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

Smoldering Multiple Myeloma Clinical Trial

— CARRISMM  

Official title:

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04144387
• Other study ID #: IFM 2017-04
• Secondary ID: 2016-002650-20
• Status: Active, not recruiting
• Phase: N/A
• Start date: February 11, 2020
• Est. completion date: December 2028

Study information

• Verified date: March 2024
• Source: Intergroupe Francophone du Myelome
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 395
• Est. completion date: December 2028
• Est. primary completion date: December 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Smoldering Multiple Myeloma

Intervention

Procedure:
• Myelogram
Two additional myelograms will be performed comparing to standard of care.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Intergroupe Francophone du Myelome

Countries where clinical trial is conducted

Belgium,  France,  Monaco, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	Describe annual risk of progression from SMM to MM at 5 years		5 years