[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"trial:NCT06315309":3,"trial-entities:NCT06315309":93,"trial-summary:NCT06315309":110},{"id":4,"nct_id":4,"org_study_id":5,"brief_title":6,"official_title":7,"overall_status":8,"completion_date":9,"status_verified_date":10,"last_update_date":11,"start_date":12,"sponsor_name":13,"lead_sponsor_class":14,"has_dmc":15,"brief_summary":16,"detailed_description":17,"conditions":18,"keywords":23,"study_type":26,"primary_purpose":27,"phases":28,"enrollment_info":30,"interventions":33,"primary_outcomes":40,"secondary_outcomes":45,"sex":46,"minimum_age":47,"maximum_age":48,"healthy_volunteers":49,"eligibility_criteria":50,"std_ages":56,"locations":58,"central_contacts":82,"overall_officials":90,"references":91,"see_also_links":92},"NCT06315309","IRB-300012281 (UAB 23146)","Trial of 2 Step ATG for Acute GVHD Prevention Post Myeloablative Allogeneic Stem Cell Transplant","Phase II Clinical Trial of 2 Step ATG Combined With Tacrolimus and Mini Methotrexate for Prevention of Acute GVHD Post Myeloablative Allogeneic Stem Cell Transplant","RECRUITING","2027-05","2025-10","2025-10-08","2025-04-15","University of Alabama at Birmingham","OTHER",true,"The purpose of this study is to test whether the combination of the drugs called tacrolimus (Tac), methotrexate (MTX) and new dosing strategy of another drug called (rabbit Anti-thymocyte Globulin \\[ATG\\]) will help prevent the development and\u002For improve severity of acute and\u002For chronic GVHD.","The goal is to study the effectiveness and drug levels of new dosing strategy of ATG (GVHD preventing medicine) in preventing graft versus host disease post allogeneic stem cell transplantation.\n\nIn an effort to reduce graft versus host disease (GVHD) and enhance graft versus leukemia (GVL) effect post allogenic hematopoietic stem cell transplantation (AHSCT), recent research has focused on host immune cell depletion. Frame shifting anti-thymocyte globulin (ATG) backwards to earlier days before days 0 can result in deeper host and less graft T-cell depletion, leading to better immune reconstitution. Preliminary data where 80% of the ATG dose is given on days -6,-5,-4 and 20% given on day -1, showed effective prevention of severe acute GVHD, chronic GVHD and favorable early immune reconstitution. We hypothesize that our 2 step ATG dosing platform when combined with standard tacrolimus and mini methotrexate in a myeloablative setting can prevent grade III-IV acute GVHD and chronic GVHD, resulting in improvement of GVHD\u002Frelapse free survival at one year post transplant.\n\nThis study aims to:\n\n1. Confirm the effectiveness of ATG based GVHD prevention regimen based on the encouraging clinical outcomes observed above.\n2. Examine ATG blood levels pre and post-transplant to evaluate any possible correlation between ATG levels and its ability to protect from GVHD.\n3. Examine post-transplant immune cell recovery as part of routine post-transplant immune monitoring at UABMC.",[19,20,21,22],"GVHD,Acute","Acute Leukemia","Myelodysplastic Syndromes","Myeloproliferative Disorders",[24,25,22],"Leukemia","Myelodysplastic Syndrome","INTERVENTIONAL","TREATMENT",[29],"PHASE2",{"count":31,"type":32},29,"ESTIMATED",[34],{"type":35,"name":36,"description":37,"armGroupLabels":38},"DRUG","ATG Combined with Tacrolimus and Mini Methotrexate","On Day -7, subjects will be admitted to the hospital and receive a dose of prednisone at 1 mg\u002Fkg (ATG premedication). Subjects will receive a steroid injection 3 hours before every ATG infusion. On day -6, subjects will receive a small dose of ATG as an IV infusion. ATG will be repeated on days -5,-4 and -1. Routine transplant chemotherapy agent fludarabine will be given on days -6 to -2 as daily IV infusions. Busulfan, a routine transplant chemotherapy will be given on days -5 to -2 as IV infusion. Subjects with lymphoblastic leukemia will receive an alternative regimen of cyclophosphamide, a routine chemotherapy on days -6 and -5, followed by total body radiation on days -3 to -1. Tacrolimus (standard immune suppression agent) starts on day -3 as continuous IV infusion and switched to oral after engraftment. Methotrexate a standard immune suppression medication which is given IV on day +1,+3,+6, and +11 post-transplant. Blood draws on days -4,-1,+3,+7,+14 to measure ATG levels.",[39],"phase II single arm study of 2 step ATG dosing in prevention of aGVHD.",[41],{"measure":42,"description":43,"timeFrame":44},"To estimate the therapeutic success of 2-step ATG dosing platform in patients undergoing reduced intensity allogeneic transplantation for treatment of hematologic malignances","Rate