Bortezomib and Romidepsin in Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Phase I Study of Bortezomib and Romidepsin in Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Indolent B-Cell Lymphoma, Peripheral T-Cell Lymphoma or Cutaneous T-Cell Lymphoma|
- Maximum tolerated dose [ Time Frame: 2 years ]Dose at which no more than 1 dose-limiting toxicity is observed in as many as 6 patients
- Pharmacodynamic responses [ Time Frame: 2 years ]To explore candidate pharmacodynamic markers for use in subsequent phase II trials.
|Actual Study Start Date:||April 26, 2010|
|Estimated Study Completion Date:||April 30, 2018|
|Primary Completion Date:||July 17, 2014 (Final data collection date for primary outcome measure)|
Experimental: bortezomib + romidepsin
Bortezomib via a short intravenous infusion (3-5 seconds) followed by romidepsin via a 4 hour intravenous infusion weekly x 3 every 4 weeks. In order to identify appropriate doses, different subjects will be treated with different drug doses and observed for the effects, especially the side effects associated with higher doses.
Starting dose: 1.3 mg/sq m
Other Names:Drug: Romidepsin
Starting dose: 8 mg/sq m
- Determine the maximum tolerated dose (MTD) for the combination of bortezomib and romidepsin administered weekly x 3 every (q) 4wk in patients with CLL/SLL, indolent B-cell lymphoma, PTCL or cutaneous T-cell lymphoma (CTCL).
- Determine safety and tolerance and describe the toxicities of the combination.
- Demonstrate adequate methods for the assessment of pharmacodynamic responses of CLL cells to the combination with respect to effects on NF-kappa B (nuclear RelA and processing of p52 as a marker of p100 processing), expression of the NF-kappa B-dependent proteins XIAP and Bcl-xL, and Bim, and document pharmacodynamic responses observed in the course of this study * Document the pharmacodynamic responses associated with this regimen in these patients.
- Document the anticancer activity of this regimen in these patients.
OUTLINE: Patients receive bortezomib IV over 3-5 seconds and romidepsin IV over 4 hours on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Blood samples from patients with chronic lymphocytic leukemia are collected at baseline and after day 1 of course 1 of study treatment for pharmacodynamic and correlative laboratory studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00963274
|United States, Illinois|
|Robert H. Lurie Comprehensive Cancer Center, Northwestern University|
|Chicago, Illinois, United States, 60611|
|United States, Maryland|
|University of Maryland Greenebaum Cancer Center|
|Baltimore, Maryland, United States, 21201|
|United States, North Carolina|
|University of North Carolina|
|Chapel Hill, North Carolina, United States, 27599|
|United States, Tennessee|
|Vanderbilt-Ingram Cancer Center, Vanderbilt University|
|Nashville, Tennessee, United States, 37232|
|United States, Virginia|
|Virginia Commonwealth University/Massey Cancer Center|
|Richmond, Virginia, United States, 23298|
|Principal Investigator:||Beata Holkova, MD||Massey Cancer Center|
|Principal Investigator:||Thomas C. Shea, MD||UNC Lineberger Comprehensive Cancer Center|
|Study Chair:||Steven Grant, MD||Virginia Commonwealth University|
|Principal Investigator:||Sho Ma, MD, PhD||Northwestern University & Robert H Lurie Comprehensive Cancer Center|
|Principal Investigator:||Amy Kimball, MD, PhD||University of Maryland Greenebaum Cancer Center|
|Principal Investigator:||Nishitha Reddy, MBBS||Vanderbilt-Ingram Cancer Center, Vanderbilt University|