RATIONALE: Bortezomib and azacitidine may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. PURPOSE: This phase I trial is studying the side effects and best dose of bortezomib when given together with 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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
8
Given SC
Given IV
Correlative studies will be collected pre-treatment, day 4 , day 15, day 29(pre-cycle 2)
Ohio State University Medical Center
Columbus, Ohio, United States
Maximum tolerable dose (MTD) of bortezomib in combination with azacitidine
Time frame: up to 28 days
Specific toxicities and the dose limiting toxicity (DLT) of bortezomib in combination with azacitidine as assessed by NCI CTCAE (Common Toxicity Criteria for Adverse Effects) v4.0
Time frame: up to 2 years
Overall response rate
Time frame: up to 2 years
Correlation of the biological activity of Azacitidine as a demethylating agent with clinical endpoints and plasma pharmacokinetics
Time frame: up to 2 years
Biological activity of bortezomib as a potential demethylating agent
Time frame: up to 2 years
Correlation of intracellular concentration of azacitidine-triphosphate with global DNA methylation and other biological endpoints as well as clinical response
Time frame: up to 2 years
Biologic role of microRNAs in determining clinical response to the bortezomib plus azacitidine combination and achievement of the other pharmacodynamic endpoints
Time frame: up to 2 years
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.