Familial Hemophagocytic Lymphohistiocytosis Type 3 (FHL 3)Phase 1/2MUNC13-4NCT06736080
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 1/2 study testing MUNC-CD34 and MUNC-T3 in people with Familial Hemophagocytic Lymphohistiocytosis Type 3 (FHL 3), run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial 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… Read more about this study
- Who is it for?
- Ages 3 months to 45 years
- Conditions the study is for
- Familial Hemophagocytic Lymphohistiocytosis Type 3 (FHL 3)
- What is being tested?
- MUNC-CD34 and MUNC-T3
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteFrance
- Study dates
- May 2026to Jan 2030
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 months to 45 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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)
Show all 13Show fewer
- 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
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site
Department of Biotherapy, Hopital Necker Enfants Malades
Paris, 75015
Marina CAVAZZANA, MD, PhD, 01 44 49 50 68 ext. +33, m.cavazzana@aphp.fr
About this study
Official title: 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
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.
- Being tested
- MUNC-CD34, MUNC-T3
- Keywords
- Familial Hemophagocytic Lymphohistiocytosis type 3 (FHL 3), Munc13.4, Gene Therapy, Lentiviral Vector
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MUNC-CD34Genetic
- Dosage: ≥ 2 x10e6 CD34/kg after thawing, dose limit: 20x10e6 CD34+ cells/kg
- Route of administration: intravenous, on D0
MUNC-T3Genetic
- 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 group | Role | What they receive |
|---|---|---|
| MUNC | Experimental | Not described Receives: Genetic: MUNC-CD34; Genetic: MUNC-T3 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Transplantation Related Mortality (TRM)
Measured: up to 6 months post treatment
Frequency and severity of clinical AEs and laboratory parameters
Adverse event will be measured using CTCAE
Measured: throughout the whole period of the research, up to 60 months
Incidence of clinically detectable malignancy and/or abnormal clonal dominance assessed as related to study treatment
Bone marrow analysis and VISA
Measured: At 12 months post treatment
Detection of Replication -Competent Lentivirus (RCL)
Measured: at 3, 6 and 12 months post treatment, then yearly up to 60 months
Secondary outcomes (14)
Neutrophil and platelet recovery
ANC> 500/µl, Platelets > 20.000/µl on two consecutive days without transfusion
Measured: throughout the whole period of the research, up to 60 months
Quantification of the transgene copy number (VCN) on drug substance at time of cryopreservation, on PBMC, sorted T-CD3+ and sorted NK cells
Measured: at 1, 2, 3, 6, 9, 12, 18 and 24 months post treatment
Quantification of the UNC13D RNA on PBMC
by Q-PCR
Measured: at 1, 2, 3, 6, 9, 12, 18 and 24 post treatment
Quantification of Munc13.4 protein level in the drug substance and on peripheral blood mononuclear cells and on sorted CD3+ and CD56+ cells in function of their number
by western blot
Measured: at 6, 12 and 24 months post treatment
Disease-free survival (DFS). evaluate the Persistent HLH remission
Disease-free survival (DFS).
Measured: at M6 and 24 months post treatment.
Vector Copy Number (VCN) in Peripheral Blood Mononuclear Cells (PBMC)
> 0.2.
Measured: At M6 and 24 months post treatment.
Determination of the total number of T-cells and distribution of different subpopulations.
Naïve and memory CD4+ and CD8+ T cells will be evaluated using CCR7/CD45RA/RO markers, and the quantification of activation marker will be performed by the expression of DR+, by flow cytometry.
Measured: At 1, 2, 3, 6, 12, 18 and 24 months post treatment
Correction of degranulation function in T-CD3
Measured: at 6 months and 24 months post treatment
Integration site analyse study
Measured: at 24 months post treatment
Needs of PICU support
Measured: up to 24 months post treatment
Endothelial complications
Measured: up to 24 months post treatment
Infectious diseases
Measured: up to 24 months post treatment
Estimate of the cost of the complete procedure, from mobilisation to transplant
Measured: up to 24 months post treatment
Estimate of the 24 months total cost.
