Study of Mantle Cell Lymphoma Treatment by RiBVD

Study Overview
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Brief Summary
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Study of First line mantle cell lymphoma treatment by Rituximab, Velcade, Bendamustine and Dexamethasone schema in patients older than 65 years or 18 to 65 years old who cannot or refuse receive conditioning regimen followed by autograft.

Detailed Description
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Demonstration of Improvement of progression-free survival (PFS) compared to literature data. 6 months prolongation equal 24 months compared to 18 months obtained whatever the current regimen and in particular compared to RCHOP regimen

Official Title
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First Line Mantle Cell Lymphoma (MCL) Treatment by RiBVD Schema in Patients Older Than 65 Years or 18 to 65 Years Old Who Cannot or Refuse Receive Conditioning Regimen Followed by Autograft

Conditions
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Mantle Cell Lymphoma

Intervention / Treatment
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* Drug: RiBVD


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: mantle cell Lymphoma CD20 positive Untreated patients 65 ans years old patients or 18 to 65 years old patients who can't or refuse receive conditioning regimen followed by autograft. Stages Ann Arbor II, III or IV, ECOG performance status of 0, 1 or 2 Without history of neoplasm, except in situ cervix carcinoma and cutaneous basal cell epithelioma, or in complete remission since 3 years, Without drug contraindication used in the schema (Rituximab, benda-mustine, Velcade, Dexamethasone), Without heart insufficiency or stabilized, With the following biological values limits except if pathological values are due to Medullary invading or hypersplenism, hepatic involvement) :PNN more than 1 G/L, Platelets more than 50 G/L,Transaminases (SGOT and SGPT) and alkalin phosphatases alcalines less than 4 x normal,Bilirubin less than 3 x N,- Clearance creatinemia more than 20 mL/min Hepatitis B negative serology unless the seropositivity is clearly linked to a vaccination. Can be regularly followed Who signed the informed consent, Affiliated to a national insurance or such a same scheme . Exclusion Criteria: Other type of lymphoma than mantle cell lymphoma according to OMS 2008 classification Patients in relapse, except those in relapse due to localized stade who only received locoregional irradiation or splenectomized, Central nervous system localization in particular meninge, Drug used in the schema contraindication Rituximab , Bendamustine , Velcade® or Dexamethasone Non stable diabetes, HIV positive or active hepatitis C or B ECOG performance status equal or more than 3 Peripheral neuropathy, whatever its origin, rated more than 2 from NCI Non stabilized heart insufficiency, Patient who can't receive hyperhydration in order to treat tumoral lysis syndrome or in prophylaxis, Patient who can't, whatever the reason, be regularly followed, Major patient who are on legal protection, or can't give their consent Patient who has not signed the informed consent

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 85 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: RiBVD<br>Rituximab Bendamustine Velcade® Dexamethasone 6 cycles every 28 days | Drug: RiBVD<br>* Every cycle: Rituximab intravenous infusion dosage 375 mg/m² day 1 Bendamustine direct intervenous 90 mg/m² day 1 and day 2 Velcade®subcutaneous 1,3 mg/m² day 1,4, 8 and 11 dexamethasone 40 mg IVD on day 2<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement of progression-free survival (PFS) | Improvement of progression-free survival (PFS) compared to litterature data 6 months prolongation 24 months compared to 18 months obtained whatever the current regimen and in particular compared to RCHOP regimen in reference with Lenz JCO 2005 | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall and complete response rate after 4 cures and 6 cures | Overall and complete response rate after 4 cures equal intermediate response and after 6 cures equal final response according to Cheson 1999 criteria without Positron Emission Tomography and 2007 with Positron Emission Tomography | 6 months | 
| Residual disease evaluated by molecular biology | Residual disease evaluated by molecular biology on blood and bone marrow, by Hybridation Fluorescente In Situ and Flow cytometry on blood cells | 6 years | 
| Intermediate response predictive factors study | Predictive factors are determined at diagnosis are watched at Intermediate response | 4 months | 
| Toxicity of RiBVD regimen according to NCI criteria Hematological and non-hematological toxicity | Toxicities are collected at every course = every 28 days during 6 months | 6 months | 
| Prognosis value on Overall survival and progression free survival and on duration of response, of the MIPI index, MIPIb index and goelams index |  | 36 months | 
| Residual disease evaluated by molecular biology Q-PCR on blood and bone marrow, by Hybridation Fluorescente In Situ and Flow cytometry on blood cells | blood and bone marrow samples sent to central laboratory for molecular residual disease at diagnosis, treatment evaluation and follow-up | 42 months | 
| Diagnostic PET scan results, at intermediate and final analysis | Pet scan results at intermediate analysis = 4 months Pet scan results at final analysis = 6 months | 4 and 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Velcade, Mantle cell lymphoma, Rituximab, bendamustine, Dexamethasone