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Bendamustine, Lenalidomide (Revlimid®) and Dexamethasone (BRd) as 2nd-line Therapy for Patients With Relapsed or Refractory Multiple Myeloma

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2013 by Cantonal Hospital of St. Gallen
Sponsor:
Collaborators:
Celgene Corporation
Mundipharma Research GmbH & Co KG
Mundipharma Medical Company
Amgen
Information provided by (Responsible Party):
PD Dr. Ulrich Mey, Kantonsspital Graubünden
ClinicalTrials.gov Identifier:
NCT01701076
First received: September 27, 2012
Last updated: August 12, 2013
Last verified: August 2013
  Purpose

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.


Condition Intervention Phase
Multiple Myeloma
Drug: Bendamustine
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Cantonal Hospital of St. Gallen:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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


Estimated Enrollment: 50
Study Start Date: March 2012
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bendamustine
All patients are treated with bendamustine in combination with lenalidomide and dexamethasone for a maximum of 6 cycles.
Drug: Bendamustine

Induction treatment phase (cycle 1-6):

  • Bendamustine 75 mg/m2 i.v day 1 and 2
  • Lenalidomide 25 mg p.o. day 1-21
  • Dexamethasone 40/20 mg p.o., day 1, 8, 15, 22
  • Pegfilgrastim 6 mg s.c., day 3 in case of severe neutropenia

Maintenance treatment phase (cycles 7-18):

  • Lenalidomide 25 mg p.o. day 1-21
  • Dexamethasone 40/20 mg p.o., day 1, 8, 15, 22
Other Names:
  • Lenalidomide
  • Dexamethasone
  • Pegfilgrastim

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

  Eligibility

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

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
  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: NCT01701076

Contacts
Contact: Ulrich Mey, MD +41-81 256 7170 ulrich.mey@ksgr.ch
Contact: Christoph Driessen, MD +41-71 494 1162 christoph.driessen@ssg.ch

Locations
Switzerland
Kantonsspital St. Gallen Recruiting
St. Gallen, Switzerland, 9000
Contact: Christoph Driessen, MD, Prof.    +41 71 494 1162    christoph.driessen@kssg.ch   
Sponsors and Collaborators
Cantonal Hospital of St. Gallen
Celgene Corporation
Mundipharma Research GmbH & Co KG
Mundipharma Medical Company
Amgen
Investigators
Study Chair: Ulrich Mey, MD Kantonsspital Graubünden
  More Information

Publications:
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

Responsible Party: PD Dr. Ulrich Mey, PD Dr.med., Kantonsspital Graubünden
ClinicalTrials.gov Identifier: NCT01701076     History of Changes
Other Study ID Numbers: CTU10.041/BRd, 2010-022253-42
Study First Received: September 27, 2012
Last Updated: August 12, 2013
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
Switzerland: Swissmedic

Keywords provided by Cantonal Hospital of St. Gallen:
Relapsed / refractory multiple myeloma
2nd line treatment

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
BB 1101
Bendamustine
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Lenalidomide
Nitrogen Mustard Compounds
Thalidomide
Alkylating Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Anti-Inflammatory Agents
Antiemetics
Antineoplastic Agents

ClinicalTrials.gov processed this record on November 25, 2014