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.

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.

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