Rituximab, Bortezomib,Bendamustine , Dexamethasone, Patients With Mantle Cell Lymphoma

Study Overview
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Brief Summary
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RATIONALE: 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. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as doxorubicin, dexamethasone, and chlorambucil, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving combination chemotherapy together with rituximab and bortezomib may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving rituximab together with bortezomib, doxorubicin, dexamethasone, and chlorambucil works as first-line therapy in treating older patients with stage II, stage III, or stage IV mantle cell lymphoma.

Detailed Description
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OBJECTIVES: Primary Evaluate the efficacy of rituximab, bortezomib, doxorubicin hydrochloride, dexamethasone, and chlorambucil as first-line therapy in patients with stage II-IV mantle cell lymphoma. Secondary Determine the complete response rate in these patients. Determine the efficacy, in terms of complete and overall response, by F18 fludeoxyglucose scan. Determine overall, disease-free, and event-free survival of these patients. Assess tolerability of this regimen in these patients. Evaluate the impact of factors, described in previous protocols, on response to therapy and survival. Assess the impact of residual disease in cerebrospinal fluid on survival. OUTLINE: This is a multicenter study. Patients receive rituximab IV on day 1 (days 1 and 8 of the first course only); bortezomib IV on days 1, 4, 8, and 11; doxorubicin hydrochloride IV continuously over 24 hours on days 1-4; dexamethasone IV on days 1-4; and oral chlorambucil on days 20-29. Treatment repeats every 5 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve at least 50% response receive 2 additional courses of therapy.

Official Title
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First-line Treatment of Mantle Cell Lymphoma of Old Patients . Evaluate the Efficacy, Toxicity, and Molecular Prognostic Factors of Velcade®) in Association With Chemotherapy and Immunotherapy With Rituximab

Conditions
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Lymphoma

Intervention / Treatment
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* Biological: rituximab
* Drug: bortezomib
* Drug: dexamethasone
* Drug: Bendamustine


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of mantle cell lymphoma Stage II-IV disease No neuromeningeal disease PATIENT CHARACTERISTICS: WHO performance status 0-2 No prior cancer except for carcinoma in situ of the cervix or basal cell skin cancer LVEF > 50% HIV-negative Hepatitis B- and C-negative No hepatocellular, renal, or bone marrow insufficiency unrelated to lymphoma PRIOR CONCURRENT THERAPY: Not specified

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 80 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ARM RiBVD<br>RiBVD 6 cycles every 28 days day 1 : Rituximab /Mabthera®, 375 mg/m2 en IV Bendamustine, 90 mg/m2 en IVD Bortezomib/Velcade®, 1,3 mg/m2 en IVD day 2 : - Bendamustine, 90 mg/m2 en IVD Dexamethasone, 40 mg IV day 4 : - Bortezomib/Velcade®, 1,3 mg/m2 en IVD day 8 : - Bortezomib/Velcade®, 1,3 mg/m2 en IVD day 11 : - Bortezomib/Velcade®, 1,3 mg/m2 en IVD | Biological: rituximab<br>* Rituximab, 375 mg/m2 Intraveinous<br>* Other names: Mabthera ®,;Drug: bortezomib<br>* -Velcade®, 1,3 mg/m2 Intraveinous on days 1, 4, 8 and 11<br>* Other names: Velcade;Drug: dexamethasone<br>* day - Dexamethasone, 40 mg Intraveinous<br>Drug: Bendamustine<br>* -Day 1 and day 2 Bendamustine/Levact ®,, 90 mg/m2 Intraveinous<br>* Other names: Levact ®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate after 4 courses of therapy |  | 4 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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contiguous stage II mantle cell lymphoma, noncontiguous stage II mantle cell lymphoma, stage III mantle cell lymphoma, stage IV mantle cell lymphoma