[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100572654":3},{"organization":4,"armGroups":7,"interventions":15,"overallOfficials":25,"centralContacts":33,"locations":44,"responsibleParty":59,"collaborators":61,"id":64,"slug":65,"hasResults":66,"nctId":67,"briefTitle":68,"officialTitle":69,"acronym":70,"eligibilityCriteria":71,"healthyVolunteers":66,"sex":72,"minAge":73,"maxAge":74,"enrollmentInfo":75,"targetDuration":11,"studyType":78,"phases":79,"briefSummary":82,"conditions":83,"keywords":85,"overallStatus":90,"whyStopped":11,"lastUpdateSubmitDate":91,"lastUpdatePostDateStruct":92,"startDateStruct":95,"completionDateStruct":97,"leadSponsor":99,"locationsCount":100},{"fullName":5,"class":6},"Assistance Publique - Hôpitaux de Paris","OTHER",[8],{"label":9,"type":10,"description":11,"interventionNames":12},"MUNC","EXPERIMENTAL",null,[13,14],"Genetic: MUNC-CD34","Genetic: MUNC-T3",[16,21],{"type":17,"name":18,"description":19,"armGroupLabels":20,"otherNames":11},"GENETIC","MUNC-CD34","* Dosage: ≥ 2 x10e6 CD34\u002Fkg after thawing, dose limit: 20x10e6 CD34+ cells\u002Fkg\n* Route of administration: intravenous, on D0",[9],{"type":17,"name":22,"description":23,"armGroupLabels":24,"otherNames":11},"MUNC-T3","* Dosage: \\[1.10e4; 5.10e6\\] T-CD3+\u002Fkg after thawing,\n* Route of administration: intravenous, on D14 post-GT +\u002F- D28 In case of persistent circulating T-cell after the HLH remission at inclusion, the MUNC-CD34 will be completed by MUNC-T3 infusion",[9],[26,30],{"name":27,"affiliation":28,"role":29},"Jean-Sébastien DIANA, MD, PhD","Assitance publique - Hôpitaux de Paris","STUDY_DIRECTOR",{"name":31,"affiliation":32,"role":29},"Chantal LAGRESLE, PHD","Inserm Institut Imagine",[34,40],{"name":35,"role":36,"phone":37,"phoneExt":38,"email":39},"Marina CAVAZZANA, MD, PhD","CONTACT","01 44 49 50 68","+33","m.cavazzana@aphp.fr",{"name":41,"role":36,"phone":42,"phoneExt":38,"email":43},"Aline DECHANET, Project Manager","01 71 19 61 69","aline.dechanet@aphp.fr",[45],{"facility":46,"status":11,"city":47,"state":11,"zip":48,"country":49,"countryCode":50,"cosmosGeoPoint":51,"geoPoint":56,"contacts":57},"Department of Biotherapy, Hopital Necker Enfants Malades","Paris","75015","France","FR",{"type":52,"coordinates":53},"Point",[54,55],2.3488,48.85341,{"lat":55,"lon":54},[58],{"name":35,"role":36,"phone":37,"phoneExt":38,"email":39},{"type":60,"investigatorFullName":11,"investigatorTitle":11,"investigatorAffiliation":11,"oldNameTitle":11,"oldOrganization":11},"SPONSOR",[62],{"name":63,"class":6},"URC-CIC Paris Descartes Necker Cochin","100572654","phase-1-safety-and-efficacy-of-gene-therapy-of-fhl-type-3-caused-by-mutations-in-the-human-unc13d-gene-by-transplantation-of-a-single-dose-of-autologous-cd34-cells-transduced-ex-vivo-with-the-unc13d-lv-vector-expressing-the-unc13d-cdna-100572654",false,"NCT06736080","Safety and Efficacy of Gene Therapy of FHL Type 3 Caused by Mutations in the Human UNC13D Gene by Transplantation of a Single Dose of Autologous CD34+ Cells Transduced ex Vivo With the UNC13D LV Vector Expressing the UNC13D cDNA","A Phase I\u002FII Open Label Non Randomized Study, Monocentric, Single Arm, Evaluating Safety and Efficacy of Gene Therapy of FHL 3 Caused by Mutations in the Human UNC13D Gene by Transplantation of a Single Dose of Autologous CD34+ Cells Transduced ex Vivo With the UNC13D LV Vector Expressing the UNC13D cDNA","MUNC13-4","Inclusion Criteria:\n\n1. Patient aged from 3 months up to 45 years old.\n2. Patient with a FHL caused by mutation of the UNC13D gene.