Denosumab for the Treatment of Adult LCH

NCT03270020 | Completed Phase 2

• 1 other identifier: 20159460
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This study is aiming to evaluate the efficacy of denosumab among adult patients suffering from Langerhans Cell Histiocytosis (LCH).

Conditions

Langerhans Cell Histiocytosis

Keywords

treatment; denosumab; Positron Emission Tomography (PET) CT scan

Outcome Measures

Primary Outcomes (1)

• Primary efficacy endpoint: effect of denosumab treatment on the activity status of the disease (Incidence of patients with active disease)

  The primary efficacy endpoint will be measured through the incidence of patients with active disease at Month 8. Given that all patients have active disease at baseline the incidence of patients with active disease at Month 8 will provide the efficacy of denosumab in controlling the disease within this time frame.

  8 months

Secondary Outcomes (1)

• Secondary efficacy endpoint: development of disease-related permanent sequelae during the study period (Incidence of disease-related permanent sequelae)

  18 months

Other Outcomes (2)

• Safety endpoints: Incidence of all Adverse Events during the trial

  18 months

• Safety endpoint: Incidence of all adverse events on bone metabolism following Denosumab treatment and its withdrawal

  30 months

Study Arms (1)

Treatment arm

EXPERIMENTAL

This is a single arm study; the study arm include all patients participating in the study who will all receive Denosumab 70 MG/ML \[Xgeva\]

Drug: Denosumab 70 MG/ML [Xgeva]

Interventions

Denosumab 70 MG/ML [Xgeva] DRUG

As already described in arm description

Also known as: Xgeva

Treatment arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults (\>18 years of age)
• Definitive diagnosis of LCH \[Based on clinic-pathological evidence with microscopic examination and at least one of the following immunological staining: Langerin (CD 207) positivity, Cluster of Differentiation 1a (CD1a) positivity, Presence of Birbeck granules on electronic microscopy\]
• Mild symptoms (symptoms of low intensity; no need for hospitalization) and low risk disease needing first line systemic therapy for LCH because of:
• single system disease with multifocal lesions, or
• single system disease with "special site" lesions (vertebral lesions with intraspinal extension, craniofacial bone lesions with soft tissue extension), or
• multi-system disease without involvement of risk organs \[hematopoietic system, spleen, liver, tumorous central nervous system (CNS)\].
• Have signed the informed consent form (consent should be taken before any study-specific procedure is performed).
• 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).

You may not qualify if:

• Symptomatic multi system LCH - no risk organs involved.
• Multi-system LCH (with or without symptoms) - risk organs involved.
• Isolated pulmonary LCH disease
• Previous administration of denosumab from clinical trials or other use (e.g. commercial use).
• Current participation in another clinical trial or having received any investigational product within the last 3 months.
• Impaired renal function as determined by an estimated glomerular filtration rate (eGFR) of ≤ 30 mL/min/1,73m2 \[using the Chronic Kidney Disease-Epidemiology, (CKD-EPI) formula\].
• 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.
• Treatment with immune suppressive agents within 4 weeks from baseline evaluation.
• Patients with severe impairment of clinical condition including: severely impaired pulmonary function \[for example total lung capacity (TLC)\<60%, forced expiratory volume 1 (FEV1)\<30%, diffusing capacity of the lungs for carbon monoxide (DLCO)\<30%, partial pressure of oxygen (PaO2)\<55 mmHg), long term oxygen therapy or cor pulmonale.
• Known to have a liver failure or chronic hepatic disease e.g. cirrhosis, chronic hepatitis; or elevated transaminases defined as alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) \> 2 fold the upper limit of normal laboratory range.
• Heart failure \[New York Heart Association (NYHA) Functional Classification above 2\].
• Patients with life expectancy of less than one year.
• 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.
• Pregnancy, planning a pregnancy or currently lactating
• 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.

Sponsors & Collaborators

• Hellenic Society for the Study of Bone Metabolism: lead

Study Sites (1)

251 Hellenic AirForce & VA General Hospital, Dpt of Endocrinology

Athens, Attica, 11525, Greece

Location

Related Publications (4)

• Makras P, Tsoli M, Anastasilakis AD, Thanou M, Kaltsas G. Denosumab for the treatment of adult multisystem Langerhans cell histiocytosis. Metabolism. 2017 Apr;69:107-111. doi: 10.1016/j.metabol.2017.01.004. Epub 2017 Jan 12.

  PMID: 28285639 BACKGROUND

• Makras P, Salagianni M, Revelos K, Anastasilakis AD, Schini M, Tsoli M, Kaltsas G, Andreakos E. Rationale for the application of RANKL inhibition in the treatment of Langerhans cell histiocytosis. J Clin Endocrinol Metab. 2015 Feb;100(2):E282-6. doi: 10.1210/jc.2014-2654. Epub 2014 Nov 6.

  PMID: 25375981 BACKGROUND

• Makras P, Polyzos SA, Anastasilakis AD, Terpos E, Kanakis G, Schini M, Papatheodorou A, Kaltsas GA. Serum osteoprotegerin, RANKL, and Dkk-1 levels in adults with Langerhans cell histiocytosis. J Clin Endocrinol Metab. 2012 Apr;97(4):E618-21. doi: 10.1210/jc.2011-2962. Epub 2012 Jan 25.

  PMID: 22278426 BACKGROUND

• Girschikofsky M, Arico M, Castillo D, Chu A, Doberauer C, Fichter J, Haroche J, Kaltsas GA, Makras P, Marzano AV, de Menthon M, Micke O, Passoni E, Seegenschmiedt HM, Tazi A, McClain KL. Management of adult patients with Langerhans cell histiocytosis: recommendations from an expert panel on behalf of Euro-Histio-Net. Orphanet J Rare Dis. 2013 May 14;8:72. doi: 10.1186/1750-1172-8-72.

  PMID: 23672541 BACKGROUND

MeSH Terms

Conditions

Histiocytosis, Langerhans-Cell

Interventions

Denosumab

Condition Hierarchy (Ancestors)

Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; 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

Study Officials

• Polyzois Makras, MD, PhD

  Dpt of Endocrinology & Diabetes, 251 Hellenic AirForce & VA General Hospital, Athens, Greece

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The investigational arm will recruit patients who will receive denosumab 120mg sc every 2 months. The estimated duration of the recruitment period is 12 months. The treatment period would be 6 months (denosumab administration on months: 0, 2, 4, 6) and the follow-up period would be 12 months.

Study Record Dates

• First Submitted: August 26, 2017
• First Posted: September 1, 2017
• Study Start: September 7, 2017
• Primary Completion: June 22, 2022
• Study Completion: January 14, 2025
• Last Updated: January 15, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

GR (1)