Bendamustine Plus Bortezomib Plus Dexamethasone in Relapsed or Refractory Multiple Myeloma (BBD)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Austrian Forum Against Cancer
ClinicalTrials.gov Identifier:
NCT01168804
First received: July 22, 2010
Last updated: November 21, 2013
Last verified: November 2013
  Purpose

The purpose of this study is to evaluate efficacy and safety of the combination regimen of bortezomib-bendamustine-dexamethasone in patients with relapsed or refractory multiple myeloma


Condition Intervention Phase
Multiple Myeloma
Drug: bendamustine plus bortezomib plus dexamethasone
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Bendamustine Plus Bortezomib Plus Dexamethasone in the Treatment of Stage II/III Relapsed or Refractory Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Austrian Forum Against Cancer:

Primary Outcome Measures:
  • efficacy [ Time Frame: 8 cycles à 28 days plus follow-up phase ] [ Designated as safety issue: No ]
    evaluation of the overall response rate (sCR + CR + VGPR + PR + MR)


Secondary Outcome Measures:
  • efficacy and safety [ Time Frame: 8 cycles à 28 days plus follow-up phase ] [ Designated as safety issue: Yes ]
    assessment of progression-free survival, overall survival, time to maximum response and toxicity


Enrollment: 79
Study Start Date: June 2010
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: single arm bendamustine bortezomib dexamethasone
single arm combination regimen: bendamustine - bortezomib- dexamethasone
Drug: bendamustine plus bortezomib plus dexamethasone
Bendamustine 70 mg/m2 on days 1+4 Velcade 1.3 mg/m2 on days 1,4,8,11 Dexamethasone 20 mg on days 1,4,8 and 11 Repeated every 4 weeks

Detailed Description:

After relapse after or early progression on first-line treatment the prognosis of multiple myeloma patients is unfavourable, with no remaining chance for cure. Therefore the search for new treatment regimens, including drugs with novel, and different, mechanisms of action is mandatory.

Both bendamustine and bortezomib are not yet established parts of standard first-line regimens, but showed to have high activity both in chemo-naïve 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. 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 favourable risk/benefit ratio for the combination of bendamustine, bortezomib and a glucocorticoid drug, warranting the exploration in a larger, prospectively designed multicenter phase II study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age min. 18 years at the time of signing the informed consent form
  • Life expectancy of at least 3 months
  • Able to adhere to the study visit schedule and other protocol requirements
  • Measurable disease, defined as any quantifiable monoclonal protein value, defined by at least one of the following three measurements: Serum M-protein ≥ 10g/l; Urine light-chain (M-protein) of ≥ 200 mg/24 hours; Serum FLC assay: involved FLC level ≥10 mg/dl provided sFLC ratio is abnormal
  • Relapsed or refractory MM in stage II or III after autologous SCT or conventional chemotherapy (histologically or cytologically proven/ Salmon and Durie criteria) in need of therapy
  • All previous cancer therapy, including cytostatic therapy and surgery, must have been discontinued at least 4 weeks prior to treatment in this study, except corticosteroid therapy (dosage 40 to max. 160mg). Localised radiation therapy is allowed, but the increased risk of leukocytopenia, erythrocytopenia and thrombocytopenia based on the combination of a polychemotherapy and radiation therapy has to be considered and a close monitoring of the patients has to be assured.
  • ECOG performance status of 0-2 at study entry
  • Laboratory test results within these ranges:

    • Absolute neutrophil count min. 1.5 x 109/L
    • Platelet count min. 75 x 109/L
    • Total bilirubin max. 1.5 mg/dL
    • AST (SGOT) and ALT (SGPT) max. 2 x ULN or max. 5 x ULN if hepatic lesions are present.
  • Disease free of prior malignancies for min. 5 years with exception of curatively treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast
  • Fertile patients must use effective contraception during and for 6 months after study treatment

No study treatment or any other procedure within the framework of the trial (except for screening) will be performed in any patient prior to receipt of written informed consent.

Exclusion Criteria:

  • Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form
  • Pregnant or breast feeding females
  • Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
  • Peripheral neuropathy or neuropathic pain of grade 2 or greater intensity, as defined by NCI CTCAE, version 3.0.
  • Use of any other experimental drug or therapy within 28 days of pre-study visit.
  • Known hypersensitivity to the study drugs
  • Any prior use of bortezomib or bendamustine in the last six months
  • Concurrent use of other anti-cancer agents or treatments other than those stated in this treatment plan
  • Known positive for HIV or infectious hepatitis, type A, B or C
  • Active, uncontrolled infections
  • Acute diffuse infiltrative pulmonary disease and pericardial disease.
  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: NCT01168804

Locations
Austria
Medical University Hospital Graz
Graz, Austria, 8036
Hospital Elisabethinen Linz
Linz, Austria, 4010
LKH Salzburg, 3rd Med. Dept.
Salzburg, Austria, 5020
Hanusch Hospital Vienna
Vienna, Austria, 1140
Med. University Vienna, Clinic for Internal Medicine 1 (Hematology and Hemostaseology)
Vienna, Austria, 1090
Wilhelminenspital Vienna
Vienna, Austria, 1160
Clinic Wels-Grieskirchen, 4th Internal Dept.
Wels, Austria, 4600
Czech Republic
Faculty Hospital Brno
Brno, Czech Republic, 63900
Sponsors and Collaborators
Austrian Forum Against Cancer
Investigators
Principal Investigator: Heinz P. Ludwig, Univ. Prof. Wilhelminenspital Vienna
  More Information

Additional Information:
No publications provided

Responsible Party: Austrian Forum Against Cancer
ClinicalTrials.gov Identifier: NCT01168804     History of Changes
Other Study ID Numbers: BBD
Study First Received: July 22, 2010
Last Updated: November 21, 2013
Health Authority: Austria: Agency for Health and Food Safety
Austria: Ethikkommission
Czech Republic: Ethics Committee
Czech Republic: State Institute for Drug Control

Keywords provided by Austrian Forum Against Cancer:
multiple myeloma
bendamustine
bortezomib
dexamethasone

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