Bortezomib-Melphalan Conditioning Regimen vs Melphalan for Frontline Transplant Eligible Patients With Multiple Myeloma (IFM2014-02)

IFM 2014-02 Study: A Randomized Phase III Study of Bortezomib-Melphalan 200 Conditioning Regimen Versus Melphalan 200 for Frontline Transplant Eligible Patients With Multiple Myeloma

Phase III multicenter randomized, open-label study comparing the efficacy of a combined high dose chemotherapy using melphalan and bortezomib versus melphalan alone followed by stem cell transplant in frontline multiple myeloma patients, non-progressive after induction therapy.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Bortezomib-Melphalan; Drug: Melphalan

• Study Type: Interventional
• Enrollment (Actual): 300
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium
    • Clinique Universitaire Saint LUC
  • Charleroi, Belgium
    • Grand Hôpital de Charleroi - Site Notre-Dame
  • Liege, Belgium
    • Chu Liege
  • Yvoir, Belgium
    • CHU Dinant-Godinne UCL Namur
• France
  • Amiens, France
    • CHU Amiens
  • Angers, France
    • CHU Angers
  • Argenteuil, France
    • CH Argenteuil Victor Dupouy
  • Bayonne, France
    • CH Bayonne
  • Besancon, France
    • Hopital Jean Minjoz
  • Bobigny, France
    • Hôpital Avicenne
  • Bordeaux, France
    • Hôpital du Haut Lévêque
  • Brest, France
    • CHU DE BREST Hôpital A.Morvan
  • Caen, France
    • CHU caen
  • Clamart, France
    • Hopital D'Instruction Des Armees Percy
  • Clermont-ferrand, France
    • CHU d'Estaing
  • Colmar, France
    • Hôpitaux Civils de Colmar
  • Creteil, France
    • CHU Henri Mondor
  • Dijon, France
    • CHRU Dijon - Hôpital des Enfants
  • Dunkerque, France
    • Centre Hospitalier Général
  • Grenoble, France
    • CHU Grenoble
  • Lille, France
    • CHRU Lille- Hopital Claude Huriez
  • Limoges, France
    • CHU Limoges
  • Lyon, France
    • Centre Léon Bérard
  • Lyon, France
    • Centre Hospitalier Lyon Sud
  • Marseille, France
    • Institut Paoli Calmettes
  • Metz, France
    • Hôpital de Mercy - CHR Metz Thionville
  • Mulhouse, France
    • Centre Hospitalier de Mulhouse
  • Nancy, France
    • CHU Nancy
  • Nantes, France
    • Hotel Dieu
  • Nice, France
    • Hôpital Archet
  • Orleans, France
    • CH d'Orleans
  • Paris, France
    • Hopital de la Pitie Salpetriere
  • Paris, France
    • Hopital Saint-Louis
  • Paris, France
    • Hopital Cochin
  • Paris, France
    • Hôpital St-Antoine
  • Poitiers, France
    • CHU - Hôpital Jean Bernard
  • Reims, France
    • CHU de Reims- Hôpital R.Debré
  • Rennes, France
    • Hopital de Pontchaillou
  • Rouen, France
    • Centre Henri Becquerel
  • St Cloud, France
    • Hopital René Huguenin
  • St-priest-en-jarez, France
    • Institut de Cancérologie de la Loire Lucien Neuwirth
  • Toulouse, France, 31000
    • CHU de Toulouse
  • Tours, France
    • CHU Tours
  • Versailles, France
    • Centre Hospitalier de Versailles-Hôpital André Mignot
  • ILE DE LA Reunion
    • Saint Pierre, ILE DE LA Reunion, France
      • CH Sud Réunion
    • St-denis, ILE DE LA Reunion, France
      • Hôpital Félix Guyon

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Must have results from their initial diagnosis available at the time of screening to confirm all the following :

  1. Diagnosis of multiple myeloma according to the diagnostic
  2. Symptomatic de novo Multiple Myeloma
• Be eligible for high-dose therapy with autologous stem cell transplantation
• Autologous cell graft with a total number of CD 34 cells > or = 5 X 106/kg before freezing

Exclusion Criteria:

• Progressive disease
• Females participants pregnant or breast-feeding
• A known infection by the human immunodeficiency virus
• An active viral hepatitis B or C
• Unstable angina or myocardial infarction within 4 months prior to inclusion, heart failure NYHA class III or IV angina, uncontrolled, history of severe coronary artery disease, an uncontrolled serious ventricular arrhythmia, a sick sinus syndrome, or electrocardiographic evidence of acute ischemia or conduction disturbances grade 3 unless the patient has a pacemaker
• Uncontrolled hypertension or uncontrolled diabetes within 14 days before enrollment
• A history of another malignancy. If cancer was diagnosed more than 10 years and considered as cured, an authorization may be requested on a case-by-case basis after discussion with the principal investigator
• A significant neuropathy of grade 3-4 or grade 2 with pain in the 14 days prior to enrollment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bortezomib-Melphalan; Bortezomib will be administered on days: -6, -3 +1, +4. Melphalan will be administered on day -2. The PBSC will be injected on day 0.	Drug: Bortezomib-Melphalan; Bortezomib will be administered on days: -6, -3, +1, +4. Melphalan will be administered on day -2. The PBSC will be injected on day 0.
Active Comparator: Melphalan; Melphalan will be administered on day -2. The PBSC will be injected on day 0.	Drug: Melphalan; Melphalan will be administered on day -2. The PBSC will be injected on day 0.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
overall survival	60 months
Complete Response rates (according to IMWG 2011 criteria)	60 days post Autologous Stem Cells Transplantation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rates (according to IMWG 2011 criteria)	Compare response rate after ASCT and after the completion of consolidation therapy	post ASCT and consolidation therapy
Serious adverse event		End of study
progression-free survival between the two arms		60 months

