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

NCT01701076 | Completed Phase 2

• 2 other identifiers: CTU10.041/BRd2010-022253-42
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Multiple Myeloma

Keywords

Relapsed / refractory multiple myeloma; 2nd line treatment

Outcome Measures

Primary Outcomes (1)

• 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

  Every 4 weeks up to 7 months

Secondary Outcomes (5)

• Objective response rates (sCR, CR, VGPR, PR, MR)

  Every 4 weeks up to 7 months

• Best response (sCR, CR, VGPR, PR, MR)

  Every 4 weeks up to 36 months

• Time to progression (TTP)

  Every 4 weeks up to 36 months

• Overall survival (OS)

  Every 8 weeks up to 36 months

• Safety and tolerability

  Every 4 weeks until 30 days after completion of study treatment

Study Arms (1)

Bendamustine

EXPERIMENTAL

All patients are treated with bendamustine in combination with lenalidomide and dexamethasone for a maximum of 6 cycles.

Drug: Bendamustine

Interventions

Bendamustine DRUG

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

Also known as: Lenalidomide, Dexamethasone, Pegfilgrastim

Bendamustine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Cantonal Hospital of St. Gallen: lead
• Celgene Corporation: collaborator
• Mundipharma Research GmbH & Co KG: collaborator
• Mundipharma Medical Company: collaborator
• Amgen: collaborator

Study Sites (1)

Kantonsspital St. Gallen

Sankt Gallen, 9000, Switzerland

Location

Related Publications (6)

• 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.

  PMID: 18032763 BACKGROUND

• 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.

  PMID: 18032762 BACKGROUND

• 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.

  PMID: 19626046 BACKGROUND

• 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.

  PMID: 19638622 BACKGROUND

• 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.

  PMID: 22451423 BACKGROUND

• 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

  BACKGROUND

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Bendamustine Hydrochloride; Lenalidomide; Dexamethasone; pegfilgrastim

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Isoindoles; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Ulrich Mey, MD

  Kantonsspital Graubünden

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PD Dr.med.

Study Record Dates

• First Submitted: September 27, 2012
• First Posted: October 4, 2012
• Study Start: March 1, 2012
• Primary Completion: February 1, 2016
• Study Completion: February 1, 2016
• Last Updated: August 24, 2016

Record last verified: 2016-08

Locations

CH (1)