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

Randomised, Controlled, Open-labelled, Multi-centre Comparison of Thalidomide Versus High-dose Dexamethasone for the Treatment of Relapsed Refractory Multiple Myeloma

The primary objective is to compare the time to progression (TTP) of three daily doses of thalidomide (100, 200 and 400 mg) with high-dose dexamethasone in relapsed refractory multiple myeloma (MM) patients and to subsequently select the optimum thalidomide dose in terms of median TPP and toxicity.

Inclusion Criteria:

• Male or female patients, aged ≥ 18 years at the time of signing the informed consent form
• Patients who have been previously diagnosed with MM who have received between 1 & 3 prior lines of treatment for their disease, and who require therapy because of disease progression
• Secretory MM with measurable levels of monoclonal protein in serum (> 10 g/L of IgG M-protein or > 5 g/L of IgA M-protein) or urine (≥ 200 mg/ 24hours); Patient with the following rare subclasses of the immunoglobulin: IgD, IgE, IgM can be included in the study if the level of monoclonal protein in serum is > 5g/L or ≥ 200 mg/24hours in urine. As IgM immunoglobulin isotype can be related to Waldenstrom's macroglobulinemia, it is important to distinguish and not include in the study patients 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 at least 4weeks before starting the therapy, during the Treatment Period, & for 4 weeks after the last dose
• Males must agree to use barrier contraception (latex condoms) when engaging in reproductive 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 that would prevent the patient from signing the Informed Consent Form
• Pregnant or lactating women. A serum β-hCG pregnancy test must be performed at the Screening visit for female patients of child-bearing potential. If the test is positive, the patient must be excluded from the study. Confirmation that the patient is not pregnant must be established by a negative serum or urinary pregnancy test with the result obtained 1day prior to the Baseline visit (or the day of the visit if results are available before drug delivery). A pregnancy test is not required for naturally post-menopausal women (who have not had menses at any time in the preceding 24 consecutive months) or surgically sterilized women (hysterectomy, bilateral ovariectomy, bilateral salpingectomy)
• Non-secretory MM
• Any of the following laboratory abnormalities: Absolute neutrophil count (ANC) <500 cells/mm3 (0.5 x 109/L); Platelet count <30,000/mm3 (30.0 x 109L) without transfusion support within 7 days before the test; Serum creatinine >3.0mg/dL (265μmol/L); Serum aspartate aminotransferase (ASAT) or alanine aminotransferase (ALAT) >3.0 x upper limit of normal (ULN); Serum total bilirubin >2.0mg/dL (34μmol/L)
• Any condition, including the presence of laboratory abnormalities, which places the patient at unacceptable risk if s/he were to participate in the study, or which confounds 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 the skin or carcinoma in situ of the cervix or breast) unless the patient has been free of disease for ≥5years
• Patient received any chemotherapy, corticosteroids (> 10 mg/day prednisone or equivalent 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 PR to dexamethasone, or PD within 6months after discontinuing dexamethasone, or discontinued dexamethasone because of ≥Grade 3 dexamethasone-related toxicity. Previous high-dose dexamethasone therapy is defined as >500mg dexamethasone or equivalent over a 10week period, whether administered alone or as part of the VAD regimen)
• Contraindications for high-dose dexamethasone
• Active or chronic gastrointestinal ulcers, active viral infections (herpes, varicella, HIV, hepatitis B, hepatitis C), glaucoma, uncontrolled hypertension, or diabetes mellitus, unless well controlled & under strict supervision during dexamethasone treatment
• Patient enrolled in another clinical trial or who have participated in another trial with the last 4weeks before randomization