Collaborators and Investigators

• Sponsor: University Hospital, Toulouse
• Collaborators: Ministry of Health, France; Janssen, LP
• Investigators: Principal Investigator: Michel ATTAL, MD, PhD, CHU Toulouse; Principal Investigator: Murielle ROUSSEL, MD, CHU Toulouse; Principal Investigator: ROYER, MD, CHU Amiens; Principal Investigator: DIB, MD, University Hospital, Angers; Principal Investigator: CHAOUI, MD, CH Argenteuil; Principal Investigator: ARAUJO, MD, CH Bayonne; Principal Investigator: FONTAN, MD, CH Besancon; Principal Investigator: BRECHIGNAC, MD, Hôpital Avicenne BOBIGNY; Principal Investigator: MARIT, Pr, CHU Bordeaux; Principal Investigator: EVEILLARD, MD, CHU Brest; Principal Investigator: MACRO, MD, CHU caen; Principal Investigator: MALFUSON, MD, CLAMART PERCY-Hôpital Instruction des Armées; Principal Investigator: CHALETEIX, MD, University Hospital, Clermont-Ferrand; Principal Investigator: HUMBRECHT-KRAUT, MD, Hôpitaux Civils de Colmar; Principal Investigator: BELHADJ, MD, CHU Henri Mondor de Creteil; Principal Investigator: CAILLOT, MD, CHU Dijon; Principal Investigator: WETTERWALD, MD, Ch Dunkerque; Principal Investigator: PEGOURIE, MD, University Hospital, Grenoble; Principal Investigator: AGAPE, MD, CH LA REUNION-ST DENIS; Principal Investigator: ZUNIC, MD, CH LA REUNION SAINT PIERRE; Principal Investigator: LELEU, MD, Chu Lille; Principal Investigator: JACCARD, MD, CHU Limoges; Principal Investigator: KARLIN, MD, Hospices Civils de Lyon; Principal Investigator: NICOLAS, MD, Centre Léon BERARD de Lyon; Principal Investigator: STOPPA, MD, Institut Paoli Calmettes Marseille; Principal Investigator: DORVAUX, MD, CH Metz; Principal Investigator: EISENMANN, MD, CH Mulhouse; Principal Investigator: HULIN, MD, CHU Nancy; Principal Investigator: MOREAU, Pr, CHU Nantes; Principal Investigator: LEGROS, MD, CHU Nice; Principal Investigator: BENBRAHIM, MD, CH Orléans; Principal Investigator: BOUSCARY, MD, Hôpital Cochin Paris; Principal Investigator: KUHNOWSKI, MD, Institut Curie Paris; Principal Investigator: MOREL, MD, Hôpital La Pitié Salpétrière Paris; Principal Investigator: GARDERET, MD, Hôpital Saint Antoine Paris; Principal Investigator: ARNULF, MD, Hôpital Saint Louis Paris; Principal Investigator: LACOTTE, MD, CHU Poitiers; Principal Investigator: DELMER, Pr, Chu Reims; Principal Investigator: ESCOFFRE, MD, Chu Rennes; Principal Investigator: LENAIN, MD, Centre Henri Becquerel de Rouen; Principal Investigator: GLAISNER, MD, Hôpital René Huguenin - St Cloud; Principal Investigator: AUGEL MEUNIER, MD, CHU ST PRIEST EN JAREZ; Principal Investigator: BENBOUBKER, MD, CHU Tours; Principal Investigator: RIGAUDEAU, MD, CH Versailles

Publications and helpful links

General Publications

• Roussel M, Lauwers-Cances V, Macro M, Leleu X, Royer B, Hulin C, Karlin L, Perrot A, Touzeau C, Chretien ML, Rigaudeau S, Dib M, Nicolas-Virelizier E, Escoffre-Barbe M, Belhadj K, Mariette C, Stoppa AM, Araujo C, Doyen C, Fontan J, Kolb B, Garderet L, Brechignac S, Malfuson JV, Jaccard A, Lenain P, Borel C, Hebraud B, Benbrahim O, Dorvaux V, Manier S, Augeul-Meunier K, Vekemans MC, Randriamalala E, Chaoui D, Caers J, Chaleteix C, Benboubker L, Vincent L, Glaisner S, Zunic P, Slama B, Eveillard JR, Humbrecht-Kraut C, Morel V, Mineur P, Eisenmann JC, Demarquette H, Richez V, Vignon M, Caillot D, Facon T, Moreau P, Colin AL, Olivier P, Wuilleme S, Avet-Loiseau H, Corre J, Attal M. Bortezomib and high-dose melphalan conditioning regimen in frontline multiple myeloma: an IFM randomized phase 3 study. Blood. 2022 May 5;139(18):2747-2757. doi: 10.1182/blood.2021014635.

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (Actual): December 31, 2018
• Study Completion (Actual): December 31, 2018

Study Registration Dates

• First Submitted: July 18, 2014
• First Submitted That Met QC Criteria: July 21, 2014
• First Posted (Estimate): July 22, 2014

Study Record Updates

• Last Update Posted (Actual): May 23, 2022
• Last Update Submitted That Met QC Criteria: May 17, 2022
• Last Verified: May 1, 2022

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; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Melphalan; Bortezomib
• Other Study ID Numbers: 13 7045 01