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

Multiple Myeloma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01526694
• Other study ID #: BDT-01-2011
• Status: Completed
• Phase: Phase 2
• Start date: July 2012
• Est. completion date: April 8, 2017

Study information

• Verified date: July 2018
• Source: Azienda Ospedaliera di Bolzano
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: April 8, 2017
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Bendamustine
Bifunctional alkylating agent consisting of a purine and amino acid antagonist (a benzimidazole ring) and an alkylating nitrogen mustard moiety.
• 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.
• Dexamethasone
It's a corticosteroid.

Locations

Country	Name	City	State
Italy	Ospedale S. Martino	Belluno
Italy	Division of Hematology and CBMT	Bolzano	BZ
Italy	Presidio Ospedaliero di Camposampiero	Camposampiero	Padova
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	Padova
Italy	A.O di Padova Ematologia e Immunologia Clinica	Padova
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	Trieste
Italy	A.O.U Ospedali Riuniti di Trieste Medicina II	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

Sponsors (2)

Lead Sponsor	Collaborator
Azienda Ospedaliera di Bolzano	Mundipharma Pte Ltd.

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response rate	The proportion of patient with a Complete Response (CR) or Very Good Partial Response or partial response	18 months
Primary	Incidence of haematological toxicity of BDT	The incidence of haematological toxicities is the proportion of patients with haematological toxicity	18 months
Secondary	Time to treatment Failure (TTF)	To evaluate time to treatment failure	18 months
Secondary	Survival (OS)	To evaluate overall survival	18 months
Secondary	Disease Free Survival (DFS)	To evaluate disease free survival	18 months