- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01701076
Bendamustine, Lenalidomide (Revlimid®) and Dexamethasone (BRd) as 2nd-line Therapy for Patients With Relapsed or Refractory Multiple Myeloma (BRd)
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
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 [4].
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.
Treatment regimen:
- 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 Overview
Detailed Description
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
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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St. Gallen, Switzerland, 9000
- Kantonsspital St. Gallen
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Written informed consent
- Patients with first relapsed or refractory multiple myeloma (including patients with relapse after high dose chemotherapy followed by autologous stem cell transplantation) who have received no more than one prior line of anti-myeloma treatment
- Treatment with a lenalidomide/ dexamethasone-based 2nd-line regimen is indicated and intended
Measurable disease as defined by at least one of the following 3 measurements
- serum monoclonal protein level ≥ 1 g/dl (≥ 10 g/l) or
- urine M-protein level ≥ 200 mg/24hours or
- serum FLC assay: Involved FLC level ≥ 10 mg/dl (≥ 100 mg/l) provided serum FLC ratio is abnormal
- ECOG performance status 0, 1, or 2
- Age ≥ 18 years
- All previous cancer therapy (except corticosteroid therapy), including radiation, cytostatic therapy and surgery, must have been discontinued at least 4 weeks prior to treatment in this study.
- No prior treatment with a bendamustine-containing regimen allowed
- Prior treatment with lenalidomide is allowed if the treatment is completed > 12 month prior to study entry and the patient responded to prior lenalidomide treatment
Adequate hematological values:
- absolute neutrophil count ≥ 1.5 x 109/L
- platelets ≥ 100 x 109/L
- hemoglobin > 80 g/L, unless considered to be caused by the underlying hematologic malignancy, based on the investigator's clinical judgement
Adequate hepatic function:
- total bilirubin < 1.2 mg/dL
- AST (SGOT) ≤ 2.5 x ULN
Adequate renal function:
o calculated creatinine clearance > 50 ml/min, according to the formula of Cockcroft-Gault
Disease free of prior malignancies for > 5 years unless the patient
- has been treated with a curative intent and is considered to be in complete remission for ≥2 years prior to study enrolment
or has a curatively-treated
- basal cell/ squamous cell carcinoma of the skin,
- carcinoma "in situ"of the cervix,
- ductal breast carcinoma in situ with complete surgical resection (i.e. negative margins),
- medullary or papillary thyroid tumor
- or low grade, early stage localized prostate cancer treated surgically with curative intent
Exclusion Criteria:
- Pregnant or breast feeding females
- Any prior use of bendamustine
- Patients who are unable or unwillingly to undergo antithrombotic therapy
- Any serious underlying medical condition (at the judgment of the investigator) which impairs the ability of the patient to participate in the trial (e.g. active autoimmune disease, uncontrolled diabetes, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, psychiatric disorder)
- Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she would participate in the study or any condition significantly confounding the ability to interpret data from the study, based on the local investigator's judgement
- Severe cardiovascular disease, including myocardial infarction within 6 months before study entry, New York Heart Association Class III or IV heart failure, uncontrolled angina or severe uncontrolled ventricular arrhythmias (≥ Lown 3)
- Use of any other experimental drug or therapy/ treatment in a clinical trial within 30 days prior to trial entry
- Known hypersensitivity to study drug(s) or hypersensitivity to any other component of the study drugs
- Any concurrent antineoplastic therapy with chemotherapeutic agents or biologic agents or radiation therapy
- Any major surgical procedure within 30 days prior to study therapy
- Known chronic hepatitis B or C, known HIV infection
- Jaundice or any other severe damage of the liver parenchyma
- Any contraindication for the treatment with bendamustine, lenalidomide, dexamethasone and / or pegfilgrastim in accordance with the appropriate SmPCs
- Any other concomitant drugs contraindicated for use with the study drugs according to the national health authorities
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Bendamustine
All patients are treated with bendamustine in combination with lenalidomide and dexamethasone for a maximum of 6 cycles.