of GRFS (graft versus host disease GVHD, relapse free survival) at one year post transplant. To meet that end point the patient needs to be alive without relapse, or grade III-IV acute GVHD, or chronic GVHD requiring systemic immune suppression.","1 year post transplant",[],"ALL","18 Years","60 Years",false,{"inclusion":51,"exclusion":54,"raw_text":55},[52,53],"B-cell ALL: High white blood cell count at diagnosis (ie, \\>30,000\u002Fµl), Clonalcytogenetic abnormalities - t(4;11), t(1;19), t(9;22), or BCR-ABL gene positivity, BCR-ABL1-like (Ph-like) gene signature, progenitor-B cell immunophenotype (eg, blasts expressing membrane CD19, CD79a, and cytoplasmic CD22, but not CD10), Length of time from start of induction therapy to attainment of CR greater than four weeks, and minimal residual disease (MRD) post-remission bone marrow MRD+.(Akabane \\& Logan, 2020; Lafage-Pochitaloff et al., 2017)","T-cell ALL: Failure to achieve CR after one induction, MRD\\> 1X 10-4 after 2 courses of induction, Presenting WBC \\> 100 X 109\u002FL, complex cytogenetics ≥5,early T-cell Precursor ALL, poor risk genetics including lack of NOTCH1 ith\u002FFBXW7 or presence of N-RAS \\& K-RAS, EZH2 and age\\>40 years.(Marks \\& Rowntree, 2017) G- ALL in \\>CR1 12. The subject is willing and able to sign informed consent and abide by the protocol requirements.",[],"Inclusion Criteria:\n\n1. Adult male or female, age 18-60 years\n2. Patients must have a related or unrelated peripheral blood stem cell donor. Sibling donor must be a 6\u002F6 match for HLA-A and -B at intermediate (or higher) resolution, and -DRB1 at high resolution using DNA-based typing, and must be willing to donate peripheral blood stem cells and meet institutional criteria for donation. Unrelated donor must be 8\u002F8 match at HLA-A, -B, -C and -DRB1 at high resolution using DNA-based typing. Unrelated donor must be willing to donate peripheral blood stem cells and be medically eligible to donate stem cells according to NMDP criteria.\n3. A candidate for Myeloablative preparative regimen, based on age ≤ 60, or HCT-CI of ≤ 4, and considered by the treating physician to be a candidate for such regimen.\n4. Cardiac function: Ejection fraction ≥ 45%\n5. Calculated creatinine clearance greater than 50 mL\u002Fminute (using the Cockcroft-Gault formula and actual body weight).\n6. Pulmonary function: DLCO ≥50% (adjusted for hemoglobin) and FEV1≥50%\n7. Liver function: total bilirubin \\\u003C 1.5x the upper limit of normal and ALT\u002FAST \\\u003C 2.5x the upper normal limit. Patients who have been diagnosed with Gilbert's Disease are allowed to exceed the defined bilirubin value up to \\\u003C3mg\u002Fdl.\n8. Female subjects (unless postmenopausal for at least 1 year before the screening visit, or surgically sterilized), agree to practice two effective methods of contraception (hormonal contraception and male partner to use condom) or agree to complete abstain from heterosexual intercourse from the time of signing the informed consent through 12 months post-transplant.\n9. Male subjects (even if surgically sterilized), of partners of women of childbearing potential must agree to practice effective barrier contraception or abstain from heterosexual intercourse from the time of signing the informed consent through 12 months post-transplant.\n10. Karnofsky performance status KPS ≥ 80 (Appendix B)\n11. Patients must have a diagnosis of one of the following:\n\n    A-Acute myeloid leukemia (AML) in complete remission CR 1 with intermediate or high risk for relapse as defined by ELN 2022 criteria(Dohner et al., 2022) (appendix C), or deemed to be at high risk for relapse by treating physician, based on, therapy related, or extra medullary presentation.\n\n    B-AML in \\>CR1. C-Myelodysplastic syndrome (MDS) with IPSS-M ≥ intermediate-low.(Bernard et al., 2022; Mohty et al., 2022) D- Chronic myeloproliferative disorder (ET, PV, myelofibrosis) with bone marrow blasts \\> 5% and\u002For other evidence of progression to acute leukemia or Int or high-risk disease by MIPPS v2 score.(Ali et al., 2019; Guglielmelli et al., 2018) E- CMML especially those with high-risk features based in: The CMML-specific prognostic scoring system with molecular features (CPSS-Mol) - high risk and intermediate-2 risk, Mayo molecular model - high risk and Intermediate-2 risk, Groupe Francophone des Myélodysplasies (GFM) - high risk and selected patients with intermediate risk.