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Interest of Denosumab Treatment in Osteoporosis Associated to Systemic Mastocytosis (DenosuMast)

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ClinicalTrials.gov Identifier: NCT03401060
Recruitment Status : Recruiting
First Posted : January 17, 2018
Last Update Posted : May 23, 2018
Sponsor:
Collaborator:
CEREMAST
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Brief Summary:

The study is looking at the efficacy of subcutaneously administrated denosumab 60 mg every 6 months versus placebo after 3 years, by analyze of lumbar spine bone mineral density (BMD) in systemic mastocytosis.

Investigators hypothesize that use of denosumab subcutaneously in patients with osteoporosis related to systemic mastocytosis is effective and safe to improve bone mineral density and prevent new bone events, based on targeted specific RANKL secretion by mast cells and short half-life of denosumab.


Condition or disease Intervention/treatment Phase
Osteoporosis Systemic Mastocytosis Drug: Denosumab Drug: Placebo Phase 3

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Interest of Denosumab Treatment in Osteoporosis Associated to Systemic Mastocytosis
Actual Study Start Date : March 2, 2018
Estimated Primary Completion Date : March 30, 2021
Estimated Study Completion Date : March 30, 2023


Arm Intervention/treatment
Experimental: Experimental medication 1
Denosumab 60 mg subcutaneously injection with prefilled syringe
Drug: Denosumab
Each subcutaneous injection will occur every 6 months during 3 years for a total of 7 injections
Other Name: XGeva®

Placebo Comparator: Experimental medication 2
NaCl 0.9%, 20ml phial, solution for injection
Drug: Placebo
Each subcutaneous injection will occur every 6 months during 3 years for a total of 7 injections




Primary Outcome Measures :
  1. Analysis of the lumbar spine bone mineral density (BMD) [ Time Frame: 3 years ]
    Dual energy x-ray absorptiometry at lumbar spine (L2-L4)


Secondary Outcome Measures :
  1. Occurrence of a low energy vertebral fracture and non vertebral fracture [ Time Frame: Baseline, 1 year, 2 years and 3 years ]
    Lateral and front lumbar x-ray

  2. BMD at the total left hip [ Time Frame: Baseline, 3 years ]
    Dual energy x-ray absorptiometry at lumbar spine (L2-L4)

  3. BMD at lumbar spine and the total left hip [ Time Frame: Baseline, 1 year, 2 years ]
    Dual energy x-ray absorptiometry at left femoral neck and total left hip

  4. Biological assays with bone turnover marker of resorption and tryptase levels to assess mastocytosis activity [ Time Frame: Baseline, then every 6 months in 3 years ]
    Withdrawal of 45 ml of blood

  5. Number of serious adverse events to evaluate drug tolerance [ Time Frame: Every 6 months in 3 years ]
    • Biological assessment: complete blood count, creatinemia, electrolytes, aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin, c-reactive protein (CRP), phosphocalcic analyses with calcemia, phosphoremia, parathormone, vitamin D (25-OH-D), β-Human Chorionic Gonadotropin (HCG) (if needed)
    • Clinical assessment: blood pressure, pulse, weight, height, PS, temperature

  6. Number of non-serious adverse events to evaluate drug tolerance [ Time Frame: Every 6 months in 3 years ]
    • Biological assessment: complete blood count, creatinemia, electrolytes, aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin, c-reactive protein (CRP), phosphocalcic analyses with calcemia, phosphoremia, parathormone, vitamin D (25-OH-D), β-Human Chorionic Gonadotropin (HCG) (if needed)
    • Clinical assessment: blood pressure, pulse, weight, height, PS, temperature

  7. Annual variation of BMD in placebo group and number of low energy fracture compared to historical postmenopausal data [ Time Frame: Baseline, 1 year, 2 years, 3 years ]
    Dual energy x-ray absorptiometry at lumbar spine (L2-L4), left femoral neck and total left hip



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female >/= 18 years of age at time of informed consent
  • Patient with Indolent systemic or cutaneous mastocytosis according to WHO criteria (Appendix 4) with any specific treatment including corticosteroid, chemotherapy and immunomodulating drugs.
  • Patient with osteoporosis defined as
  • bone mineral density T score of less than -2.5 at the lumbar spine, OR
  • osteopenia defined as BMD T-score between -2,5 and -1 at the lumbar spine and low energy fracture (defined as fractures that are associated with decreased bone mineral density. Are excluded fractures of skull, face, mandible, metacarpals, fingers, or toes, pathologic fracture, and fracture that are associated with severe trauma).
  • Willingness and ability to sign informed consent, comply with scheduled visits, treatment plan, laboratory tests and other study procedures.

