Study of Bendamustine, Velcade and Dexamethasone in the Treatment of Elderly Patients With Multiple Myeloma

Multiple Myeloma Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01045681
• Other study ID #: IFM2009-01
• Secondary ID: Eudract 2009-012
• Status: Completed
• Phase: Phase 2
• Start date: March 3, 2010
• Est. completion date: March 28, 2013

Study information

• Verified date: March 2012
• Source: Intergroupe Francophone du Myelome
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: March 28, 2013
• Est. primary completion date: March 28, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Bendamustine, Velcade and Dexamethasone
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

Locations

Country	Name	City	State
France	CHRU Hôpital Sud	Amiens
France	CHRU, Hôpital du Bocage	Angers
France	Centre Hospitalier H.Duffaut	Avignon
France	Centre Hospitalier de la Cote Basque	Bayonne
France	Hôpital Jean Minjoz / CHU BESANCON	Besançon
France	Centre Hospitalier	Blois
France	Hôpital Avicenne	Bobigny
France	Polyclinique Bordeaux Nord Aquitaine	Bordeaux
France	Hôpital A.Morvan	Brest
France	Centre F.Baclesse	Caen
France	CHU Clermont Ferrand	Clermont Ferrand
France	CH Sud Francilien	Corbeil-essonnes
France	CHU DIJON, Hôpital Le Bocage	Dijon
France	Centre Hospitalier Général	Dunkerque
France	Hôpital A.Michallon	Grenoble
France	CH Départemental	La Roche Sur Yon
France	Centre Hospitalier de Chartres	Le Coudray
France	Centre Jean Bernard	Le Mans
France	CHRU Hôpital Claude Huriez	Lille
France	Institut Paoli Calmette	Marseille
France	CH MEAUX	Meaux
France	CHRU Hôtel Dieu	Nantes
France	Hôpital de l'Archet 1	Nice
France	CHU Hôpital St-Antoine	Paris
France	Intitut Curie	Paris
France	Centre Hopsitalier Lyon Sud	Pierre Benite
France	Centre Hospitalier René Dubos	Pontoise
France	Centre Hospitalier de la Région d'Annecy	Pringy
France	CHU Reims Hôpital R.Debré	Reims
France	CHRU - Hôpital sud	Rennes
France	Centre Henri Becquerel	Rouen
France	Centre René Huguenin	Saint-cloud
France	CHRU Hopital Purpan	Toulouse
France	CHRU Hopital Bretonneau	Tours
France	Centre Hospitalier	Valence
France	CHRU - Hôpitaux de Brabois	Vandœuvre-lès-Nancy
France	CH P.Chubert	Vannes

Sponsors (1)

Lead Sponsor	Collaborator
Intergroupe Francophone du Myelome

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To assess of the overall response rate (complete response (CR) + partial response (PR))		After four 28-day consecutives cycles
Secondary	Time to best response		the time from treatment start to the first detection of the best response category, calculated for all patients, which are not primarily refractory
Secondary	Progression-free survival		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)
Secondary	Time to progression		The time from baseline to the development of progressive disease
Secondary	Overall survival		The time interval from initial dose to the date of death or last observation (censored)
Secondary	Rate of additional response		Following 2 consolidation cycles and following 6 maintenance cycles
Secondary	Toxicity/Adverse events		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