\n3. Complete remission is defined by the normalization of clinical and laboratory parameters:\n\n   1. Resolution of fever\n   2. Resolution of splenomegaly or reduced and isolated splenomegaly.\n   3. Improvement of cytopenia: absolute neutrophil count \\> 500\u002Fµl AND platelets cout \\> 100 000\u002F µl (unsupported by transfusion)\n   4. Normalization of serum fibrinogen level (Fibrinogen ≥1.5g\u002Fl)\n   5. Resolution of hyperferritinemia (Ferritin level \\\u003C 2000µg\u002Fl)\n   6. Normalization of T-cell activation\n4. Patient eligible for an allogeneic HSCT in absence of an HLA geno-identical donor (at diagnostic or 6 months after failure of a previous HSCT (rejection or loss of the graft))\n5. Patint or parental, guardian's patient signed informed consent.\n6. For patients of childbearing age : willing to use an effective method of contraception\\* during the trial and for at least 12 months post-infusion\n7. Affiliation to Social Security\n\nExclusion Criteria:\n\n1. Active CNS encephalitis related to HLH\n2. Existence of a matched -sibling donor\n3. Unwillingness to return for follow-up during the 2 years study and lifelong for off study review.\n4. HIV-1 or 2 or HTLV1 infections.\n5. Patient on AME (state medical aid) (unless exemption from affiliation)\n6. Pregnancy or breast feeding in a post-partum female\n7. Diagnosis of significant psychiatric disorder of the subject that could seriously impeded the ability to participate in the study\n8. Known allergies, hypersensitivity, or intolerance to any of busulfan, fludarabine, rituximab, G-CSF, plerixafor or excipients, or similar compounds\n9. Unable to tolerate general anesthesia and\u002For apheresis\n10. Participation in another clinical study with an investigational drug within 30 days of inclusion.\n11. Uncontrolled HLH manifestation","ALL","3 Months","45 Years",{"count":76,"type":77},5,"ESTIMATED","INTERVENTIONAL",[80,81],"PHASE1","PHASE2","The investigators propose to replace HLA- partially compatible allogeneic Hematopoietic Stem Cell Transplantation (HSCT) for FHL type 3 patients, with autologous transplantation of immunoselected gene-modified CD34+ cells, combined with transduced autologous T-cell each time this is possible and also to propose this alternative treatment as salvage in case of failure of a previous allogeneic HSCT. This approach should avoid the severe immunological complications (failure to engraft, acute or chronic graft versus host disease (GVHD)) and conditioning toxicities such as severe Veno-Occlusive Disease (VOD). As the clinical manifestations of FHL type 3 patients are triggered by opportunistic viral infections (often EBV) and can be poorly controlled or only transiently controlled by the available drugs , providing the patient after the conditioning with immediately functional autologous cytotoxic T-cells could be key to maintain the control of the viral infection and hopefully its eradication awaiting for the hematopoietic reconstitution . This procedure should avoid any reactivation of the viral infection and thus improving the patients' overall survival and event-free survival while clearing the ongoing triggering infections.",[84],"Familial Hemophagocytic Lymphohistiocytosis Type 3 (FHL 3)",[86,87,88,89],"Familial Hemophagocytic Lymphohistiocytosis type 3 (FHL 3)","Munc13.4","Gene Therapy","Lentiviral Vector","NOT_YET_RECRUITING","2026-05-18",{"date":93,"type":94},"2026-05-22","ACTUAL",{"date":96,"type":77},"2026-05",{"date":98,"type":77},"2030-01",{"name":5,"class":6},1]