Study of Bendamustine, Velcade and Dexamethasone in the Treatment of Elderly Patients With Multiple Myeloma (BVD)
Primary Purpose
Multiple Myeloma
Status
Completed
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Bendamustine, Velcade and Dexamethasone
Sponsored by

About this trial
This is an interventional treatment trial for Multiple Myeloma focused on measuring Multiple Myeloma, Elderly patients, first relapse, refractory to first line therapy, Bendamustine Velcade Dexamethasone Association
Eligibility Criteria
Inclusion Criteria:
- Symptomatic multiple myeloma (MM) patient at the time of diagnosis (but not necessarily at the time of relapse), according to International Myeloma Working Group criteria.
- Patient having received conventional chemotherapy in 1st line treatment because of age 65 years or over, or younger than 65 years and ineligible to high-dose therapy plus stem cell transplantation.
- Measurable disease (≥10g/L monoclonal gammapathy and/or ≥ 200 mg/24h proteinuria or involved serum free light chain ≥ 100mg/L with abnormal FLC ratio < 0.26 or > 1.65)
- Patient in 1st relapse or refractory to 1st line therapy. Relapse is defined by M-component increase of ≥25% from baseline, in serum and/or urine (the absolute increase in serum must be ≥ 5 g/l - the absolute increase of BJ proteins in urine must be ≥200 mg/24 h). (It is recommended to treat only symptomatic or rapidly evolutive relapses)
- Life expectancy of at least 3 months
- ECOG performance status <= 2 at study entry
- Laboratory test results within these ranges:
- Absolute neutrophil count >= 1.5 x 109/L
- Platelet count >= 100 x 109/L
- Serum creatinine <= 250 umol/l
- AST (SGOT) and ALT (SGPT) <= 3 x ULN
- Disease free of prior malignancies for >= 5 years, with exception of curatively treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast
- Able to adhere to the study visit schedule and other protocol requirements
- Using effective contraceptive methods during and for 6 months after study treatment (for fertile men, women of childbearing potential).
- Provision of informed consent.
- A period of at least 15 days must be respected between the last treatment of myeloma and the beginning of the study.
Exclusion Criteria:
- Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
- Any comorbidity which places the subject at unacceptable risk if he/she were to participate in the study.
- Patients treated with high-dose therapy plus stem cell transplantation in 1st line therapy
- Any prior use of bortezomib (Velcade) or bendamustine (Ribomustin)
- Concurrent use of other anti-cancer agents or treatments other than those stated in this treatment plan
- Use of any other experimental drug or therapy within 28 days prior to the start of study treatment.
- Known hypersensitivity to the study drugs
- Positive HIV serology, positive hepatitis C serology, active infection hepatitis A, active infection hepatitis B.
- Severe cardiovascular disorders within 12 months prior to the start of study treatment (e.g. myocardial infarct, ischemic episodes, arrhythmias)
- Previous major surgery less than 30 days before start of treatment
- Active infection,
- Pregnant or lactating women.
Sites / Locations
- CHRU Hôpital Sud
- CHRU, Hôpital du Bocage
- Centre Hospitalier H.Duffaut
- Centre Hospitalier de la Cote Basque
- Hôpital Jean Minjoz / CHU BESANCON
- Centre Hospitalier
- Hôpital Avicenne
- Polyclinique Bordeaux Nord Aquitaine
- Hôpital A.Morvan
- Centre F.Baclesse
- CHU Clermont Ferrand
- CH Sud Francilien
- CHU DIJON, Hôpital Le Bocage
- Centre Hospitalier Général
- Hôpital A.Michallon
- CH Départemental
- Centre Hospitalier de Chartres
- Centre Jean Bernard
- CHRU Hôpital Claude Huriez
- Institut Paoli Calmette
- CH MEAUX
- CHRU Hôtel Dieu
- Hôpital de l'Archet 1
- Intitut Curie
- CHU Hôpital St-Antoine
- Centre Hopsitalier Lyon Sud
- Centre Hospitalier René Dubos
- Centre Hospitalier de la Région d'Annecy
- CHU Reims Hôpital R.Debré
- CHRU - Hôpital sud
- Centre Henri Becquerel
- Centre René Huguenin
- CHRU Hopital Purpan
- CHRU Hopital Bretonneau
- Centre Hospitalier
- CHRU - Hôpitaux de Brabois
- CH P.Chubert
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
BVD
Arm Description
Bendamustine, Velcade and Dexamethasone
Outcomes
Primary Outcome Measures
To assess of the overall response rate (complete response (CR) + partial response (PR))
Secondary Outcome Measures
Time to best response
Progression-free survival
Time to progression
Overall survival
Rate of additional response
Toxicity/Adverse events
Full Information
NCT ID
NCT01045681
First Posted
January 7, 2010
Last Updated
December 3, 2020
Sponsor
Intergroupe Francophone du Myelome
1. Study Identification
Unique Protocol Identification Number
NCT01045681
Brief Title
