Bortezomib in Treating Patients With Diffuse Large B-Cell Lymphoma That Is Refractory To Chemotherapy

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Phase II Study Of PS-341 (VELCADE) In Chemotherapy-Refractory Diffuse Large B-Cell Lymphoma (DLBCL)

Conditions
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Lymphoma

Intervention / Treatment
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* Drug: bortezomib


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: bortezomib|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (combined complete response and partial response) |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety |  |  | 
| Tolerability |  |  | 
| Time to disease progression |  |  | 
| Possible mechanism of resistance |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent adult diffuse large cell lymphoma