[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100652704":3},{"organization":4,"outcomesModule":7,"designInfo":29,"detailedDescription":35,"studyPopulation":28,"armGroups":36,"interventions":47,"overallOfficials":69,"centralContacts":74,"locations":79,"responsibleParty":99,"collaborators":28,"id":101,"slug":102,"hasResults":103,"nctId":104,"briefTitle":105,"officialTitle":106,"acronym":28,"eligibilityCriteria":107,"healthyVolunteers":103,"sex":108,"minAge":109,"maxAge":110,"enrollmentInfo":111,"targetDuration":28,"studyType":114,"phases":115,"briefSummary":118,"conditions":119,"keywords":125,"overallStatus":128,"whyStopped":28,"lastUpdateSubmitDate":129,"lastUpdatePostDateStruct":130,"startDateStruct":133,"completionDateStruct":135,"leadSponsor":137,"locationsCount":138},{"fullName":5,"class":6},"National Institutes of Health Clinical Center (CC)","NIH",{"primaryOutcomes":8,"secondaryOutcomes":13,"otherOutcomes":28},[9],{"measure":10,"description":11,"timeFrame":12},"To evaluate the safety of base-edited autologous CD34+ cells","Safety of gene therapy using base-edited autologous hematopoietic stem and progenitor cells as measured by study agent-related adverse events and serious adverse events","Initiated from the time of the infusion of base-edited cells through 2 years post-infusion",[14,18,22,25],{"measure":15,"description":16,"timeFrame":17},"Evaluate the efficacy of base-edited autologous CD34+ cells","Efficacy of gene therapy as determined by percentage of participants who have \\>= 5 percent gene edited circulating myeloid cells","Assessed 12 months post-infusion of base-edited cells",{"measure":19,"description":20,"timeFrame":21},"Evaluate genetic correction","Genetic correction as determined by the presence of \\>200\u002FuL edited neutrophils","Assessed 12 months post-infusion of base edited cells",{"measure":23,"description":24,"timeFrame":21},"Evaluate immune reconstitution","Immune reconstitution as determined by: T, B, and NK cell number improvement from baseline; immunoglobulin production",{"measure":26,"description":27,"timeFrame":21},"Evaluate clinical efficacy","Clinical efficacy as determined by: improvement from baseline problems (i.e., recurrent infections, wart burden)",null,{"allocation":30,"interventionModel":31,"interventionModelDescription":28,"primaryPurpose":32,"observationalModel":28,"timePerspective":28,"maskingInfo":33},"NA","SINGLE_GROUP","TREATMENT",{"masking":34,"maskingDescription":28,"whoMasked":28},"NONE","Study Description:\n\nThis is a phase 1\u002F2, non-randomized study of a single infusion of autologous hematopoietic stem\u002Fprogenitor cells (HSPC) base-edited to repair CXCR4 mutations in 10 participants with (Warts, Hypogammaglobulinemia, Infections, and Myelokathexis) WHIM syndrome.\n\nPrimary Objective: Evaluate safety of treatment with BE-HSPC CXCR4 in participants with WHIM syndrome.\n\nSecondary Objectives:\n\nEvaluate:\n\n* Efficacy.\n* Genetic correction.\n* Immune reconstitution.\n* Clinical efficacy.\n\nExploratory Objective:\n\nEvaluate off-target (OT) editing activity.\n\nPrimary Endpoint:\n\nSafety assessed by:\n\n* Incidence of adverse events (AEs) for each participant.\n* Evaluate overall incidence of AEs for the study.\n* Incidence of serious adverse events (SAEs).\n\nSecondary Endpoints (24 months post-study agent infusion):\n\n* Efficacy: \\>= 5% gene edited circulating myeloid cells by 12 months after BE HSPC infusion.\n* Gene correction:\n\n  --Frequency of corrected alleles in peripheral blood cells (such as myeloid, T, B, and natural killer \\[NK\\] cells).\n\n  --\\>200\u002FmicroL edited neutrophils by 12 months post receipt of the BE HSPC infusion.\n* Immune reconstitution:\n\n  * T, B, and NK cell number improvement from baseline.\n  * B-cell function: immunoglobulin (Ig) production.