Study of Bendamustine, Velcade and Dexamethasone in the Treatment of Elderly Patients With Multiple Myeloma
Acronym
BVD
Official Title
A Phase II Study of Bendamustine, Velcade and Dexamethasone (BVD) in the Treatment of Elderly Patients (>= 65 Years) With Multiple Myeloma in 1st Relapse or Refractory to 1st Line Therapy
Study Type
Interventional
2. Study Status
Record Verification Date
March 2012
Overall Recruitment Status
Completed
Study Start Date
March 3, 2010 (Actual)
Primary Completion Date
March 28, 2013 (Actual)
Study Completion Date
March 28, 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Intergroupe Francophone du Myelome
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The present trial is designed as a phase II study that aims at estimating the efficacy of the combination of bendamustine, bortezomib and dexamethasone in relapsed/refractory multiple myeloma (MM). The response rate, i.e. the rate of the patients achieving a Complete Response or Partial Response at cycle 4, divided by the total intent to treat patient number is chosen as primary efficacy endpoint.
The estimation of the efficacy rate is to be based on an explorative pilot study, since immediate embarking on a large-scale comparative efficacy trial would not be acceptable from the point of view of resources. Moreover, this would induce ethical objections, as it does not seem to be justifiable to expose a large number of patients to an experimental approach without sufficient exploratory indications of an improved risk-benefit ratio.
Detailed Description
After relapse or after early progression on first-line treatment, the prognosis of multiple myeloma (MM) patients is unfavourable, and the search for new treatment regimens, including drugs with novel mechanisms of action is essential.
Bendamustine and bortezomib have shown high activity boch in first-line regimens and pre-treated patients. The novel mechanism of action of the proteasome inhibitor and the non-cross resistance of bendamustine to other alkylating agents established in the first-line treatment of multiple myeloma seem to recommend a combination of the two drugs for salvage therapy (second-line regimen). Finally, the promising response data in a series of relapsing MM patients treated with bendamustine, bortezomib and prednisone support this assumption, as well as the feasibility and tolerability of the combination.
In summary, there is some evidence for a favorable risk/benefit ratio for the combination of bendamustine, bortezomib and a corticoid drug, warranting the exploration in a larger, prospectively designed multicenter phase II study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
Multiple Myeloma, Elderly patients, first relapse, refractory to first line therapy, Bendamustine Velcade Dexamethasone Association
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
75 (Actual)
8. Arms, Groups, and Interventions
Arm Title
BVD
Arm Type
Experimental
Arm Description
Bendamustine, Velcade and Dexamethasone
Intervention Type
Drug
Intervention Name(s)
Bendamustine, Velcade and Dexamethasone
Other Intervention Name(s)
Robimustin : Bendamustine, Velcade : Bortezomib, Dexamethasone
Intervention Description
Bendamustine : 70 mg/m2 iv on D1 and 8, for each cycle Velcade : 1.3 mg/m2 iv on D1, 8, 15 and 22, for each cycle Dexamethasone : 20 mg/day po on D1, 8, 15 and 22, given prior to Bendamustine and Velcade
Primary Outcome Measure Information:
Title
To assess of the overall response rate (complete response (CR) + partial response (PR))
Time Frame
After four 28-day consecutives cycles
Secondary Outcome Measure Information:
Title
Time to best response
Time Frame
the time from treatment start to the first detection of the best response category, calculated for all patients, which are not primarily refractory
Title
Progression-free survival
Time Frame
The time form the initial dose of chemotherapy to the time of disease progression or death, or to the date of last assessment without any such event (censored observation)
Title
Time to progression
Time Frame
The time from baseline to the development of progressive disease
Title
Overall survival
Time Frame
The time interval from initial dose to the date of death or last observation (censored)
Title
Rate of additional response
Time Frame
Following 2 consolidation cycles and following 6 maintenance cycles
Title
Toxicity/Adverse events
Time Frame
From the time a signed and dated informed consent form is obtained until 60 days following the lase dose of study medication or until the start of a new subsequent antimyeloma therapy
10. Eligibility
Sex
All
Minimum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Symptomatic multiple myeloma (MM) patient at the time of diagnosis (but not necessarily at the time of relapse), according to International Myeloma Working Group criteria.
