[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"trial:NCT07634536":3,"trial-entities:NCT07634536":132,"trial-summary:NCT07634536":140},{"id":4,"nct_id":4,"org_study_id":5,"brief_title":6,"official_title":6,"overall_status":7,"completion_date":8,"status_verified_date":9,"last_update_date":10,"start_date":11,"sponsor_name":12,"lead_sponsor_class":13,"has_dmc":14,"brief_summary":15,"detailed_description":16,"conditions":17,"keywords":21,"study_type":22,"primary_purpose":23,"phases":24,"enrollment_info":26,"interventions":29,"primary_outcomes":58,"secondary_outcomes":67,"sex":87,"minimum_age":88,"maximum_age":89,"healthy_volunteers":14,"eligibility_criteria":90,"std_ages":105,"locations":108,"central_contacts":125,"overall_officials":128,"references":130,"see_also_links":131},"NCT07634536","IRB-86777","Automated Total Marrow and Lymphoid Irradiation for Allogeneic Hematopoietic Cell Transplant","NOT_YET_RECRUITING","2028-08","2026-06","2026-06-09","2026-08","Stanford University","OTHER",false,"Intensive conditioning regimens used in allogeneic hematopoietic cell transplant (HCT) help to eliminate hematologic tumors and reduce the risk of relapse, but are also characterized by high toxicity. Total marrow and lymphoid irradiation (TMLI) is a specialized radiation technique that specifically targets marrow and lymphoid tissue to maximize antitumor efficacy while reducing off target toxicity. Despite these benefits, TMLI is technically challenging and time consuming. The radiation oncology team at Stanford has developed an automated TMLI platform to overcome these challenges. In this phase II trial, automation will be incorporated into a previously validated conditioning regimen of fludarabine\u002Fcyclophosphamide\u002FTMLI HCT with post-transplant cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis to confirm the feasibility and safety of automation in patients receiving allogeneic HCT for high-risk myeloid malignancies.",null,[18,19,20],"Acute Myeloid Leukemia","Myeloproliferative Neoplasm","Myelodysplastic Syndromes",[],"INTERVENTIONAL","TREATMENT",[25],"PHASE2",{"count":27,"type":28},30,"ESTIMATED",[30,37,42,46,51,55],{"type":31,"name":32,"description":33,"armGroupLabels":34},"RADIATION","VMAT-Based Total Marrow and Lymphoid Irradiation (TMLI)","Patients receive VMAT-based TMLI with daily image-guided radiation therapy (IGRT) for treatment localization and verification prior to radiation delivery.",[35,36],"Cohort A: Total Marrow and Lymphoid Irradiation (TMLI) 200 cGy BID Conditioning Regimen","Cohort B: Total Marrow and Lymphoid Irradiation 150 cGy BID Conditioning Regimen",{"type":38,"name":39,"description":40,"armGroupLabels":41},"DRUG","Fludarabine","Fludarabine 25 mg\u002Fm² IV administered daily on Days -7 through -3.",[35,36],{"type":38,"name":43,"description":44,"armGroupLabels":45},"Cyclophosphamide","Cyclophosphamide 14.5 mg\u002Fkg IV on Days -7 and -6 as part of conditioning and 50 mg\u002Fkg IV on Days +3 and +4 as post-transplant GVHD prophylaxis.",[35,36],{"type":47,"name":48,"description":49,"armGroupLabels":50},"BIOLOGICAL","Allogeneic Peripheral Blood Stem Cell Transplantation (PBSCT)","Allogeneic peripheral blood stem cell transplantation administered on Day 0.",[35,36],{"type":38,"name":52,"description":53,"armGroupLabels":54},"Mycophenolate mofetil (MMF)","Mycophenolate mofetil initiated on Day +5 and continued through Day +35 for GVHD prophylaxis.",[35,36],{"type":38,"name":56,"description":53,"armGroupLabels":57},"Tacrolimus",[35,36],[59,63],{"measure":60,"description":61,"timeFrame":62},"Non-Relapse Mortality (NRM)","Death without prior disease relapse following allogeneic peripheral blood stem cell transplantation.","Day 100 after transplantation",{"measure":64,"description":65,"timeFrame":66},"Neutrophil Engraftment","Neutrophil engraftment following allogeneic peripheral blood stem cell transplantation.","Through Day 100 after transplantation",[68,72,75,78,81,84],{"measure":69,"description":70,"timeFrame":71},"Risk of Relapse","Disease relapse following allogeneic peripheral blood stem cell transplantation.","Day 100 post-transplant",{"measure":73,"description":74,"timeFrame":71},"Disease-Free