\n* Clinical efficacy: Improvement from baseline problems such as recurrent infection, wart burden, gastrointestinal complaints, or immune dysregulation.\n\nExploratory Endpoint:\n\nEvaluate for frequency of OTs by high-throughput sequencing (HTS) of the target mutation at the genomic locus 2 years post-infusion.",[37],{"label":38,"type":39,"description":40,"interventionNames":41},"Single arm study","EXPERIMENTAL","The study cell product is base edited autologous HSPCs which will be administered as a one-time infusion following myeloid conditioning using busulfan.",[42,43,44,45,46],"Drug: Busulfan","Drug: Palifermin","Drug: Plerixafor","Drug: Filgrastim","Biological: Base-edited hematopoietic stem and progenitor cells",[48,53,57,61,64],{"type":49,"name":50,"description":51,"armGroupLabels":52,"otherNames":28},"DRUG","Busulfan","Myeloid conditioning agent, administered once daily x 2 days, targeting a total AUC of 9000 micromol\\*min\u002FL.",[38],{"type":49,"name":54,"description":55,"armGroupLabels":56,"otherNames":28},"Palifermin","Mucositis prophylaxis agent, will be administered at 60 mcg\u002Fkg\u002Fday for 3 days before initiation of busulfan (days -6 to -4), as well as for the 3 days following study agent administration (days 1 to 3).",[38],{"type":49,"name":58,"description":59,"armGroupLabels":60,"otherNames":28},"Plerixafor","Hematopoietic stem cell mobilizing agent necessary for the collection of the hematopoietic stem and progenitor cells (HSPCs) to create the study product.",[38],{"type":49,"name":62,"description":59,"armGroupLabels":63,"otherNames":28},"Filgrastim",[38],{"type":65,"name":66,"description":67,"armGroupLabels":68,"otherNames":28},"BIOLOGICAL","Base-edited hematopoietic stem and progenitor cells","The study cell product is base edited autologous HSPCs which will be administered as a one-time infusion following myeloid conditioning.",[38],[70],{"name":71,"affiliation":72,"role":73},"Suk S De Ravin, M.D.","National Institute of Allergy and Infectious Diseases (NIAID)","PRINCIPAL_INVESTIGATOR",[75],{"name":71,"role":76,"phone":77,"phoneExt":28,"email":78},"CONTACT","(301) 496-6772","sderavin@mail.nih.gov",[80],{"facility":81,"status":28,"city":82,"state":83,"zip":84,"country":85,"countryCode":86,"cosmosGeoPoint":87,"geoPoint":92,"contacts":93},"National Institutes of Health Clinical Center","Bethesda","Maryland","20892","United States","US",{"type":88,"coordinates":89},"Point",[90,91],-77.10026,38.98067,{"lat":91,"lon":90},[94],{"name":95,"role":76,"phone":96,"phoneExt":97,"email":98},"NIH Clinical Center Office of Patient Recruitment (OPR)","800-411-1222","TTY dial 711","ccopr@nih.gov",{"type":100,"investigatorFullName":28,"investigatorTitle":28,"investigatorAffiliation":28,"oldNameTitle":28,"oldOrganization":28},"SPONSOR","100652704","phase-1-base-edited-hematopoietic-stemprogenitor-cell-gene-therapy-for-treatment-of-cxcr4-whim-100652704",false,"NCT07775313","Base-Edited Hematopoietic Stem\u002FProgenitor Cell Gene Therapy for Treatment of CXCR4-WHIM","Phase 1\u002F2 Base-Edited Hematopoietic Stem\u002FProgenitor Cell Gene Therapy for Treatment of CXCR4-WHIM","* INCLUSION CRITERIA:\n\nIn order to be eligible to participate in this study, an individual must meet all of the following criteria:\n\n* Aged \\>= 3 years and weighing \\>=15 kg.\n* Confirmed CXCR c.1000C\\>T, pR334X mutation.\n* Ability to undergo apheresis for stem cell collection.\n* Medical lab data (historical) of neutropenia, or B cell dysfunction (low or absent IgG levels, or on IV gamma globulin.\n* Expected survival of at least 120 days.\n* Must be willing to have blood and tissue samples stored.\n* Participants of reproductive potential must agree to consistently use effective contraception from start of busulfan conditioning through at least one-year post-treatment. Acceptable forms of contraception are:\n\n  * Hormonal contraception in continuously effective use.