Hemophagocytic Lymphohistiocytosis (HLH)Phase 1/2C-HLHNCT02472054
Treatment of Familiar Lymphohistiocytosis
A Phase 1/2 study testing Alemtuzumab, Methyl Prednisolone (MP) and Cyclosporin A (CSA) in people with Hemophagocytic Lymphohistiocytosis (HLH), run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
The purpose of this project is to study the number of surviving patients until hematopoietic stem cell transplantation (HSCT) after first line treatment of hemophagocytic lymphohistiocytosis (HLH) by Alemtuzumab Read more about this study
- Who is it for?
- Ages Up to 17 years
- Conditions the study is for
- Hemophagocytic Lymphohistiocytosis (HLH)
- What is being tested?
- Alemtuzumab, Methyl Prednisolone (MP) and Cyclosporin A (CSA)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 1 siteFrance
- Study dates
- 29 Jun 2015to 20 May 2020
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
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 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Patient < 18 years
- Patient with diagnosis of hemophagocytic lymphohistiocytic syndrome confirmed by at least one of the following two criteria :
- Genetic diagnosis FHL or other genetic disease predisposing to HLH like Chediak-Higashi syndrome, Griscelli syndrome type II and X-linked lymphoproliferative syndrome type I and II (XLP-1 and XLP-2) or positive family history of HLH
- Presence of at least 5 of the following 8 criteria (diagnostic criteria as defined by the "Histiocyte Society" ) :
- Fever
- Splenomegaly
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- Cytopenia (affecting at least two cell lineages : Hemoglobin <9.0 g / dl, Platelets <100.000/μl, Absolute neutrophil count (ANC) <1.000/µl)
- Hypertriglyceridemia and / or hypofibrinogenemia (Fasting triglycerides ≥ 3 mmol / l, Fibrinogen ≤ 1.5 g / l)
- Haemophagocytosis found in a histological specimen (without evidence of a malignant process and rheumatic disease)
- Decreased or absent NK function (<10% of the laboratory standard)
- Ferritin ≥ 500μg / l
- Soluble CD25 ≥ 2.400U/ml or presence of activated T cells in the immune phenotyping
- Patient without prior specific treatment of lymphohistiocytic activation syndrome or under treatment with corticosteroids and / or ciclosporin.
- Patient beneficiary of a health insurance scheme
- Holder (s) of parental authority who signed the informed consent
- Man or woman in reproductive age willing to take reliable contraceptive measures during the treatment and 6 months after the end of the treatment
- Specific situation of patients with neurological involvement :
- Most patients with neurological involvement caused by a HLH will meet the inclusion criteria. However some patients may present an isolated neurological involvement as the first manifestation of familiar lymphohistiocytosis as described in the literature. These patients do not always present all the inclusion criteria. However their clinical condition may justify their inclusion prior to the confirmation of a genetic diagnosis and/or the detection of all required diagnostic inclusion criteria.
- In the absence of the required 5 out of 8 diagnostic criteria, the eventual inclusion of patients with predominant neurological involvement will be evaluated by a scientific committee to judge their inclusion or not in the study. The remaining inclusion and exclusion criteria must be fulfilled. A written report will be established.
Who cannot join
- Age ≥ 18 years
- Patients previously treated with Anti-Thymoglobulin (SAL), etoposide (VP16) or Alemtuzumab.
- Confirmed or suspected diagnosis of a malignant or rheumatic disease
- Contraindication (s) to the administration of Alemtuzumab :
- Hypersensitivity to murine proteins or to any of the excipients (sodium chloride, dibasic sodium phosphate, potassium chloride, potassium dihydrogen phosphate, polysorbate 80, disodium edetate dihydrate, and water for injection)
- General evolving infection except infections that are the triggering factor of the HLH .
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- HIV
- Progressing malignant tumors
- Pregnancy
Trial locations and contacts
1 site in 1 country.
