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ACVBP Plus Rituximab Versus CHOP Plus Rituximab in Patients With Diffuse Large B-cell Lymphoma and Age-adjusted IPI of 1

Primary Purpose

Diffuse Large-Cell Lymphoma

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
rituximab
doxorubicin
cyclophosphamide
Sponsored by
Lymphoma Study Association
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diffuse Large-Cell Lymphoma focused on measuring Lymphoma, diffuse large B-cell, rituximab, chemotherapy

Eligibility Criteria

18 Years - 59 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Patient with histologically proven CD20+ diffuse large B-cell lymphoma (WHO classification) Aged from 18 to 59 years. Age-adjusted International Prognostic Index equal to 1 (elevated LDH level OR stage III-IV OR ECOG status 2-3-4). Patient not previously treated. With a minimum life expectancy of 3 months. Negative HIV, HBV and HCV serologies test 4 weeks (except after vaccination). Having previously signed a written informed consent. Exclusion Criteria: Any other histological type of lymphoma. Any history of treated or non-treated indolent lymphoma. However, patients not previously diagnosed and having a diffuse large B-cell lymphoma with some small cell infiltration in bone marrow or lymph node may be included. Central nervous system or meningeal involvement by lymphoma. Contra-indication to any drug contained in the chemotherapy regimens. Any serious active disease (according to the investigator's decision). Poor renal function (creatinin level>150µmol/l), poor hepatic function (total bilirubin level>30mmol/l, transaminases>2.5 maximum normal level) unless these abnormalities are related to the lymphoma. Poor bone marrow reserve as defined by neutrophils <1.5 G/l or platelets <100 G/l, unless related to bone marrow infiltration. Any history of cancer during the last 5 years with the exception of non-melanoma skin tumors or stage 0 (in situ) cervical carcinoma. Treatment with any investigational drug within 30 days before planned first cycle of chemotherapy and during the study. Pregnant or lactating women. Adult patient under tutelage.

Sites / Locations

  • Groupe d'étude des lymphomes de l'adulte
  • Hôpital Henri Mondor
  • Centre Léon Bérard
  • Hôpital Saint Louis
  • Hématologie Adultes - Hôpital Necker
  • Service d'Hématologie - Centre Hospitalier Lyon-Sud
  • Centre Hospitalier Robert Debré
  • Centre Henri Becquerel
  • Hématologie CHU Purpan
  • Institut Gustave Roussy

Outcomes

Primary Outcome Measures

Event-free survival (EFS), events defined as death from any cause, relapse for complete responders (CR) and unconfirmed complete responders (CRu), progression during or after treatment, changes of therapy during allocated treatment.

Secondary Outcome Measures

Response rate at the end of the treatment, progression rate, relapse rate, disease-free survival for complete responders, overall survival, neuromeningeal relapse rate and additional toxicities with ACVBP+rituximab combination

Full Information

First Posted
August 31, 2005
Last Updated
March 3, 2011
Sponsor
Lymphoma Study Association
Collaborators
Amgen
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1. Study Identification

Unique Protocol Identification Number
NCT00140595
Brief Title
ACVBP Plus Rituximab Versus CHOP Plus Rituximab in Patients With Diffuse Large B-cell Lymphoma and Age-adjusted IPI of 1
Official Title
Randomized Study of ACVBP Plus Rituximab Versus CHOP Plus Rituximab in Patients Aged From 18 to 59 Years With Diffuse Large B-cell Lymphoma and a Age-adjusted IPI of 1.
Study Type
Interventional

2. Study Status

Record Verification Date
March 2011
Overall Recruitment Status
Completed
Study Start Date
December 2003 (undefined)
Primary Completion Date
January 2009 (Actual)
Study Completion Date
January 2009 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Lymphoma Study Association
Collaborators
Amgen

