ClinicalTrials.gov record 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

Record copied from ClinicalTrials.gov: Oct 10, 2026AI summaries generated: Jul 27, 2026

A Phase I/II 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

StatusNot yet recruitingThe study has been registered but has not started enrolling. Sites and contacts may not be listed yet.
Study typeInterventionalA study in which researchers assign participants to one or more interventions, such as a drug, procedure, device, behavioural programme or other approach, to measure their effects.
PhasePhase 1/2A study that combines safety and dose-finding (phase 1) with a first look at whether the treatment has an effect (phase 2).
Age3 months old to 45 years old
SexAll
LocationFrance
AI summaryWhat this study is about, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

This Phase I/II open‑label, single‑arm study evaluates a single infusion of a patient's own CD34+ cells modified to carry the UNC13D gene for people with FHL type 3. Investigators propose this autologous gene therapy as an alternative to partially HLA‑matched allogeneic stem-cell transplant and as a possible salvage option after a failed allogeneic transplant. The trial will monitor safety, transplantation‑related outcomes, immune function, and long‑term transgene persistence.

What it is studying. The study is testing the safety and efficacy of autologous gene therapy for FHL type 3: patients' own CD34+ hematopoietic cells are transduced ex vivo with a lentiviral UNC13D vector and given back as a single intravenous infusion. In some cases a transduced autologous T‑cell infusion may be given after the stem‑cell infusion. The trial measures clinical safety, blood/immune recovery, persistence of the introduced gene, and other treatment‑related outcomes over extended follow‑up.

What the researchers hope to learn. To evaluate safety and efficacy of autologous UNC13D gene therapy for FHL 3 and to collect scientific data including: transplantation‑related mortality, adverse events, detection of treatment‑related malignancy or abnormal clonal dominance, presence of replication‑competent lentivirus, neutrophil and platelet recovery, vector copy number and transgene RNA/protein levels, immune cell counts and function (including degranulation), integration‑site analysis, infection and endothelial complication rates, disease‑free survival, and estimates of procedure costs.

What this study is about

The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.

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.

Interventions being studied

Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.

Genetic
  • MUNC-CD34
  • MUNC-T3

Eligibility

The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.

Inclusion criteria

  • Patient aged from 3 months up to 45 years old.
  • Patient with a FHL caused by mutation of the UNC13D gene.
  • Complete remission is defined by the normalization of clinical and laboratory parameters:
  • Resolution of fever
  • Resolution of splenomegaly or reduced and isolated splenomegaly.
  • Improvement of cytopenia: absolute neutrophil count > 500/µl AND platelets cout > 100 000/ µl (unsupported by transfusion)
  • Normalization of serum fibrinogen level (Fibrinogen ≥1.5g/l)
  • Resolution of hyperferritinemia (Ferritin level < 2000µg/l)
  • Normalization of T-cell activation
  • 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))
  • Patint or parental, guardian's patient signed informed consent.
  • For patients of childbearing age : willing to use an effective method of contraception* during the trial and for at least 12 months post-infusion
  • Affiliation to Social Security

Exclusion criteria

  • Active CNS encephalitis related to HLH
  • Existence of a matched -sibling donor
  • Unwillingness to return for follow-up during the 2 years study and lifelong for off study review.
  • HIV-1 or 2 or HTLV1 infections.
  • Patient on AME (state medical aid) (unless exemption from affiliation)
  • Pregnancy or breast feeding in a post-partum female
  • Diagnosis of significant psychiatric disorder of the subject that could seriously impeded the ability to participate in the study
  • Known allergies, hypersensitivity, or intolerance to any of busulfan, fludarabine, rituximab, G-CSF, plerixafor or excipients, or similar compounds
  • Unable to tolerate general anesthesia and/or apheresis
  • Participation in another clinical study with an investigational drug within 30 days of inclusion.
  • Uncontrolled HLH manifestation

Study description and what participation involves

The registry record has no detailed description beyond the summary above.

AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

Participation involves collection of the participant's own stem cells (apheresis; general anesthesia may be required), laboratory modification of those CD34+ cells, and return by intravenous infusion (MUNC‑CD34 on Day 0; a supplemental MUNC‑T3 IV infusion may be given on Day 14 ± Day 28 if specified). The procedure includes a conditioning (preparation) treatment before infusion, repeated blood tests and clinical exams, and scheduled bone marrow sampling to check for malignancy or clonal changes. Safety tests for the vector, monitoring of blood counts and immune function, and recording of adverse events will occur at many time points. Follow-up visits and testing continue for months to years (safety monitoring up to 60 months), and participants must be willing to attend study follow-up for 2 years and for long‑term off‑study review.

How the study is structured. Phase I/II interventional trial, open‑label, non‑randomized, single‑group (monocentric). Participants receive an infusion of their own gene‑modified CD34+ cells (one dose); an additional gene‑modified T‑cell infusion may be given later if specified. No masking is used. Safety and effectiveness measures, laboratory tests, and long‑term follow‑up are planned (outcomes tracked up to multiple years).

Questions you could ask

These questions are suggestions for a conversation with the study team or your own clinician, not advice.

  • This is an early-phase study, mainly about safety and dose. What is already known about this treatment?
  • The registry says recruitment has not started. When is it expected to open, and can I register interest now?
  • The listed sites are in France. Is any of them reachable for me, and does the study help with travel?
  • Which of the eligibility criteria would need to be checked with tests before I could join?

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Important dates

Study start
May 2026 (estimated)
Primary completion
January 2029 (estimated)
Study completion
January 2030 (estimated)
Target enrollment
5 participants (estimated)
Last updated on registry
May 22, 2026
Data verified
Oct 10, 2026

Sponsor and research team

The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.

Lead sponsor
Assistance Publique - Hôpitaux de Paris
Collaborators
  • URC-CIC Paris Descartes Necker Cochin

Central study contact

If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.

Participating sites (1)

Terms used on this page · explanations by MedicalUpdates.ai

HSCT
A procedure that replaces blood-forming cells after high-dose treatment. 'Autologous' uses the person's own cells collected beforehand; 'allogeneic' uses cells from a donor.
overall survival
The length of time from the start of the study or treatment that participants are alive, whatever the cause of death.
Complete remission
No sign of the condition can be found with the tests used in the study. It does not always mean the condition is gone permanently, and the definition depends on the condition and the study.
absolute neutrophil count
The number of neutrophils, a type of white blood cell that fights infection, in a blood sample. Studies often require it to be above a set level.
informed consent
The process of explaining a study, including its risks and what participation involves, so that a person can decide freely whether to take part. Consent is usually documented in writing, and a participant can choose to leave the study later.
follow-up
The period after treatment or enrolment during which participants are observed or contacted, for example to record side effects or outcomes.
investigational drug
A treatment that is being tested and has not been approved for this use. It may be approved for a different condition. Being studied does not mean it works or is available outside the study.
Inclusion Criteria
The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
Exclusion Criteria
The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.

The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.

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