A Phase I/II Trial of VELCADE & Gemcitabine for Patients With Relapsed or Refractory Aggressive B- and T-cell Non-Hodgkin's Lymphoma
- Registration Number
- NCT00290706
- Lead Sponsor
- Northwestern University
- Brief Summary
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.
- Detailed Description
OBJECTIVES:
Primary
* 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.
Secondary
* 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 32
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Gemcitabine 800 mg/m2 + Bortezomib IVP over 3-5 seconds gemcitabine hydrochloride 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. Gemcitabine 800 mg/m2 + Bortezomib IVP over 3-5 seconds bortezomib 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.
- Primary Outcome Measures
Name Time Method Response Rate in Patients With Relapsed or Refractory B- and T-cell NHL With Gemcitabine and Bortezomib Combination Treatment. 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
- Secondary Outcome Measures
Name Time Method Overall Survival 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
Time to Treatment Failure and Duration of Response 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
Evaluate Safety and Tolerability of Bortezomib and Gemcitabine Therapy 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
Trial Locations
- Locations (3)
Northwestern University
🇺🇸Chicago, Illinois, United States
Veterans Affairs Medical Center - Lakeside Chicago
🇺🇸Chicago, Illinois, United States
University of Chicago Cancer Research Center
🇺🇸Chicago, Illinois, United States