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

NCT ID: NCT01526694

Last Updated: 2018-07-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-07-31
• Study Completion Date: 2017-04-08

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.

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.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Bendamustine

Intervention Type: DRUG

Bifunctional alkylating agent consisting of a purine and amino acid antagonist (a benzimidazole ring) and an alkylating nitrogen mustard moiety.

Thalidomide

Intervention Type: DRUG

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.

Dexamethasone

Intervention Type: DRUG

It's a corticosteroid.

Interventions

Bendamustine

Bifunctional alkylating agent consisting of a purine and amino acid antagonist (a benzimidazole ring) and an alkylating nitrogen mustard moiety.

Intervention Type: 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.

Intervention Type: DRUG

Dexamethasone

It's a corticosteroid.

Intervention Type: DRUG

Other Intervention Names

Ribomustin

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mundipharma Pte Ltd.

INDUSTRY

Sponsor Role: collaborator

Azienda Ospedaliera di Bolzano

OTHER

Sponsor Role: lead

Responsible Party

Michael Mian

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Michael Mian, MD

Role: PRINCIPAL_INVESTIGATOR

Azienda Ospedaliera di Bolzano

Locations

Division of Hematology and CBMT

Bolzano, BZ, Italy

Presidio Ospedaliero di Camposampiero

Camposampiero, Padova, Italy

Ospedale S. Martino

Belluno, , Italy

Ospedale di Castelfranco Veneto

Castelfranco Veneto, , Italy

Ospedale Civile di Dolo

Dolo, , Italy

AULSS 2 Feltre

Feltre, , Italy

Azienda Ospedaliera Universitaria G. Martino

Messina, , Italy

Ospedale dell'Angelo di Mestre

Mestre, , Italy

A.O di Padova Ematologia e Immunologia Clinica

Padua, , Italy

A.O di Padova Ematologia

Padua, , Italy

AULLS 18 di Rovigo

Rovigo, , Italy

Ospedale di Trento - P.O. S. Chiara

Trento, , Italy

Ospedale Ca Foncello

Treviso, , Italy

A.O.U Ospedali Riuniti di Trieste Medicina II

Trieste, , Italy

A.O.U Ospedali Riuniti di Trieste

Trieste, , Italy

A.O.U S. Maria della Misericordia

Udine, , Italy

Ospedale Policlinico G.B Rossi (Borgo Roma) Ematologia

Verona, , Italy

Ospedale Policlinico G.B Rossi (Borgo Roma) Medicina II

Verona, , Italy

AULSS 6 Vicenza

Vicenza, , Italy

Countries

Italy

Other Identifiers

BDT-01-2011

Identifier Type: -

Identifier Source: org_study_id