Measured: up to 24 months post treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Dec 2024
- Study startMay 2026 (estimated)
- Primary completionJan 2029 (estimated)
- Study completionJan 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Familial Hemophagocytic Lymphohistiocytosis Type 3 (FHL 3)Studies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- URC-CIC Paris Descartes Necker Cochin
- Responsible party
- Sponsor
- Investigators
- Jean-Sébastien DIANA, MD, PhD, Study director, Assitance publique - Hôpitaux de ParisChantal LAGRESLE, PHD, Study director, Inserm Institut Imagine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06736080
- Sponsor's protocol ID
- APHP240201
- Other IDs
- 2023-507334-24-00, 2023
- Acronym
- MUNC13-4
- Status last verified
- May 2026
- First submitted
- 4 Dec 2024
- Last updated
- 22 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT06736080
- Acronym / sponsor ID
- MUNC13-4 / APHP240201
- Keywords
- Familial Hemophagocytic Lymphohistiocytosis type 3 (FHL 3), Munc13.4, Gene Therapy, Lentiviral Vector
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 5 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- URC-CIC Paris Descartes Necker Cochin
- Study start
- May 2026 (estimated)
- Primary completion
- Jan 2029 (estimated)
- Study completion
- Jan 2030 (estimated)
- First posted
- 16 Dec 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| MUNC | Experimental | Genetic: MUNC-CD34, Genetic: MUNC-T3 |
Who may qualify
- Ages
- 3 months to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (13 listed)
- 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:
- 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.
Key exclusion criteria (11 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MUNC-CD34* Dosage: ≥ 2 x10e6 CD34/kg after thawing, dose limit: 20x10e6 CD34+ cells/kg * Route of administration: intravenous, on D0 | Genetic | MUNC |
| 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 | Genetic | MUNC |
Primary outcome
Incidence of Transplantation Related Mortality (TRM)
Time frame: up to 6 months post treatment
Frequency and severity of clinical AEs and laboratory parameters
Time frame: 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
Time frame: At 12 months post treatment
Bone marrow analysis and VISA
Detection of Replication -Competent Lentivirus (RCL)
Time frame: at 3, 6 and 12 months post treatment, then yearly up to 60 months
14 secondary outcomes
Neutrophil and platelet recovery
Time frame: throughout the whole period of the research, up to 60 months
Quantification of the transgene copy number (VCN) on drug substance at time of cryopreservation, on PBMC, sorted T-CD3+ and sorted NK cells
Time frame: at 1, 2, 3, 6, 9, 12, 18 and 24 months post treatment
Quantification of the UNC13D RNA on PBMC
Time frame: at 1, 2, 3, 6, 9, 12, 18 and 24 post treatment
Quantification of Munc13.4 protein level in the drug substance and on peripheral blood mononuclear cells and on sorted CD3+ and CD56+ cells in function of their number
Time frame: at 6, 12 and 24 months post treatment
Disease-free survival (DFS). evaluate the Persistent HLH remission
Time frame: at M6 and 24 months post treatment.
Vector Copy Number (VCN) in Peripheral Blood Mononuclear Cells (PBMC)
Time frame: At M6 and 24 months post treatment.
Determination of the total number of T-cells and distribution of different subpopulations.
Time frame: At 1, 2, 3, 6, 12, 18 and 24 months post treatment
Correction of degranulation function in T-CD3
Time frame: at 6 months and 24 months post treatment
Integration site analyse study
Time frame: at 24 months post treatment
Needs of PICU support
Time frame: up to 24 months post treatment
Endothelial complications
Time frame: up to 24 months post treatment
Infectious diseases
Time frame: up to 24 months post treatment
Estimate of the cost of the complete procedure, from mobilisation to transplant
Time frame: up to 24 months post treatment
Estimate of the 24 months total cost.
Time frame: up to 24 months post treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2026.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Jean-Sébastien DIANA, MD, PhD study director
Assitance publique - Hôpitaux de Paris
Chantal LAGRESLE, PHD study director
Inserm Institut Imagine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing MUNC-CD34 and MUNC-T3 in people with Familial Hemophagocytic Lymphohistiocytosis Type 3 (FHL 3), run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 22 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Marina CAVAZZANA, MD, PhD (01 44 49 50 68 ext. +33, m.cavazzana@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Transplantation Related Mortality (TRM) (time frame: up to 6 months post treatment). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 May 2026.