Cytomegalovirus InfectionsPhase 2NCT06572462
ATG Individualized Dosing Model in URD-PBSCT.
A Phase 2 study testing individualized ATG dosing strategy in people with Cytomegalovirus Infections and Infection Reactivation, run by Chinese PLA General Hospital at 1 site in China.
Trial summary
Anti-thymocyte globulin (ATG) is widely used in allogeneic hematopoietic stem cell transplantation to prevent severe graft-versus-host disease (GVHD) and graft failure. However, overexposure to ATG may increase cytomegalovirus (CMV), Epstein-Barr virus (EBV) reactivation, non-relapse mortality, and disease recurrence. Read more about this study
- Who is it for?
- Ages 14 to 65 years
- Conditions the study is for
- Cytomegalovirus Infections, Infection Reactivation, Stem Cell Transplant Complications
- What is being tested?
- individualized ATG dosing strategy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteChina
- Study dates
- 31 Dec 2020to 30 Jun 2025
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients with malignant hematological tumors who have indications for allogeneic hematopoietic stem cell transplantation.
- HLA-matched unrelated donor
- Patient age ≥14 years old and ≤65 years old
- ALT and AST ≤ 2.5 times the upper limit of normal values, bilirubin ≤ 2 times the upper limit of normal values
- Creatinine ≤ high limit of normal value
- No uncontrollable infection or serious mental illness
- Physical strength score is 0-2 (ECOG)
- Sign the informed consent form
Who cannot join
- Unrelated donor who is not HLA matched
- No indication for allogeneic hematopoietic stem cell transplantation
- Patient age <14 years old or >65 years old
- The donor or recipient are pregnant
- Suffering from mental illness or other conditions and being unable to proceed as planned
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Department of Hematology, First Medical Center of Chinese PLA General Hospital
Beijing
jiang Cao, 010-66937166
About this study
Official title: Application of Thymoglobulin (ATG) Individualized Dosing Model in Unrelated Allogeneic Hematopoietic Stem Cell Transplantation.
Anti-thymocyte globulin (ATG) is widely used in allogeneic hematopoietic stem cell transplantation to prevent severe graft-versus-host disease (GVHD) and graft failure. However, overexposure to ATG may increase cytomegalovirus (CMV), Epstein-Barr virus (EBV) reactivation, non-relapse mortality, and disease recurrence. A targeted dosing strategy was established based on ATG concentration monitoring and conducted a phase 2 trial to evaluate the safety and efficacy of the dosing strategy in adult unmanipulated haplo-PBSCT, a encouraging result was attained. In this trial, The ATG-targeted dosing strategy was extended to adult unrelated donor allogeneic hematopoietic stem cell transplantation, ATG was administered for 4 days (-5 days to -2 days) during conditioning. The ATG doses on-3 days and- 2days were adjusted by our dosing strategy to achieve the optimal ATG exposure. The primary endpoint was CMV reactivation on +180 days.
Read the detailed description
Allogeneic hematopoietic cell transplantation(allo-HCT) is a curative therapy for hematological disorders and the ATG is commonly used as prophylaxis for GVHD. Previous studies have indicated that there is an optimal dosage for ATG administration, if the dosage is too high, it may affect engraftment and increase the risk of infection and relapse, whereas an inadequate dosage may increase the risk of acute or chronic GVHD, there is still controversy about the optimal dose of ATG, its pharmacologic effects on clinical outcomes of HSCT are associated with donor source, human leukocyte antigen (HLA) disparity, conditioning intensity, and GVHD prophylaxis, so although has been investigated for decades, the optimal dosage of ATG in allogeneic hematopoietic stem cell transplantation remains undetermined.
