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

Diffuse Large-Cell Lymphoma Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00140595
• Other study ID #: LNH03-2B
• Status: Completed
• Phase: Phase 3
• First received: August 31, 2005
• Last updated: March 3, 2011
• Start date: December 2003
• Est. completion date: January 2009

Study information

• Verified date: March 2011
• Source: Lymphoma Study Association
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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).

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 380
• Est. completion date: January 2009
• Est. primary completion date: January 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 59 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diffuse Large-Cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• rituximab

• doxorubicin

• cyclophosphamide

Locations

Country	Name	City	State
Belgium	Groupe d'étude des lymphomes de l'adulte	Yvoir
France	Hôpital Henri Mondor	Créteil
France	Centre Léon Bérard	Lyon
France	Hématologie Adultes - Hôpital Necker	Paris
France	Hôpital Saint Louis	Paris
France	Service d'Hématologie - Centre Hospitalier Lyon-Sud	Pierre-Bénite cedex
France	Centre Hospitalier Robert Debré	Reims
France	Centre Henri Becquerel	Rouen
France	Hématologie CHU Purpan	Toulouse
France	Institut Gustave Roussy	Villejuif

Sponsors (2)

Lead Sponsor	Collaborator
Lymphoma Study Association	Amgen

Countries where clinical trial is conducted

Belgium,  France, 

References & Publications (3)

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. — View Citation

Feugier P, Van Hoof A, Sebban C, Solal-Celigny P, Bouabdallah R, Fermé 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. — View 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. Epub 2003 Aug 14. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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