(Elena et al., 2016; Itzykson et al., 2013; Patnaik et al., 2014). F- Acute lymphoblastic leukemia (ALL) in CR1 with high risk for relapse\n    * B-cell ALL: High white blood cell count at diagnosis (ie, \\>30,000\u002Fµl), Clonalcytogenetic abnormalities - t(4;11), t(1;19), t(9;22), or BCR-ABL gene positivity, BCR-ABL1-like (Ph-like) gene signature, progenitor-B cell immunophenotype (eg, blasts expressing membrane CD19, CD79a, and cytoplasmic CD22, but not CD10), Length of time from start of induction therapy to attainment of CR greater than four weeks, and minimal residual disease (MRD) post-remission bone marrow MRD+.(Akabane \\& Logan, 2020; Lafage-Pochitaloff et al., 2017)\n    * T-cell ALL: Failure to achieve CR after one induction, MRD\\> 1X 10-4 after 2 courses of induction, Presenting WBC \\> 100 X 109\u002FL, complex cytogenetics ≥5,early T-cell Precursor ALL, poor risk genetics including lack of NOTCH1 ith\u002FFBXW7 or presence of N-RAS \\& K-RAS, EZH2 and age\\>40 years.(Marks \\& Rowntree, 2017) G- ALL in \\>CR1\n12. The subject is willing and able to sign informed consent and abide by the protocol requirements.\n\nExclusion Criteria:\n\n1. Autologous hematopoietic stem cell transplant \\\u003C 3 months prior to enrollment.\n2. Patients with florid residual AML with \\> 5% blast in the marrow or circulating blast in the peripheral blood are not eligible for this study.\n3. Previous allogeneic stem cell transplant.\n4. Uncontrolled angina, severe uncontrolled ventricular arrhythmias, or EKG suggestive of acute ischemia or active conduction system abnormalities.\n5. Known hypersensitivity to the study agent (ATG)\n6. Received any investigational drugs within the 14 days prior to the first day of transplant conditioning\n7. Pregnant and\u002For breastfeeding\n8. Evidence of HIV infection or known HIV positive serology.\n9. Current uncontrolled bacterial, viral or fungal infection (currently taking medication with evidence of progression of clinical symptoms or radiologic findings).\n10. Non-hematologic malignancy within prior three (3) years, with the exception of squamous cell or basal cell skin carcinoma.\n11. Participation in another clinical study with an investigational product during the last 28 days.",[57],"ADULT",[59],{"facility":13,"status":8,"city":60,"state":61,"zip":62,"country":63,"contacts":64,"geoPoint":79},"Birmingham","Alabama","35294","United States",[65,68,71,73,75,77],{"name":66,"role":67},"Zaid S Al Kadhimi, MD","PRINCIPAL_INVESTIGATOR",{"name":69,"role":70},"Manuel Espinoza-Gutarra, MD","SUB_INVESTIGATOR",{"name":72,"role":70},"Omer Jamy, MD",{"name":74,"role":70},"Donna Salzman, MD",{"name":76,"role":70},"Razan Mohty, MD",{"name":78,"role":70},"Lauren Shea, MD",{"lat":80,"lon":81},33.52066,-86.80249,[83,87],{"name":66,"role":84,"phone":85,"email":86},"CONTACT","205-975-1269","zsalkadhimi@uabmc.edu",{"name":88,"role":84,"email":89},"Margaret A Thomas, MPH","margaretannthomas@uabmc.edu",[],[],[],{"nct_id":4,"conditions":94,"biomarkers":99},[95,96,97,25,98],"Acute Lymphoblastic Leukemia","Acute Myeloid Leukemia","Chronic Myelomonocytic Leukemia","Myeloproliferative disorder",[100,101,102,103,104,105,106,107,108,109],"BCR\u002FABL1 Fusion Gene","F-Box\u002FWD Repeat-Containing Protein 7","GTPase KRas","Histone-Lysine N-Methyltransferase EZH2","HLA-A Gene","HLA-B Gene","HLA-C Gene","HLA-DRB1 Gene","NOTCH1 Gene","NRAS wt Allele",{"nct_id":4,"found":15,"summary":111,"prompt_version":121},{"design":112,"status":113,"heading":114,"summary":115,"follow_up":116,"word_count":117,"commitments":118,"compensation":119,"drugs_mentioned":120},"This interventional study plans to enroll 29 participants. The phase of the study is not specified.","completed","Study of 2-Step ATG for GVHD Prevention After Stem Cell Transplant","This study is testing a new way to give a drug called rabbit Anti-thymocyte Globulin (ATG) along with tacrolimus (Tac) and methotrexate (MTX). The goal is to see if this combination can better prevent or reduce the severity of acute (sudden and severe) and chronic (long-lasting) Graft-versus-Host Disease (GVHD) after an allogeneic stem cell transplant. GVHD is a complication where the new immune cells from the donor attack the patient's body. The study is looking to see if this treatment is successful in preventing severe GVHD and improving survival one year after transplant. You may be able to join if you are between 18 and 60 years old and need a stem cell transplant for certain blood cancers like acute leukemia or myelodysplastic syndromes, and have a suitable donor.","The study will measure therapeutic success at one year post transplant.",129,"On Day -7, you would be admitted to the hospital and receive prednisone. You would also receive a steroid injection before each ATG infusion, with a small dose of ATG given on Day -6.","Not stated in the trial record.",[],"v2"]