Efficacy Study Comparing Velcade Dexamethasone Thalidomide Versus Velcade Cyclophosphamide Dexamethasone as Induction Treatment in the Initial Management of Multiple Myeloma (IFM2013-04) (IFM2013-04)

A PHASE III STUDY OF VELCADE (BORTEZOMIB) THALIDOMIDE DEXAMETHASONE (VTD) VERSUS VELCADE (BORTEZOMIB) CYCLOPHOSPHAMIDE DEXAMETHASONE (VCD) AS AN INDUCTION TREATMENT PRIOR TO AUTOLOGOUS STEM CELL TRANSPLANTATION IN PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA."

This is a phase III, multicenter, prospective with a clinical benefit, open-label and randomized study to compare two different treatments : Velcade (Bortezomib) Thalidomide Dexamethasone (VTD) versus Velcade (Bortezomib) Cyclophosphamide Dexamethasone (VCD) as an Induction Treatment prior to Autologous Stem Cell Transplantation in patients with Newly Diagnosed Multiple Myeloma.

Eligible patients will be randomized into 2 treatment arms. Each patient will receive 4 consecutive 21 day cycles of an induction treatment with either VTD or VCD.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Cyclophosphamide; Drug: Thalidomide®; Drug: Velcade®; Drug: Dexaméthasone

Detailed Description

The patient population will consist of adult men and women who have a confirmed diagnosis of Multiple Myeloma and who meet eligibility criteria. They will be recruited from among the patients consulting in an investigating centre's haematology service for newly diagnosed, symptomatic, untreated multiple myeloma.

in each treatment arm there will be :

1. Induction therapy : 4 cycles of VTD (21 days)or VCD
2. Systematic stem cell harvest after cycle 3

• Study Type: Interventional
• Enrollment (Actual): 358
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Amiens, France, 80054
    • CHRU Hopital Sud
  • Angers, France, 49033
    • Chu Angers
  • Argenteuil, France, 95 100
    • Centre Hospitalier Argenteuil
  • Avignon, France, 84902
    • Centre Hospitalier H.Duffaut
  • Bayonne, France, 64109
    • Centre Hospitalier de la Cote Basque
  • Besançon, France, 25030
    • CHRU De Besancon
  • Bobigny, France, 93009
    • Hopital Avicenne
  • Bordeaux, France, 33 300
    • Polyclinique Bordeaux Nord Aquitaine
  • Bourgoin Jallieu, France, 38300
    • Centre Hospitalier Pierre Oudot
  • Brest, France, 29609
    • Hôpital A.Morvan
  • Caen, France, 14033
    • CHU Caen Côte de Nacre
  • Cergy-pontoise, France, 95303
    • CH René Dubos
  • Chalon/saone, France, 71 321
    • Centre Hospitalier William Morey
  • Clamart, France, 92141
    • Hôpital d'instruction des armées Percy
  • Clermont-ferrand, France, 63000
    • CHU d'Estaing
  • Colmar, France, 68024
    • Hôpitaux Civils de Colmar
  • Corbeil-essonnes, France, 91100
    • Centre Hospitalier Sud Francilien
  • Creteil, France, 94 010
    • Chu Henri Mondor
  • Dijon, France, 21000
    • CHRU Dijon
  • Dunkerque, France, 59 385
    • Centre Hospitalier Général
  • Grenoble, France, 38043
    • CHRU - Hôpital A.Michallon
  • La Roche Sur Yon, France, 85925
    • Centre Hospitalier Départemental Vendée
  • Le Coudray, France, 28000
    • Hôpital Louis Pasteur
  • Le Mans, France, 72000
    • CH Le Mans
  • Le Mans, France, 72000
    • Centre Jean Bernard
  • Lille, France, 59020
    • Hôpital Saint Vincent de Paul
  • Lille, France, 59037
    • CHRU - Hôpital Claude Huriez
  • Limoges, France, 87042
    • CHU de Limoges
  • Lorient, France, 56100
    • Hôpital du Scorff
  • Lyon, France, 69008
    • Centre Leon Berard
  • Marseille, France, 13273
    • Institut Paoli Calmettes
  • Meaux, France, 77104
    • Centre Hospitalier de Meaux
  • Metz, France, 57085
    • CHR Metz Thionville
  • Meulan, France, 78250
    • Centre Hospitalier intercommunale Meulan les mureaux
  • Mulhouse, France, 68100
    • Hôpital E Muller
  • Nantes, France, 44093
    • Nantes University Hospital
  • Nice, France, 06202
    • Hôpital de l'Archet 1
  • Nimes, France, 30029
    • Groupe Hospitalo-Universitaire Carémeau
  • PARIS cedex 12, France, 75571
    • CHU - Hôpital St-Antoine
  • Paris, France, 75014
    • Hôpital Cochin
  • Paris, France, 75005
    • Institut Curie
  • Paris, France, 75651
    • Hôpital Pitié-Salpétrière
  • Paris, France, 75743
    • AP-HP Hôpital Necker
  • Paris, France, 75571
    • CHU - Hôpital St-Antoine
  • Perigueux, France, 24000
    • Centre Hospitalier de Périgueux
  • Perpignan, France, 66046
    • CH Saint Jean
  • Pessac, France, 33604
    • CHRU - Hôpital du Haut Lévêque
  • Pierre Benite, France, 69495
    • Centre Hospitalier Lyon Sud
  • Poitiers, France, 86021
    • CHRU - Hôpital Jean Bernard
  • Reims, France, 51092
    • Hôpital R.Debré
  • Rennes, France, 35033
    • CHRU - Hôpital de Pontchaillou
  • Rouen, France, 76038
    • Centre Henri Becquerel
  • ST Malo, France, 35400
    • Centre Hospitalier
  • Saint Quentin, France, 02 321
    • Centre Hospitalier
  • St Brieuc, France, 22 027
    • Centre hospitalier Yves Le Foll
  • St Cloud, France, 92210
    • Centre Rene Huguenin
  • St Priest-en-jarez, France, 42 271
    • Institut De Cancerologie De La Loire
  • Strasbourg, France, 67091
    • Hôpitaux Universitaires de Strasbourg
  • Toulouse, France, 31059
    • CHRU - Hôpital Purpan
  • Tours, France, 37044
    • CHRU - Hôpital Bretonneau
  • Vandoeuvre Les Nancy, France, 54511
    • CHRU - Hôpitaux de Brabois
  • Vannes, France, 56017
    • CH Bretagne Atlantique Vannes et Auray
  • Pringy
    • Annecy, Pringy, France, 74374
      • Centre hospitalier de la région d'Annecy

