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

Sponsor

Azienda Ospedaliera di Bolzano (Other)

Overall Status

Completed

CT.gov ID

NCT01526694

Collaborator

Mundipharma Pte Ltd. (Industry)

Enrollment

Locations

Arm

57.2

Actual Duration (Months)

1.6

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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 Design

Study Type:

Interventional

Actual Enrollment :

30 participants

Allocation:

N/A

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 :

Jul 1, 2012

Actual Primary Completion Date :

Dec 1, 2015

Actual Study Completion Date :

Apr 8, 2017

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Time to treatment Failure (TTF) [18 months]
To evaluate time to treatment failure
Survival (OS) [18 months]
To evaluate overall survival
Disease Free Survival (DFS) [18 months]
To evaluate disease free survival

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Division of Hematology and CBMT	Bolzano	BZ	Italy	39100
2	Presidio Ospedaliero di Camposampiero	Camposampiero	Padova	Italy	35012
3	Ospedale S. Martino	Belluno		Italy	32100
4	Ospedale di Castelfranco Veneto	Castelfranco Veneto		Italy	31033
5	Ospedale Civile di Dolo	Dolo		Italy	30031
6	AULSS 2 Feltre	Feltre		Italy	32032
7	Azienda Ospedaliera Universitaria G. Martino	Messina		Italy	98125
8	Ospedale dell'Angelo di Mestre	Mestre		Italy	30170
9	A.O di Padova Ematologia e Immunologia Clinica	Padova		Italy	35127
10	A.O di Padova Ematologia	Padova		Italy	35127
11	AULLS 18 di Rovigo	Rovigo		Italy	45100
12	Ospedale di Trento - P.O. S. Chiara	Trento		Italy	38100
13	Ospedale Ca Foncello	Treviso		Italy	31100
14	A.O.U Ospedali Riuniti di Trieste Medicina II	Trieste		Italy	34142
15	A.O.U Ospedali Riuniti di Trieste	Trieste		Italy	34142
16	A.O.U S. Maria della Misericordia	Udine		Italy	33100
17	Ospedale Policlinico G.B Rossi (Borgo Roma) Ematologia	Verona		Italy	37134
18	Ospedale Policlinico G.B Rossi (Borgo Roma) Medicina II	Verona		Italy	37134
19	AULSS 6 Vicenza	Vicenza		Italy	36100

Sponsors and Collaborators

Azienda Ospedaliera di Bolzano
Mundipharma Pte Ltd.

Investigators

Principal Investigator: Michael Mian, MD, Azienda Ospedaliera di Bolzano

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Michael Mian, MD, Azienda Ospedaliera di Bolzano

ClinicalTrials.gov Identifier:

NCT01526694

Other Study ID Numbers:

BDT-01-2011

First Posted:

Feb 6, 2012

Last Update Posted:

Jul 3, 2018

Last Verified:

Jul 1, 2018

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Keywords provided by Michael Mian, MD, Azienda Ospedaliera di Bolzano

relapsed or refractory multiple myeloma

Additional relevant MeSH terms:

Multiple Myeloma

Thalidomide

Dexamethasone

Bendamustine Hydrochloride

Study Results

No Results Posted as of Jul 3, 2018