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. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving bortezomib together with gemcitabine hydrochloride and rituximab may kill more cancer cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of bortezomib and gemcitabine hydrochloride when given together with rituximab and to see how well they work in treating patients with progressive or relapsed B-cell non-Hodgkin lymphoma.
OBJECTIVES: Primary: I. To evaluate the safety and feasibility of combining VELCADE (bortezomib) with gemcitabine (gemcitabine hydrochloride) in patients with recurrent lymphoma after standard therapy. II. To define the maximum tolerated dose (MTD) of gemcitabine and Rituxan (rituximab) administered in combination with VELCADE given on a 21-day (old schema - Schema I) or 28-day (amended schema - Schema II) schedule. Secondary: I. To obtain preliminary data for response to this regimen in this patient population. OUTLINE: This is a phase I, dose-escalation study of bortezomib and gemcitabine hydrochloride followed by a phase II study. Patients receive bortezomib intravenously (IV), gemcitabine hydrochloride IV over 3-4 hours, and rituximab IV on days 1 and 15. Treatment repeats every 28 days for at least 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
33
City of Hope Medical Center
Duarte, California, United States
South Pasadena Cancer Center
South Pasadena, California, United States
Number of Participants With at Least One Dose Limiting Toxicity (DLT)
Adverse events were graded by NCI CTCAE, Version 3.0. DLT defined as grade 4 thrombocytopenia, or grade 3 thrombocytopenia lasting greater than 7 days. Grade 4 neutropenia lasting 7 days or more despite use of growth factors. Febrile neutropenia only is it occurs after 7 days of neutropenia. Any grade 3 or higher non-hematologic toxicity related to the study drug, with the exception of alopecia, inadequately treated nausea, vomiting and/or diarrhea and fatigue.
Time frame: 28 days from start of treatment, up to 2 years.
Recommended Phase II Dose
The maximum tolerated dose (MTD) of Gemcitabine in combination with 1.3 mg/m2 of velcade on days 1 and 15 is based on toxicities observed during the first cycle and is defined as the highest dose tested in which fewer than 33% of patients experience an attributable DLT to the study drug, when at least 6 patients are treated at that dose and are evaluable for toxicity. Dose escalations proceeded according to a standard 3+3 design.
Time frame: 28 days from start of treatment, up to 2 years.
Number of Subject With Complete Response
Per standard lymphoma response criteria (Cheson): Complete Response (CR), 1. Complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease related symptoms if present before therapy, with normalization of LDH if elevated prior to therapy. 2. All lymph nodes and masses must regress to normal size (\<1.5 cm in greatest transverse diameter if \>1.5 cm prior to treatment). 3. The spleen, if enlarged prior to therapy, must have regressed to normal size. 3. If bone marrow was involved by lymphoma, it must be cleared as documented by biopsy at the same location.
Time frame: Up to 1 year
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