Escalating Doses of Thalidomide in Conjunction With Bortezomib and HIgh Dose Melphalan for BSCT

Exclusion Criteria

• •Cytotoxic chemotherapy or radiotherapy within 21 days of initiating treatment in this study.
• •Prior dose-intense therapy within 56 days of initiating treatment in this study.
• •Uncontrolled bacterial, viral, fungal or parasitic infections .
• •Uncontrolled CNS metastases.
• •Known amyloid deposition in heart.
• •Organ dysfunction:
• •LVEF \<40% or cardiac failure not responsive to therapy. DLCO \<50% of predicted and/or receiving supplementary continuous oxygen. Evidence of hepatic synthetic dysfunction, or total bilirubin \>2x or AST \>3x ULN.
• •Measured creatinine clearance \<20 ml/min. Sensory peripheral neuropathy grade 4 within 14 days of enrollment.
• •Karnofsky score \<70% unless as a result of bone disease directly caused by myeloma.
• •Life expectancy limited by another co-morbid illness.
• •Diagnosed or treated for another malignancy within 2 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy
• •Female subject is pregnant or breast-feeding (women) or unwilling to use acceptable birth control methods (men or women) for twelve months after treatment or unwilling to participate in the S.T.E.P.S program.
• •Documented hypersensitivity to melphalan, thalidomide or to bortezomib, boron or mannitol or any components of the formulation
• •Patients unable or unwilling to provide consent
• •Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening has to be documented by the investigator as not medically relevant.
• •Patient has received other investigational drugs with 14 days before enrollment
• •Serious medical or psychiatric illness likely to interfere with participation in this clinical study.