ATG exerts pharmacologic effects in its active form upon binding to lymphocytes, and its exposure is presented as the area under the concentration-time curve (AUC). To obtain plasma active ATG concentrations, investigators developed an active ATG concentration detection method based on flow-cytometry with HUT-78 T-cells. In previous study, investigators quantified active ATG exposure in 106 haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) recipients, who received a conventional fixed dose of 10 mg/kg ATG during conditioning, the optimal concentration range of active ATG-AUC was determined through the application of machine learning methods, was found to be 100-148.5 × 10^3 UE·d/L. This concentration range was associated with a reduction in CMV/EBV reactivation, without an increase in acute GVHD or malignant disease relapse. Mathematical function was then exploited to determine the total targeted ATG dose on -3days to -2days based on concentrations of active ATG on -5daysto -4days. Based on this function, a dosing strategy was established that aimed to maintain the active ATG-AUC within the optimal range. To validate this individualized dosing strategy, investigators conducted a single-arm, phase 2 trial, demonstrating that this strategy could reduce CMV/EBV reactivation and improve survival without increasing the incidence of GVHD after haplo-PBSCT. Given the similarity between unrelated donor hematopoietic stem cell transplantation (URD-HSCT) and haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in terms of conditioning regimens, GVHD prophylaxis, and supportive therapies, as well as the conventional fixed dose of 10mg/kg employed in both settings, investigators have designed and conducted a single-center, prospective, single-arm clinical trial. The aim of this trial is to translate the individualized ATG dosing strategy, which was originally developed based on ATG concentration monitoring in haplo-HSCT patients, to URD-HSCT, with the goal of further validating its effectiveness.
- Being tested
- individualized ATG dosing strategy
- Medical subject headings
- Cytomegalovirus Infections, Latent Infection
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
individualized ATG dosing strategyDrug
Investigators quantified active ATG exposure in 106 haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) recipients, who received a conventional fixed dose of 10 mg/kg ATG during conditioning, the optimal concentration range of active ATG-AUC was determined through the application of machine learning methods, was found to be 100-148.5 × 10^3 UE·d/L. This concentration range was associated with a reduction in CMV/EBV reactivation, without an increase in acute GVHD or malignant disease relapse. Mathematical function was then exploited to determine the total targeted ATG dose on -3days to -2days based on concentrations of active ATG on -5daysto -4days. Based on this function, investigators established a dosing strategy that aimed to maintain the active ATG-AUC within the optimal range.
| Study group | Role | What they receive |
|---|---|---|
| targeted dosing ATG cohort | Experimental | The targeted dosing ATG cohort received the same dose of medication at -5 days and -4 days as the traditional administration method (-5days, 1.5mg/kg; -4days 2.5mg/kg), Two individual doses were given on -3days and day -2days according to the dose adjustment strategy. Receives: Drug: individualized ATG dosing strategy |
What is being measured
The primary outcome is the main question the study is designed to answer.
cumulative incidence of CMV reactivation
The primary endpoint was the cumulative incidence of CMV reactivation on +180 days after transplantation.
Measured: 0Day-180Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Aug 2024
- Study start31 Dec 2020
- Primary completion30 Dec 2024 (estimated)
- Study completion30 Jun 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cytomegalovirus InfectionsStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chinese PLA General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Daihong Liu, Chinese PLA General Hospital
- Investigators
- diahong Liu, MD, Principal investigator, The First Medical Center of Chinese PLA General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06572462
- Sponsor's protocol ID
- S2023-794-01
- Status last verified
- Nov 2024
- First submitted
- 23 Aug 2024
- Last updated
- 3 Dec 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Chen S, Wang L, Luan S, Wang H, Du J, Ge D, Li F, Wu Y, Gu Z, Dou L, Liu D. Reduced cytomegalovirus reactivation and viremia without increasing GVHD after URD-PBSCT: A prospective study using targeted ATG dosing strategy. Cancer Pathog Ther. 2025 Apr 5;4(2):145-152. doi: 10.1016/j.cpt.2025.04.001. eCollection 2026 Mar.
PubMed 41624481
Study at a glance
From the registry record, last updated by the sponsor on 3 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Application of Thymoglobulin (ATG) Individualized Dosing Model in Unrelated Allogeneic Hematopoietic Stem Cell Transplantation.
