A Phase I/II Trial of VELCADE & Gemcitabine for Patients With Relapsed or Refractory Aggressive B- and T-cell Non-Hodgkin's Lymphoma
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|ClinicalTrials.gov Identifier: NCT00290706|
Recruitment Status : Terminated (Closed per Data Monitoring Committee due to lack of efficacy)
First Posted : February 13, 2006
Results First Posted : May 28, 2019
Last Update Posted : May 28, 2019
RATIONALE: Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving gemcitabine together with bortezomib may kill more cancer cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of bortezomib when given together with gemcitabine and to see how well they work in treating patients with relapsed or refractory B-cell or T-cell non-Hodgkin's lymphoma.
|Condition or disease||Intervention/treatment||Phase|
|Lymphoma||Drug: bortezomib Drug: gemcitabine hydrochloride||Phase 1 Phase 2|
- Determine the response rate (complete and partial remission) in patients with relapsed or refractory aggressive B- or T-cell non-Hodgkin's lymphoma treated with gemcitabine hydrochloride and bortezomib.
- Determine the maximum tolerated dose of bortezomib when administered with gemcitabine hydrochloride in these patients.
- Determine the time to treatment failure, duration of response, and overall survival of patients treated with this regimen.
- Determine the safety and tolerability of this regimen in these patients.
OUTLINE: This is a phase I, dose-escalation study of bortezomib followed by a phase II, open-label study.
- Phase I: Patients receive gemcitabine hydrochloride IV over 30 minutes and bortezomib IV over 3-5 seconds on days 1 and 8. Treatment repeats every 21 days for up to 9 courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of bortezomib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 3 of 6 patients experience dose-limiting toxicity (DLT) OR the dose that at which 2 of 6 patients experience DLT.
- Phase II: Patients receive gemcitabine hydrochloride and bortezomib as in phase I at the MTD.
After completion of study therapy, patients are followed periodically for 3 years.
PROJECTED ACCRUAL: A total of 37 patients will be accrued for this study.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||32 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I/II Trial of Combination Bortezomib (VELCADE) and Gemcitabine Therapy for Patients With Relapsed or Refractory Aggressive B- and T-cell Non-Hodgkin's Lymphoma|
|Actual Study Start Date :||April 7, 2006|
|Actual Primary Completion Date :||February 11, 2011|
|Actual Study Completion Date :||September 5, 2012|
Experimental: Gemcitabine 800 mg/m2 + Bortezomib IVP over 3-5 seconds
Gemcitabine dose of 800 mg/m2 over 30 minutes followed by Bortezomib IVP given over 3-5 seconds on day 1 and day 15 of each cycle every 28 days for up to 8 cycles.
Bortezomib 1.6mg/m2 on days 1 and 15 of each cycle, given over 3-5 seconds on day 1 and day 15 of each cycle every 28 days for up to 8 cycles.
Drug: gemcitabine hydrochloride
Gemcitabine dose of 800 mg/m2 over 30 minutes on day 1 and day 15 of each cycle every 28 days for up to 8 cycles.
Other Name: Gemzar®
- Response Rate in Patients With Relapsed or Refractory B- and T-cell NHL With Gemcitabine and Bortezomib Combination Treatment. [ Time Frame: At screening and after completing cycle 3, cycle 6 and 30 days after Cycle 8 ]
Response rate in patients with relapsed or refractory B- and T-cell NHL with Gemcitabine and Bortezomib combination treatment will be defined as the number of patients with Complete Remission [CR] and Partial Remission [PR]. CT scans at screening and after completing cycle 3, cycle 6 and 30 days after Cycle 8 assessed by the Response Criteria for Non-hodgkins Lymphoma will be used to determine response where:
CR=Complete disappearance of all detectable clinical and radiographic evidence of disease PR=> 50% decrease in SPD of the six largest dominant nodes or nodal masses
- Time to Treatment Failure and Duration of Response [ Time Frame: At screening and after completing cycle 3, cycle 6 and 30 days after cycle 8, then every 6 months for 3 years ]Time to treatment failure and duration of response will be measured by CT Scan at screening and after completing cycle 3, cycle 6 and 30 days after cycle 8, then every 6 months for 3 years
- Overall Survival [ Time Frame: Every 6 months while on treatment and then every 6 months while off of treatment for up to 3 years ]Overall survival will be evaluated every 6 months while on treatment and then every 6 months while off of treatment for up to 3 years
- Evaluate Safety and Tolerability of Bortezomib and Gemcitabine Therapy [ Time Frame: During treatment through a maximum of 8 Cycles (1 Cycle = 28 Days) and 30 days post last treatment ]
Safety and tolerability of the study drugs will be assessed on Day 1 and on either Day 8 or Day 15 of each treatment cycle (1 Cycle - 28 days) while on active treatment; and 30 days post last treatment. Adverse Events that are experienced by patients, determined to be either grade 3 or grade 4 and at least possibly related to at least one of the study drugs as assessed according to the National Cancer Institute's Common Toxicity Criteria for adverse events version 3.0 (CTCAE v3.0) will be collected. In general adverse events (AEs) will be graded according to the following:
Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE
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): NCT00290706
|United States, Illinois|
|Chicago, Illinois, United States, 60611|
|Veterans Affairs Medical Center - Lakeside Chicago|
|Chicago, Illinois, United States, 60611|
|University of Chicago Cancer Research Center|
|Chicago, Illinois, United States, 60637|
|Principal Investigator:||Leo Gordon, MD||Northwestern University|