Study of Mantle Cell Lymphoma Treatment by RiBVD (RIBVD)

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

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.

Study Overview

• Status: Completed
• Conditions: Mantle Cell Lymphoma
• Intervention / Treatment: Drug: RiBVD

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 76
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Grenoble, France, 38043
    • Valerie ROLLAND NEYRET

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years to 85 years (OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: RiBVD; Rituximab Bendamustine Velcade® Dexamethasone 6 cycles every 28 days	Drug: RiBVD; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: French Innovative Leukemia Organisation
• Collaborators: Mundipharma Pte Ltd.; Roche Pharma AG; Janssen-Cilag Ltd.; Lymphoma Study Association; Chugai Pharma Europe Ltd.
• Investigators: Principal Investigator: Rémy GRESSIN, MD, Groupe Est Ouest des Leucémies et autres Maladies du Sand

Publications and helpful links

Helpful Links

• FILO internet site

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (ACTUAL): September 1, 2014
• Study Completion (ACTUAL): March 1, 2016

Study Registration Dates

• First Submitted: October 20, 2011
• First Submitted That Met QC Criteria: October 20, 2011
• First Posted (ESTIMATE): October 21, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): March 16, 2016
• Last Update Submitted That Met QC Criteria: March 15, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: Rituximab; Dexamethasone; Velcade; Mantle cell lymphoma; bendamustine
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, Mantle-Cell
• Other Study ID Numbers: Manteau RiBVD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO