Evaluation of the Impact of the Update SMM Criteria on the Natural History of SMM to Establish New Recommendations. (CARRISMM)

Evaluation of the Impact of the Update Multiple Myeloma Criteria on the Natural History of Smoldering Myeloma in Order to Establish New Recommendations About Follow-up and Prognostic Evaluation of Smoldering Myeloma (CARRISMM)

This study is a prospective open label interventional multicenter study evaluating the impact of the update multiple myeloma criteria on the natural history of smoldering myeloma in order to establish new recommendations about follow up and prognostic evaluation of smoldering myeloma.

Study Overview

• Status: Active, not recruiting
• Conditions: Smoldering Multiple Myeloma
• Intervention / Treatment: Procedure: Myelogram

Detailed Description

In 2014, the International Myeloma Working Group (IMWG) proposed a revised classification of multiple myeloma (MM) and smoldering myeloma (SMM). Since the new definition of SMM proposed excludes "ultra-high risk SMM", the evolution profile of SMM will change. Therefore, investigators need to update their knowledge of SMM to optimize the management of patients. This project is expected to describe more precisely the new landscape of SMM.

The results will help to establish new recommendations for the standard care of SMM and especially for defining accurate follow-up and risk stratifying.

• Study Type: Interventional
• Enrollment (Actual): 395
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Intergroupe Francophone du Myelome

Study Locations

• Belgium
  • Bruxelles, Belgium
    • Institut Jules Bordet
  • Bruxelles, Belgium
    • Cliniques universitaires Saint-Luc
  • Yvoir, Belgium
    • CHU UCL Namur ASBL Site Godinne
• France
  • Abbeville, France
    • Centre Hospitalier
  • Amiens, France
    • CHU Amiens Sud
  • Angers, France
    • CHRU - Hôpital du Bocage
  • Annecy, France
    • Ch Annecy Genevois
  • Argenteuil, France
    • Centre Hospitalier d'Argenteuil Victor Dupouy
  • Arras, France
    • CH d'Arras
  • Auch, France
    • Centre Hospitalier de Auch
  • Avignon, France
    • Centre Hospitalier H. Duffaut
  • Bayonne, France
    • Centre Hospitalier de la Cote Basque
  • Belfort, France
    • Hopital Nord Franche Comte
  • Blois, France
    • Centre Hospitalier Simone Veil
  • Bobigny, France
    • Hôpital Avicenne
  • Bordeaux, France
    • Polyclinique Bordeaux Nord Aquitaine
  • Bordeaux, France
    • Institut Bergonié - Pavillon Saint Genès - 1er étage
  • Bourgoin-Jallieu, France
    • Centre hospitalier Pierre Oudot
  • Brest, France
    • CHRU Brest - Hôpital A. Morvan
  • Caen, France
    • CHU Caen - Côte de Nacre
  • Cannes, France
    • Centre Hospitalier
  • Cergy Pontoise, France
    • CH René Dubos
  • Challes-les-Eaux, France
    • Médipôle de Savoie
  • Chalon-sur-Saône, France
    • Centre Hospitalier William Morey
  • Chambéry, France
    • CH Chambery
  • Clamart, France
    • Hôpital d'Instruction des Armées PERCY
  • Corbeil-Essonnes, France
    • Centre Hospitalier Sud Francilien
  • Créteil, France
    • CHU Henri Mondor
  • Dax, France
    • Centre Hospitalier
  • Dijon, France
    • CHU François Mitterand
  • Dunkerque, France
    • Centre Hospitalier de Dunkerque
  • Fréjus, France
    • Hôpital de Fréjus
  • Grenoble, France
    • CHU de Grenoble
  • Grenoble, France
    • Institut Daniel Hollard
  • La Roche-sur-Yon, France
    • CHD Vendée
  • La Rochelle, France
    • Groupe Hospitalier de La Rochelle
  • Le Havre, France
    • Hospital Jacques Monod
  • Le Mans, France
    • Centre Hospitalier
  • Lens, France
    • Centre Hospitalier
  • Libourne, France
    • Centre hospitalier Robert Boulin
  • Lille, France
    • CHRU Hôpital Claude Huriez
  • Limoges, France
    • Centre Hospitalier Universitaire (CHU) de Limoges
  • Lorient, France
    • Hôpital du Scorff
  • Lyon, France
    • Centre Leon Berard
  • Lyon, France
    • Centre Hospitalier Lyon Sud
  • Meaux, France
    • CH Meaux
  • Metz, France
    • Hospital Sainte Blandine
  • Metz, France
    • Hôpital de Mercy (CHR Metz-Thionville)
  • Mont-de-Marsan, France
    • Centre de Recherche Clinique / GHT des Landes
  • Montpellier, France
    • Clinique du parc
  • Montpellier, France
    • Hopital Saint Eloi - CHU Montpellier
  • Mulhouse, France
    • Hôpital E. Muller
  • Nancy, France
    • CHRU Hôpitaux de Brabois
  • Nantes, France
    • CHRU Hôtel Dieu
  • Nantes, France
    • Centre Catherine de Sienne
  • Nice, France
    • Hôpital Archet 1
  • Nîmes, France
    • CHU Carémeau, Institut de Cancérologie du Guard
  • Orléans, France
    • CH La Source
  • Paris, France
    • Hôpital Saint Louis
  • Paris, France
    • Hopital Cochin
  • Paris, France
    • Hôpital Necker
  • Paris, France
    • La Pitié
  • Paris, France
    • CHU Hopital Saint Antoine
  • Perpignan, France
    • CH Saint Jean
  • Pessac, France
    • CHRU - Hôpital du Haut Lévêque - Centre François Magendie
  • Poitiers, France
    • CHU Poitiers - Pôle régional de Cancérologie
  • Périgueux, France
    • Centre Hospitalier de Perigueux
  • Quimper, France
    • Centre Hospitalier de Quimper Cornouaille
  • Reims, France
    • Hôpital Robert Debré
  • Rennes, France
    • CHRU Hopital de Pontchaillou
  • Rennes, France
    • Hôpital Privé Sévigné
  • Rodez, France
    • Centre Hospitalier Jacques Puel
  • Roubaix, France
    • CH Roubaix
  • Rouen, France
    • Centre Henri Becquerel
  • Saint-Brieuc, France
    • Centre Hospitalier Yves Le Foll
  • Saint-Malo, France
    • CH Saint Malo
  • Saint-Priest, France
    • Institut de Cancérologie Lucien Neuwirth
  • Saint-Quentin, France
    • Centre Hospitalier
  • Strasbourg, France
    • Strasbourg Oncologie Libérale
  • Strasbourg, France
    • CHU STRASBOURG - Hôpital de Hautepierre
  • Tarbes, France
    • Centre hospitalier de Tarbes
  • Toulon, France
    • Hôpital Inter-Armées Ste Anne
  • Toulouse, France
    • Pôle IUCT Oncopole CHU
  • Tours, France
    • CHRU Hôpital Bretonneau - Centre Henry Kaplan
  • Troyes, France
    • Centre Hospitalier de Troyes
  • Valence, France
    • Centre Hospitalier de Valence
  • Valenciennes, France
    • Centre Hospitalier
  • Vannes, France
    • CH Bretagne Atlantique Vannes et Auray - P. Chubert
  • Versailles, France
    • CHV André Mignot - Université de Versailles
• Monaco
  • Monaco, Monaco
    • Centre Hospitalier Princesse Grace

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years.

• SMM defined by IMWG 2014 criteria

  1. Serum monoclonal protein (IgG or IgA) ≥30 g/L and/or urinary monoclonal protein ≥500 mg per 24 h and/or clonal bone marrow plasma cells 10-60%
  2. Absence of myeloma defining events or amyloidosis
• Diagnosed less than 1 year before the inclusion
• Able and willing to give valid written informed consent. Patients must give written informed consent (IC) in accordance with institutional and local guidelines.

