Study of Velcade and Thalidomide in Patients With Myelodysplasia

Phase I Dose Escalation Trial of Bortezomib in Combination With Thalidomide in Patients With Myelodysplasia

The purpose of this study is to find out what the maximal tolerated dose of Velcade can be given with thalidomide in patients with myelodysplasia.

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.

Inclusion Criteria:

• Myelodysplastic syndrome with a IPSS score of 0.5 or greater
• May have had prior chemo/radiotherapy for another malignancy or myelodysplasia
• ECOG performance status of 0-2
• Life expectancy greater than 3 months
• Total bilirubin </+ 2xULN
• ALT and AST </+ 3xULN
• Calculated creatinine clearance > 30 ml/min
• Use of appropriate method of contraception during the study
• ANC > 0.5 x 10(9)
• Platelet count > 30 x 10(9)
• Consideration of treatment with 5 azacytidine is encouraged by not required

Exclusion Criteria:

• Ejection fraction < 40%
• myocardial infarction within 6 months of enrollment of New York Heart Association Class III or IV heart failure, uncontrolled angina, uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
• Women who are pregnant or breast-feeding
• Major surgery within 4 weeks prior to enrollment
• >/= grade 2 peripheral neuropathy within 14 days prior to enrollment
• Uncontrolled intercurrent illness
• Serious medical or psychiatric illness that could potentially interfere with the completion of treatment
• Hypersensitivity to bortezomib, boron, or mannitol
• Received an investigational drug within 14 days of enrollment