Treatment of Familiar Lymphohistiocytosis

• Status: Completed
• Trial end date: 2020-05-20
• Target enrollment: 0
• Participant gender: All

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

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Assistance Publique - Hôpitaux de Paris
• Treatments: Alemtuzumab; Cyclosporine; Cyclosporins; Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate

Criteria

Inclusion Criteria :

• 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

• 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.

Exclusion Criteria :

• 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 .

• HIV

• Progressing malignant tumors

• Pregnancy