- ClinicalTrials.gov ID
- NCT06572462
- Acronym / sponsor ID
- S2023-794-01
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Chinese PLA General HospitalUniversity, hospital or other
- Study start
- 31 Dec 2020 (actual)
- Primary completion
- 30 Dec 2024 (estimated)
- Study completion
- 30 Jun 2025 (estimated)
- First posted
- 27 Aug 2024 (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.
Anti-thymocyte globulin (ATG) is widely used in allogeneic hematopoietic stem cell transplantation to prevent severe graft-versus-host disease (GVHD) and graft failure. However, overexposure to ATG may increase cytomegalovirus (CMV), Epstein-Barr virus (EBV) reactivation, non-relapse mortality, and disease recurrence. A targeted dosing strategy was established based on ATG concentration monitoring and conducted a phase 2 trial to evaluate the safety and efficacy of the dosing strategy in adult unmanipulated haplo-PBSCT, a encouraging result was attained. In this trial, The ATG-targeted dosing strategy was extended to adult unrelated donor allogeneic hematopoietic stem cell transplantation, ATG was administered for 4 days (-5 days to -2 days) during conditioning. The ATG doses on-3 days and- 2days were adjusted by our dosing strategy to achieve the optimal ATG exposure. The primary endpoint was CMV reactivation on +180 days.
Detailed description
Allogeneic hematopoietic cell transplantation(allo-HCT) is a curative therapy for hematological disorders and the ATG is commonly used as prophylaxis for GVHD. Previous studies have indicated that there is an optimal dosage for ATG administration, if the dosage is too high, it may affect engraftment and increase the risk of infection and relapse, whereas an inadequate dosage may increase the risk of acute or chronic GVHD, there is still controversy about the optimal dose of ATG, its pharmacologic effects on clinical outcomes of HSCT are associated with donor source, human leukocyte antigen (HLA) disparity, conditioning intensity, and GVHD prophylaxis, so although has been investigated for decades, the optimal dosage of ATG in allogeneic hematopoietic stem cell transplantation remains undetermined.
ATG exerts pharmacologic effects in its active form upon binding to lymphocytes, and its exposure is presented as the area under the concentration-time curve (AUC). To obtain plasma active ATG concentrations, investigators developed an active ATG concentration detection method based on flow-cytometry with HUT-78 T-cells. In previous study, investigators quantified active ATG exposure in 106 haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) recipients, who received a conventional fixed dose of 10 mg/kg ATG during conditioning, the optimal concentration range of active ATG-AUC was determined through the application of machine learning methods, was found to be 100-148.5 × 10^3 UE·d/L. This concentration range was associated with a reduction in CMV/EBV reactivation, without an increase in acute GVHD or malignant disease relapse. Mathematical function was then exploited to determine the total targeted ATG dose on -3days to -2days based on concentrations of active ATG on -5daysto -4days. Based on this function, a dosing strategy was established that aimed to maintain the active ATG-AUC within the optimal range. To validate this individualized dosing strategy, investigators conducted a single-arm, phase 2 trial, demonstrating that this strategy could reduce CMV/EBV reactivation and improve survival without increasing the incidence of GVHD after haplo-PBSCT. Given the similarity between unrelated donor hematopoietic stem cell transplantation (URD-HSCT) and haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in terms of conditioning regimens, GVHD prophylaxis, and supportive therapies, as well as the conventional fixed dose of 10mg/kg employed in both settings, investigators have designed and conducted a single-center, prospective, single-arm clinical trial. The aim of this trial is to translate the individualized ATG dosing strategy, which was originally developed based on ATG concentration monitoring in haplo-HSCT patients, to URD-HSCT, with the goal of further validating its effectiveness.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| targeted dosing ATG cohort | Experimental | Drug: individualized ATG dosing strategyThe targeted dosing ATG cohort received the same dose of medication at -5 days and -4 days as the traditional administration method (-5days, 1.5mg/kg; -4days 2.5mg/kg), Two individual doses were given on -3days and day -2days according to the dose adjustment strategy. |
Who may qualify
- Ages
- 14 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- Patients with malignant hematological tumors who have indications for allogeneic hematopoietic stem cell transplantation.