About this study
Official title: First Line Treatment of Familiar Lymphohistiocytosis by Alemtuzumab (CAMPATH®)
The purpose of this project is to study the number of surviving patients until hematopoietic stem cell transplantation (HSCT) after first line treatment of hemophagocytic lymphohistiocytosis (HLH) by Alemtuzumab
Read the detailed description
The hemophagocytic lymphohistiocytosis (HLH) or lymphohistiocytic activation syndrome is an inflammatory condition caused by a uncontrolled proliferation of activated lymphocytes and macrophages secreting an excess of inflammatory cytokines. Familial hemophagocytic lymphohistiocytosis (FHL) is a rare disorder of the immune system, which is invariably fatal when untreated. Treatment requires the achievement of remission of HLH prior to allogeneic hematopoietic stem cell transplantation, the only curative therapy to date.
Despite significant progress in the treatment, mortality remains high and an important number of patients will die before being eligible for HSCT.
A better understanding of the pathophysiology of FHL has opened new avenues for immunotherapy. Based on previous observations concerning the utilization of Anti-thymoglobulins (ATG) for the treatment of patients with FHL, the protocol propose a new therapeutic strategy using Alemtuzumab in association with steroids as first line treatment in FHL. This proposition is based on the hypothesis that Alemtuzumab, capable of killing T lymphocytes efficiently in vivo, should be better tolerated than ATG. In fact, in contrast to the mechanism of action of ATG, Alemtuzumab does not activate T lymphocytes.
A better tolerance and efficacy of Alemtuzumab is expected in the treatment of the hemophagocytic lymphohistiocytic syndrome. This may have a positive impact not only on survival until HSCT, but also on overall survival and quality of life with regard to long-term neurological sequelae.
This is a multicenter, open, phase I/II, non-comparative, non randomized study. Patients are recruited by the investigators during hospitalization for a first episode of lymphohistiocytic activation syndrome requiring specific treatment.
Several visits (including the final visit) are scheduled within the trial over a period of approximately 10 months for all patients, from the signature of the consent up to 6 months after hematopoietic stem cell transplantation.
The recruitment period will be 48 months; the total period of the study is 58 months. The treatment consists in an intravenous administration of CAMPATH®.
For the research purpose, investigators will collect specific samples for:
- biobank (Cytokine dosage) at the inclusion visit and the day prior to the conditioning;
- pharmacokinetics of CAMPATH® : at every cure of CAMPATH® and every week. Also diagnostic lumbar puncture at the inclusion visit, day 14 is required to document the response to treatment and to determine the result of the therapeutic care.
The efficacy of the treatment will be measured to Day14, Day21 and Day28. All adverse events must be reported in the e-Case Report Form (e-CRF)
- Conditions
- Hemophagocytic Lymphohistiocytosis (HLH)
- Being tested
- Alemtuzumab, Methyl Prednisolone (MP), Cyclosporin A (CSA)
- Keywords
- hemophagocytic lymphohistiocytosis (HLH), Alemtuzumab (CAMPATH®)
- Medical subject headings
- Lymphohistiocytosis, Hemophagocytic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlemtuzumabDrug
Also called CAMPATH®
Methyl Prednisolone (MP)Drug
Cyclosporin A (CSA)Drug
| Study group | Role | What they receive |
|---|---|---|
| hemophagocytic lymphohistiocytosis (HLH) | Experimental | Alemtuzumab (CAMPATH®)
1. Initial Treatment (D1 to D3) D1: 0.5 mg / kg / day Alemtuzumab combined with 2 mg /kg/d of IV Methylprednisolone (MP) or PO Prednisolone, and IVC or PO cyclosporine (CSA) (target rate from 150 to 200 ng / ml in the absence of renal failure) D2 and D3: 1 mg / kg / day Alemtuzumab combined with 2 mg / kg / d of IV MP or PO Prednisolone and IVC or PO CSA (target rate 150-200 ng / ml)
The maximum dose of Alemtuzumab is limited to 30 mg per day (1 vial).
