Phase II Trial Designed to Determine Efficacy and Safety of Bendamustine+Dexamethasone+Thalidomide in R/R MM

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01526694
Recruitment Status : Completed
First Posted : February 6, 2012
Last Update Posted : July 3, 2018
Mundipharma Pte Ltd.
Information provided by (Responsible Party):
Michael Mian, Azienda Ospedaliera di Bolzano

Brief Summary:
This is a prospective, multicenter phase II trial designed to determine efficacy and safety of a combination chemotherapy consisting of Bendamustine + Dexamethasone + Thalidomide in patients with multiple myeloma (MM) after treatment with lenalidomide and bortezomib or which are ineligible to one of these drugs.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Bendamustine Drug: Thalidomide Drug: Dexamethasone Phase 2

Detailed Description:

Eligible patients will be treated according to the following scheme until the occurrence of maximum response, dose limiting toxicity or disease progression. Repeat cycles every 28 days for a maximum of 6 cycles and a minimum of 4.

  • Bendamustine 60 mg/m2 i.v. days 1, 8, 15
  • Dexamethasone 20 mg p.o. days 1,8 , 15, 22
  • Thalidomide 100 mg daily p.o. days 1-28; initial dose of 50 mg/day, with an increment to 100 mg after the first 15 days of treatment.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Multicenter Clinical Trial to Investigate the Efficacy and Safety of Bendamustine, Dexamethasone and Thalidomide in R/R MM Pts After Treatment With Lenalidomide and Bortezomib or Which Are Ineligible to One of These Drugs
Actual Study Start Date : July 2012
Actual Primary Completion Date : December 2015
Actual Study Completion Date : April 8, 2017

Arm Intervention/treatment
Experimental: treatment with BDT
Bendamustine + Dexamethasone + Thalidomide in patients with multiple myeloma (MM) patients after treatment with lenalidomide and bortezomib or which are ineligible to one of these drugs.
Drug: Bendamustine
Bifunctional alkylating agent consisting of a purine and amino acid antagonist (a benzimidazole ring) and an alkylating nitrogen mustard moiety.
Other Name: Ribomustin

Drug: Thalidomide
Thalidomide can directly inhibit the growth and survival of myeloma cells, by oxidative damage to DNA mediated by free radicals. The drug can induce apoptosis even in drug resistant myeloma cells. Thalidomide modulates cell adhesion molecule expression, so it may interfere with the mutually stimulatory interactions between myeloma cells and the bone marrow microenvironment.

Drug: Dexamethasone
It's a corticosteroid.

Primary Outcome Measures :
  1. Response rate [ Time Frame: 18 months ]
    The proportion of patient with a Complete Response (CR) or Very Good Partial Response or partial response

  2. Incidence of haematological toxicity of BDT [ Time Frame: 18 months ]
    The incidence of haematological toxicities is the proportion of patients with haematological toxicity

Secondary Outcome Measures :
  1. Time to treatment Failure (TTF) [ Time Frame: 18 months ]
    To evaluate time to treatment failure

  2. Survival (OS) [ Time Frame: 18 months ]
    To evaluate overall survival

  3. Disease Free Survival (DFS) [ Time Frame: 18 months ]
    To evaluate disease free survival

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Understand and voluntarily sign an informed consent form.
  • Age 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
  • Relapsed or refractory active MM (according to the International Myeloma Working Group guidelines) after treatments containing bortezomib and lenalidomide or ineligible (intolerance or toxicity) to one of these drugs with detectable myeloma protein in blood or urine.
  • Disease free of prior malignancies for at least 5 years.
  • All previous multiple myeloma treatments, including radiation, cytostatic therapy and surgery, must have been discontinued at least 4 weeks prior to treatment in this study, except corticosteroids therapy.
  • ECOG performance status <2 at study entry, unless it is due to MM.
  • At least the following laboratory findings at the day of treatment start:
  • Platelet count ≥ 75 x 10^9/L without transfusional support within 7 days.
  • Neutrophil count > 1.5 x 10^9/L without G-CSF.
  • Corrected calcium ≤ 14 mg/dL (3.5 mmol/L).
  • AST: ≤ 2.5 times the normal upper limit.
  • ALT: ≤ 2.5 times the normal upper limit.
  • Total bilirubin: ≤ 1.5 times the normal upper limit.
  • Measured or calculated creatinine clearance of ≥ 20 mL/minute
  • Women of child bearing potential and male patients whose partner is a woman of child bearing potential must be prepared to use two effective methods of contraception both before and during protocol treatment, or commit to absolute and continuous abstinence.The pregnancy test must be negative 14-28 days and 72 hours before treatment start. Only in case of hysterectomy or presence of menopause for at least 24 consecutive months pregnancy tests as well as contraception are not necessary. Men must not father a child for up to 6 months following cessation of treatment and must use condoms.

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.
  • Patients with contraindications for treatment with bendamustine, dexamethasone and thalidomide.
  • Uncontrolled or 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 within 28 days of baseline.
  • Known hypersensitivity to thalidomide or purine analogues
  • Concurrent use of other anti-cancer agents or treatments other stated in this treatment plan.
  • Peripheral neuropathy grade ≥2 according to WHO
  • Known positive for HIV or infectious hepatitis, type A, B or C.
  • Major surgery less than 30 days before start of treatment

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01526694

Division of Hematology and CBMT
Bolzano, BZ, Italy, 39100
Presidio Ospedaliero di Camposampiero
Camposampiero, Padova, Italy, 35012
Ospedale S. Martino
Belluno, Italy, 32100
Ospedale di Castelfranco Veneto
Castelfranco Veneto, Italy, 31033
Ospedale Civile di Dolo
Dolo, Italy, 30031
AULSS 2 Feltre
Feltre, Italy, 32032
Azienda Ospedaliera Universitaria G. Martino
Messina, Italy, 98125
Ospedale dell'Angelo di Mestre
Mestre, Italy, 30170
A.O di Padova Ematologia e Immunologia Clinica
Padova, Italy, 35127
A.O di Padova Ematologia
Padova, Italy, 35127
AULLS 18 di Rovigo
Rovigo, Italy, 45100
Ospedale di Trento - P.O. S. Chiara
Trento, Italy, 38100
Ospedale Ca Foncello
Treviso, Italy, 31100
A.O.U Ospedali Riuniti di Trieste Medicina II
Trieste, Italy, 34142
A.O.U Ospedali Riuniti di Trieste
Trieste, Italy, 34142
A.O.U S. Maria della Misericordia
Udine, Italy, 33100
Ospedale Policlinico G.B Rossi (Borgo Roma) Ematologia
Verona, Italy, 37134
Ospedale Policlinico G.B Rossi (Borgo Roma) Medicina II
Verona, Italy, 37134
AULSS 6 Vicenza
Vicenza, Italy, 36100
Sponsors and Collaborators
Azienda Ospedaliera di Bolzano
Mundipharma Pte Ltd.
Principal Investigator: Michael Mian, MD Azienda Ospedaliera di Bolzano

Responsible Party: Michael Mian, MD, Azienda Ospedaliera di Bolzano Identifier: NCT01526694     History of Changes
Other Study ID Numbers: BDT-01-2011
First Posted: February 6, 2012    Key Record Dates
Last Update Posted: July 3, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Michael Mian, Azienda Ospedaliera di Bolzano:
relapsed or refractory multiple myeloma

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Bendamustine Hydrochloride
BB 1101
Anti-Inflammatory Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Hormones, Hormone Substitutes, and Hormone Antagonists