BBD: Bendamustine Plus Bortezomib Plus Dexamethasone in Relapsed or Refractory Multiple Myeloma

Sponsor

Austrian Forum Against Cancer (Other)

Overall Status

Completed

CT.gov ID

NCT01168804

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

9.9

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: bendamustine plus bortezomib plus dexamethasone	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

79 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Bendamustine Plus Bortezomib Plus Dexamethasone in the Treatment of Stage II/III Relapsed or Refractory Multiple Myeloma

Study Start Date :

Jun 1, 2010

Actual Primary Completion Date :

May 1, 2013

Actual Study Completion Date :

May 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
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

Arm

Intervention/Treatment

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

Outcome Measures

Primary Outcome Measures

efficacy [8 cycles à 28 days plus follow-up phase]
evaluation of the overall response rate (sCR + CR + VGPR + PR + MR)

Secondary Outcome Measures

efficacy and safety [8 cycles à 28 days plus follow-up phase]
assessment of progression-free survival, overall survival, time to maximum response and toxicity

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	Country	Postal Code
1	Medical University Hospital Graz	Graz	Austria	8036
2	Hospital Elisabethinen Linz	Linz	Austria	4010
3	LKH Salzburg, 3rd Med. Dept.	Salzburg	Austria	5020
4	Med. University Vienna, Clinic for Internal Medicine 1 (Hematology and Hemostaseology)	Vienna	Austria	1090
5	Hanusch Hospital Vienna	Vienna	Austria	1140
6	Wilhelminenspital Vienna	Vienna	Austria	1160
7	Clinic Wels-Grieskirchen, 4th Internal Dept.	Wels	Austria	4600
8	Faculty Hospital Brno	Brno	Czech Republic	63900