Denosumab for the Treatment of Adult LCH
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|ClinicalTrials.gov Identifier: NCT03270020|
Recruitment Status : Recruiting
First Posted : September 1, 2017
Last Update Posted : February 22, 2019
|Condition or disease||Intervention/treatment||Phase|
|Langerhans Cell Histiocytosis||Drug: Denosumab 70 MG/ML [Xgeva]||Phase 2|
The majority and diversity of clinical manifestations in LCH are attributed to immunological dysfunction resulting from langerhans cell (LC) derived cytokine secretion both at the lesional and systemic level. In a recent study, Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL) was found to be abundantly expressed in cells within diverse LCH lesions from adult patients, especially in inflammatory infiltrates, a finding in line with a previously reported high osteoprotegerin (OPG) and low RANKL levels in the serum of patients with or without bone involvement. RANKL expression was associated with concomitant p65 Nuclear Factor Kappa-B (NFκB) nuclear staining, the main downstream effector of RANKL signaling, suggesting that lesional cell activation may be triggered locally by RANKL. Combining the serum and the lesional results, it can be inferred that there is an ongoing process of countervailing OPG production against lesional RANKL, which could be one of the self defense mechanisms among LCH patients. Therefore, the use of denosumab seems a rational treatment option in LCH in order to support and enhance the defensive OPG action and hopefully control or even interrupt the lesional immunological process.
The primary study objective is to assess the therapeutic efficacy of denosumab 120 mg every 8 weeks (Q8W) sc in adult LCH patients.
- To define an uniform treatment approach for LCH patients with mild symptoms and low risk disease.
- To explore the efficacy of denosumab 120 mg Q8W sc in reducing disease reactivations after treatment completion.
- To illustrate the safety profile of denosumab in LCH patients. The primary efficacy endpoint is defined as the percentage of patients with progression of disease at Month 8.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||12 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||
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.
|Masking:||None (Open Label)|
|Official Title:||Evaluation of Efficacy of Denosumab in Adult Patients With Langerhans Cell Histiocytosis (LCH): a Multiple-site, Single Arm, Open Label Clinical Trial|
|Actual Study Start Date :||September 7, 2017|
|Estimated Primary Completion Date :||February 28, 2021|
|Estimated Study Completion Date :||June 30, 2021|
Experimental: Treatment arm
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]
As already described in arm description
Other Name: Xgeva
- Primary efficacy endpoint: effect of denosumab treatment on the activity status of the disease (Incidence of patients with active disease) [ Time Frame: 8 months ]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.
- Secondary efficacy endpoint: development of disease-related permanent sequelae during the study period (Incidence of disease-related permanent sequelae) [ Time Frame: 18 months ]Incidence of disease-related permanent sequelae, developed during the study, at month 18. In specific, permanent sequelae such as diabetes insipidus, anterior pituitary deficiencies, and pulmonary failure will be assessed at the end of the study in order to evaluate the efficacy of denosumab in preventing those conditions.
- Safety endpoints: Incidence of all Adverse Events during the trial [ Time Frame: 18 months ]Incidence of Adverse Events during the trial. In specific, all adverse events will be assessed at the end of the study period in order to evaluate the safety issues of denosumab treatment in LCH.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03270020
|Contact: Polyzois Makras, MD, PhDfirstname.lastname@example.org|
|Contact: Gregory Kaltsas, Professoremail@example.com|
|Principal Investigator:||Polyzois Makras, MD, PhD||Dpt of Endocrinology & Diabetes, 251 Hellenic AirForce & VA General Hospital, Athens, Greece|