Treatment of Familiar Lymphohistiocytosis

NCT02472054 | Completed Phase 1 DMC

• 2 other identifiers: P1201092014-005585-30
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Hemophagocytic Lymphohistiocytosis (HLH)

Keywords

hemophagocytic lymphohistiocytosis (HLH); Alemtuzumab (CAMPATH®)

Outcome Measures

Primary Outcomes (1)

• Number of surviving patients until HSCT

  Day 1 until transplantation, up to 4 months

Secondary Outcomes (4)

• Number of complete remissions following treatment

  Day 14, Day 21, Day 28

• Time of delay between the first administration of Alemtuzumab and complete remission

  Day 14, Day 21, Day 28

• Dosage of Alemtuzumab

  Day1-3, Day7, Day15-16, Day22-23, Day28

• Number of side effects

  Day 1 until transplantation, up to 4 months

Study Arms (1)

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

Drug: Alemtuzumab; Drug: Methyl Prednisolone (MP); Drug: Cyclosporin A (CSA)

Interventions

Alemtuzumab DRUG

Also known as: CAMPATH®

hemophagocytic lymphohistiocytosis (HLH)

Methyl Prednisolone (MP) DRUG

hemophagocytic lymphohistiocytosis (HLH)

Cyclosporin A (CSA) DRUG

hemophagocytic lymphohistiocytosis (HLH)

Eligibility Criteria

• Age: Up to 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• URC-CIC Paris Descartes Necker Cochin: collaborator

Study Sites (1)

Hôpital Necker-Enfants Malades

Paris, 75015, France

Location

MeSH Terms

Conditions

Lymphohistiocytosis, Hemophagocytic

Interventions

Alemtuzumab; Cyclosporine

Condition Hierarchy (Ancestors)

Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Lymphatic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides

Study Officials

• Alain FISCHER, MD, PhD

  Assistance Publique - Hôpitaux de Paris

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 8, 2015
• First Posted: June 15, 2015
• Study Start: June 29, 2015
• Primary Completion: September 12, 2019
• Study Completion: May 20, 2020
• Last Updated: March 30, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)