Bortezomib and Azacitidine in Treating Patients With Relapsed or Refractory T-Cell Lymphoma

PRIMARY OBJECTIVES I. To determine the maximum tolerated dose (MTD) of VELCADE (BORTEZOMIB) in combination with Azacitidine in patients with relapsed/refractory CTCL/PTCL. II. To define the specific toxicities and the dose-limiting toxicity (DLT) of VELCADE (BORTEZOMIB) in combination with Azacitidine. SECONDARY OBJECTIVES I. To determine the overall response rate (ORR). II. To correlate the biological activity of Azacitidine as a demethylating agent (changes in target gene methylation and gene expression, DNMT1 protein expression, global methylation) with clinical endpoints and plasma pharmacokinetics of Azacitidine. III. To characterize the biological activity of VELCADE (BORTEZOMIB) as a potential demethylating agent. IV. To correlate intracellular concentration of Azacitidine-triphosphate with global DNA methylation and other biological endpoints as well as clinical response. V. To explore the biologic role of microRNAs in determining clinical response to the VELCADE (BORTEZOMIB) plus Azacitidine combination and achievement of the other pharmacodynamic endpoints. OUTLINE: This is a dose-escalation study of bortezomib. Patients receive bortezomib IV on days 4, 8, 11, and 15 and azacitidine subcutaneously (SC) on days 1-5. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment patients are followed up for at least 30 days.