ACVBP Plus Rituximab Versus CHOP Plus Rituximab in Patients With Diffuse Large B-Cell Lymphoma and Age-Adjusted IPI of 1 - Full Text View

Sponsored by:	Groupe d'Etudes de Lymphomes de L'Adulte
Information provided by:	Groupe d'Etudes de Lymphomes de L'Adulte
ClinicalTrials.gov Identifier:	NCT00140595

Purpose

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).

Condition	Intervention	Phase
Diffuse Large-Cell Lymphoma	Drug: rituximab Drug: doxorubicin Drug: cyclophosphamide	Phase III

MedlinePlus related topics: Lymphoma

Drug Information available for: Doxorubicin Doxorubicin hydrochloride Cyclophosphamide Rituximab

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
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.

Further study details as provided by Groupe d'Etudes de Lymphomes de L'Adulte:

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

Estimated Enrollment:	380
Study Start Date:	December 2003
Estimated Study Completion Date:	December 2008

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

Eligibility

Ages Eligible for Study:	18 Years to 59 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00140595

Contacts

Contact: Christian Recher, MD	+33561772078	recher.c@chu-toulouse.fr
Contact: Hervé Tilly, MD	+33232082223	herve.tilly@gela.org

Locations

Belgium
Groupe d'étude des lymphomes de l'adulte	Recruiting
Yvoir, Belgium
Contact: André Bosly, MD
France
Hématologie CHU Purpan	Recruiting
Toulouse, France, 31059
Contact: Christian Recher, MD
Principal Investigator: Christian Recher, MD
Sub-Investigator: Guy Laurent, MD
Centre Henri Becquerel	Recruiting
Rouen, France, 76038
Contact: Herve Tilly, MD 33232082221 herve.tilly@gela.org
Principal Investigator: Herve Tilly, MD
Sub-Investigator: Aspasia Stamatoullas, MD
Sub-Investigator: Stephane Lepretre, MD
Sub-Investigator: Fabrice Jardin, MD
Sub-Investigator: Pascal Lenain, MD
Sub-Investigator: Nathalie Contentin, MD
Centre Hospitalier Robert Debré	Recruiting
Reims, France, 51092
Contact: Alain Delmer, MD
Principal Investigator: Alain Delmer, MD
Centre Léon Bérard	Recruiting
Lyon, France, 69008
Contact: Catherine Sebban, MD
Principal Investigator: Catherine Sebban, MD
Hématologie Adultes - Hôpital Necker	Recruiting
Paris, France, 75743
Contact: Richard Delarue, MD +33144495462 richard.delarue@nck.ap-hop-paris.fr
Principal Investigator: Richard Delarue, MD
Sub-Investigator: Olivier Hermine, MD
Sub-Investigator: Bruno Varet, MD
Hôpital Saint Louis	Recruiting
Paris, France, 75010
Contact: Christian Gisselbrecht, MD +33142499296 gela@chu-stlouis.fr
Principal Investigator: Christian Gisselbrecht, MD
Sub-Investigator: Pauline Brice, MD
Sub-Investigator: Nicolas Mounier, MD
Institut Gustave Roussy	Recruiting
Villejuif, France
Contact: Vincent Ribrag, MD
Principal Investigator: Vincent Ribrag, MD
Service d'Hématologie - Centre Hospitalier Lyon-Sud	Recruiting
Pierre-Bénite cedex, France, 69495
Contact: Bertrand Coiffier, MD +33 478 86 43 00 bertrand.coiffier@chu-lyon.fr
Sub-Investigator: Gilles A Salles, MD PhD
Principal Investigator: Bertrand Coiffier, MD
Sub-Investigator: Catherine Thieblemont, MD
Sub-Investigator: Catherine Traullé, MD
Sub-Investigator: Daniel Espinouse, MD
Hôpital Henri Mondor	Recruiting
Créteil, France, 94010
Contact: Felix Reyes, MD +33149812051 felix.reyes@hmn.ap-hop-paris.fr
Contact: Corinne Haioun, MD +33149812051 corinne.haioun@hmn.ap-hop-paris.fr
Sub-Investigator: Felix Reyes
Principal Investigator: Corinne Haioun
Sub-Investigator: Karim Belhadj

Sponsors and Collaborators

Groupe d'Etudes de Lymphomes de L'Adulte

Investigators

Principal Investigator:	Christian Recher, MD	Groupe d'Etudes de Lymphomes de L'Adulte
Study Chair:	Hervé Tilly, MD	Groupe d'Etudes de Lymphomes de L'Adulte
Study Chair:	Corinne Haioun, MD	Groupe d'Etudes de Lymphomes de L'Adulte

More Information

Publications:

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. Epub 2003 Aug 14.

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. Epub 2005 May 2.

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.

Study ID Numbers:	LNH03-2B
Study First Received:	August 31, 2005
Last Updated:	July 2, 2007
ClinicalTrials.gov Identifier:	NCT00140595
Health Authority:	France: Afssaps - French Health Products Safety Agency

Keywords provided by Groupe d'Etudes de Lymphomes de L'Adulte:

Lymphoma, diffuse large B-cell
rituximab
chemotherapy

Study placed in the following topic categories:

Lymphoma, large-cell
Lymphoma, B-Cell
Lymphatic Diseases
Lymphoma, Large B-Cell, Diffuse
Immunoproliferative Disorders
Rituximab

B-cell lymphomas
Cyclophosphamide
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Lymphoma
Doxorubicin

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Immune System Diseases
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Immunosuppressive Agents

Pharmacologic Actions
Neoplasms
Therapeutic Uses
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Alkylating Agents

ClinicalTrials.gov processed this record on January 13, 2009