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Systemic MastocytosisEvaTryMSNCT02441166

Diagnostic Value of Bone Marrow Tryptase in Systemic Mastocytosis

A study testing Mastocytosis diagnosis in people with Systemic Mastocytosis, run by University Hospital, Toulouse at 8 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Systemic Mastocytosis
What is being tested?
Mastocytosis diagnosis
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
250 participants
Where
8 sitesin 2 countries
Study dates
6 Oct 2015to Jul 2019
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.

Trial locations and contacts

8 sites in 2 countries.

8 sites in 2 countries

France7 sites
  • CHU Bordeaux Hôpital Haut-Lévêque, service de dermatologie

    Bordeaux

  • CHU de Caen, service d'hématologie

    Caen

  • CHU Dupuytren service d'hématologie

    Limoges

  • CHU Lyon Sud, service de médecine interne

    Lyon

  • Hôpital Necker, service d'hématologie

    Paris

  • Hôpital Pité Salpétrière

    Paris

  • CHU Toulouse, Hôpital Larrey, service de dermatologie

    Toulouse

Other trials in France

Martinique1 site
  • CHU Fort de France, service de dermatologie

    Fort-de-France

Other trials in Martinique

About this study

Official title: Evaluation of the Diagnostic Value of Level of Bone Marrow Tryptase in Adult Systemic Mastocytosis

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.

Read the detailed description

Mastocytosis are a group of disorders characterized by clonal accumulation of mast cells in various organs. Diagnosis of mastocytosis is challenging and patients remain undiagnosed for years. Using the diagnostic criteria defined by the World Health Organization (WHO) mastocytosis can be divided between Cutaneous Mastocytosis (CM) and Systemic Mastocytosis (SM).

Study suggested that measurement of tryptase in plasma from a Bone Marrow Aspirate (from BMA) could be useful for the diagnosis of SM. Results from a preliminary study at Toulouse University Hospital suggested that a Bone Marrow Tryptase Level (MT) of 50 µg/L or more may be a more sensitive diagnostic criterion (sensitivity of 94.7%) than the histological result of BMB (the major diagnostic criterion for SM with a sensitivity of 68 to 80% in expert centers) for diagnosis of SM in patients with mastocytosis in skin.

Because this preliminary study was done on a limited number of patients and in a single center, the diagnostic value of MT for the diagnosis of SM, has to be confirmed on a larger and more representative population.

In addition, the investigators propose to evaluate:

  • The diagnostic accuracy of MT for diagnosis of SM in patients without mastocytosis in skin;
  • The diagnostic accuracy of absolute and corrected MT for diagnosis of SM with and without mastocytosis in skin;
  • The diagnostic accuracy of MT/ST ratio for diagnosis of SM with and without mastocytosis in skin;
  • The diagnostic accuracy of flow cytometry performed on cells collected by BMA and maintained in a preservative solution for diagnosis of SM with and without mastocytosis in skin;
  • The diagnostic accuracy of quantification of the fraction of KIT mutation-positive cells in peripheral blood for diagnosis of SM with and without mastocytosis in skin;
  • Correlation the results of quantification of the fraction of KIT mutation-positive cells in peripheral blood with results of MT level, results of MT/ST ratio and results of absolute and corrected MT;
  • Correlation the results of the CF performed both on the EDTA/TransFix® tubes and on sodium heparin tubes and validate the transport conditions (20-25°C within 24 to 96H) for the CF; these analyzes will be performed on the first 50 samples of BMA.

The samples for these diagnosis tests will be made on the day of inclusion. For each enrolled patient, one 5 mL sample of peripheral blood (EDTA) and 1 mL samples of BM aspirate (0,5 mL in a EDTA/TransFix® tube et 0,5 mL in a sodium heparinate tube) will be collected the same day, and shipped in less than 24 to 96H (+20-25°C) to a central laboratory.