Patient having received conventional chemotherapy in 1st line treatment because of age 65 years or over, or younger than 65 years and ineligible to high-dose therapy plus stem cell transplantation.
Measurable disease (≥10g/L monoclonal gammapathy and/or ≥ 200 mg/24h proteinuria or involved serum free light chain ≥ 100mg/L with abnormal FLC ratio < 0.26 or > 1.65)
Patient in 1st relapse or refractory to 1st line therapy. Relapse is defined by M-component increase of ≥25% from baseline, in serum and/or urine (the absolute increase in serum must be ≥ 5 g/l - the absolute increase of BJ proteins in urine must be ≥200 mg/24 h). (It is recommended to treat only symptomatic or rapidly evolutive relapses)
Life expectancy of at least 3 months
ECOG performance status <= 2 at study entry
Laboratory test results within these ranges:
Absolute neutrophil count >= 1.5 x 109/L
Platelet count >= 100 x 109/L
Serum creatinine <= 250 umol/l
AST (SGOT) and ALT (SGPT) <= 3 x ULN
Disease free of prior malignancies for >= 5 years, with exception of curatively treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast
Able to adhere to the study visit schedule and other protocol requirements
Using effective contraceptive methods during and for 6 months after study treatment (for fertile men, women of childbearing potential).
Provision of informed consent.
A period of at least 15 days must be respected between the last treatment of myeloma and the beginning of the study.
Exclusion Criteria:
Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
Any comorbidity which places the subject at unacceptable risk if he/she were to participate in the study.
Patients treated with high-dose therapy plus stem cell transplantation in 1st line therapy
Any prior use of bortezomib (Velcade) or bendamustine (Ribomustin)
Concurrent use of other anti-cancer agents or treatments other than those stated in this treatment plan
Use of any other experimental drug or therapy within 28 days prior to the start of study treatment.
Known hypersensitivity to the study drugs
Positive HIV serology, positive hepatitis C serology, active infection hepatitis A, active infection hepatitis B.
Severe cardiovascular disorders within 12 months prior to the start of study treatment (e.g. myocardial infarct, ischemic episodes, arrhythmias)
Previous major surgery less than 30 days before start of treatment
Active infection,
Pregnant or lactating women.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Philippe RODON, Doctor
Organizational Affiliation
Unité Hématologie Biologique Institut Curie PARIS
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Cyrille HULIN, Doctor
Organizational Affiliation
Service Hématologie Hôpitaux de Brabois VANDOEUVRE LES NANCY
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jean-Luc HAROUSSEAU, Professor
Organizational Affiliation
Service Hématologie CHU Nantes
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Claire MATHIOT, Doctor
Organizational Affiliation
IFM Hématologie Biologique Institut Curie PARIS
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Marie-Odile PETILLON, Doctor
Organizational Affiliation
IFM Hôpital Claude Huriez Lille
Official's Role
Study Chair
Facility Information:
Facility Name
CHRU Hôpital Sud
City
Amiens
ZIP/Postal Code
80054
Country
France
Facility Name
CHRU, Hôpital du Bocage
City
Angers
ZIP/Postal Code
49033
Country
France
Facility Name
Centre Hospitalier H.Duffaut
City
Avignon
ZIP/Postal Code
84902
Country
France
Facility Name
Centre Hospitalier de la Cote Basque
City
Bayonne
ZIP/Postal Code
64109
Country
France
Facility Name
Hôpital Jean Minjoz / CHU BESANCON
City
Besançon
ZIP/Postal Code
25030
Country
France
Facility Name
