Bortezomib and Rituximab in Treating Patients With Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma

Study Overview
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Brief Summary
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RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. 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 rituximab may be an effective treatment for non-Hodgkin's lymphoma. PURPOSE: This phase II trial is studying how well giving bortezomib together with rituximab works in treating patients with relapsed or refractory B-cell non-Hodgkin's lymphoma, including Waldenstrom's macroglobulinemia.

Detailed Description
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OBJECTIVES: Primary Assess the safety and tolerability of bortezomib and rituximab in patients with relapsed or refractory, B-cell non-Hodgkin's lymphoma. Determine the overall response rate (partial response, complete response unconfirmed, and complete response) in these patients. Secondary Estimate the duration of response in patients treated with this regimen. Estimate the time to disease progression in patients treated with this regimen. OUTLINE: This is an open-label study. Patients receive bortezomib IV over 3-5 seconds once weekly in weeks 1-4 and rituximab IV over 5-6 hours once weekly in weeks 1-5*. Treatment repeats every 5 weeks for 2 courses. Patients achieving stable disease or better receive an additional 4 courses of bortezomib alone. NOTE: *Patients receive rituximab in weeks 1-3 only during course 2 of treatment. After completion of study treatment, patients are followed periodically for at least 18 months. PROJECTED ACCRUAL: A total of 46 patients will be accrued for this study.

Official Title
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VELCADE (Bortezomib) for Injection - Phase II Study of Bortezomib and Rituximab in Relapsed or Refractory Non-Hodgkin's Lymphoma

Conditions
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Lymphoma

Intervention / Treatment
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* Drug: bortezomib
* Drug: rituximab
* Procedure: antibody therapy
* Procedure: biological therapy
* Procedure: enzyme inhibitor therapy
* Procedure: monoclonal antibody therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed B-cell non-Hodgkin's lymphoma (NHL) including the following subtypes: B-cell small lymphocytic lymphoma Marginal zone lymphoma (extranodal, nodal, or splenic) Grade 1-3 follicular lymphoma Mantle cell lymphoma Waldenstrom's macroglobulinemia Bidimensionally measurable disease by CT scan with ≥ 1 lesion measuring > 1.5 cm in a single dimension Relapsed or refractory disease after prior antineoplastic therapy, meeting 1 of the following criteria: No response to prior treatment Relapsed disease after prior therapy Confirmed CD20-positive disease by immunohistochemistry on biopsy specimen Prior transformation allowed provided there is no evidence of aggressive histology on recent biopsy No chronic lymphocytic lymphoma with absolute lymphocyte count > 5,000/mm³ No CNS involvement PATIENT CHARACTERISTICS: ECOG performance status 0-2 Absolute neutrophil count ≥ 1,500/mm^3 (≥ 1,000/mm³ if due to extensive bone marrow involvement with NHL or splenomegaly) Absolute lymphocyte count ≤ 5,000/mm³ (except mantle cell lymphoma with a leukemic phase) Platelet count ≥ 50,000/mm^3 Bilirubin ≤ 2.0 mg/dL AST and ALT ≤ 2.5 times upper limit of normal (ULN) (4 times ULN if liver involvement with NHL) Creatinine ≤ 2.0 mg/dL Not pregnant or nursing Negative pregnancy test Fertile male and female patients must use effective contraception during study No serious nonmalignant disease No active infection No peripheral neuropathy ≥ grade 2 within past 14 days No myocardial infarction within the past 6 months No New York Heart Association class III or IV heart failure No uncontrolled angina pectoris No severe uncontrolled ventricular arrhythmias No EKG evidence of acute ischemia or active conduction system abnormalities Any EKG abnormality must be documented as not medically relevant No hypersensitivity to bortezomib, boron, or mannitol No known anaphylaxis or immunoglobulin E-mediated hypersensitivity to murine proteins or any component of rituximab (including polysorbate 80 and sodium citrate dehydrate) No known infection or exposure to HIV No serious psychiatric or medical illness that would preclude study participation No active hepatitis B infection No other primary malignancy requiring active treatment More than 4 weeks since prior significant traumatic injury PRIOR CONCURRENT THERAPY: At least 3 weeks since prior and no concurrent radiotherapy More than 4 weeks since prior major surgery or open biopsy Other diagnostic surgery allowed More than 4 weeks since prior cytotoxic chemotherapy (6 weeks for nitrosoureas) At least 3 months since prior unconjugated monoclonal antibody therapy At least 10 weeks since prior radioimmunoconjugates or toxin immunoconjugates (e.g., iodine I 131 tositumomab [Bexxar] or ibritumomab tiuxetan [Zevalin]) More than 2 weeks since prior investigational agent No prior bortezomib No concurrent systemic corticosteroid at greater than the equivalent dose of 20 mg/day of prednisone, unless for treatment of allergic reactions to CT scan dye No concurrent major surgery No other immunosuppressive agents, unless for treatment of allergic reactions to CT scan dye No other concurrent antilymphoma agents No other concurrent investigational agent Concurrent participation in another nontreatment study allowed if it does not interfere with participation in this study

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|
|Drug: rituximab|nan|
|Procedure: antibody therapy|nan|
|Procedure: biological therapy|nan|
|Procedure: enzyme inhibitor therapy|nan|
|Procedure: monoclonal antibody therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent mantle cell lymphoma, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, splenic marginal zone lymphoma, recurrent adult diffuse small cleaved cell lymphoma, nodal marginal zone B-cell lymphoma, Waldenstrom's macroglobulinemia