Exclusion Criteria:

  • Patient with aggressive mastocytosis or/and Associated Hematologic Non-Mastocytosis Disease (AHNMD)
  • Patient with conditions that influence bone metabolism (primitive hyperparathyroidism, hyperaldosteronism, hypercorticism, etc …)
  • Patient treated with intravenous bisphosphonate within 1 year prior to enrolment or with any other antiosteoporotic treatment within 3 months before enrolment. (per os bisphosphonate, strontium ranelate) Calcium and vitamin supplementation will be accepted
  • Patient previously treated with denosumab
  • Patient with hypocalcemia and/or hypo25-hydroxyvitamin D level non substituted prior enrolment
  • Woman without contraceptive treatment if of childbearing age.
  • Pregnant or breastfeeding woman
  • Patient with contraindication to denosumab
  • Patient with medical, psychiatric or other conditions that may interfere with patient safety
  • Patient with dental problem that need any dental surgery within 6 months after enrolment.
  • Patient with clearance of creatinine less than 30 mL/min/1,73m2 (MDRD) or patient receiving dialysis

Information from the National Library of Medicine

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): NCT03401060


Contacts
Contact: Laurent Frenzel, MD +33 (0)1 44 49 52 90 laurent.frenzel@aphp.fr
Contact: Valérie Jolaine +33 (0)1 42 19 28 79 valerie.jolaine@aphp.fr

Locations
France
Jean Minjoz Hospital, Dermatology department Not yet recruiting
Besançon, France, 25030
Contact: Fabien Pelletier, MD       fabien.pelletier@univ-fcomte.fr   
Caen Hospital, Clinical haematology department Not yet recruiting
Caen, France, 14033
Contact: Gandhi Damaj, MD       damaj-gl@chu-caen.fr   
Estaing Hospital, Cellular therapy and clinical haematology department Not yet recruiting
Clermont-Ferrand, France, 63100
Contact: Richard Lemal, MD       richard.lemal@hotmail.fr   
Lille CHRU Hospital, Internal medicine and clinical immunology department Not yet recruiting
Lille, France, 59037
Contact: David Launay, MD         
La Timone Hospital, Dermatology and cutaneous oncology department Recruiting
Marseille, France, 13385
Contact: Caroline Gaudy, MD       caroline.gaudy@ap-hm.fr   
Lapeyronie Hospital, Rheumatology and Immunology department Not yet recruiting
Montpellier, France, 34295
Contact: Jacques Morel, MD       j-morel@chu-montpellier.fr   
La Pitié-Salpêtrière Hospital, Internal medicine and clinical immunology department Recruiting
Paris, France, 75013
Contact: Stéphane Barete, MD       stephane.barete@aphp.fr   
Cochin Hospital, Rheumatology department Not yet recruiting
Paris, France, 75014
Contact: Karine Briot, MD       karine.briot@aphp.fr   
Necker Hospital, Adult haematology department Recruiting
Paris, France, 75015
Contact: Laurent Frenzel, MD    +33 (0)1 44 49 52 90    Laurent.frenzel@aphp.fr   
Strasbourg Hospital, Rheumatology department Not yet recruiting
Strasbourg, France, 67098
Contact: Rose-Marie Javier, MD       rose-marie.javier@chru-strasbourg.fr   
Toulouse Hospital, Dermatology department Recruiting
Toulouse, France, 31060
Contact: Cristina Livideanu, MD       livideanu.c@chu-toulouse.fr   
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
CEREMAST
Investigators
Study Director: Olivier Hermine, MD Hospital Necker, Department of haematology and immunology

Publications:

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT03401060     History of Changes
Other Study ID Numbers: P150918J
2016-000596-25 ( EudraCT Number )
First Posted: January 17, 2018    Key Record Dates
Last Update Posted: May 23, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Systemic mastocytosis
Osteoporosis
Bone mineral density (BMD)
Denosumab
RANKL

Additional relevant MeSH terms:
Osteoporosis
Mastocytosis
Mastocytosis, Systemic
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Metabolic Diseases
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Skin Diseases
Denosumab
Bone Density Conservation Agents
Physiological Effects of Drugs