2. Maintenance treatment (D4 to D14)
* MP/Prednisolone progressive tapering starting at D4 (2 mg / kg / day) to reach the dose 0.5 mg / kg / day at D14
* CSA IVC or PO at a target rate of 150-200 ng / ml Receives: Drug: Alemtuzumab; Drug: Methyl Prednisolone (MP); Drug: Cyclosporin A (CSA) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of surviving patients until HSCT
Measured: Day 1 until transplantation, up to 4 months
Secondary outcomes (4)
Number of complete remissions following treatment
To assess the efficacy of the Alemtuzumab
Measured: Day 14, Day 21, Day 28
Time of delay between the first administration of Alemtuzumab and complete remission
To assess the efficacy of the Alemtuzumab
Measured: Day 14, Day 21, Day 28
Dosage of Alemtuzumab
Pharmacokinetic
Measured: Day1-3, Day7, Day15-16, Day22-23, Day28
Number of side effects
To assess the tolerance of the Alemtuzumab
Measured: Day 1 until transplantation, up to 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2015 (estimated)
- Study start29 Jun 2015
- Primary completion12 Sep 2019
- Study completion20 May 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hemophagocytic Lymphohistiocytosis (HLH)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
- 29 participants (actual)
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
- Alain FISCHER, MD, PhD, Study director, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02472054
- Sponsor's protocol ID
- P120109
- Other IDs
- 2014-005585-30, 2014
- Acronym
- C-HLH
- Status last verified
- Mar 2026
- First submitted
- 8 Jun 2015
- Last updated
- 30 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- First Line Treatment of Familiar Lymphohistiocytosis by Alemtuzumab (CAMPATH®)
- ClinicalTrials.gov ID
- NCT02472054
- Acronym / sponsor ID
- C-HLH / P120109
- Conditions
- Hemophagocytic Lymphohistiocytosis (HLH)
- Keywords
- hemophagocytic lymphohistiocytosis (HLH), Alemtuzumab (CAMPATH®)
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- URC-CIC Paris Descartes Necker Cochin
- Study start
- 29 Jun 2015 (actual)
- Primary completion
- 12 Sep 2019 (actual)
- Study completion
- 20 May 2020 (actual)
- First posted
- 15 Jun 2015 (estimated)
- 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 purpose of this project is to study the number of surviving patients until hematopoietic stem cell transplantation (HSCT) after first line treatment of hemophagocytic lymphohistiocytosis (HLH) by Alemtuzumab
Detailed description
The hemophagocytic lymphohistiocytosis (HLH) or lymphohistiocytic activation syndrome is an inflammatory condition caused by a uncontrolled proliferation of activated lymphocytes and macrophages secreting an excess of inflammatory cytokines. Familial hemophagocytic lymphohistiocytosis (FHL) is a rare disorder of the immune system, which is invariably fatal when untreated. Treatment requires the achievement of remission of HLH prior to allogeneic hematopoietic stem cell transplantation, the only curative therapy to date.
Despite significant progress in the treatment, mortality remains high and an important number of patients will die before being eligible for HSCT.
A better understanding of the pathophysiology of FHL has opened new avenues for immunotherapy. Based on previous observations concerning the utilization of Anti-thymoglobulins (ATG) for the treatment of patients with FHL, the protocol propose a new therapeutic strategy using Alemtuzumab in association with steroids as first line treatment in FHL. This proposition is based on the hypothesis that Alemtuzumab, capable of killing T lymphocytes efficiently in vivo, should be better tolerated than ATG. In fact, in contrast to the mechanism of action of ATG, Alemtuzumab does not activate T lymphocytes.
A better tolerance and efficacy of Alemtuzumab is expected in the treatment of the hemophagocytic lymphohistiocytic syndrome. This may have a positive impact not only on survival until HSCT, but also on overall survival and quality of life with regard to long-term neurological sequelae.
This is a multicenter, open, phase I/II, non-comparative, non randomized study. Patients are recruited by the investigators during hospitalization for a first episode of lymphohistiocytic activation syndrome requiring specific treatment.
