumulative incidence of CMV reactivation
The cumulative incidences of CMV reactivation after transplantation.
Measured: 1 years after transplantation
Neutrophil engraftment
Neutrophil engraftment is defined as the first of 3 consecutive days with an absolute neutrophil count > 0.5 × 10^9/L.
Measured: 1 month after transplantation
Platelet engraftment
Platelet engraftment is defined as the first of 7 consecutive days with an absolute platelet count > 20 × 10^9/L independent from transfusion.
Measured: 1 month after transplantation
Overall survival (OS)
Overall survival (OS) is defined as the time from randomization to death resulting from any cause.
Measured: 1 years after transplantation
GVHD-free and relapse-free survival (GRFS)
GRFS is defined as the time from graft infusion to the onset of grades 3 to 4 aGVHD, moderate to severe cGVHD, or relapse/disease progression/death.
Measured: 1 years after transplantation
Non-relapse mortality (NRM)
Non-relapse mortality (NRM) is defined as the time from enrollment to death of any causes other than hematologic disease relapse.
Measured: 1 years after transplantation
Relapse-related mortality (RRM)
Relapse-related mortality (RRM) is defined as the time from enrollment to death of relapse.
Measured: 1 years after transplantation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Dec 2022
- Study start20 Dec 2022
- Primary completion1 Dec 2024 (estimated)
- Study completion1 May 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hematopoietic Stem Cell TransplantationStudies of the same condition, open and under way.
- More trials run by The First Affiliated Hospital of Soochow UniversityThe sponsor's other registered studies.
- 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Xiaowen Tang, PhD, Study chair, The First Affiliated Hospital of Soochow University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05634915
- Sponsor's protocol ID
- ATGIA2022
- Status last verified
- Nov 2022
- First submitted
- 22 Nov 2022
- Last updated
- 15 Feb 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Study of rATG Individualized Administration for Prevention of GVHD and Maintenance of GVL in Haploidentical Hematopoietic Stem Cell Transplantation.
- ClinicalTrials.gov ID
- NCT05634915
- Acronym / sponsor ID
- ATGIA2022
- Keywords
- Antithymocyte Globulin, Population pharmacokinetic model, Haploidentical Hematopoietic Stem Cell Transplantation, Acute Leukemia
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- The First Affiliated Hospital of Soochow UniversityUniversity, hospital or other
- Study start
- 20 Dec 2022 (actual)
- Primary completion
- 1 Dec 2024 (estimated)
- Study completion
- 1 May 2025 (estimated)
- First posted
- 2 Dec 2022 (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.
The purpose of this prospective, open-label, pairing design, single-center study is to evaluate the effect of individualized rATG dosing vs traditional weight-based rATG dosing regimen（10mg/kg）for patients with acute leukemia undergoing a myeloablative conditioning regimen and haploidentical hematopoietic stem cell transplantation (haplo-HSCT).
Detailed description
Allogeneic hematopoietic stem-cell transplantation (HSCT) is a potentially curative treatment option for acute leukemia. Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) has become the main choice for acute leukemia in China. Major difficulties of the procedure include graft-versus-host disease (GVHD), graft failure, and relapse. As an important role of haplo-HSCT, Rabbit anti-thymocyte globulin (rATG), a polyclonal rabbit-derived antibody that depletes lymphocytes, including T cells, was introduced to prevent GVHD and transplant rejection.
The recommended dose of rATG in haplo-HSCT is 10 mg/kg. However, while the traditional weight-based rATG dosing regimen (10mg/kg) reduces the incidence of GVHD, it increases the risk of delayed immune reconstitution, viral reactivation, and relapse in patients. Our previous retrospective study showed that active ATG exposure (area under the curve, AUC)) post-transplantation is associated with immune reconstitution, GVHD, relapse, survival, and viral reactivation in HSCT of acute leukemia patients. Identifying the optimal dose of ATG to achieve the optimal exposure range of active ATG is a pressing clinical issue.