- HLA-matched unrelated donor
- Patient age ≥14 years old and ≤65 years old
- ALT and AST ≤ 2.5 times the upper limit of normal values, bilirubin ≤ 2 times the upper limit of normal values
- Creatinine ≤ high limit of normal value
Key exclusion criteria (5 listed)
- Unrelated donor who is not HLA matched
- No indication for allogeneic hematopoietic stem cell transplantation
- Patient age <14 years old or >65 years old
- The donor or recipient are pregnant
- Suffering from mental illness or other conditions and being unable to proceed as planned
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 |
|---|---|---|
| individualized ATG dosing strategyInvestigators quantified active ATG exposure in 106 haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) recipients, who received a conventional fixed dose of 10 mg/kg ATG during conditioning, the optimal concentration range of active ATG-AUC was determined through the application of machine learning methods, was found to be 100-148.5 × 10^3 UE·d/L. This concentration range was associated with a reduction in CMV/EBV reactivation, without an increase in acute GVHD or malignant disease relapse. Mathematical function was then exploited to determine the total targeted ATG dose on -3days to -2days based on concentrations of active ATG on -5daysto -4days. Based on this function, investigators established a dosing strategy that aimed to maintain the active ATG-AUC within the optimal range. | Drug | targeted dosing ATG cohort |
Primary outcome
cumulative incidence of CMV reactivation
Time frame: 0Day-180Days
The primary endpoint was the cumulative incidence of CMV reactivation on +180 days after transplantation.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Dec 2024.
- Derived from this study: PubMed 41624481Chen S, Wang L, Luan S, Wang H, Du J, Ge D, Li F, Wu Y, Gu Z, Dou L, Liu D. Reduced cytomegalovirus reactivation and viremia without increasing GVHD after URD-PBSCT: A prospective study using targeted ATG dosing strategy. Cancer Pathog Ther. 2025 Apr 5;4(2):145-152. doi: 10.1016/j.cpt.2025.04.001. eCollection 2026 Mar.
- Individual participant dataSharing planned: No
Related trials for Cytomegalovirus Infections
RecruitingObservational study
The Natural History of Severe Viral Infections and Characterization of Immune Defects in Patients Without Known Immunocompromise
EBV, HSV
RecruitingPhase 2
Virus Specific Cytotoxic T-Lymphocytes (CTLs) for Refractory Cytomegalovirus (CMV)
Cytomegalovirus Infections, Primary Immune Deficiency Disorder
RecruitingPhase 2
CMV-MVA Triplex Vaccination in HLA-Matched Related Stem Cell Donors for the Prevention of CMV Infection in Patients Undergoing Hematopoietic Stem Cell Transplant
Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia
Active, not recruitingObservational study
Infection Prophylaxis and Management in Treating Cytomegalovirus (CMV) Infection in Patients With Hematologic Malignancies Previously Treated With Donor Stem Cell Transplant
Hematopoietic/Lymphoid Cancer, Accelerated Phase Chronic Myelogenous Leukemia
Not yet recruitingEarly Phase 1
25BT056: Basket Study of Viral Cytotoxic T Lymphocytes
EBV Viremia, CMV Viremia
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.
diahong Liu, MD principal investigator
The First Medical Center of Chinese PLA General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing individualized ATG dosing strategy in people with Cytomegalovirus Infections and Infection Reactivation, run by Chinese PLA 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 8 inclusion and 5 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: looking for participants now, as of the sponsor's last update on 3 Dec 2024. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Sheng Chen, master (15101156205, csto301@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
cumulative incidence of CMV reactivation (time frame: 0Day-180Days). 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 NCT06572462, which also lists 1 linked publication.
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 3 Dec 2024.