Several visits (including the final visit) are scheduled within the trial over a period of approximately 10 months for all patients, from the signature of the consent up to 6 months after hematopoietic stem cell transplantation.
The recruitment period will be 48 months; the total period of the study is 58 months. The treatment consists in an intravenous administration of CAMPATH®.
For the research purpose, investigators will collect specific samples for:
- biobank (Cytokine dosage) at the inclusion visit and the day prior to the conditioning;
- pharmacokinetics of CAMPATH® : at every cure of CAMPATH® and every week. Also diagnostic lumbar puncture at the inclusion visit, day 14 is required to document the response to treatment and to determine the result of the therapeutic care.
The efficacy of the treatment will be measured to Day14, Day21 and Day28. All adverse events must be reported in the e-Case Report Form (e-CRF)
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| hemophagocytic lymphohistiocytosis (HLH) | Experimental | Drug: Alemtuzumab, Drug: Methyl Prednisolone (MP), Drug: Cyclosporin A (CSA)Alemtuzumab (CAMPATH®) 1. Initial Treatment (D1 to D3) D1: 0.5 mg / kg / day Alemtuzumab combined with 2 mg /kg/d of IV Methylprednisolone (MP) or PO Prednisolone, and IVC or PO cyclosporine (CSA) (target rate from 150 to 200 ng / ml in the absence of renal failure) D2 and D3: 1 mg / kg / day Alemtuzumab combined with 2 mg / kg / d of IV MP or PO Prednisolone and IVC or PO CSA (target rate 150-200 ng / ml) The maximum dose of Alemtuzumab is limited to 30 mg per day (1 vial). 2. Maintenance treatment (D4 to D14) * MP/Prednisolone progressive tapering starting at D4 (2 mg / kg / day) to reach the dose 0.5 mg / kg / day at D14 * CSA IVC or PO at a target rate of 150-200 ng / ml |
Who may qualify
- Ages
- Up to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (19 listed)
- Patient < 18 years
- Patient with diagnosis of hemophagocytic lymphohistiocytic syndrome confirmed by at least one of the following two criteria :
- Patient without prior specific treatment of lymphohistiocytic activation syndrome or under treatment with corticosteroids and / or ciclosporin.
- Patient beneficiary of a health insurance scheme
- Holder (s) of parental authority who signed the informed consent
Key exclusion criteria (9 listed)
- Age ≥ 18 years
- Patients previously treated with Anti-Thymoglobulin (SAL), etoposide (VP16) or Alemtuzumab.
- Confirmed or suspected diagnosis of a malignant or rheumatic disease
- Contraindication (s) to the administration of Alemtuzumab :
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 |
|---|---|---|
| AlemtuzumabAlso: CAMPATH® | Drug | hemophagocytic lymphohistiocytosis (HLH) |
| Methyl Prednisolone (MP) | Drug | hemophagocytic lymphohistiocytosis (HLH) |
| Cyclosporin A (CSA) | Drug | hemophagocytic lymphohistiocytosis (HLH) |
Primary outcome
Number of surviving patients until HSCT
Time frame: Day 1 until transplantation, up to 4 months
4 secondary outcomes
Number of complete remissions following treatment
Time frame: Day 14, Day 21, Day 28
Time of delay between the first administration of Alemtuzumab and complete remission
Time frame: Day 14, Day 21, Day 28
Dosage of Alemtuzumab
Time frame: Day1-3, Day7, Day15-16, Day22-23, Day28
Number of side effects
Time frame: Day 1 until transplantation, up to 4 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 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. This study is not recruiting at the moment.
Alain FISCHER, MD, PhD study director
Assistance Publique - Hôpitaux de Paris
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 Alemtuzumab, Methyl Prednisolone (MP) and Cyclosporin A (CSA) in people with Hemophagocytic Lymphohistiocytosis (HLH), 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 19 inclusion and 9 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: finished, as of the sponsor's last update on 30 Mar 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of surviving patients until HSCT (time frame: Day 1 until transplantation, up to 4 months). 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 30 Mar 2026.