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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2012 by Intergroupe Francophone du Myelome.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
Intergroupe Francophone du Myelome
ClinicalTrials.gov Identifier:
NCT01045681
First received: January 7, 2010
Last updated: March 28, 2012
Last verified: March 2012
  Purpose

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.


Condition Intervention Phase
Multiple Myeloma
Drug: Bendamustine, Velcade and Dexamethasone
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Intergroupe Francophone du Myelome:

Primary Outcome Measures:
  • To assess of the overall response rate (complete response (CR) + partial response (PR)) [ Time Frame: After four 28-day consecutives cycles ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • Time to progression [ Time Frame: The time from baseline to the development of progressive disease ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: The time interval from initial dose to the date of death or last observation (censored) ] [ Designated as safety issue: No ]
  • Rate of additional response [ Time Frame: Following 2 consolidation cycles and following 6 maintenance cycles ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 70
Study Start Date: January 2010
Estimated Study Completion Date: June 2013
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BVD
Bendamustine, Velcade and Dexamethasone
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
Other Names:
  • Robimustin : Bendamustine
  • Velcade : Bortezomib
  • Dexamethasone

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.

  Eligibility

Ages Eligible for Study:   65 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01045681

Locations
France
CHRU Hôpital Sud
Amiens, France, 80054
CHRU, Hôpital du Bocage
Angers, France, 49033
Centre Hospitalier H.Duffaut
Avignon, France, 84902
Centre Hospitalier de la Cote Basque
Bayonne, France, 64109
Hôpital Jean Minjoz / CHU BESANCON
Besançon, France, 25030
Centre Hospitalier
Blois, France, 41016
Hôpital Avicenne
Bobigny, France, 93009
Polyclinique Bordeaux Nord Aquitaine
Bordeaux, France, 33000
Hôpital A.Morvan
Brest, France, 29609
Centre F.Baclesse
Caen, France, 14076
CHU Clermont Ferrand
Clermont Ferrand, France, 63003
CH Sud Francilien
Corbeil-essonnes, France, 91106
CHU DIJON, Hôpital Le Bocage
Dijon, France, 21034
Centre Hospitalier Général
Dunkerque, France, 59385
Hôpital A.Michallon
Grenoble, France, 38043
CH Départemental
La Roche Sur Yon, France, 85925
Centre Hospitalier de Chartres
Le Coudray, France, 28629
Centre Jean Bernard
Le Mans, France, 72000
CHRU Hôpital Claude Huriez
Lille, France, 59038
Institut Paoli Calmette
Marseille, France, 13273
CH Meaux
Meaux, France, 77104
CHRU Hôtel Dieu
Nantes, France, 44035
Hôpital de l'Archet 1
Nice, France, 06202
CHU Hôpital St-Antoine
Paris, France, 75571
Intitut Curie
Paris, France, 75005
Centre Hopsitalier Lyon Sud
Pierre Benite, France, 69495
Centre Hospitalier René Dubos
Pontoise, France, 95300
Centre Hospitalier de la Région d'Annecy
Pringy, France, 74374
CHU Reims Hôpital R.Debré
Reims, France, 51032
CHRU - Hôpital sud
Rennes, France, 35056
Centre Henri Becquerel
Rouen, France, 76038
Centre René Huguenin
Saint-cloud, France, 92210
CHRU Hopital Purpan
Toulouse, France, 31059
CHRU Hopital Bretonneau
Tours, France, 37044
Centre Hospitalier
Valence, France, 26953
CHRU - Hôpitaux de Brabois
Vandoeuvre, France, 54511
CH P.Chubert
Vannes, France, 56017
Sponsors and Collaborators
Intergroupe Francophone du Myelome
Investigators
Principal Investigator: Philippe RODON, Doctor Unité Hématologie Biologique Institut Curie PARIS
Principal Investigator: Cyrille HULIN, Doctor Service Hématologie Hôpitaux de Brabois VANDOEUVRE LES NANCY
Study Director: Jean-Luc HAROUSSEAU, Professor Service Hématologie CHU Nantes
Study Chair: Claire MATHIOT, Doctor IFM Hématologie Biologique Institut Curie PARIS
Study Chair: Marie-Odile PETILLON, Doctor IFM Hôpital Claude Huriez Lille
  More Information

No publications provided

Responsible Party: Dr Claire Mathiot, Intergroupe Francophone du Myelome
ClinicalTrials.gov Identifier: NCT01045681     History of Changes
Other Study ID Numbers: IFM2009-01, Eudract 2009-012359-91
Study First Received: January 7, 2010
Last Updated: March 28, 2012
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
France: Institutional Ethical Committee

Keywords provided by Intergroupe Francophone du Myelome:
Multiple Myeloma
Elderly patients
first relapse
refractory to first line therapy
Bendamustine Velcade Dexamethasone Association

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Bendamustine
Bortezomib
Nitrogen Mustard Compounds
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents

ClinicalTrials.gov processed this record on August 28, 2014