Familial LymphohistiocytosisLongRead-HLHNCT07741747
Impact of Ultra-fast Genetic Diagnosis of Familial Lymphohistiocytosis on the Time to Bone Marrow Transplantation and Overall Survival
A study testing Third-generation sequencing in people with Familial Lymphohistiocytosis and Lymphohistiocytosis, run by Assistance Publique Hopitaux De Marseille at 1 site in France.
Trial summary
Familial lymphohistiocytosis (FHL) is a group of rare genetic diseases (around fifteen cases per year in France). The defect in T lymphocyte cytotoxicity resulting from this disease is responsible for hemophagocytic lymphohistiocytosis (HLH). Promptly treatment of HLH is essential for prognosis. Read more about this study
- Who is it for?
- Ages Up to 18 years
- Conditions the study is for
- Familial Lymphohistiocytosis, Lymphohistiocytosis
- What is being tested?
- Third-generation sequencing
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 240 participants
- Where
- 1 siteFrance
- Study dates
- Oct 2026to Oct 2030
- Phase
- Interventional
- 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 Up to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Children under 18 years old
- Confirmed or suspected diagnosis of FHL or a related genetic syndrome predisposing to HLH (e.g. Griscelli Syndrome, Chédiak-Higashi Syndrome, XLP1, XLP2) or a family history of lymphohistiocytic activation syndrome
- Presence of at least 5 of the 8 following criteria (diagnostic criteria according to the definition of the "Histiocyte Society" (1)):
- Fever
- Splenomegaly
- Hypertriglyceridemia ≥ 3 mmol/l and/or hypofibrinogenemia≤ 1.5g/l
Show all 13Show fewer
- Hemophagocytosis found in a histological sample
- Decreased or absent NK function (<10% of the laboratory normal)
- Ferritin ≥ 500μg/l
- Soluble CD25 ≥ 2,400U/ml or presence of activated T cells in phenotyping
- Cytopenia (affecting at least two blood cell lines): Haemoglobin < 9.0 g/dl, Platelets <100 G/L, Neutrophils <1,0 G/L
- Patient benefiting from social security coverage
- The legal guardian(s) who have signed the informed consent form
Who cannot join
- Age ≥ 18 years
- Solid tumor, leukemia, lymphoma
- Subjects covered by articles L1121-5 to 1121-8 of the public health code (patients under guardianship or curatorship, patient deprived of liberty, pregnant or breadtfeeding woman)
- Persons who do not understand the French language
- Patient in the exclusion period of another research protocol at the time of signing the consent form
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
Assistance Publique - Hôpitaux de Marseille
Marseille
Vincent BARLOGIS, Pr, 04 91 38 98 21 ext. 33, vincent.barlogis@ap-hm.fr
About this study
Official title: Impact of Ultra-rapid Genetic Diagnosis of Primary Haemophagocytic Lymphohistiocytosis on the Time to Haematopoietic Stem Cell Transplantation
Familial lymphohistiocytosis (FHL) is a group of rare genetic diseases (around fifteen cases per year in France). The defect in T lymphocyte cytotoxicity resulting from this disease is responsible for hemophagocytic lymphohistiocytosis (HLH). Promptly treatment of HLH is essential for prognosis. These diseases are fatal without a bone marrow transplant, with an overall 5-year survival rate of no more than 80% for FHL. The genetic or acquired nature of HLH is not easy to determine. An infectious trigger can be confounding when it occurs in an FHL. But above all, functional biological tests demonstrating a T lymphocyte cytotoxicity defects are difficult to interpret. Genetic diagnosis is therefore essential for confirming the primary nature of HLH, and for initiating targeted treatments (first stage: putting HLH into remission with chemotherapy or immunotherapy; second stage: bone marrow transplant). Genetic diagnosis of FHL is therefore a matter of emergency, and is currently based on targeted gene panel exploration (fragmentation sequencing) requiring 6 to 8 weeks. Recently, the development of third-generation sequencing (TGS) has revolutionized genomic medicine, enabling unitary sequencing in real time. As a result of this innovation, certain private molecular diagnostic specialties can now access this new emergency genomic medicine.
Aim: the main aim of this study is to demonstrate the feasibility of a national circuit for ultra-rapid genetic diagnosis of pediatric HLH revealing familial lymphohistiocytosis. The secondary objective is to evaluate the impact of this early genetic diagnosis on the delay to remission of HLH and the delay to transplantation.