4. Oversight

5. Study Description

Brief Summary
This study is a multicentric randomized trial evaluating the efficacy of the combination ACVBP+rituximab compared to the combination of CHOP+rituximab in patients aged from 18 to 59 years with diffuse large B-cell lymphoma and one factor of the age-adjusted international prognostic index (IPI).
Detailed Description
This phase III multicentric open label randomized study is based on the results of previous LNH 93-5 and LNH98-5 studies. The LNH93-5 study has shown that the ACVBP regimen gave a longer EFS (39% vs 29% at 5 years, p=0.005) and a longer overall survival (46% vs 38% at 5 years, p=0.036) than CHOP in patients aged between 61 and 69 with an IPI score ≥1. However ACVBP had a more important toxicity and a higher treatment related mortality (13% vs 7%, p<0.01), specially after 65 years. In younger patients ACVBP is better tolerated. The addition of Rituximab to standard CHOP (R-CHOP) has been shown in LNH98-5 study to improve complete remission rate (CR), event-free survival (EFS) and overall survival (OS) in elderly patients with B-DLCL. Considering only patients with an aa-IPI score of 1, the 2 year EFS was 75% in the R-CHOP group as compared with 42% in the CHOP group. This study is designed to test whether addition of rituximab to ACVBP is better than R-CHOP in patients younger than 60. Primary endpoint is event-free survival, we expect a gain in 2 years-EFS of 10% in R-ACVBP group as compared with R-CHOP group. This study is a multicentric, phase III open-label, randomized trial evaluating the efficacy of ACVBP+rituximab compared to CHOP+rituximab in patients aged from 18 to 59 years with non previously treated diffuse large B-cell lymphoma and one factor of the age-adjusted international prognostic index

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diffuse Large-Cell Lymphoma
Keywords
Lymphoma, diffuse large B-cell, rituximab, chemotherapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
380 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
rituximab
Intervention Type
Drug
Intervention Name(s)
doxorubicin
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Primary Outcome Measure Information:
Title
Event-free survival (EFS), events defined as death from any cause, relapse for complete responders (CR) and unconfirmed complete responders (CRu), progression during or after treatment, changes of therapy during allocated treatment.
Secondary Outcome Measure Information:
Title
Response rate at the end of the treatment, progression rate, relapse rate, disease-free survival for complete responders, overall survival, neuromeningeal relapse rate and additional toxicities with ACVBP+rituximab combination

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
59 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patient with histologically proven CD20+ diffuse large B-cell lymphoma (WHO classification) Aged from 18 to 59 years. Age-adjusted International Prognostic Index equal to 1 (elevated LDH level OR stage III-IV OR ECOG status 2-3-4). Patient not previously treated. With a minimum life expectancy of 3 months. Negative HIV, HBV and HCV serologies test 4 weeks (except after vaccination). Having previously signed a written informed consent. Exclusion Criteria: Any other histological type of lymphoma. Any history of treated or non-treated indolent lymphoma. However, patients not previously diagnosed and having a diffuse large B-cell lymphoma with some small cell infiltration in bone marrow or lymph node may be included. Central nervous system or meningeal involvement by lymphoma. Contra-indication to any drug contained in the chemotherapy regimens. Any serious active disease (according to the investigator's decision). Poor renal function (creatinin level>150µmol/l), poor hepatic function (total bilirubin level>30mmol/l, transaminases>2.5 maximum normal level) unless these abnormalities are related to the lymphoma. Poor bone marrow reserve as defined by neutrophils <1.5 G/l or platelets <100 G/l, unless related to bone marrow infiltration. Any history of cancer during the last 5 years with the exception of non-melanoma skin tumors or stage 0 (in situ) cervical carcinoma. Treatment with any investigational drug within 30 days before planned first cycle of chemotherapy and during the study. Pregnant or lactating women. Adult patient under tutelage.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christian Recher, MD
Organizational Affiliation
Lymphoma Study Association
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Hervé Tilly, MD
Organizational Affiliation
Lymphoma Study Association
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Corinne Haioun, MD
Organizational Affiliation
Lymphoma Study Association
Official's Role
Study Chair
Facility Information:
Facility Name
Groupe d'étude des lymphomes de l'adulte
City
Yvoir
Country
Belgium
Facility Name
Hôpital Henri Mondor
City
Créteil
ZIP/Postal Code
94010
Country
France
Facility Name
Centre Léon Bérard
City
Lyon
ZIP/Postal Code
69008
Country
France
Facility Name
Hôpital Saint Louis
City
Paris
ZIP/Postal Code
75010
Country
France
Facility Name
Hématologie Adultes - Hôpital Necker
City
Paris
ZIP/Postal Code
75743
Country
France
Facility Name
Service d'Hématologie - Centre Hospitalier Lyon-Sud
City
Pierre-Bénite cedex
ZIP/Postal Code
69495
Country
France
Facility Name
Centre Hospitalier Robert Debré
City
Reims
ZIP/Postal Code
51092
Country
France
Facility Name
Centre Henri Becquerel
City
Rouen
ZIP/Postal Code
76038
Country
France
Facility Name
Hématologie CHU Purpan
City
Toulouse
ZIP/Postal Code
31059
Country
France
Facility Name
Institut Gustave Roussy
City
Villejuif
Country
France

