Diagnostic Value of Bone Marrow Tryptase in Systemic Mastocytosis

NCT02441166 | Completed

• 2 other identifiers: RC31/14/73872015-A00351-48
• Study Type: interventional
• Target: 250
• Locations: 2 countries
• Sites: 8

Brief Summary

The hypothesis of the study is that Bone Marrow Tryptase (MT) level is a diagnostic marker of Systemic Mastocytosis (SM). Determination of the bone marrow tryptase in Bone Marrow Aspirate (BMA) could be a new diagnostic criteria for systemic mastocytosis with sensitivity close to 100% and a low false negative rate. This new test could be useful to improve the ability to diagnose accurately systemic mastocytosis (in particular the indolent forms). Because of its limited invasiveness compared to bone marrow biopsy, it could also be considered as a test performed before bone marrow biopsy. Only patients with high bone marrow tryptase would then undergo bone marrow biopsy. In the future and if validated by this study, bone marrow tryptase could be a useful marker of mast cell load and help to monitor the efficacy of treatment in systemic mastocytosis.

Conditions

Systemic Mastocytosis

Keywords

Bone marrow tryptase; cutaneous mastocytosis

Outcome Measures

Primary Outcomes (1)

• Bone marrow tryptase level

  Aliquot of the bone marrow aspirate sample will be used after centrifugation for measurements of bone marrow tryptase level.

  Day 4 after bone marrow aspiration

Secondary Outcomes (5)

• The bone marrow tryptase level for differential diagnosis between systemic mastocytosis and cell mast activation syndrome

  Day 4 after bone marrow aspiration

• The bone marrow tryptase/serum tryptase ratio for diagnosis of systemic mastocytosis with and without mastocytosis in skin

  Day 4 after bone marrow aspiration

• The absolute and corrected bone marrow tryptase level for diagnosis of systemic mastocytosis with and without mastocytosis in skin

  Day 4 after bone marrow aspiration

• Flow cytometry performed on cells collected by bone marrow aspirate and maintained in a preservative solution (TransFix®) to detect mast cells expressing CD25 and/or CD2 for diagnosis of systemic mastocytosis with and without mastocytosis in skin

  Day 4 after bone marrow aspiration

• Quantification of KIT mutations-positive cells fraction in peripheral blood for systemic mastocytosis diagnosis,correlation with results of medullar tryptase level, medullar/systemic tryptase ratio and absolute and corrected medullar tryptase level

  Day 4 after bone marrow aspiration

Study Arms (1)

Mastocytosis diagnosis

OTHER

For each enrolled subject, 5 mL sample of peripheral blood and 1 mL sample of BM aspirate will be collected the same day to do diagnosis mastocytosis tests (quantification of the kit mutations by qPCR, plasma tryptase level, immunophenotyping of BM mastocytes by flow cytometry, BM tryptase level, degree of dilution of the BM aspirate...) using the WHO criteria as the reference standard.

Procedure: Mastocytosis diagnosis

Interventions

Mastocytosis diagnosis PROCEDURE

Some samples will be extracted from bone marrow aspirate and peripheral blood on the inclusion day to do diagnosis tests. WHO criteria will be used as the reference standard.

Mastocytosis diagnosis

Eligibility Criteria

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

You may qualify if:

• Suspicion of systemic mastocytosis, for whom bone marrow sampling (bone marrow biopsy and/or bone marrow aspiration) is carried out as part of normal workup of the disease in the center of reference and centers of competence in mastocytosis.
• Patient whose written informed consent has been obtained.

You may not qualify if:

• Patients with a contra-indication to marrow sampling (anticoagulant and/or anti-clotting treatments,
• Thrombocytopenia \< 50 000/mm2) for whom it is impossible to formally conclude the final type of mast cell disease: SM, CM, mast cell activation syndrome.