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:

Patients newly diagnosed with symptomatic Multiple Myeloma (MM) patient

1. - 18 ≤ age < 66 years
2. - Eastern Cooperative Oncology Group Performance Status of 0, 1 or 2
3. - Patients must be eligible for Autologous Stem Cell Transplantation
4. - Patients must have measurable disease by serum M-protein ≥ 10 g/L and/or urine M-protein ≥200mg/day

5. - Female patients of child-bearing potential (FCBP):

   • Must agree to have medically supervised pregnancy tests prior to starting study and every 21 days, including 4 weeks after the end of study treatment. This applies even if the patient practices complete and continued sexual abstinence.
   • Must agree to use and be able to comply with effective contraception without interruption, 28 days prior to starting study drug, during the study therapy (including during periods of dose interruptions), and for 28 days after discontinuation of study therapy.

6. - Male Patients:

   • Must agree to use a condom during sexual contact with a FCBP, throughout study drug therapy, during any dose interruption and for one week after discontinuation of study therapy
   • Must agree to not donate semen during study drug therapy and for one week after discontinuation of study therapy

7. - All patients must:

   • Agree to abstain from donating blood while taking study drug therapy and for one week after discontinuation of study drug therapy
   • Agree not to share study medication with another person.
8. - Patients must be capable of giving informed consent
9. - Patients must be affiliated with French social security system

Exclusion Criteria:

1. - Asymptomatic Multiple myeloma
2. - Non-secretory Multiple myeloma
3. - Proven AL-amyloidosis
4. - Age ≥ 66 years old
5. - Prior or current systemic therapy for Multiple myeloma, including steroids (except for emergency use of a 4-day block of dexamethasone before randomization, maximum total dose allowed 160 mg)
6. - Radiation therapy in the 2 weeks preceding randomization
7. - National Cancer Institute grade ≥ 2 peripheral neuropathy
8. - Haemoglobin < 8g/dL
9. - Absolute neutrophil count < 1,000 cells / µL, platelet count < 50,000 cells / µL
10. - Creatinine level > 170 µmol/L or requiring dialysis.
11. - Bilirubin, transaminases or GamaGT > 3 UNL (upper normal limit)
12. - Positive HIV serology, evidence of active Hepatitis B and C infection
13. - Severe active infection
14. - Inability to comply with an anti-thrombotic treatment regimen
15. - A personal medical history of severe psychiatric disease
16. - Uncontrolled diabetes contraindicating the use of high-dose dexamethasone
17. - Non-controlled or severe cardiovascular disease (including a myocardial infarction in the 6 months prior to recruitment)
18. - A personal medical history of cancer unless the patient has been without relapse after treatment discontinuation > or = 5 years (except for basocellular skin cancer or in situ cervical cancer)
19. - Use of any investigational drug in the 30 days preceding randomization