Centre Hospitalier
City
Blois
ZIP/Postal Code
41016
Country
France
Facility Name
Hôpital Avicenne
City
Bobigny
ZIP/Postal Code
93009
Country
France
Facility Name
Polyclinique Bordeaux Nord Aquitaine
City
Bordeaux
ZIP/Postal Code
33000
Country
France
Facility Name
Hôpital A.Morvan
City
Brest
ZIP/Postal Code
29609
Country
France
Facility Name
Centre F.Baclesse
City
Caen
ZIP/Postal Code
14076
Country
France
Facility Name
CHU Clermont Ferrand
City
Clermont Ferrand
ZIP/Postal Code
63003
Country
France
Facility Name
CH Sud Francilien
City
Corbeil-essonnes
ZIP/Postal Code
91106
Country
France
Facility Name
CHU DIJON, Hôpital Le Bocage
City
Dijon
ZIP/Postal Code
21034
Country
France
Facility Name
Centre Hospitalier Général
City
Dunkerque
ZIP/Postal Code
59385
Country
France
Facility Name
Hôpital A.Michallon
City
Grenoble
ZIP/Postal Code
38043
Country
France
Facility Name
CH Départemental
City
La Roche Sur Yon
ZIP/Postal Code
85925
Country
France
Facility Name
Centre Hospitalier de Chartres
City
Le Coudray
ZIP/Postal Code
28629
Country
France
Facility Name
Centre Jean Bernard
City
Le Mans
ZIP/Postal Code
72000
Country
France
Facility Name
CHRU Hôpital Claude Huriez
City
Lille
ZIP/Postal Code
59038
Country
France
Facility Name
Institut Paoli Calmette
City
Marseille
ZIP/Postal Code
13273
Country
France
Facility Name
CH MEAUX
City
Meaux
ZIP/Postal Code
77104
Country
France
Facility Name
CHRU Hôtel Dieu
City
Nantes
ZIP/Postal Code
44035
Country
France
Facility Name
Hôpital de l'Archet 1
City
Nice
ZIP/Postal Code
06202
Country
France
Facility Name
Intitut Curie
City
Paris
ZIP/Postal Code
75005
Country
France
Facility Name
CHU Hôpital St-Antoine
City
Paris
ZIP/Postal Code
75571
Country
France
Facility Name
Centre Hopsitalier Lyon Sud
City
Pierre Benite
ZIP/Postal Code
69495
Country
France
Facility Name
Centre Hospitalier René Dubos
City
Pontoise
ZIP/Postal Code
95300
Country
France
Facility Name
Centre Hospitalier de la Région d'Annecy
City
Pringy
ZIP/Postal Code
74374
Country
France
Facility Name
CHU Reims Hôpital R.Debré
City
Reims
ZIP/Postal Code
51032
Country
France
Facility Name
CHRU - Hôpital sud
City
Rennes
ZIP/Postal Code
35056
Country
France
Facility Name
Centre Henri Becquerel
City
Rouen
ZIP/Postal Code
76038
Country
France
Facility Name
Centre René Huguenin
City
Saint-cloud
ZIP/Postal Code
92210
Country
France
Facility Name
CHRU Hopital Purpan
City
Toulouse
ZIP/Postal Code
31059
Country
France
Facility Name
CHRU Hopital Bretonneau
City
Tours
ZIP/Postal Code
37044
Country
France
Facility Name
Centre Hospitalier
City
Valence
ZIP/Postal Code
26953
Country
France
Facility Name
CHRU - Hôpitaux de Brabois
City
Vandœuvre-lès-Nancy
ZIP/Postal Code
54511
Country
France
Facility Name
CH P.Chubert
City
Vannes
ZIP/Postal Code
56017
Country
France
12. IPD Sharing Statement
Citations:
PubMed Identifier
25398832
Citation
Rodon P, Hulin C, Pegourie B, Tiab M, Anglaret B, Benboubker L, Jardel H, Decaux O, Kolb B, Roussel M, Garderet L, Leleu X, Fitoussi O, Chaleteix C, Casassus P, Lenain P, Royer B, Banos A, Benramdane R, Cony-Makhoul P, Dib M, Fontan J, Stoppa AM, Traulle C, Vilque JP, Petillon MO, Mathiot C, Dejoie T, Avet-Loiseau H, Moreau P. Phase II study of bendamustine, bortezomib and dexamethasone as second-line treatment for elderly patients with multiple myeloma: the Intergroupe Francophone du Myelome 2009-01 trial. Haematologica. 2015 Feb;100(2):e56-9. doi: 10.3324/haematol.2014.110890. Epub 2014 Nov 14. No abstract available.
Results Reference
derived
Learn more about this trial
Study of Bendamustine, Velcade and Dexamethasone in the Treatment of Elderly Patients With Multiple Myeloma
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