12. IPD Sharing Statement

Citations:
PubMed Identifier
12920037
Citation
Tilly H, Lepage E, Coiffier B, Blanc M, Herbrecht R, Bosly A, Attal M, Fillet G, Guettier C, Molina TJ, Gisselbrecht C, Reyes F; Groupe d'Etude des Lymphomes de l'Adulte. Intensive conventional chemotherapy (ACVBP regimen) compared with standard CHOP for poor-prognosis aggressive non-Hodgkin lymphoma. Blood. 2003 Dec 15;102(13):4284-9. doi: 10.1182/blood-2003-02-0542. Epub 2003 Aug 14.
Results Reference
background
PubMed Identifier
15867204
Citation
Feugier P, Van Hoof A, Sebban C, Solal-Celigny P, Bouabdallah R, Ferme C, Christian B, Lepage E, Tilly H, Morschhauser F, Gaulard P, Salles G, Bosly A, Gisselbrecht C, Reyes F, Coiffier B. Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol. 2005 Jun 20;23(18):4117-26. doi: 10.1200/JCO.2005.09.131. Epub 2005 May 2.
Results Reference
background
PubMed Identifier
12100150
Citation
Dumontet C, Mounier N, Munck JN, Bosly A, Morschauser F, Simon D, Marit G, Casasnovas O, Reman O, Molina T, Reyes F, Coiffier B. Factors predictive of early death in patients receiving high-dose CHOP (ACVB regimen) for aggressive non-Hodgkin's lymphoma: a GELA study. Br J Haematol. 2002 Jul;118(1):210-7. doi: 10.1046/j.1365-2141.2002.03565.x.
Results Reference
background
PubMed Identifier
27282998
Citation
Ghesquieres H, Larrabee BR, Haioun C, Link BK, Verney A, Slager SL, Ketterer N, Ansell SM, Delarue R, Maurer MJ, Fitoussi O, Habermann TM, Peyrade F, Dogan A, Molina TJ, Novak AJ, Tilly H, Cerhan JR, Salles G. FCGR3A/2A polymorphisms and diffuse large B-cell lymphoma outcome treated with immunochemotherapy: a meta-analysis on 1134 patients from two prospective cohorts. Hematol Oncol. 2017 Dec;35(4):447-455. doi: 10.1002/hon.2305. Epub 2016 Jun 10.
Results Reference
derived
PubMed Identifier
26373676
Citation
Copie-Bergman C, Cuilliere-Dartigues P, Baia M, Briere J, Delarue R, Canioni D, Salles G, Parrens M, Belhadj K, Fabiani B, Recher C, Petrella T, Ketterer N, Peyrade F, Haioun C, Nagel I, Siebert R, Jardin F, Leroy K, Jais JP, Tilly H, Molina TJ, Gaulard P. MYC-IG rearrangements are negative predictors of survival in DLBCL patients treated with immunochemotherapy: a GELA/LYSA study. Blood. 2015 Nov 26;126(22):2466-74. doi: 10.1182/blood-2015-05-647602. Epub 2015 Sep 15.
Results Reference
derived
PubMed Identifier
25385729
Citation
Molina TJ, Canioni D, Copie-Bergman C, Recher C, Briere J, Haioun C, Berger F, Ferme C, Copin MC, Casasnovas O, Thieblemont C, Petrella T, Leroy K, Salles G, Fabiani B, Morschauser F, Mounier N, Coiffier B, Jardin F, Gaulard P, Jais JP, Tilly H. Young patients with non-germinal center B-cell-like diffuse large B-cell lymphoma benefit from intensified chemotherapy with ACVBP plus rituximab compared with CHOP plus rituximab: analysis of data from the Groupe d'Etudes des Lymphomes de l'Adulte/lymphoma study association phase III trial LNH 03-2B. J Clin Oncol. 2014 Dec 10;32(35):3996-4003. doi: 10.1200/JCO.2013.54.9493. Epub 2014 Nov 10.
Results Reference
derived
PubMed Identifier
22118442
Citation
Recher C, Coiffier B, Haioun C, Molina TJ, Ferme C, Casasnovas O, Thieblemont C, Bosly A, Laurent G, Morschhauser F, Ghesquieres H, Jardin F, Bologna S, Fruchart C, Corront B, Gabarre J, Bonnet C, Janvier M, Canioni D, Jais JP, Salles G, Tilly H; Groupe d'Etude des Lymphomes de l'Adulte. Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial. Lancet. 2011 Nov 26;378(9806):1858-67. doi: 10.1016/S0140-6736(11)61040-4.
Results Reference
derived

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ACVBP Plus Rituximab Versus CHOP Plus Rituximab in Patients With Diffuse Large B-cell Lymphoma and Age-adjusted IPI of 1

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