22 - Pregnant or lactating women. 23 - Adults under juridical protection 24 - Known or suspected hypersensitivity to any of the study therapies or excipients 25 - Necessity of vaccination for yellow fever or with any other live vaccines

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
Active Comparator: VELCADE (BORTEZOMIB) THALIDOMIDE DEXAMETHASONE (VTD); Arm A: Induction therapy 4 cycles of VTD (21 days) Thalidomide® 100 mg/day Per Os Day1 to Day21 Velcade® 1.3 mg/m²/day Subcutaneous Day1, 4, 8 and 11 Dexamethasone 40 mg/day Per Os Day 1 to 4 and Day 9 to 12; Systematic stem cell harvest after cycle 3 Mobilization: Cyclophosphamide and one week after the last dose of Thalidomide, stem cells have to be harvested	Drug: Thalidomide®; Drug: Velcade®; Drug: Dexaméthasone
Active Comparator: VELCADE (BORTEZOMIB) CYCLOPHOSPHAMIDE DEXAMETHASONE (VCD); For arm B: Induction therapy : 4 cycles of VCD (21 days)Cyclophosphamide 500 mg/m²/day, Per Os Day 1, 8, 15Velcade® and Dexamethasone identical treatment to Arm A; Systematic stem cell harvest after cycle 3 Mobilization: Cyclophosphamide and two weeks after the last dose of Cyclophosphamide, stem cells have to be harvested	Drug: Cyclophosphamide; Drug: Velcade®; Drug: Dexaméthasone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response assessment according to the criteria IMWG	compare the Response assessment in both arms: the Very good partial remission rate (according to the criteria IMWG) achieved with four courses of VTD with that achieved with four courses of VCD	15-17 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response assessment according to the criteria IMWG	compare the Response assessment in both arms: the following parameters after induction treatment with four courses of VTD or four courses of VCD the Complete remission rate (according to the criteria IMWG)	15 - 17 month
Number of Adverse Events	To evaluate the Safety of induction therapy	15-17 month
Number of collected stem cell		17 month
Number of death	To evaluate Overall and Progression-Free Survival	17 month
Response assessment according to the criteria IMWG	compare the Response assessment in both arms: Compare the following parameters after induction treatment with four courses of VTD or four courses of VCD the Partial remission rate (according to the criteria IMWG)	15-17 month
Number of relapse according to the criteria IMWG	Progression-Free Survival	17 month

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of three techniques for the quantification of urinary monoclonal components in patients with Newly Diagnosed Multiple Myeloma.	The detection and the estimation of the urinary monoclonal components is an inescapable element of the diagnosis and the evaluation of the therapeutic efficacy in the myeloma. Urinary protein, electrophoresisin agarose gel is the quantitative method of choice. In these labs, the quantification of the urinary monoclonal peak is not performed. In the absence of quantitative data on urinary monoclonal components, the patient is considered as non-assessable. Recently, the company Sebia has developed the quantification on two other materials used specifically for the characterization of monoclonal component and / or proteinuria (HYDRAGEL BENCE JONES and HYDRAGEL URINE PROFILE). The objective of this study is to compare the quantification of monoclonal components between the reference HR electrophoresis technique and the other two above-mentioned techniques.	17 month

Collaborators and Investigators

• Sponsor: Nantes University Hospital
• Investigators: Principal Investigator: Philippe MOREAU, Nantes University Hospital

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): August 1, 2015

Study Registration Dates

• First Submitted: September 30, 2013
• First Submitted That Met QC Criteria: October 23, 2013
• First Posted (Estimate): October 29, 2013

Study Record Updates

• Last Update Posted (Estimate): October 7, 2015
• Last Update Submitted That Met QC Criteria: October 6, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: Multiple myeloma; Newly Diagnosed
• 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; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Anti-Bacterial Agents; Leprostatic Agents; Dexamethasone; Cyclophosphamide; Thalidomide; Bortezomib
• Other Study ID Numbers: RC13_0284; 2013-003174-27 (EudraCT Number)