Read more
Methods: This prospective, multicenter study measures the time required for genetic diagnosis of FHL in pediatric HLH, using innovative TGS sequencing technology.
Perspectives: Fast genomic diagnosis of FHL will considerably shorten the time to confirm the diagnosis, to obtain HLH remission and, finally, to reach transplantation faster.
- Conditions
- Familial Lymphohistiocytosis, Lymphohistiocytosis
- Being tested
- Third-generation sequencing
- Keywords
- Lymphohistiocytosis, Rare disease, Fast-genomic, Precision medecin, Bone marrow transplant
- Medical subject headings
- Rare Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Third-generation sequencingDiagnostic test
Blood sample will be collected in order to perform the third-generation sequencing testing which sould give results in a 5 day delay, instead of 6-8 weeks (standard testing)
| Study group | Role | What they receive |
|---|---|---|
| Prospectif Group | Experimental | Group of 200 patients who will be tested prospectively Receives: Diagnostic Test: Third-generation sequencing |
| Retrospectif Group | No intervention | Group of 40 patients whose data will be retrospectivly compared to the prospectif group |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time (in days) from clinical suspicion to hematopoietic stem cell transplantation
Measured: From enrollment until 24 months post transplantation
Secondary outcomes (9)
Proportion of patients completing the full diagnostic pathway
Measured: From enrollment until 24 months post transplantation
Time from clinical suspicion to receipt of the genetic result (in days)
Measured: From enrollment until 24 months post transplantation
Time from clinical suspicion to initiation of specific immunomodulatory therapy (in days)
Measured: From enrollment until 24 months post transplantation
Overall survival
Measured: From enrollment until 6, 12 and and 24 months post transplation
Total length of hospital stays (in days)
Measured: From enrollment until 24 months post transplantation
Number of days in intensive care
Measured: From enrollment until 24 months post transplantation
Direct hospital and medical costs
Measured: From enrollment until 24 months post transplantation
Number of inappropriate or unnecessary treatments avoided
Measured: From enrollment until 24 months post transplantation
Progression-free survival
Measured: From enrollment until 6, 12 and and 24 months post transplation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Aug 2026
- Study startOct 2026 (estimated)
- Primary completionOct 2028 (estimated)
- Study completionOct 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Familial LymphohistiocytosisStudies of the same condition, open and under way.
- More trials run by Assistance Publique Hopitaux De MarseilleThe 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 N/A
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 240 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique Hopitaux De Marseille
- Sponsor type
- University, hospital or other
- Collaborators
- Aix Marseille Université, Etablissement Français du Sang
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07741747
- Sponsor's protocol ID
- RCAPHM25_0567
- Other IDs
- 2026-A00463-48
- Acronym
- LongRead-HLH
- Status last verified
- Jul 2026
- First submitted
- 27 Jul 2026
- Last updated
- 3 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- 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 3 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Ultra-rapid Genetic Diagnosis of Primary Haemophagocytic Lymphohistiocytosis on the Time to Haematopoietic Stem Cell Transplantation
- ClinicalTrials.gov ID
- NCT07741747
- Acronym / sponsor ID
- LongRead-HLH / RCAPHM25_0567
- Conditions
- Familial Lymphohistiocytosis, Lymphohistiocytosis
- Keywords
- Lymphohistiocytosis, Rare disease, Fast-genomic, Precision medecin, Bone marrow transplant
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 240 participants (estimated)
- Lead sponsor
- Assistance Publique Hopitaux De MarseilleUniversity, hospital or other
- Collaborators
- Aix Marseille Université, Etablissement Français du Sang
- Study start
- Oct 2026 (estimated)
- Primary completion
- Oct 2028 (estimated)
- Study completion
- Oct 2030 (estimated)
- First posted
- 3 Aug 2026 (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.
