[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100653867":3},{"organization":4,"outcomesModule":7,"designInfo":49,"detailedDescription":55,"studyPopulation":48,"armGroups":56,"interventions":63,"overallOfficials":69,"centralContacts":73,"locations":78,"responsibleParty":97,"collaborators":48,"id":100,"slug":101,"hasResults":102,"nctId":103,"briefTitle":104,"officialTitle":105,"acronym":48,"eligibilityCriteria":106,"healthyVolunteers":102,"sex":107,"minAge":108,"maxAge":109,"enrollmentInfo":110,"targetDuration":48,"studyType":113,"phases":114,"briefSummary":116,"conditions":117,"keywords":48,"overallStatus":80,"whyStopped":48,"lastUpdateSubmitDate":119,"lastUpdatePostDateStruct":120,"startDateStruct":123,"completionDateStruct":125,"leadSponsor":127,"locationsCount":128},{"fullName":5,"class":6},"Chinese PLA General Hospital","OTHER",{"primaryOutcomes":8,"secondaryOutcomes":13,"otherOutcomes":48},[9],{"measure":10,"description":11,"timeFrame":12},"1-year GVHD-free and relapse-free survival rate(1-year-GRFS)","GRFS is defined as the time from randomization to the first occurrence of grade III-IV acute GVHD, chronic GVHD requiring systemic immunosuppressive therapy, or death due to disease relapse, whichever occurs first. The cumulative incidence of GRFS will be estimated using the Fine-Gray competing risk model.","1 year after treatment",[14,18,22,26,29,32,36,39,42,45],{"measure":15,"description":16,"timeFrame":17},"+180 days CMV virus reactivation rate","+180 days CMV virus reactivation rate refers to the time from randomization to CMV virus reactivation, relapse or death within 180 days post-transplant. The actual incidence rate is calculated as the number of patients with events \u002F total number of cases × 100%.","180 days post-transplant",{"measure":19,"description":20,"timeFrame":21},"Acute GVHD incidence","Acute GVHD incidence refers to the time from randomization to acute GVHD onset, relapse or death within 100 days post-transplant. The actual incidence rate is calculated as the number of patients with events \u002F total number of cases × 100%.","100 days post-transplant",{"measure":23,"description":24,"timeFrame":25},"disease free survival (DFS)","Disease free survival (DFS) refers to the time from treatment to the first lymphoma recurrence.","1 years after treatment",{"measure":27,"description":28,"timeFrame":25},"Cumulative incidence of relapse (CIR)","Cumulative incidence of relapse (CIR) refers to the number of patients with hematologic or MRD relapse from randomization to the last follow-up.",{"measure":30,"description":31,"timeFrame":25},"Cumulative non-relapse mortality (NRM)","Cumulative non-relapse mortality (NRM) refers to death due to non-relapse causes while in complete remission (CR), measured as the number of patients with NRM from randomization to the last follow-up.",{"measure":33,"description":34,"timeFrame":35},"PTLD cumulative incidence","Treatment-related safety indicator: cumulative incidence of post-transplant lymphoproliferative disorder (PTLD) from randomization to the last follow-up.","[Time Frame: 1 year after treatment]",{"measure":37,"description":38,"timeFrame":17},"+180 days EBV virus reactivation rate","The +180-day EBV virus reactivation rate refers to the time from randomization to EBV virus reactivation, relapse, or death within 180 days post-transplant. The actual incidence rate is calculated as the number of patients with events \u002F total number of cases × 100%.",{"measure":40,"description":41,"timeFrame":35},"Chronic GVHD cumulative incidence","Treatment-related safety indicator: cumulative incidence of chronic graft-versus-host disease (chronic GVHD) from randomization to the last follow-up.",{"measure":43,"description":44,"timeFrame":25},"Immune reconstitution status","Immune reconstitution status refers to the actual incidence rate calculated as the number of patients with immune reconstitution \u002F total number of cases × 100% from randomization to the last follow-up.",{"measure":46,"description":47,"timeFrame":12},"Overall Survival (OS)","Overall survival (OS) refers to death from any cause from randomization to the last follow-up. The 1-year OS rate is estimated using the Kaplan-Meier method, calculated as the proportion of patients alive at 1 year after treatment; patients lost to follow-up are censored at the date of last contact.",null,{"allocation":50,"interventionModel":51,"interventionModelDescription":48,"primaryPurpose":52,"observationalModel":48,"timePerspective":48,"maskingInfo":53},"NA","SINGLE_GROUP","TREATMENT",{"masking":54,"maskingDescription":48,"whoMasked":48},"NONE","Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) has demonstrated remarkable clinical efficacy in treating hematologic malignancies and has become the primary allogeneic transplantation modality in China. However, graft-versus-host disease (GVHD) remains a critical complication that significantly reduces early survival and long-term quality of life (QoL). GVHD not only severely suppresses immune function but also presents challenges in treatment, including complexity, high costs, prolonged duration, and limited efficacy. Therefore, optimizing GVHD prevention strategies offers greater clinical value than expanding treatment options, as it effectively reduces acute and chronic GVHD incidence and improves overall survival (OS) and long-term QoL.