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

NCT06736080 · tracked via the Priya Life Science France tracker

Sponsor

Assistance Publique - Hôpitaux de Paris

Phase

Phase 1/2

Started

2026-05

Last updated

2026-05-22

Condition(s) studied

Familial Hemophagocytic Lymphohistiocytosis Type 3 (FHL 3)

Investigational drug(s) / intervention(s)

MUNC-CD34MUNC-T3

MUNC-CD34: * Dosage: ≥ 2 x10e6 CD34/kg after thawing, dose limit: 20x10e6 CD34+ cells/kg * Route of administration: intravenous, on D0

MUNC-T3: * Dosage: \[1.10e4; 5.10e6\] T-CD3+/kg after thawing, * Route of administration: intravenous, on D14 post-GT +/- D28 In case of persistent circulating T-cell after the HLH remission at inclusion, the MUNC-CD34 will be completed by MUNC-T3 infusion

Study summary

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.

Eligibility

Sex

ALL

Min age

3 Months

Max age

45 Years

Healthy volunteers

Inclusion Criteria: 1. Patient aged from 3 months up to 45 years old. 2. Patient with a FHL caused by mutation of the UNC13D gene. 3. Complete remission is defined by the normalization of clinical and laboratory parameters: 1. Resolution of fever 2. Resolution of splenomegaly or reduced and isolated splenomegaly. 3. Improvement of cytopenia: absolute neutrophil count \> 500/µl AND platelets cout \> 100 000/ µl (unsupported by transfusion) 4. Normalization of serum fibrinogen level (Fibrinogen ≥1.5g/l) 5. Resolution of hyperferritinemia (Ferritin level \< 2000µg/l) 6. Normalization of T-cell activation 4. 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)) 5. Patint or parental, guardian's patient signed informed consent. 6. For patients of childbearing age : willing to use an effective method of contraception\* during the trial and for at least 12 months post-infusion 7. Affiliation to Social Security Exclusion Criteria: 1. Active CNS encephalitis related to HLH 2. Existence of a matched -sibling donor 3. Unwillingness to return for follow-up during the 2 years study and lifelong for off study review. 4. HIV-1 or 2 or HTLV1 infections. 5. Patient on AME (state medical aid) (unless exemption from affiliation) 6. Pregnancy or breast feeding in a post-partum female 7. Diagnosis of significant psychiatric disorder of the subject that could seriously impeded the ability to participate in the study 8. Known allergies, hypersensitivity, or intolerance to any of busulfan, fludarabine, rituximab, G-CSF, plerixafor or excipients, or similar compounds 9. Unable to tolerate general anesthesia and/or apheresis 10. Participation in another clinical study with an investigational drug within 30 days of inclusion. 11. Uncontrolled HLH manifestation

Primary outcome measure(s)

Incidence of Transplantation Related Mortality (TRM) — up to 6 months post treatment
Frequency and severity of clinical AEs and laboratory parameters — throughout the whole period of the research, up to 60 months
Adverse event will be measured using CTCAE
Incidence of clinically detectable malignancy and/or abnormal clonal dominance assessed as related to study treatment — At 12 months post treatment
Bone marrow analysis and VISA
Detection of Replication -Competent Lentivirus (RCL) — at 3, 6 and 12 months post treatment, then yearly up to 60 months

Trial sites (1)

Facility	City	Region	Status
Department of Biotherapy, Hopital Necker Enfants Malades	Paris	France

More Assistance Publique - Hôpitaux de Paris trials in France

Identification of Cutaneous and Blood Biomarkers Predictive of Response to Systemic Treatments During Chronic Inflammatory Skin Diseases Recruiting

VExUS in Ards Patients and Association with AKI Recruiting

Periodontitis and Inflammation: Study on Biological Samples Recruiting

Kinematic Analysis of Latissimus Dorsi Transfer Results for Shoulder External Rotation Resuscitation Starting soon

Creation of a Biological Collection for Medical Research Purposes for Patients at the Reference Center for Rare Diseases of the Blood Vessels of the Brain and Eye at Lariboisière Hospital Active, not recruiting

Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT06736080 on ClinicalTrials.gov ↗ ← All trials in France