ACVBP Plus Rituximab in Patients Aged From 18 to 59 Years With High-risk Diffuse Large B-cell Lymphoma

NCT ID: NCT00144807

Last Updated: 2015-09-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

128 participants

Study Classification

INTERVENTIONAL

Study Start Date

2003-12-31

Study Completion Date

2012-04-30

Brief Summary

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This study is a multicentric trial evaluating the efficacy of R-ACVBP in patients aged 18 to 59 years with high risk diffuse large B-cell lymphoma

Detailed Description

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This phase II non randomized study is based on the results of the LNH 98-5, LNH 87-2, LNH 93-3 and LNH 98-3B studies.

To date, the ACVBP regimen is considered as the reference induction treatment of the GELA in patients with 2-3 adverse prognostic factors. Indeed neither NCVBP regimen (LNH87-2) nor ECVBP (LNH93-3) led to increase the complete remission rate. More recently, the addition of etoposide to doxorubicin and cyclophosphamide (LNH98-3B) did not enhanced the complete remission rate with more toxicity. In patients \< 60 years with 2-3 adverse prognostic factors the complete remission rate remained less than 65% in all these studies. Consequently, increasing the quality of response remains a major goal in this group of young patients with adverse prognostic factors.

It has been shown that the addition of rituximab to CHOP regimen significantly improved the CR rate in elderly patients with previously untreated large B-cell lymphoma when compared with CHOP alone without additional toxicities. Moreover, event-free survival and overall survival were found to be longer in the R-CHOP group. The present trial will evaluate the response rate obtained after four cycles of ACVBP combined to rituximab (R-ACVBP) before high dose therapy consolidative treatment in this group of higher risk patients.

The LNH87-2 study has shown that intensive consolidation treatment with autologous stem cell support was beneficial to high risk patients in good response after a full induction phase. The long-term results of this randomised study prompted us to consider high dose therapy as the best consolidative option for these patients.

Conditions

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Diffuse Large Cell Lymphoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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R-AC

rituximab + doxorubicin + cyclophosphamide + autologous stem cell transplantation

Group Type EXPERIMENTAL

rituximab

Intervention Type DRUG

doxorubicin

Intervention Type DRUG

cyclophosphamide

Intervention Type DRUG

autologous stem cell transplantation

Intervention Type PROCEDURE

Interventions

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rituximab

Intervention Type DRUG

doxorubicin

Intervention Type DRUG

cyclophosphamide

Intervention Type DRUG

autologous stem cell transplantation

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

Patient with histologically proven CD20+ diffuse large B-cell lymphoma (WHO classification).

Age from 18 to 59 years, eligible for transplant. Patient not previously treated. Age adjusted IPI = 2 or 3 With a minimum life expectancy of 3 months Negative HIV, HBV and HCV serologies \< 4 weeks (except after vaccination). Having signed a written informed consent.

Exclusion Criteria

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. Poor renal function (creatinin level \>150 mmol/l), poor hepatic function (total bilirubin level \>30 mmol/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.

Any serious active disease (according to the investigator's decision). 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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

59 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Lymphoma Study Association

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Olivier Fitoussi, MD

Role: PRINCIPAL_INVESTIGATOR

Lymphoma Study Association

Christian Gisselbrecht, MD

Role: STUDY_DIRECTOR

Lymphoma Study Association

Corinne Haioun, MD

Role: STUDY_CHAIR

Lymphoma Study Association

Hervé Tilly, MD

Role: STUDY_CHAIR

Lymphoma Study Association

Locations

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Groupe d'Etude des Lymphomes de l'adulte

Mont-Godinne, , Belgium

Site Status

Polyclinique Bordeaux Nord

Bordeaux, , France

Site Status

Hôpital Henri Mondor

Créteil, , France

Site Status

Hématologie CHU de Lille

Lille, , France

Site Status

Centre Léon Bérard

Lyon, , France

Site Status

Hôpital Saint Louis

Paris, , France

Site Status

Hématologie Adultes - Hôpital Necker

Paris, , France

Site Status

Service d'Hématologie - Centre Hospitalier Lyon-Sud

Pierre-Bénite, , France

Site Status

Centre Hospitalier Robert Debré

Reims, , France

Site Status

Centre Henri Becquerel

Rouen, , France

Site Status

Hématologie CHU Purpan

Toulouse, , France

Site Status

Institut Gustave Roussy

Villejuif, , France

Site Status

Schweirische Arbeitsgruppe fur klinische Krebsforschung

Lausanne, , Switzerland

Site Status

Countries

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Belgium France Switzerland

References

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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.

Reference Type BACKGROUND
PMID: 15867204 (View on PubMed)

Haioun C, Lepage E, Gisselbrecht C, Salles G, Coiffier B, Brice P, Bosly A, Morel P, Nouvel C, Tilly H, Lederlin P, Sebban C, Briere J, Gaulard P, Reyes F. Survival benefit of high-dose therapy in poor-risk aggressive non-Hodgkin's lymphoma: final analysis of the prospective LNH87-2 protocol--a groupe d'Etude des lymphomes de l'Adulte study. J Clin Oncol. 2000 Aug;18(16):3025-30. doi: 10.1200/JCO.2000.18.16.3025.

Reference Type BACKGROUND
PMID: 10944137 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12920037 (View on PubMed)

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.

Reference Type DERIVED
PMID: 27282998 (View on PubMed)

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.

Reference Type DERIVED
PMID: 26373676 (View on PubMed)

Fitoussi O, Belhadj K, Mounier N, Parrens M, Tilly H, Salles G, Feugier P, Ferme C, Ysebaert L, Gabarre J, Herbrecht R, Janvier M, Van Den Neste E, Morschhauser F, Casasnovas O, Ghesquieres H, Anglaret B, Brechignac S, Haioun C, Gisselbrecht C. Survival impact of rituximab combined with ACVBP and upfront consolidation autotransplantation in high-risk diffuse large B-cell lymphoma for GELA. Haematologica. 2011 Aug;96(8):1136-43. doi: 10.3324/haematol.2010.038109. Epub 2011 May 5.

Reference Type DERIVED
PMID: 21546499 (View on PubMed)

Related Links

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http://www.gela.org

Official site of the Groupe d'Etudes des Lymphomes de l'Adulte (In french)

Other Identifiers

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LNH03-3B

Identifier Type: -

Identifier Source: org_study_id

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