Efficacy and Safety Study of 3 Thalidomide Doses for the Treatment of Relapsed Refractory Multiple Myeloma

Inclusion Criteria:

• Male or female patients, aged ≥ 18 years at the time of signing the informed consentform

• Patients who have been previously diagnosed with MM who have received between 1 & 3prior lines of treatment for their disease, and who require therapy because of diseaseprogression

• Secretory MM with measurable levels of monoclonal protein in serum (> 10 g/L of IgGM-protein or > 5 g/L of IgA M-protein) or urine (≥ 200 mg/ 24hours); Patient with thefollowing rare subclasses of the immunoglobulin: IgD, IgE, IgM can be included in thestudy if the level of monoclonal protein in serum is > 5g/L or ≥ 200 mg/24hours inurine. As IgM immunoglobulin isotype can be related to Waldenstrom'smacroglobulinemia, it is important to distinguish and not include in the studypatients with Waldenstrom's macroglobulinemia.

• ECOG performance status of 0, 1, or 2

• Life expectancy >3months

• Able to adhere to the study visit schedule & other protocol requirements

• Women of child-bearing potential must agree to use 2 methods of contraception for atleast 4weeks before starting the therapy, during the Treatment Period, & for 4 weeksafter the last dose

• Males must agree to use barrier contraception (latex condoms) when engaging inreproductive activity during the Treatment Period & for 4 weeks after the last dose

• Written, informed consent

Exclusion Criteria:

• Any serious medical condition, laboratory abnormality, or psychiatric illness thatwould prevent the patient from signing the Informed Consent Form

• Pregnant or lactating women. A serum β-hCG pregnancy test must be performed at theScreening visit for female patients of child-bearing potential. If the test ispositive, the patient must be excluded from the study. Confirmation that the patientis not pregnant must be established by a negative serum or urinary pregnancy test withthe result obtained 1day prior to the Baseline visit (or the day of the visit ifresults are available before drug delivery). A pregnancy test is not required fornaturally post-menopausal women (who have not had menses at any time in the preceding 24 consecutive months) or surgically sterilized women (hysterectomy, bilateralovariectomy, bilateral salpingectomy)

• Non-secretory MM

• Any of the following laboratory abnormalities: Absolute neutrophil count (ANC) <500cells/mm3 (0.5 x 109/L); Platelet count <30,000/mm3 (30.0 x 109L) without transfusionsupport within 7 days before the test; Serum creatinine >3.0mg/dL (265μmol/L); Serumaspartate aminotransferase (ASAT) or alanine aminotransferase (ALAT) >3.0 x upperlimit of normal (ULN); Serum total bilirubin >2.0mg/dL (34μmol/L)

• Any condition, including the presence of laboratory abnormalities, which places thepatient at unacceptable risk if s/he were to participate in the study, or whichconfounds the ability to interpret data from the study

• Severe cardiac dysfunction (according to the New York Heart Association [NYHA]classification III-IV)

• Severe bradycardia (<50bpm)

• Peripheral neuropathy ≥Grade 2 in severity (according to the NCI CTC Version 3.0)

• Prior history of malignancy (except for basal cell or squamous cell carcinoma of theskin or carcinoma in situ of the cervix or breast) unless the patient has been free ofdisease for ≥5years

• Patient received any chemotherapy, corticosteroids (> 10 mg/day prednisone orequivalent as a continuous dose) within 4 weeks before randomization

• Previously treated with thalidomide or thalidomide derivatives

• Patients refractory to high-dose dexamethasone (defined as experiencing less than a PRto dexamethasone, or PD within 6months after discontinuing dexamethasone, ordiscontinued dexamethasone because of ≥Grade 3 dexamethasone-related toxicity.Previous high-dose dexamethasone therapy is defined as >500mg dexamethasone orequivalent over a 10week period, whether administered alone or as part of the VADregimen)

• Contraindications for high-dose dexamethasone

• Active or chronic gastrointestinal ulcers, active viral infections (herpes, varicella,HIV, hepatitis B, hepatitis C), glaucoma, uncontrolled hypertension, or diabetesmellitus, unless well controlled & under strict supervision during dexamethasonetreatment

• Patient enrolled in another clinical trial or who have participated in another trialwith the last 4weeks before randomization