Bendamustine, Lenalidomide (Revlimid®) and Dexamethasone (BRd) as 2nd-line Therapy for Patients With Relapsed or Refractory Multiple Myeloma (BRd)
Almost all patients with multiple myeloma who survive initial treatment will eventually relapse and require further therapy.
Background: Treatment with lenalidomide and dexamethasone has proven efficacy in two large randomized trials (MM-009 and MM-010) leading to a time to progression (TTP) of 17.1 months for patients with only one prior therapy and a TTP of 10.6 months for 2 and more prior therapies, respectively [1-3]. Continuous treatment with lenalidomide and dexamethasone until disease progression is therefore considered a standard therapy for second line treatment in multiple myeloma patients. However, only a relatively low rate of high quality response (CR, complete response and VGPR, very good partial response) is achieved. High quality responses are associated with with improved progression-free survival and overall survival .
Trial: The aim of this trial is to improve high quality response rates for patients with relapsed or refractory multiple myeloma in the 2nd line treatment. This aim shall be achieved by the addition a third anti-myeloma drug (bendamustine) to the established backbone of lenalidomide/ dexamethasone.
- Induction Treatment Phase: Cycles 1-6 Bendamustine 75mg/m2/d day 1 and 2, lenalidomide 25mg/d 1-21, dexamethasone 40mg / 20mg (for patients > 75years) d 1, 8, 15, 22.
- Maintenance Treatment Phase: Cycles 7-18 lenalidomide 25mg/d 1-21, dexamethasone 40mg / 20mg (for patients > 75 years) d 1, 8, 15, 22.
Due to hematoxicity of bendamustine and lenalidomide, administration of pegfilgrastim is mandatory in the induction treatment phase (BRd-regimen)for all patients experiencing severe neutropenia.
The aim of this study is to achieve high quality response rates (CR, VGPR) of ≥ 40%. If this aim is achieved, the treatment of bendamustine in combination with the established lenalidomide/ dexamethasone regimen will be considered promising.
Besides efficacy, the safety of this three-drug regimen is evaluated in this trial.
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||An Open, Multicentric Phase II Trial to Evaluate the Efficacy and Safety of Bendamustine, Lenalidomide (Revlimid®) and Dexamethasone (BRd) as 2nd-line Therapy for Patients With Relapsed or Refractory Multiple Myeloma|
- Efficacy (combined CR-/VGPR-rate) achieved during the induction treatment phase or within four weeks after the last administration of six induction cycles of the BRd regimen [ Time Frame: Every 4 weeks up to 7 months ] [ Designated as safety issue: No ]
- Objective response rates (sCR, CR, VGPR, PR, MR) [ Time Frame: Every 4 weeks up to 7 months ] [ Designated as safety issue: No ]
- Best response (sCR, CR, VGPR, PR, MR) [ Time Frame: Every 4 weeks up to 36 months ] [ Designated as safety issue: No ]
- Time to progression (TTP) [ Time Frame: Every 4 weeks up to 36 months ] [ Designated as safety issue: No ]
- Overall survival (OS) [ Time Frame: Every 8 weeks up to 36 months ] [ Designated as safety issue: No ]
- Safety and tolerability [ Time Frame: Every 4 weeks until 30 days after completion of study treatment ] [ Designated as safety issue: Yes ]
- Type, frequency, severity, and relationship of adverse events to study therapy
- According to NCI CTCAE v4.0
|Study Start Date:||March 2012|
|Estimated Study Completion Date:||August 2017|
|Estimated Primary Completion Date:||January 2016 (Final data collection date for primary outcome measure)|
All patients are treated with bendamustine in combination with lenalidomide and dexamethasone for a maximum of 6 cycles.
Induction treatment phase (cycle 1-6):
Maintenance treatment phase (cycles 7-18):
Assessments for efficacy / response evaluation:
- M-protein quantitation in serum and 24 h urine collection samples by serum- and urine protein electrophoresis
- Quantitation of immunoglobulin levels by nephelometry
- Serum and urine immunofixation
- Free light chain concentrations and ratio in the serum
- Plasma cell percentage in the bone marrow by conventional cytology and biopsy with immunohistochemistry
- Radiologic assessments of the skeleton
Response criteria: Response will be assessed according to IMWG criteria
Please refer to this study by its ClinicalTrials.gov identifier: NCT01701076
|Kantonsspital St. Gallen|
|St. Gallen, Switzerland, 9000|
|Study Chair:||Ulrich Mey, MD||Kantonsspital Graubünden|