[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"trial:NCT03128996":3,"trial-entities:NCT03128996":202,"trial-summary:NCT03128996":209},{"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":25,"study_type":31,"primary_purpose":32,"phases":33,"enrollment_info":36,"interventions":39,"primary_outcomes":55,"secondary_outcomes":60,"sex":101,"minimum_age":102,"maximum_age":103,"healthy_volunteers":104,"eligibility_criteria":105,"std_ages":130,"locations":133,"central_contacts":191,"overall_officials":194,"references":196,"see_also_links":201},"NCT03128996","201611172","Reduced Intensity Conditioning and Familial HLA-Mismatched BMT for Non-Malignant Disorders","A Phase I\u002FII Trial of Reduced Intensity Conditioning and Familial HLA-Mismatched Bone Marrow Transplantation in Children With Non-Malignant Disorders","RECRUITING","2033-04","2026-05","2026-05-29","2017-03-20","Washington University School of Medicine","OTHER",true,"This study is designed to estimate the efficacy and toxicity of familial HLA mismatched bone marrow transplants in patients with non-malignant disease who are less than 21 years of age and could benefit from the procedure.","Patients \\\u003C 21 years of age with a non-malignant disorder benefited by hematopoietic stem cell transplant will receive a reduced intensity conditioning regimen consisting of hydroxyurea, alemtuzumab, fludarabine, thiotepa, and melphalan.\n\nThis will be followed by a familial HLA-mismatched bone marrow transplant. The primary objective is to establish safety and donor cell engraftment at 100 days and 1 year post-transplant.",[19,20,21,22,23,24],"Severe Sickle Cell Disease","Bone Marrow Failure Syndromes","Metabolic Disorders","Immunologic Disorders","Hemoglobinopathies","Non-malignant Disorders",[26,27,28,29,30],"Bone marrow transplant","Transplant","Transplantation","Reduced Intensity","Familial HLA mismatched","INTERVENTIONAL","TREATMENT",[34,35],"PHASE1","PHASE2",{"count":37,"type":38},29,"ESTIMATED",[40,49],{"type":41,"name":42,"description":43,"armGroupLabels":44,"otherNames":46},"DRUG","RIC regimen","Days -60 to -21: hydroxyurea (30mg\u002Fkg\u002Fday po) \\>6hrs prior to 1st dose: alemtuzumab (3mg IV) Day -21: alemtuzumab (10mg IV or S\u002FC) Day -20: alemtuzumab (15mg IV or S\u002FC) (10mg if \\\u003C 10kg) Day -19: alemtuzumab (20mg IV or S\u002FC) (10mg if \\\u003C 10kg) Days -8 to -4: fludarabine (30mg\u002Fm2\u002Fday IV) Day -4: thiotepa (8mg\u002Fkg IV) Day -3: melphalan (140mg\u002Fm2) Days -2 to -1: rest days\u002Fno therapy Day 0: bone marrow transplant",[45],"RIC Prep Regimen & GVHD Prophylaxis",[47,48],"Transplant Preparative Regimen","Transplant Conditioning Regimen",{"type":41,"name":50,"description":51,"armGroupLabels":52,"otherNames":53},"GVHD prophylaxis regimen","Day +3 to +4: cyclophosphamide (50mg\u002Fkg\u002Fday IV) Day +5: Start of tacrolimus \\& Start of mycophenolate mofetil (MMF) Days +5, +14, +30, +60, +90: abatacept (IND) (10mg\u002Fkg\u002Fday IV) Day +90: rituximab (375mg\u002Fm2 IV once) Patients \\>\u002F= 12 yrs - Days +120 to +180: abatacept (IND) monthly (10mg\u002Fkg\u002Fday IV) Patients \\>\u002F= 12 yrs - Days +210 to +390: abatacept (IND) monthly (5mg\u002Fkg\u002Fday) Patients \\\u003C12 yrs - Days +120 to +390: abatacept (IND) monthly (5mg\u002Fkg\u002Fday IV)",[45],[54],"Graft versus Host Disease prophylaxis regimen",[56],{"measure":57,"description":58,"timeFrame":59},"Donor engraftment","as measured by chimerism","100 days and 1 year post-transplant",[61,65,67,71,75,78,81,83,87,91,95,98],{"measure":62,"description":63,"timeFrame":64},"Time to neutrophil engraftment","as measured by complete blood