Exclusion Criteria:

• Previous antimyeloma treatment including bisphosphonates
• Second Primary Malignancy and/or auto-immune disease treated by immunosuppressive drugs.

• Evidence of end organ damage that can be attributed to the underlying SMM:

  1. Hypercalcaemia: serum calcium >0.25 mmol/L (>10 mg/L) higher than the upper limit of normal or >2.75 mmol/L (>110 mg/L)
  2. Renal insufficiency: creatinine clearance <40 mL/min or serum creatinine >177 μmol/L (>20 mg/L)
  3. Anaemia: haemoglobin value of >2 g/dL below the lower limit of normal, or a haemoglobin value <10 g/dL
  4. Bone lesions: one or more osteolytic lesions on skeletal radiography, CT, or Positron Emission Tomography-Computed Tomography (PET-CT)

• Presence of one of the following biomarkers of malignancy:

  1. Clonal bone marrow plasmocytosis ≥60%
  2. Involved/uninvolved serum Free Light Chain (FLC) ratio ≥ 100 (The involved free light chain must be ≥100 mg/L)
  3. Presence of one or more focal lesions on MRI studies (each focal lesion must be 5 mm or more in size)
• History of malignancy other than SMM within 3 years before inclusion
• Amyloidosis
• POEMS syndrome
• Contraindication to MRI
• Pregnancy
• Nursing mother
• Legally protected adults (under judicial protection, guardianship, or supervision)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Test group; Each patient included in the study will be followed for 5 years	Procedure: Myelogram; Two additional myelograms will be performed comparing to standard of care.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess the annual risk estimated at 2 years of progression from SMM to MM	Progression to MM will be defined, according to IMWG 2014 revised classification, by the apparition of one or more myeloma defining events: Evidence of end organ damage that can be attributed to the underlying MM (CRAB criteria); Presence of one of the following biomarkers of malignancy (new criteria of MM introduced in 2014 IMWG recommendations)	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess the risk of progression to MM evaluating biological factors	Progression of monoclonal component level (serum M component, urine M component or FLC involved/uninvolved) defined by increase of ≥ 25% from inclusion value.; Progression of percentage of phenotypically abnormal Bone Marrow Plasma Cells defined by increase of ≥ 10 % from inclusion value or an increase to over 95%	5 years
Assess the risk of progression to MM evaluating radiological markers	MRI progression : Progression of MRI abnormalities defined by any one or more of the following; Appearance of new focal lesion or new diffuse infiltration of previously unaffected regions; Growth of previously preexisting < 5mm focal(s) lesion(s); Progressive diffuse infiltration of already affected bones	5 years
Describe the clonal and sub-clonal evolution of SMM	Genetic analysis of bone marrow plasma cells at inclusion and during follow up to give data about the clonal and subclonal evolution of SMM (analysis of the mutations present in the tumor plasma cells, the allele frequency of each mutations, the determination of the clonal evolution mode for patients who will evolve to overt MM, the evaluation of copy number changes enabling to detect all the prognostic changes (1p32, 1q, 17p13), and (v) all the 14q32 translocations).	5 years
Describe annual risk of progression from SMM to MM at 5 years		5 years

Collaborators and Investigators

• Sponsor: Intergroupe Francophone du Myelome
• Investigators: Principal Investigator: Pr. Olivier Decaux, Rennes University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 11, 2020
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: October 18, 2019
• First Submitted That Met QC Criteria: October 26, 2019
• First Posted (Actual): October 30, 2019

Study Record Updates

• Last Update Posted (Estimated): March 6, 2024
• Last Update Submitted That Met QC Criteria: March 5, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Precancerous Conditions; Hypergammaglobulinemia; Multiple Myeloma; Neoplasms, Plasma Cell; Smoldering Multiple Myeloma
• Other Study ID Numbers: IFM 2017-04; 2016-002650-20 (Other Identifier: IDRCB Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No