Inclusion Criteria:

1. Established diagnosis of multiple myeloma according to International Myeloma Working
Group diagnostic criteria

2. Age ≥ 18 years

3. Patient relapsed after at least 2 lines of conventional chemotherapy or high dose
therapy with autologous or allogeneic stem cell support, and/or for whom no
alternative treatments are available/suitable

4. Increasing trend of monoclonal immunoglobulin or Bence-Jones proteinuria through the
last 4 consecutive pre-screening measurements, already available in the patient
history

5. No chemotherapy or other investigational anticancer therapy for at least 3 weeks
before the start of the study

6. Full recovery from previous toxicities

7. ECOG performance status 0-2

8. Adequate bone marrow reserve: absolute neutrophil count ≥ 1000/ml; platelet count ≥
90000/ml

9. Adequate liver function: total bilirubin within normal institutional limits (PI
center); AST(SGOT)/ALT(SGPT) ≤ 2.5 x institutional upper limit of normal (PI center)

10. Adequate renal function: Creatinine ≤ 2.5 mg/dl or creatinine clearance ≥ 50 ml/min

11. Either men or women, accepting to practice effective contraception during the entire
study period unless documentation of infertility exists. Should a woman become
pregnant or suspect she is pregnant while participating in this study, she should
immediately inform her treating physician; in this case ITF 2357 treatment will be
promptly discontinued

12. Able to understand and willing to sign the informed consent form.

Exclusion Criteria:

1. Planned autologous or allogeneic bone marrow transplantation within 4 weeks of the
initiation of ITF 2357 administration

2. Concurrent use of medicines that would confound the interpretation of toxicities and
anti-tumour activity of ITF 2357 (i.e. quinolons, macrolides, 5-HT3 antagonists
except for palonosetron,)

3. Clinically significant illness including, but not limited to, the following: active
infection, uncontrolled hypertension, symptomatic congestive heart failure, unstable
angina pectoris, myocardial infarction within the past 6 months, cardiac arrhythmia
(present or documented in the past, of any kind), any other condition (including
laboratory abnormalities) that in the opinion of the Investigator places the patient
to unacceptable risk for adverse outcome if he/she were to participate in the study

4. Psychiatric illness/social situations that would limit compliance with study
medication and protocol requirements

5. Pregnant or lactating women

6. Positive blood tests for HIV, HBV, HCV, active EBV and CMV

7. Diseases related to active viral infections

8. Patients with a marked baseline prolongation of QTc interval (e.g. repeated
demonstration of a QTc interval >440 ms for men and >450 ms for women)

9. Patients with history of additional risk factors for Torsade de Pointes (e.g. heart
failure, family history of Long QT Syndrome).

10. The use of concomitant medications with potential risk of Torsade de Pointes and/or
that can prolong QTc interval

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