counts","100 days post-transplant",{"measure":66,"description":63,"timeFrame":64},"Time to platelet engraftment",{"measure":68,"description":69,"timeFrame":70},"Effect of BMT on pulmonary function","as measured by pulmonary function tests","90 days, 1 year, and 2 years post-transplant",{"measure":72,"description":73,"timeFrame":74},"Effect of BMT on hepatic function","as measured by laboratory evaluations","90 days, 180 days, 1 year, and 2 years post-transplant",{"measure":76,"description":77,"timeFrame":70},"Effect of BMT on neurologic function","as measured by cognitive testing and quality of life surveys",{"measure":79,"description":80,"timeFrame":70},"Effect of BMT on cardiac function","as measured by echocardiograms",{"measure":82,"description":73,"timeFrame":74},"Effect of BMT on renal function",{"measure":84,"description":85,"timeFrame":86},"Pharmacokinetics of alemtuzumab","as measured by maximum plasma concentration of alemtuzumab","days -19, day 0, day +15, and day +30",{"measure":88,"description":89,"timeFrame":90},"Pharmacokinetics of abatacept","as measured by maximum plasma concentration of abatacept","days +30, +60, +90, 1 year, 1.5 years, and 2 years post-transplant",{"measure":92,"description":93,"timeFrame":94},"Incidence of acute graft-versus-host disease (GVHD)","as measured by protocol grading scale","1 year post-transplant",{"measure":96,"description":93,"timeFrame":97},"Incidence of chronic graft-versus-host disease (GVHD)","2 years post-transplant",{"measure":99,"description":100,"timeFrame":90},"Immune reconstitution","as measured by research laboratory evaluations","ALL","1 Day","21 Years",false,{"inclusion":106,"exclusion":120,"raw_text":129},[107,108,109,110,111,112,113,114,115,116,117,118,119],"Nonmalignant disorder requiring bone marrow transplant including bone marrow failure syndromes, metabolic disorders, immunologic disorders, or hemoglobinopathy","For patients with sickle cell disease, must have one of the following severe manifestations:","Patients with sickle cell disease must have hemoglobin S \\\u003C 30% within 30 days prior to beginning alemtuzumab","Age \\\u003C\u002F= 20.99 years at the time of enrollment","Performance score \\>\u002F= 50","Left ventricular ejection fraction \\> 40% or left ventricular shortening fraction \\> 26% by echocardiogram","DLCO \\> 40% (corrected for hemoglobin) or pulse oximetry with a baseline O2 saturation of \\>\u002F= 90% on room air if too young to perform PFTs","Serum creatinine \\\u003C\u002F= 1.5x upper limit of normal for age and\u002For GFR \\> 70 mL\u002Fmin\u002F1.73m2","Direct bilirubin \\\u003C 2x upper limit of normal for age","ALT and AST \\\u003C 5x upper limit of normal for age","Participants who have or are receiving \\>\u002F= 8 packed red blood cell transfusions for \\>\u002F= 1 year or \\>\u002F= 20 packed red blood cell transfusions (lifetime cumulative) will undergo liver MRI for estimation of hepatic iron content.","Female subjects of childbearing potential, must agree to practice 2 methods of contraception at the same time from the time of signing of informed consent through 12 months post transplant. Male subjects must agree to practice effective barrier contraception or practice true abstinence from the time of signing informed consent through 12 months post transplant.","Written informed consent must be obtained from all recipients in accordance with the guidelines of the institution's Human Studies Committee.",[121,122,123,124,125,126,127,128],"Patients who have an HLA-identical sibling who is able and willing to donate bone marrow","Patients with cirrhosis or established bridging fibrosis of the liver