Survival (DFS)","Disease-free survival following allogeneic peripheral blood stem cell transplantation.",{"measure":76,"description":77,"timeFrame":71},"Overall Survival (OS)","Overall survival following allogeneic peripheral blood stem cell transplantation.",{"measure":79,"description":80,"timeFrame":71},"Incidence of Grade II-IV Acute Graft-versus-Host Disease (GVHD)","Incidence and severity of Grade II-IV acute graft-versus-host disease following allogeneic peripheral blood stem cell transplantation.",{"measure":82,"description":83,"timeFrame":71},"Incidence of Grade III-IV Acute Graft-versus-Host Disease (GVHD)","Incidence and severity of Grade III-IV acute graft-versus-host disease following allogeneic peripheral blood stem cell transplantation.",{"measure":85,"description":86,"timeFrame":71},"Bearman Regimen-Related Toxicity","Regimen-related toxicity assessed using the Bearman Toxicity Scale. Toxicity will be evaluated by organ system and graded according to severity (Grades I-IV).","ALL","18 Years","70 Years",{"inclusion":91,"exclusion":103,"raw_text":104},[92,93,94,95,96,97,98,99,100,101,102],"Age 18 to 60 years (inclusive)","HCT Co-Morbidity score (HCT-CI) \\\u003C 5 (http:\u002F\u002Fwww.qxmd.com\u002Fcalculate-online\u002Fhematology\u002Fhct-ci)(31)","Adequate performance status is defined as Karnofsky score ≥ 70%","Patients must be receiving an allogeneic peripheral blood stem cell graft","Patients and selected donor must be HLA typed at high resolution using DNA based typing at the following HLA-loci: HLA-A, -B, -C and DRB1. Donors may be an 8\u002F8 matched sibling donor, 8\u002F8 matched unrelated donor, haploidentical related donor, or 7\u002F8 mismatched unrelated donor. 2. Eligible Diseases (Any one of the following)","Blasts \\>5% in the peripheral blood and\u002For bone marrow after \\>2 prior lines of AML directed therapy, present during the trial screening window","Adverse plus risk by AlloHCT Refined ELN Criteria: defined as having complex cytogenetics, TP53 mutation, or MECOM rearrangement confirmed at any time point.(32)","Blasts \\>10% in the peripheral blood and\u002For bone marrow after \\>1 prior line of therapy.","TP53 mutation confirmed at any time point","Blasts \\>10% in the peripheral blood and\u002For bone marrow during the trial screening window","TP53 mutation confirmed at any time point 3. Adequate organ function is defined as all of the following:",[],"Inclusion Criteria for 20 Gy Arm (Cohort A)\n\n1. Age, Performance Status, and Graft Criteria require all of the following bullet points:\n\n   * Age 18 to 60 years (inclusive)\n   * HCT Co-Morbidity score (HCT-CI) \\\u003C 5 (http:\u002F\u002Fwww.qxmd.com\u002Fcalculate-online\u002Fhematology\u002Fhct-ci)(31)\n   * Adequate performance status is defined as Karnofsky score ≥ 70%\n   * Patients must be receiving an allogeneic peripheral blood stem cell graft\n   * Patients and selected donor must be HLA typed at high resolution using DNA based typing at the following HLA-loci: HLA-A, -B, -C and DRB1. Donors may be an 8\u002F8 matched sibling donor, 8\u002F8 matched unrelated donor, haploidentical related donor, or 7\u002F8 mismatched unrelated donor.\n2. Eligible Diseases (Any one of the following)\n\n   Acute Myeloid Leukemia (AML) Must have at least one of the following characteristics:\n   * Blasts \\>5% in the peripheral blood and\u002For bone marrow after \\>2 prior lines of AML directed therapy, present during the trial screening window\n   * Adverse plus risk by AlloHCT Refined ELN Criteria: defined as having complex cytogenetics, TP53 mutation, or MECOM rearrangement confirmed at any time point.(32)\n\n   Myelodysplastic syndrome Must have at least one of the following characteristics at the time of conditioning:\n   * Blasts \\>10% in the peripheral blood and\u002For bone marrow after \\>1 prior line of therapy.