Langerhans Cell Histiocytosis (LCH) is a rare disease of unknown etiology with variable clinical course exhibiting both neoplastic and inflammatory features. It is characterized by the accumulation and/or proliferation of specific dendritic cells resembling normal epidermal Langerhans cells. MedDRA version: 21.1 Level: PT Classification code 10069698 Term: Langerhans' cell histiocytosis System Organ Class: 1002910
Conditions
Interventions
Trade Name: XGEVA
Product Name: denosumab
Pharmaceutical Form: Injection
INN or Proposed INN: denosumab
CAS Number: 615258-40-7
Sponsors
Hellenic Society for the Study of Bone Metabolism
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1)Adults (>18 years of age) 2)Definitive diagnosis of LCH [1] [Based on clinic-pathological evidence with microscopic examination and at least one of the following immunological staining: Langerin (CD 207) positivity, CD1a positivity, Presence of Birbeck granules on electronic microscopy] 3)Mild symptoms needing first line systemic therapy for LCH because of: -single system disease with multifocal lesions; -single system disease with “special site” lesions (vertebral lesions with intraspinal extension, craniofacial bone lesions with soft tissue extension); -multi-system disease without involvement of risk organs (hematopoietic system, spleen, liver, tumorous CNS.). 4) Have signed the informed consent form (consent should be taken before any study-specific procedure is performed). 5) A patient should undergo a PET-CT imaging test, in order for him to be deemed suitable for the study. The initial PET-CT either may have been carried out, within 3 months prior to visit 1, regardless of the diagnostic center or the type of the device, which has been used for, or may take place in the context of visit 2, at the diagnostic center(s) specialized on Nuclear Medicine, which have been partnered with the Sponsor. Whichever is the case, the initial PET-CT report should be legible and accurate, so that to be assessed by the qualified physician, responsible for the PET-CT test at the partnered diagnostic center(s). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 9 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 1
Exclusion criteria
Exclusion criteria: 1. Symptomatic multi system LCH - no risk organs involved. 2. Multi-system LCH (with or without symptoms) - risk organs involved. 3. Isolated pulmonary LCH disease 4. Previous administration of denosumab from clinical trials or other use (e.g. commercial use). 5. Current participation in another clinical trial or having received any investigational product within the last 3 months. 6. Impaired renal function as determined by an estimated glomerular filtration rate eGFR of = 30 mL/min/1,73m2 [using the Chronic Kidney Disease-Epidemiology, (CKD-EPI) formula]. 7. Patients that have received oral bisphosphonates within 6 months of study enrollment or intravenous bisphosphonates, fluoride and strontium ranelate within 1 year of study enrollment. 8. Treatment with immune suppressive agents within 4 weeks from baseline evaluation. 9. Patients with severe impairment of clinical condition including: severely impaired pulmonary function (for example TLC 2 fold the upper limit of normal laboratory range. 11. Heart failure (NYHA above 2). 12. Patients with life expectancy of less than one year. 13. Female subjects of childbearing potential who refuse to use a reliable contraceptive method throughout the study, defined as use of 2 highly effective forms of contraception and continuation of use for 7 months after last administration of study drug. Birth control methods that can achieve a failure rate of less than 1% per year, when used consistently and correctly, are considered as highly effective. Highly effective methods of birth control include: •Combined (estrogen and progestogen) hormonal methods (pills, vaginal ring, or skin patch) •Single hormonal methods (progesterone) to stop release of the egg from the ovary (pills, shots/injections, or implants placed under the skin by a healthcare provider) •Intrauterine device (IUD) •Intrauterine hormonal-releasing system (IUS) •Surgery to tie both fallopian tubes (bilateral tubal ligation/occlusion •A male partner has had a vasectomy and testing shows there is no sperm in the semen •Sexual abstinence (not having sex) 14. Pregnancy, planning a pregnancy or currently lactating 15. Severe concurrent illness which in the investigator’s opinion may confound patient evaluation, e.g. malignancy (except basal cell carcinoma, cervical or breast ductal carcinoma in situ) within the last 5 years. 16. Known alcohol or drug abuse. 17. PTH, PTH derivatives, teriparatide, odanacatib, anabolic steroids, testosterone, glucocorticosteroids (> 5 mg/day of prednisone equivalent for > 10 days), systemic hormone-replacement therapy, selective estrogen receptor modulators (SERMs), raloxifene, tibolone, calcitonin use within the last 6 weeks. 18. Evidence of hyper- or hypothyroidism; patients with an abnormal TSH level on thyroid treatment (patients on stable thyroid treatment with a nor
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary study objective is to assess the therapeutic efficacy of denosumab 120 mg, administered sc every 8 weeks (Q8W) in adult LCH patients. ;Primary end point(s): The primary efficacy endpoint is defined as the percentage of patients with progression of disease.;Timepoint(s) of evaluation of this end point: Month 8; Secondary Objective: 1) To define an uniform treatment approach for LCH patients with mild symptoms and low risk disease. 2) To explore the efficacy of denosumab 120 mg Q8W sc in reducing disease reactivations after treatment completion. 3) To illustrate the safety profile of denosumab in LCH patients. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: month 18 ; Secondary end point(s): The secondary efficacy endpoints include the following: - Reactivation-free survival. - Percentage of patients with disease-related permanent sequelae (developed during the study). Safety endpoints include the following: - Incidence of Adverse Events during the trial. - Changes from baseline in safety laboratory analytes (serum chemistry, hematology) and vital signs. In specific, the parameters of serum chemistry and haematology that are of particular interest include: CRP, ESR, Hemoglobin, White blood count and differential, SGOT, SGPT, urea, creatinine, and calcium. | — |
Countries
Greece
Contacts
Public ContactCharalampos Therianos
CORONIS Research S.A
Outcome results
None listed