For each patient, genomic DNA from total leucocytes will be purified from the peripheral blood EDTA samples, and used later for the quantification of the kit mutations by real-time qPCR. The plasma tryptase level will be measured from the peripheral blood EDTA sample after an aliquot has been taken for DNA extraction. The bone marrow aspirate sample will be used first for immunophenotyping of BM mastocytes by flow cytometry (FC), and then, after centrifugation, for measurement of BM tryptase level. The degree of dilution of the BM aspirate by peripheral blood will be estimated by comparing the percentage of CD16bright vs. CD16low granulocytes in BM samples, and used to adjust the BM tryptase. Tryptase measurements will be made from EDTA or Na, heparinate plasma, using a standardized fluoro enzyme immunoassay on an automated analyzer. Immunophenotyping of BM mastocytes will be performed on BM aspiration stabilized by TransFix® (a Cellular Antigen Stabilisation Reagent) (and for firsts 50 samples on BM aspiration in Na, heparinate) using a pre-defined mixture of anti-CD45/CD117/CD34/CD2/CD25/CD16 antibodies, coupled to appropriate fluorochromes. Genomic DNA from BM leucocytes will be extracted from 300-500µL of peripheral blood (both anti coagulated with EDTA) using a Promega DNA automated extractor, and subsequently stored at +4°C. Quantitative PCR will be performed using a pre-validated qPCR assay (Life Technologies, Foster City, CA) with a 7900HT Fast Real-Time PCR System (Life Technologies).

The end of study visit is performed the same day that the patient is seen to be made aware of the results of the clinical and laboratory investigations made. This is also the day when the planned medical management of mastocytosis is discussed.

Being tested
Mastocytosis diagnosis
Keywords
Bone marrow tryptase, cutaneous mastocytosis
Medical subject headings
Mastocytosis, Systemic, Mastocytosis, Cutaneous

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Mastocytosis diagnosisProcedure or surgery

    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.

Study groups in NCT02441166
Study groupRoleWhat they receive
Mastocytosis diagnosisOtherFor 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.
Receives: Procedure: Mastocytosis diagnosis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Bone marrow tryptase level

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

    Measured: Day 4 after bone marrow aspiration

Secondary outcomes (5)
  1. The bone marrow tryptase level for differential diagnosis between systemic mastocytosis and cell mast activation syndrome

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

    Measured: Day 4 after bone marrow aspiration

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

    Measured: Day 4 after bone marrow aspiration

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

    The degree of dilution of the bonne marrow aspirate by peripheral blood will be estimated by comparing the percentage of CD16bright vs CD16low granulocytes in bone marrow samples and used to adjust the bone marrow tryptase.

    Measured: Day 4 after bone marrow aspiration

  4. 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

    Immunophenotyping of bone marrow mastocytes will be performed on bone marrow aspiration stabilized by Transfix using a pre-defined mixture of anti-CD45/CD117/CD34/CD2/CD25/CD16 antibodies.

    Measured: Day 4 after bone marrow aspiration

  5. 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

    Genomic DNA from total leucocytes will be purified from the peripheral blood samples and used for the quantification of the kit mutation by qPCR

    Measured: Day 4 after bone marrow aspiration

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 May 2015 (estimated)
  2. Study start6 Oct 2015
  3. Primary completionJul 2019
  4. Study completionJul 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Diagnosis
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
250 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02441166
Sponsor's protocol ID
RC31/14/7387
Other IDs
2015-A00351-48
Acronym
EvaTryMS
Status last verified
Jul 2019
First submitted
5 May 2015
Last updated
15 Jul 2019
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 11377686
  • 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.

    PubMed 17537151
  • 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.

    PubMed 21035176
  • 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.

    PubMed 20434205
  • 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.

    PubMed 20570833
  • 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.

    PubMed 21108325

Questions about this trial

What is this clinical trial studying?

A study testing Mastocytosis diagnosis in people with Systemic Mastocytosis, run by University Hospital, Toulouse at 8 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in France, Martinique. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Bone marrow tryptase level (time frame: Day 4 after bone marrow aspiration). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02441166, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jul 2019.

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