• The primary objective is to establish the maximally tolerated dose of bortezomib that can be administered with thalidomide in patient with myelodysplasia.
  

• Assess efficacy in terms of the number of patients attaining a 50% reduction in blast percentage, or 50% reduction in number of red blood cell and/or platelet transfusions.
  
• Determine the toxicity profile of bortezomib when used in combination with thalidomide for patients with myelodysplasia.
  
• Determine the relationship between NF-kB expression and clinical response to bortezomib and thalidomide.
  

Initial studies using Velcade in myelodysplasia with early results demonstrating that 35% had a partial response and 25% had stable disease. The combination of Velcade and thalidomide has been studied in patients with multiple myeloma, but not in patients with myelodysplasia. The CRR in the MM patients was 22%, with a good safety profile.

This is a phase 1, prospective, open-label, dose escalation study to evaluate the DLT and MTD of velcade with given in combination with thalidomide in patients with myelodysplasia. Treatment will be given as an outpatient. Patients will receive 4 days of Velcade (days 1, 4, 8, 11) and 21 days of thalidomide 50 mg/day for each 21 day cycle. There will be 3 cohorts of 3-6 patients each, plus 10 additional patients. The tree dose levels ill be 0.7, 1.0 and 1.3 mg/m2. Patients may continue to be treated up to 6 cycles. Cycles 2-6 will start within 2 weeks of completion of the previous cycle. Disease response will be evaluated after cycle 3 and 6.