\n\nAnti-thymocyte globulin (ATG), a polyclonal immunosuppressant, is widely used in related haplo-HSCT. The conventional high-dose rabbit ATG (Thymoglobulin, 10 mg\u002Fkg) effectively promotes engraftment and prevents fatal GVHD but significantly increases the risk of severe viral infections (e.g., CMV, EBV) and may increase relapse rates due to excessive immunosuppression weakening the graft-versus-leukemia (GVL) effect. Dose reduction studies have shown trade-offs: lowering ATG from 10 mg\u002Fkg to 6 mg\u002Fkg reduced infections but increased severe acute GVHD from 4.5% to 16.1%; a 7.5 mg\u002Fkg regimen lowered severe acute GVHD to 7.9% but with significantly higher viral reactivation.\n\nThe area under the concentration-time curve (AUC) better reflects ATG exposure than single pharmacokinetic (PK) parameters. The investigators established an ATG-AUC assay and analyzed 106 haplo-HSCT patients receiving uniform 10 mg\u002Fkg ATG, revealing substantial inter-individual AUC variability. Some patients had ATG-AUC above or below the optimal exposure window. Modeling of over 1,000 concentration samples (2022) identified the optimal ATG-AUC range as 100-148.5 IU\u002Fday\u002FmL. A targeted individualized dosing technique was developed (2023) and validated in a prospective single-arm trial (2024), showing that individualized dosing achieved more patients within or closer to the optimal AUC range compared to fixed dosing. This approach improved post-transplant CD4+ T-cell immune reconstitution, reduced viral reactivation risk without increasing GVHD, and improved long-term survival and QoL.\n\nThe next step involves statistical modeling and clinical validation of clinical-biologic parameters (body weight, age, body surface area, lymphocyte count at infusion, graft T-cell count, HLA matching degree) with ATG-AUC from 94 patients to develop a predictive model for individualized ATG dosing. A prospective, single-arm clinical study will be conducted to validate the safety and efficacy of population PK-guided targeted ATG dosing in haplo-HSCT, including the optimal AUC attainment rate (100-148.5 IU\u002Fday\u002FmL). Outcomes to be observed include GVHD-free, relapse-free survival (GRFS), viral reactivation rate, acute\u002Fchronic GVHD incidence, treatment-related mortality (TRM), disease-free survival (DFS), OS, and immune reconstitution. The goal is to establish the optimal ATG regimen for haplo-HSCT to improve survival and QoL.",[57],{"label":58,"type":59,"description":60,"interventionNames":61},"Treatment","EXPERIMENTAL","PK-guided ATG dosing",[62],"Drug: Anti Thymocyte Globulin",[64],{"type":65,"name":66,"description":67,"armGroupLabels":68,"otherNames":48},"DRUG","Anti Thymocyte Globulin","Population pharmacokinetic formula-guided targeted ATG dosing plus classical GVHD prophylaxis regimen",[58],[70],{"name":71,"affiliation":5,"role":72},"Dai-Hong Liu, director","STUDY_CHAIR",[74],{"name":71,"role":75,"phone":76,"phoneExt":48,"email":77},"CONTACT","86-010-66937232","daihongrm@163.com",[79],{"facility":5,"status":80,"city":81,"state":82,"zip":83,"country":84,"countryCode":85,"cosmosGeoPoint":86,"geoPoint":91,"contacts":92},"RECRUITING","Beijing","Beijing Municipality","100853","China","CN",{"type":87,"coordinates":88},"Point",[89,90],116.39723,39.9075,{"lat":90,"lon":89},[93,95],{"name":94,"role":75,"phone":76,"phoneExt":48,"email":77},"Li-ping Dou, Dr.",{"name":71,"role":96,"phone":48,"phoneExt":48,"email":48},"PRINCIPAL_INVESTIGATOR",{"type":96,"investigatorFullName":98,"investigatorTitle":99,"investigatorAffiliation":5,"oldNameTitle":48,"oldOrganization":48},"Daihong Liu","director","100653867","phase-2-population-pk-guided-atg-dosing-in-haplo-hsct-100653867",false,"NCT07791576","Population PK-guided ATG Dosing in Haplo-HSCT","Pharmacokinetic Guided ATG Targeted Dosing Strategy in Unmanipulated Haploidentical Haematopoietic Stem-cell Transplantation","Inclusion Criteria:\n\n1. Patients with indications for allogeneic hematopoietic stem cell transplantation, with malignant hematologic diseases in CR1 or CR2 before transplantation.\n2. Have an HLA-matched sibling, unrelated, or haploidentical donor.\n3. Age ≥ 14 years and ≤ 65 years.\n4. Liver function: ALT and AST ≤ 2.5 × upper limit of normal, bilirubin ≤ 2 × upper limit of normal.\n5. Renal function: creatinine ≤ upper limit of normal.\n6. No uncontrolled infection or severe mental or psychological disorders.\n7. ECOG performance status score of 0-2.\n8. Signed informed consent.\n\nExclusion Criteria:\n\n1. No HLA-matched donor.\n2. Malignant hematologic disease in CR3 or higher disease stage, or refractory\u002Frelapsed status，or second transplantation.\n3. Patient age \\\u003C 14 years or \\> 65 years.\n4. Pregnancy of either the donor or the recipient.\n5. Presence of mental illness or other conditions that preclude compliance with the protocol.","ALL","14 Years","65 Years",{"count":111,"type":112},63,"ESTIMATED","INTERVENTIONAL",[115],"PHASE2","To evaluate the safety and efficacy of a population pharmacokinetics (PK)-guided targeted ATG dosing strategy in haploidentical stem cell transplantation and to observe the GVHD-free, relapse-free survival (GRFS) in the cohort receiving this strategy.",[118],"Hematopoietic Stem Cell Transplantation","2026-08-27",{"date":121,"type":122},"2026-08-28","ACTUAL",{"date":124,"type":122},"2025-05-10",{"date":126,"type":112},"2027-12-30",{"name":5,"class":6},1]