or active hepatitis","Uncontrolled bacterial, viral, or fungal infection within 6 weeks prior to enrollment","Evidence of HIV infection or known HIV positive serology","Patients who have received a previous stem cell transplant","Patients who have received an investigational drug or device or off-label use of a drug or device within 3 months of enrollment","Females who are pregnant or breast feeding","Patients with active autoimmune disease (e.g. sarcoidosis, lupus, scleroderma)","Inclusion Criteria:\n\n* Nonmalignant disorder requiring bone marrow transplant including bone marrow failure syndromes, metabolic disorders, immunologic disorders, or hemoglobinopathy\n* For patients with sickle cell disease, must have one of the following severe manifestations:\n\n  1. Overt or silent stroke or persistently elevated transcranial doppler velocities despite transfusion therapy\n  2. Recurrent acute chest syndrome with significant respiratory compromise each time\n  3. Sickle nephropathy\n  4. Recurrent admissions for vaso-occlusive episodes resulting in prolonged opioid use and poor quality of life with interrupted school attendance activity\n  5. Red cell alloimmunization with the need for chronic transfusions\n  6. Recurrent osteonecrosis or multiple joint involvement from avascular necrosis\n* Patients with sickle cell disease must have hemoglobin S \\\u003C 30% within 30 days prior to beginning alemtuzumab\n* Age \\\u003C\u002F= 20.99 years at the time of enrollment\n* Performance score \\>\u002F= 50\n* Left ventricular ejection fraction \\> 40% or left ventricular shortening fraction \\> 26% by echocardiogram\n* DLCO \\> 40% (corrected for hemoglobin) or pulse oximetry with a baseline O2 saturation of \\>\u002F= 90% on room air if too young to perform PFTs\n* Serum creatinine \\\u003C\u002F= 1.5x upper limit of normal for age and\u002For GFR \\> 70 mL\u002Fmin\u002F1.73m2\n* Direct bilirubin \\\u003C 2x upper limit of normal for age\n* ALT and AST \\\u003C 5x upper limit of normal for age\n* Participants who have or are receiving \\>\u002F= 8 packed red blood cell transfusions for \\>\u002F= 1 year or \\>\u002F= 20 packed red blood cell transfusions (lifetime cumulative) will undergo liver MRI for estimation of hepatic iron content.\n\n  1\\. Liver biopsy is indicated for hepatic iron content \\>\u002F= 7mg Fe\u002Fmg liver dry weight by liver MRI. Histologic examination of the liver must document for the absence of cirrhosis, bridging fibrosis, and active hepatitis\n* Female subjects of childbearing potential, must agree to practice 2 methods of contraception at the same time from the time of signing of informed consent through 12 months post transplant. Male subjects must agree to practice effective barrier contraception or practice true abstinence from the time of signing informed consent through 12 months post transplant.\n* Written informed consent must be obtained from all recipients in accordance with the guidelines of the institution's Human Studies Committee.\n\nExclusion Criteria:\n\n* Patients who have an HLA-identical sibling who is able and willing to donate bone marrow\n* Patients with cirrhosis or established bridging fibrosis of the liver or active hepatitis\n* Uncontrolled bacterial, viral, or fungal infection within 6 weeks prior to enrollment\n* Evidence of HIV infection or known HIV positive serology\n* Patients who have received a previous stem cell transplant\n* Patients who have received an investigational drug or device or off-label use of a drug or device within 3 months of enrollment\n* Females who are pregnant or breast feeding\n* Patients with active autoimmune disease (e.g. sarcoidosis, lupus, scleroderma)",[131,132],"CHILD","ADULT",[134,149,162,174],{"facility":135,"status":8,"city":136,"state":137,"zip":138,"country":139,"contacts":140,"geoPoint":146},"Yale School of Medicine","New Haven","Connecticut","06510","United States",[141,144],{"name":142,"role":143},"Lakshmanan Krishnamurti, MD","CONTACT",{"name":142,"role":145},"PRINCIPAL_INVESTIGATOR",{"lat":147,"lon":148},41.30815,-72.92816,{"facility":150,"status":8,"city":151,"state":152,"zip":153,"country":139,"contacts":154,"geoPoint":159},"Nemours Children's Health","Wilmington","Delaware","19803",[155,158],{"name":156,"role":143,"phone":157},"Emi Caywood, MD","800-416-4441",{"name":156,"role":145},{"lat":160,"lon":161},39.74595,-75.54659,{"facility":163,"status":8,"city":164,"state":165,"zip":166,"country":139,"contacts":167,"geoPoint":171},"Helen DeVos Children's Hospital","Grand Rapids","Michigan","49503",[168,170],{"name":169,"role":143},"Troy Quigg, DO",{"name":169,"role":145},{"lat":172,"lon":173},42.96336,-85.66809,{"facility":13,"status":8,"city":175,"state":176,"zip":177,"country":139,"contacts":178,"geoPoint":188},"St Louis","Missouri","63110",[179,183,187],{"name":180,"role":143,"phone":181,"email":182},"Shalini Shenoy, MD","314-454-6018","shalinishenoy@wustl.edu",{"name":184,"role":143,"phone":185,"email":186},"Ian Snyder, BS, CCRP","314-273-5953","ian.s@wustl.edu",{"name":180,"role":145},{"lat":189,"lon":190},38.62727,-90.19789,[192,193],{"name":180,"role":143,"phone":181,"email":182},{"name":184,"role":143,"phone":185,"email":186},[195],{"name":180,"affiliation":13,"role":145},[197],{"pmid":198,"type":199,"citation":200},"32813873","DERIVED","Ngwube A, Shah N, Godder K, Jacobsohn D, Hulbert ML, Shenoy S. Abatacept is effective as GVHD prophylaxis in unrelated donor stem cell transplantation for children with severe sickle cell disease. Blood Adv. 2020 Aug 25;4(16):3894-3899. doi: 10.1182\u002Fbloodadvances.2020002236.",[],{"nct_id":4,"conditions":203,"biomarkers":208},[204,205,22,206,24,207],"Bone Marrow Failure Syndrome","Hemoglobinopathy","Metabolic Disorder","Sickle Cell Disease",[],{"nct_id":4,"found":15,"summary":210,"prompt_version":220},{"design":211,"status":212,"heading":213,"summary":214,"follow_up":215,"word_count":216,"commitments":217,"compensation":218,"drugs_mentioned":219},"This is an interventional study, meaning participants receive a specific treatment. It plans to enroll 29 participants.","completed","Reduced Intensity Bone Marrow Transplant for Non-Malignant Disorders","This study is looking at a type of bone marrow transplant for children and young adults (up to 21 years old) with serious non-cancerous conditions like severe sickle cell disease, bone marrow failure, or certain metabolic or immune disorders. The transplant uses a donor who is a family member but not a perfect match (familial HLA-mismatched). Before the transplant, participants receive a reduced intensity conditioning (RIC) regimen, which includes medicines like hydroxyurea, alemtuzumab, fludarabine, thiotepa, and melphalan. After the transplant, they receive medicines like cyclophosphamide, tacrolimus, mycophenolate mofetil (MMF), abatacept, and rituximab to help prevent graft-versus-host disease (GVHD), a common transplant complication. The main goal is to see how safe this treatment is and if the donor cells successfully grow in the patient at 100 days and 1 year after the transplant. The study plans to enroll 29 participants.","Participants will be followed to assess donor cell engraftment at 100 days and 1 year post-transplant.",139,"Not specified in the trial record.","Not stated in the trial record.",[],"v2"]