Bortezomib and Azacitidine in Treating Patients With Relapsed or Refractory T-Cell Lymphoma
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|ClinicalTrials.gov Identifier: NCT01129180|
Recruitment Status : Completed
First Posted : May 24, 2010
Last Update Posted : December 3, 2013
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.
|Condition or disease||Intervention/treatment||Phase|
|Adult Nasal Type Extranodal NK/T-cell Lymphoma Anaplastic Large Cell Lymphoma Angioimmunoblastic T-cell Lymphoma Hepatosplenic T-cell Lymphoma Peripheral T-cell Lymphoma Post-transplant Lymphoproliferative Disorder Prolymphocytic Leukemia Recurrent Adult T-cell Leukemia/Lymphoma Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma Recurrent Mycosis Fungoides/Sezary Syndrome Small Intestine Lymphoma T-cell Large Granular Lymphocyte Leukemia||Drug: azacitidine Drug: bortezomib Procedure: Correlative studies||Phase 1|
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 (Clinical Trial)|
|Actual Enrollment :||8 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I Dose-Escalation Study of Azacitidine (Vidaza) and Bortezomib (Velcade) in T-Cell Lymphoma|
|Study Start Date :||May 2010|
|Actual Primary Completion Date :||May 2012|
|Actual Study Completion Date :||December 2012|
Experimental: Arm I
Patients receive bortezomib IV on days 4, 8, 11, and 15 and azacitidine SC on days 1-5. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity. Attempt to collect Correlative studies will be made.
Procedure: Correlative studies
Correlative studies will be collected pre-treatment, day 4 , day 15, day 29(pre-cycle 2)
- 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 ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01129180
|United States, Ohio|
|Ohio State University Medical Center|
|Columbus, Ohio, United States, 43210|
|Principal Investigator:||Pierluigi Porcu||Ohio State University|