Sponsors & Collaborators

• University Hospital, Toulouse: lead

Study Sites (8)

CHU Bordeaux Hôpital Haut-Lévêque, service de dermatologie

Bordeaux, France

Location

CHU de Caen, service d'hématologie

Caen, France

Location

CHU Dupuytren service d'hématologie

Limoges, France

Location

CHU Lyon Sud, service de médecine interne

Lyon, France

Location

Hôpital Necker, service d'hématologie

Paris, France

Location

Hôpital Pité Salpétrière

Paris, France

Location

CHU Toulouse, Hôpital Larrey, service de dermatologie

Toulouse, France

Location

CHU Fort de France, service de dermatologie

Fort-de-France, Martinique

Location

Related Publications (6)

• Valent P, Horny HP, Escribano L, Longley BJ, Li CY, Schwartz LB, Marone G, Nunez R, Akin C, Sotlar K, Sperr WR, Wolff K, Brunning RD, Parwaresch RM, Austen KF, Lennert K, Metcalfe DD, Vardiman JW, Bennett JM. Diagnostic criteria and classification of mastocytosis: a consensus proposal. Leuk Res. 2001 Jul;25(7):603-25. doi: 10.1016/s0145-2126(01)00038-8.

  PMID: 11377686 BACKGROUND

• Valent P, Akin C, Escribano L, Fodinger M, Hartmann K, Brockow K, Castells M, Sperr WR, Kluin-Nelemans HC, Hamdy NA, Lortholary O, Robyn J, van Doormaal J, Sotlar K, Hauswirth AW, Arock M, Hermine O, Hellmann A, Triggiani M, Niedoszytko M, Schwartz LB, Orfao A, Horny HP, Metcalfe DD. Standards and standardization in mastocytosis: consensus statements on diagnostics, treatment recommendations and response criteria. Eur J Clin Invest. 2007 Jun;37(6):435-53. doi: 10.1111/j.1365-2362.2007.01807.x.

  PMID: 17537151 BACKGROUND

• Akin C, Valent P, Metcalfe DD. Mast cell activation syndrome: Proposed diagnostic criteria. J Allergy Clin Immunol. 2010 Dec;126(6):1099-104.e4. doi: 10.1016/j.jaci.2010.08.035. Epub 2010 Oct 28.

  PMID: 21035176 BACKGROUND

• Alvarez-Twose I, Gonzalez de Olano D, Sanchez-Munoz L, Matito A, Esteban-Lopez MI, Vega A, Mateo MB, Alonso Diaz de Durana MD, de la Hoz B, Del Pozo Gil MD, Caballero T, Rosado A, Sanchez Matas I, Teodosio C, Jara-Acevedo M, Mollejo M, Garcia-Montero A, Orfao A, Escribano L. Clinical, biological, and molecular characteristics of clonal mast cell disorders presenting with systemic mast cell activation symptoms. J Allergy Clin Immunol. 2010 Jun;125(6):1269-1278.e2. doi: 10.1016/j.jaci.2010.02.019.

  PMID: 20434205 BACKGROUND

• Barete S, Assous N, de Gennes C, Grandpeix C, Feger F, Palmerini F, Dubreuil P, Arock M, Roux C, Launay JM, Fraitag S, Canioni D, Billemont B, Suarez F, Lanternier F, Lortholary O, Hermine O, Frances C. Systemic mastocytosis and bone involvement in a cohort of 75 patients. Ann Rheum Dis. 2010 Oct;69(10):1838-41. doi: 10.1136/ard.2009.124511. Epub 2010 Jun 22.

  PMID: 20570833 BACKGROUND

• Paul C, Sans B, Suarez F, Casassus P, Barete S, Lanternier F, Grandpeix-Guyodo C, Dubreuil P, Palmerini F, Mansfield CD, Gineste P, Moussy A, Hermine O, Lortholary O. Masitinib for the treatment of systemic and cutaneous mastocytosis with handicap: a phase 2a study. Am J Hematol. 2010 Dec;85(12):921-5. doi: 10.1002/ajh.21894.

  PMID: 21108325 BACKGROUND

MeSH Terms

Conditions

Mastocytosis, Systemic; Mastocytosis, Cutaneous

Condition Hierarchy (Ancestors)

Mastocytosis; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Mast Cell Activation Disorders; Immune System Diseases; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Cristina Livideanu, MD

  University Hospital, Toulouse

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 5, 2015
• First Posted: May 12, 2015
• Study Start: October 6, 2015
• Primary Completion: July 1, 2019
• Study Completion: July 1, 2019
• Last Updated: July 15, 2019

Record last verified: 2019-07

Locations

FR (7); MA (1)