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

Multiple Myeloma Clinical Trial

— IFM2013-04  

Official title:

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."

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01971658
• Other study ID #: RC13_0284
• Secondary ID: 2013-003174-27
• Status: Completed
• Phase: Phase 3
• First received: September 30, 2013
• Last updated: October 6, 2015
• Start date: October 2013
• Est. completion date: August 2015

Study information

• Verified date: October 2015
• Source: Nantes University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
• Study type: Interventional

Clinical Trial Summary

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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 358
• Est. completion date: August 2015
• Est. primary completion date: August 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Thalidomide®

• Cyclophosphamide

• Velcade®

• Dexaméthasone

Locations

Country	Name	City	State
France	CHRU Hôpital Sud	Amiens
France	CHU Angers	Angers
France	Centre Hospitalier de la région d'Annecy	Annecy	Pringy
France	Centre Hospitalier Argenteuil	Argenteuil
France	Centre Hospitalier H.Duffaut	Avignon
France	Centre Hospitalier de la Côte Basque	Bayonne
France	CHRU de Besançon	Besançon
France	Hôpital Avicenne	Bobigny
France	Polyclinique Bordeaux Nord Aquitaine	Bordeaux
France	Centre hospitalier Pierre Oudot	Bourgoin Jallieu
France	Hôpital A.Morvan	Brest
France	CHU Caen Côte de Nacre	Caen
France	CH René Dubos	Cergy-pontoise
France	Centre Hospitalier William Morey	Chalon/saone
France	Hôpital d'instruction des armées Percy	Clamart
France	CHU d'Estaing	Clermont-ferrand
France	Hôpitaux civils de Colmar	Colmar
France	Centre Hospitalier Sud Francilien	Corbeil-essonnes
France	CHU Henri Mondor	Creteil
France	CHRU Dijon	Dijon
France	Centre Hospitalier Général	Dunkerque
France	CHRU - Hôpital A.Michallon	Grenoble
France	Centre hospitalier départemental Vendée	La Roche Sur Yon
France	Hôpital Louis Pasteur	Le Coudray
France	Centre Jean Bernard	Le Mans
France	CH Le Mans	Le Mans
France	CHRU - Hôpital Claude Huriez	Lille
France	Hopital Saint Vincent de Paul	Lille
France	CHU de Limoges	Limoges
France	Hôpital Du Scorff	Lorient
France	Centre Léon Bérard	Lyon
France	Institut Paoli Calmettes	Marseille
France	Centre Hospitalier de Meaux	Meaux
France	CHR Metz Thionville	Metz
France	Centre Hospitalier intercommunale Meulan les mureaux	Meulan
France	Hopital E Muller	Mulhouse
France	Nantes University Hospital	Nantes
France	Hôpital de l'Archet 1	Nice
France	Groupe Hospitalo-Universitaire Carémeau	Nimes
France	AP-HP Hôpital Necker	Paris
France	CHU - Hôpital St-Antoine	Paris
France	Hôpital Cochin	Paris
France	Hôpital Pitié-Salpétrière	Paris
France	Institut CURIE	Paris
France	CHU - Hôpital St-Antoine	PARIS cedex 12
France	Centre Hospitalier de PERIGUEUX	Perigueux
France	CH Saint Jean	Perpignan
France	CHRU - Hôpital du Haut Lévêque	Pessac
France	Centre Hospitalier Lyon sud	Pierre Benite
France	CHRU - Hôpital Jean Bernard	Poitiers
France	Hôpital R.Debré	Reims
France	CHRU - Hôpital de Pontchaillou	Rennes
France	Centre Henri Becquerel	Rouen
France	Centre Hospitalier	Saint Quentin
France	Centre Hospitalier Yves le Foll	St Brieuc
France	Centre René Huguenin	St Cloud
France	Centre hospitalier	ST Malo
France	Institut de Cancérologie de la Loire	St Priest-en-jarez
France	Hôpitaux Universitaires de Strasbourg	Strasbourg
France	CHRU - Hôpital Purpan	Toulouse
France	CHRU - Hôpital Bretonneau	Tours
France	CHRU - Hôpitaux de Brabois	Vandoeuvre Les Nancy
France	CH Bretagne Atlantique Vannes et Auray	Vannes

Sponsors (1)

Lead Sponsor	Collaborator
Nantes University Hospital

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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	No
Primary	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	No
Secondary	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	No
Secondary	Number of Adverse Events	To evaluate the Safety of induction therapy	15-17 month	Yes
Secondary	Number of collected stem cell		17 month	No
Secondary	Number of death	To evaluate Overall and Progression-Free Survival	17 month	No
Secondary	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	Yes
Secondary	Number of relapse according to the criteria IMWG	Progression-Free Survival	17 month	No