The pharmacokinetics of ATG varies significantly in both pediatric and adult populations, especially the active ATG levels, and clarifying the relationship between the pharmacokinetics of ATG and the prognosis of patient outcomes can help in precise treatment. By constructing a population pharmacokinetic model of ATG, we can provide an individualized optimal dose of ATG based on factors prior to transplantation. ATG individualized administration may improve the survival and quality of life of patients undergoing haplo-HSCT. A prospective pairing design trial is required to evaluate the effect of individualized rATG dosing vs traditional weight-based rATG dosing regimen (10mg/kg) for patients with acute leukemia undergoing haplo-HSCT.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Individual dose of ATG | Experimental | Drug: Individual ATGThe total individual ATG dose was calculated based on population pharmacokinetic modeling. ATG was intravenously infused every day from day -5 to day -2. |
| ATG 10mg/kg | Active comparator | Drug: ATGThe total ATG dose was 10mg/kg. ATG was intravenously infused every day from day -5 to day -2. |
Who may qualify
- Ages
- 16 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- All patients were diagnosed with acute leukemia.
- All patients should have the indication of Haploidentical hematopoietic stem cell transplant and receive the myeloablative conditioning regimen.
- All patients should sign an informed consent document indicating that they understand the purpose of and procedures required for the study and be willing to participate in the study.
Key exclusion criteria (1 listed)
- Patients with any conditions not suitable for the trial (investigators' decision).
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 |
|---|---|---|
| Individual ATGIndividual dose of ATG: Individual dose of ATG was Intravenous infused every day from day -5 to day -2 (total ATG dose was calculated based on population pharmacokinetic modeling). Prophylaxis against graft-versus-host disease (GVHD) was performed with cyclosporine A, mycophenolate mofetil, and low-dose methotrexate. | Drug | Individual dose of ATG |
| ATGATG 10mg/kg: The total ATG dose was 10mg/kg. ATG was intravenously infused every day from day -5 to day -2. Prophylaxis against graft-versus-host disease (GVHD) was performed with cyclosporine A, mycophenolate mofetil, and low-dose methotrexate. | Drug | ATG 10mg/kg |
Primary outcome
Cumulative incidences of aGVHD
Time frame: 100 days after transplantation
The diagnosis and grading of aGVHD are based on the modified Glucksberg grading standard.
CD4+ immune reconstitution
Time frame: 3 months after transplantation
CD4+ T-cells >0·05 × 10⁹/L twice within 3 months after transplantation
Leukemia-free survival (LFS)
Time frame: 1 years after transplantation
Leukemia-free survival (LFS) is defined as the time from enrollment to relapse of primary disease or death from any cause, whichever occurred first.
9 secondary outcomes
Cumulative incidences of cGVHD
Time frame: 1 years after transplantation
Cumulative incidences of EBV reactivation
Time frame: 1 years after transplantation
Cumulative incidence of CMV reactivation
Time frame: 1 years after transplantation
Neutrophil engraftment
Time frame: 1 month after transplantation
Platelet engraftment
Time frame: 1 month after transplantation
Overall survival (OS)
Time frame: 1 years after transplantation
GVHD-free and relapse-free survival (GRFS)
Time frame: 1 years after transplantation
Non-relapse mortality (NRM)
Time frame: 1 years after transplantation
Relapse-related mortality (RRM)
Time frame: 1 years after transplantation
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2023.
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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.
Xiaowen Tang, PhD study chair
The First Affiliated Hospital of Soochow University
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 Individual ATG and ATG in people with Hematopoietic Stem Cell Transplantation and Acute Leukemia, run by The First Affiliated Hospital of Soochow University 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 3 inclusion and 1 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 15 Feb 2023. 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 Xiaowen Tang, PhD (67781525, xwtang1020@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cumulative incidences of aGVHD (time frame: 100 days after transplantation). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 15 Feb 2023; AzTrials last refreshed its copy on 7 Nov 2026.