bortezomib in treating patients with diffuse large b-cell lymphoma that is refractory to chemotherapy

Conditions: Lymphoma

Summary: rationale: bortezomib may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. purpose: phase ii trial to study the effectiveness of bortezomib in treating patients who have diffuse large b-cell lymphoma that is refractory to previous chemotherapy.

objectives: * determine the overall response rate in patients with chemotherapy-refractory diffuse large b-cell lymphoma treated with bortezomib. * determine the safety and tolerability of this drug in these patients. * determine the time to disease progression in patients treated with this drug. * determine the possible mechanism of resistance to this drug in these patients. outline: this is an open-label, multicenter study. patients receive bortezomib iv over 3-5 seconds on days 1, 4, 8, and 11. treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. patients are followed at 20 days and then every 3 months thereafter. projected accrual: a total of 22-40 patients will be accrued for this study.

Eligibility criteria:
disease characteristics: * histologically confirmed diffuse large b-cell lymphoma, meeting criteria for 1 of the following: * relapsed after prior high-dose chemotherapy with stem cell support * relapsed after prior chemotherapy, including at least 1 prior standard non-hodgkin's chemotherapy regimen, but not a candidate for high-dose chemotherapy with stem cell support * measurable disease * at least 1 bidimensionally measurable lesion at least 1.5 cm by ct scan * no primary or secondary cns lymphoma * no hiv-related lymphoma * no known brain metastases patient characteristics: age * 18 and over performance status * ecog 0-2 or * karnofsky 60-100% life expectancy * more than 3 months hematopoietic * hemoglobin at least 9 g/dl * absolute neutrophil count at least 1,000/mm\^3 * no colony-stimulating factors within 4 weeks before obtaining this result * platelet count at least 50,000/mm\^3 * no platelet transfusion within 4 weeks before obtaining this result hepatic * bilirubin no greater than 2 times upper limit of normal (uln) * ast and alt no greater than 2.5 times uln * no active hepatitis b or c viral infection renal * creatinine no greater than 2 times uln or * creatinine clearance at least 60 ml/min cardiovascular * no myocardial infarction within the past 6 months * no evidence of acute ischemia or new conduction system abnormalities on ekg * no symptomatic congestive heart failure * no unstable angina pectoris * no cardiac arrhythmia other * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception * sodium greater than 130 meq/l * hiv negative * no ongoing or active infection * no other concurrent uncontrolled illness that would preclude study participation * no psychiatric illness or social situation that would preclude study compliance * no prior allergic reaction attributable to compounds of similar chemical or biological composition to bortezomib prior concurrent therapy: biologic therapy * see disease characteristics * see chemotherapy * at least 4 weeks since prior immunotherapy chemotherapy * see disease characteristics * more than 4 weeks since prior chemotherapy * more than 12 weeks since prior high-dose chemotherapy with hematopoietic stem cell support endocrine therapy * not specified radiotherapy * more than 4 weeks since prior radiotherapy * no concurrent radiotherapy surgery * more than 4 weeks since prior major surgery unless fully recovered other * recovered from prior therapy * no other concurrent investigational agents * no other concurrent investigational or commercial agents or therapies to treat the malignancy

Keywords: recurrent adult diffuse large cell lymphoma