Familial lymphohistiocytosis (FHL) is a group of rare genetic diseases (around fifteen cases per year in France). The defect in T lymphocyte cytotoxicity resulting from this disease is responsible for hemophagocytic lymphohistiocytosis (HLH). Promptly treatment of HLH is essential for prognosis. These diseases are fatal without a bone marrow transplant, with an overall 5-year survival rate of no more than 80% for FHL. The genetic or acquired nature of HLH is not easy to determine. An infectious trigger can be confounding when it occurs in an FHL. But above all, functional biological tests demonstrating a T lymphocyte cytotoxicity defects are difficult to interpret. Genetic diagnosis is therefore essential for confirming the primary nature of HLH, and for initiating targeted treatments (first stage: putting HLH into remission with chemotherapy or immunotherapy; second stage: bone marrow transplant). Genetic diagnosis of FHL is therefore a matter of emergency, and is currently based on targeted gene panel exploration (fragmentation sequencing) requiring 6 to 8 weeks. Recently, the development of third-generation sequencing (TGS) has revolutionized genomic medicine, enabling unitary sequencing in real time. As a result of this innovation, certain private molecular diagnostic specialties can now access this new emergency genomic medicine.
Aim: the main aim of this study is to demonstrate the feasibility of a national circuit for ultra-rapid genetic diagnosis of pediatric HLH revealing familial lymphohistiocytosis. The secondary objective is to evaluate the impact of this early genetic diagnosis on the delay to remission of HLH and the delay to transplantation.
Methods: This prospective, multicenter study measures the time required for genetic diagnosis of FHL in pediatric HLH, using innovative TGS sequencing technology.
Perspectives: Fast genomic diagnosis of FHL will considerably shorten the time to confirm the diagnosis, to obtain HLH remission and, finally, to reach transplantation faster.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Prospectif Group | Experimental | Diagnostic Test: Third-generation sequencingGroup of 200 patients who will be tested prospectively |
| Retrospectif Group | No intervention | –Group of 40 patients whose data will be retrospectivly compared to the prospectif group |
Who may qualify
- Ages
- Up to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (13 listed)
- Children under 18 years old
- Confirmed or suspected diagnosis of FHL or a related genetic syndrome predisposing to HLH (e.g. Griscelli Syndrome, Chédiak-Higashi Syndrome, XLP1, XLP2) or a family history of lymphohistiocytic activation syndrome
- Presence of at least 5 of the 8 following criteria (diagnostic criteria according to the definition of the "Histiocyte Society" (1)):
- Patient benefiting from social security coverage
- The legal guardian(s) who have signed the informed consent form
Key exclusion criteria (5 listed)
- Age ≥ 18 years
- Solid tumor, leukemia, lymphoma
- Subjects covered by articles L1121-5 to 1121-8 of the public health code (patients under guardianship or curatorship, patient deprived of liberty, pregnant or breadtfeeding woman)
- Persons who do not understand the French language
- Patient in the exclusion period of another research protocol at the time of signing the consent form
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 |
|---|---|---|
| Third-generation sequencingBlood sample will be collected in order to perform the third-generation sequencing testing which sould give results in a 5 day delay, instead of 6-8 weeks (standard testing) | Diagnostic test | Prospectif Group |
Primary outcome
Time (in days) from clinical suspicion to hematopoietic stem cell transplantation
Time frame: From enrollment until 24 months post transplantation
9 secondary outcomes
Proportion of patients completing the full diagnostic pathway
Time frame: From enrollment until 24 months post transplantation
Time from clinical suspicion to receipt of the genetic result (in days)
Time frame: From enrollment until 24 months post transplantation
Time from clinical suspicion to initiation of specific immunomodulatory therapy (in days)
Time frame: From enrollment until 24 months post transplantation
Overall survival
Time frame: From enrollment until 6, 12 and and 24 months post transplation
Total length of hospital stays (in days)
Time frame: From enrollment until 24 months post transplantation
Number of days in intensive care
Time frame: From enrollment until 24 months post transplantation
Direct hospital and medical costs
Time frame: From enrollment until 24 months post transplantation
Number of inappropriate or unnecessary treatments avoided
Time frame: From enrollment until 24 months post transplantation
Progression-free survival
Time frame: From enrollment until 6, 12 and and 24 months post transplation
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 3 Aug 2026.
- Individual participant dataSharing planned: No
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Third-generation sequencing in people with Familial Lymphohistiocytosis and Lymphohistiocytosis, run by Assistance Publique Hopitaux De Marseille 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 5 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 3 Aug 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.
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 Vincent BARLOGIS, Pr (04 91 38 98 21 ext. 33, vincent.barlogis@ap-hm.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time (in days) from clinical suspicion to hematopoietic stem cell transplantation (time frame: From enrollment until 24 months post transplantation). 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 3 Aug 2026.