\n   * TP53 mutation confirmed at any time point\n\n   Myeloproliferative neoplasms (MPN) or MDS\u002FMPN overlap. Must have at least one of the following characteristics:\n   * Blasts \\>10% in the peripheral blood and\u002For bone marrow during the trial screening window\n   * TP53 mutation confirmed at any time point\n3. Adequate organ function is defined as all of the following:\n\n   Cardiac: Absence of decompensated congestive heart failure, or uncontrolled arrhythmia and left ventricular ejection fraction \\> 45% confirmed by MUGA or echocardiography Pulmonary: DLCO, FEV1, FVC \\> 50% predicted, and absence of O2 requirements. Liver: Transaminases \\\u003C 3 x upper limit of normal (ULN) and total bilirubin ≤ 2 mg\u002FdL except for patients with Gilbert's syndrome or hemolysis (as indicated by provider documentation).\n\n   Renal: Creatinine \\\u003C 2.0 mg\u002FdL (adults) and creatinine clearance \\> 40 mL\u002Fmin.\n4. Must be FIRST allogeneic HCT\n5. Sexually active females of childbearing potential and males with partners of child-bearing potential must agree to use adequate birth control during study treatment.\n6. Voluntary written consent\n\nInclusion Criteria for 12 Gy Arm (Cohort B)\n\n1. Age, Performance Status, and Graft Criteria require all of the following bullet points:\n\n   Age 18 to 70 years (inclusive) Adequate performance status is defined as Karnofsky score ≥ 70% Patients must be receiving an allogeneic peripheral blood stem cell graft Patients and selected donor must be HLA typed at high resolution using DNA based typing at the following HLA-loci: HLA-A, -B, -C and DRB1. Donors may be an 8\u002F8 matched sibling donor, 8\u002F8 matched unrelated donor, haploidentical related donor, or 7\u002F8 mismatched unrelated donor.\n2. Eligible Diseases (Any of the following) Acute Myeloid Leukemia (AML) Myelodysplastic syndrome Myeloproliferative neoplasm MDS\u002FMPN overlap\n3. Must have relapse after prior allo HCT\n4. Adequate organ function is defined as all of the following:\n\n   Cardiac: Absence of decompensated congestive heart failure, or uncontrolled arrhythmia and left ventricular ejection fraction \\> 40% confirmed by MUGA or echocardiography Pulmonary: DLCO, FEV1, FVC \\> 40% predicted, and absence of O2 requirements. Liver: Transaminases \\\u003C 3 x upper limit of normal (ULN) and total bilirubin ≤ 2 mg\u002FdL except for patients with Gilbert's syndrome or hemolysis (as indicated by provider documentation).\n\n   Renal: Creatinine \\\u003C 2.0 mg\u002FdL (adults) and creatinine clearance \\> 40 mL\u002Fmin. Sexually active females of childbearing potential and males with partners of child-bearing potential must agree to use adequate birth control during study treatment.\n5. Voluntary written consent\n\nExclusion Criteria:\n\n1. Pregnant or breast feeding. The agents used in this study include Pregnancy Category D: known to cause harm to a fetus. Females of childbearing potential must have a negative pregnancy test prior to starting therapy.\n2. Untreated active infection. Controlled or asymptomatic infections requiring continued antimicrobial therapy are permissible.\n3. Active HIV infection, defined as HIV infection with detectable viral load\n4. Active central nervous system malignancy\n5. GVHD requiring systemic therapy including \\> 0.25 mg\u002Fkg prednisone (or equivalent) or other systemic therapy for GVHD (e.g., tacrolimus, sirolimus, ruxolitinib, belumosodil, ibrutinib, axatilimab).\n6. Any other medical or psychological condition that is deemed serious and unsafe for clinical trial participation.\n7. Exposure to prior radiation that is deemed unsafe for clinical trial participation.",[106,107],"ADULT","OLDER_ADULT",[109],{"facility":12,"city":110,"state":111,"zip":112,"country":113,"contacts":114,"geoPoint":122},"Palo Alto","California","94304","United States",[115,120],{"name":116,"role":117,"phone":118,"email":119},"Hany Elmariah, MD","CONTACT","650-723-0822","he3@stanford.edu",{"name":116,"role":121},"PRINCIPAL_INVESTIGATOR",{"lat":123,"lon":124},37.44188,-122.14302,[126],{"name":127,"role":117,"phone":118,"email":119},"Hany Elmariah",[129],{"name":116,"affiliation":12,"role":121},[],[],{"nct_id":4,"conditions":133,"biomarkers":136},[18,134,135,19],"Myelodysplastic\u002FMyeloproliferative Neoplasm","Myelodysplastic Syndrome",[137,138,139],"Cytogenetics","MECOM Gene","TP53 Gene",{"nct_id":4,"found":14,"summary":16,"prompt_version":16}]