Bortezomib and Gemcitabine Hydrochloride in Treating Patients With Relapsed or Refractory Hodgkin's Lymphoma
RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as gemcitabine hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving bortezomib together with gemcitabine hydrochloride may kill more cancer cells.
PURPOSE: This phase II trial is studying how well giving bortezomib together with gemcitabine hydrochloride works in treating patients with relapsed or refractory Hodgkin's lymphoma.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Pilot Study of Bortezomib (VELCADE®) and Gemcitabine for Patients With Relapsed or Refractory Hodgkin's Lymphoma|
- Response Rate After 2 Courses of Therapy [ Time Frame: 21 Days/course for up to 2 courses ] [ Designated as safety issue: No ]Response was evaluated after two cycles of therapy using the 1999 Cheson response criteria. All responses were based on CT scans. The criteria that were developed include anatomic definitions of response, with normal lymph node size after treatment of 1.5 cm in the longest transverse diameter by computer-assisted tomography scan. A designation of complete response/unconfirmed was adopted to include patients with a greater than 75% reduction in tumor size after therapy but with a residual mass, to include patients-especially those with large-cell NHL-who may not have residual disease. For patients who had FDG-PET imaging, metabolic response was defined as a decrease in the standardized uptake value in target lesions (regions of abnormal FDG uptake on pretreatment FDG-PET images) to below three on posttreatment FDG-PET imaging). All PET scans were reviewed and interpreted by a single radiologist (SV).
- Change in Proteasome Activity Compared to Baseline (Cycle 1) [ Time Frame: baseline to 2 hours ] [ Designated as safety issue: No ]Peripheral blood (40 ml) was collected on cycle 1, day 1 of prebortezomib at baseline and 2 hrs post-bortezomib treatment. The samples were refrigerated at 4C and processed within 36 h of collection. Frozen cell lysates were thawed and the proteasome activity in 10 microliters was determined using a spectroflourometric 20S proteasome assay kit. Samples were run in triplicate on two separate days. The percent change between baseline and 2 hrs (day1, cycle 1) was calculated.
- Change in Proteasome Activity Compared to Baseline (Cycle 2) [ Time Frame: baseline and 1-2 weeks after cycle 2, day 11 ] [ Designated as safety issue: No ]Peripheral blood (40 ml) was collected at baseline and 1-2 weeks after cycle 2, day 11 post-bortezomib treatment. The samples were refrigerated at 4C and processed within 36 h of collection. Frozen cell lysates were thawed and the proteasome activity in 10 microliters was determined using a spectroflourometric 20S proteasome assay kit. Samples were run in triplicate on two separate days. The percent change between baseline and 2 hrs (day1, cycle 1) was calculated.
|Study Start Date:||April 2005|
|Primary Completion Date:||May 2008 (Final data collection date for primary outcome measure)|
|Experimental: Bortezomib, Gemcitabine Hdrochloride||Drug: bortezomib Drug: gemcitabine hydrochloride|
- Determine the overall response rate (partial and complete response) in patients with relapsed or refractory Hodgkin's lymphoma treated with bortezomib and gemcitabine hydrochloride.
- Determine the safety and toxic effects of this regimen in these patients.
- Determine the time to progression in patients treated with this regimen.
- Correlate NF-kB inhibition and proteasome activity with response in patients treated with this regimen.
OUTLINE: This is a multicenter, pilot study.
Patients receive bortezomib IV on days 1, 4, 8, and 11 and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed periodically for 2 years and then annually thereafter.
PROJECTED ACCRUAL: A total of 24 patients will be accrued for this study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00262860
|United States, Massachusetts|
|Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute|
|Boston, Massachusetts, United States, 02115|
|United States, New York|
|James P. Wilmot Cancer Center at University of Rochester Medical Center|
|Rochester, New York, United States, 14642|
|Principal Investigator:||Jonathan W. Friedberg, MD||James P. Wilmot Cancer Center|