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

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

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.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Bendamustine; Drug: Thalidomide; Drug: Dexamethasone

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
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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 Names: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate	The proportion of patient with a Complete Response (CR) or Very Good Partial Response or partial response	18 months
Incidence of haematological toxicity of BDT	The incidence of haematological toxicities is the proportion of patients with haematological toxicity	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to treatment Failure (TTF)	To evaluate time to treatment failure	18 months
Survival (OS)	To evaluate overall survival	18 months
Disease Free Survival (DFS)	To evaluate disease free survival	18 months

Collaborators and Investigators

• Sponsor: Azienda Ospedaliera di Bolzano
• Collaborators: Mundipharma Pte Ltd.
• Investigators: Principal Investigator: Michael Mian, MD, Azienda Ospedaliera di Bolzano

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2012
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): April 8, 2017

Study Registration Dates

• First Submitted: January 27, 2012
• First Submitted That Met QC Criteria: February 3, 2012
• First Posted (Estimate): February 6, 2012

Study Record Updates

• Last Update Posted (Actual): July 3, 2018
• Last Update Submitted That Met QC Criteria: July 2, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: relapsed or refractory multiple myeloma
• 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; Neoplasms, Plasma Cell; Multiple Myeloma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Immunosuppressive 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; Anti-Bacterial Agents; Leprostatic Agents; Dexamethasone; Thalidomide; Bendamustine Hydrochloride
• Other Study ID Numbers: BDT-01-2011

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No