\n  * Male or female condom with spermicide as indicated.\n  * Diaphragm or cervical cap in consistent and effective pattern of use with a spermicide.\n  * Intrauterine device in-situ\n\nEXCLUSION CRITERIA:\n\nAn individual who meets any of the following criteria will be excluded from participation in this study:\n\n* Acute onset infection as indicated by symptoms such as persistent fevers, or imaging (new pneumonia on CT for example), isolated pathogen and requiring medical intervention.\n* Severe liver dysfunction with transaminases \\> 6 fold upper limit will be excluded until approval by hepatology consult who will provide mitigating plans for liver protection.\n* Renal dysfunction-serum creatinine \\>3.0 x ULN.\n* Coagulation dysfunction- Prothrombin INR or Partial thromboplastin time \\>2 x ULN (patients on controlled anticoagulation agents will not be excluded for therapeutic levels).\n* Known hypersensitivity to busulfan or any component of the product.\n* Contraindications for administration of busulfan, including but not limited to: hypersensitivity, chronic lymphocytic leukemia, acute leukemia in blastic crisis, pregnancy, or lactation.\n* Childhood malignancy (occurring before 18 years of age) in the participant or a first degree relative, or previously diagnosed known genotype of the participant conferring a predisposition to cancer unless approved by the with appropriate consultants and approved by the study PI (no DNA or other testing for cancer predisposition genes will be performed as part of the screen for this protocol).\n* Any other condition that, in the opinion of the investigator, may compromise the safety or compliance of the participant, or would preclude the participant from successful study completion.","ALL","3 Years","75 Years",{"count":112,"type":113},10,"ESTIMATED","INTERVENTIONAL",[116,117],"PHASE1","PHASE2","Background:\n\nWarts, hypogammaglobulinemia, infections and myelokathexis syndrome (WHIMs) is a rare disorder that affects the immune system. People with WHIMs can have severe infections all over their body. WHIMs is caused by a mutation in the CXCR4 gene. Treatment with drugs can help control the infections but does not cure the disorder. Researchers want to try a treatment where they collect stem cells from a person with WHIMS, use base-editing to replace the bad gene with a healthy version, and return the new cells to the person. This could cure WHIMs.\n\nObjective:\n\nTo test a treatment using base-edited stem cells in people with WHIMs.\n\nEligibility:\n\nPeople aged 3 years and older with WHIMs.\n\nDesign:\n\nThe study has 4 stages.\n\nStage 1: Screening. Participants will be screened at 1 or more visits. They will have a physical exam with blood tests. A sample of tissue and fluid (biopsy) will be taken from the bone marrow in the hip.\n\nStage 2: Apheresis. Blood will be taken from the body through a needle; the blood will pass through a machine that separates out the stem cells. The remaining blood will be returned to the body through a different needle. The collected stem cells will undergo gene editing.\n\nStage 3: Treatment. Participants will stay in the hospital for about 4 weeks. They will receive 3 drugs to prepare their body for the procedure. Then the edited stem cells will be returned to their bloodstream. They will stay in the hospital until they recover.\n\nStage 4: Follow-up. Participants will have 8 follow-up visits over 5 years. Long-term visits will continue for 15 years.",[120,121,122,123,124],"WHIM","Warts","Hypogammaglobulinemia","Immunodeficiency","Myelokathexis",[126,127],"Gene Editing","base editing","NOT_YET_RECRUITING","2026-08-24",{"date":131,"type":132},"2026-08-25","ACTUAL",{"date":134,"type":113},"2026-08-30",{"date":136,"type":113},"2033-12-31",{"name":72,"class":6},1]