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Induction treatment phase (cycle 1-6):
Maintenance treatment phase (cycles 7-18):
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
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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
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Every 4 weeks up to 7 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Objective response rates (sCR, CR, VGPR, PR, MR)
Time Frame: Every 4 weeks up to 7 months
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Every 4 weeks up to 7 months
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Best response (sCR, CR, VGPR, PR, MR)
Time Frame: Every 4 weeks up to 36 months
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Every 4 weeks up to 36 months
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Time to progression (TTP)
Time Frame: Every 4 weeks up to 36 months
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Every 4 weeks up to 36 months
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Overall survival (OS)
Time Frame: Every 8 weeks up to 36 months
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Every 8 weeks up to 36 months
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Safety and tolerability
Time Frame: Every 4 weeks until 30 days after completion of study treatment
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Every 4 weeks until 30 days after completion of study treatment
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Chair: Ulrich Mey, MD, Kantonsspital Graubünden
Publications and helpful links
General Publications
- Dimopoulos M, Spencer A, Attal M, Prince HM, Harousseau JL, Dmoszynska A, San Miguel J, Hellmann A, Facon T, Foa R, Corso A, Masliak Z, Olesnyckyj M, Yu Z, Patin J, Zeldis JB, Knight RD; Multiple Myeloma (010) Study Investigators. Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med. 2007 Nov 22;357(21):2123-32. doi: 10.1056/NEJMoa070594. Erratum In: N Engl J Med. 2009 Jul 30;361(5):544.
- Weber DM, Chen C, Niesvizky R, Wang M, Belch A, Stadtmauer EA, Siegel D, Borrello I, Rajkumar SV, Chanan-Khan AA, Lonial S, Yu Z, Patin J, Olesnyckyj M, Zeldis JB, Knight RD; Multiple Myeloma (009) Study Investigators. Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. N Engl J Med. 2007 Nov 22;357(21):2133-42. doi: 10.1056/NEJMoa070596.
- Lentzsch S, O'Sullivan A, Kennedy RC, Abbas M, Dai L, Pregja SL, Burt S, Boyiadzis M, Roodman GD, Mapara MY, Agha M, Waas J, Shuai Y, Normolle D, Zonder JA. Combination of bendamustine, lenalidomide, and dexamethasone (BLD) in patients with relapsed or refractory multiple myeloma is feasible and highly effective: results of phase 1/2 open-label, dose escalation study. Blood. 2012 May 17;119(20):4608-13. doi: 10.1182/blood-2011-12-395715. Epub 2012 Mar 26.
- Dimopoulos MA, Chen C, Spencer A, Niesvizky R, Attal M, Stadtmauer EA, Petrucci MT, Yu Z, Olesnyckyj M, Zeldis JB, Knight RD, Weber DM. Long-term follow-up on overall survival from the MM-009 and MM-010 phase III trials of lenalidomide plus dexamethasone in patients with relapsed or refractory multiple myeloma. Leukemia. 2009 Nov;23(11):2147-52. doi: 10.1038/leu.2009.147. Epub 2009 Jul 23.
- Harousseau JL, Attal M, Avet-Loiseau H. The role of complete response in multiple myeloma. Blood. 2009 Oct 8;114(15):3139-46. doi: 10.1182/blood-2009-03-201053. Epub 2009 Jul 28.
- Pönisch W, Heyn S, Wagner I, et al. Combined Bendamustine, Prednisolone and Lenalidomide (RBP) In Refractory or Relapsed Multiple Myeloma. First Results of a Phase I Clinical Trial. Blood, Nov 2010; 116: 1971
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Immunoproliferative Disorders
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Autonomic Agents
- Peripheral Nervous System Agents
- Anti-Inflammatory Agents
- Antineoplastic Agents
- Immunologic Factors
- Antiemetics
- Gastrointestinal Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Dexamethasone
- Lenalidomide
- Bendamustine Hydrochloride
Other Study ID Numbers
- CTU10.041/BRd
- 2010-022253-42 (EudraCT Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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