R-ACVBP Versus R-CHOP in Patients Aged 60-65 With Diffuse Large B-cell Lymphoma

NCT ID: NCT00135499

Last Updated: 2018-08-23

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

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

138 participants

Study Classification

INTERVENTIONAL

Study Start Date

2001-10-16

Study Completion Date

2010-04-27

Brief Summary

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The primary objective of this study is to evaluate the efficacy of doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone (ACVBP) plus rituximab in comparison to cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) plus rituximab in patients aged from 60 to 65 years with non-previously treated diffuse large B-cell lymphoma as measured by the event-free survival. The goal is to obtain a 10% increase of event-free survival at 3 years.

Detailed Description

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In Europe, 50% or more of new non-Hodgkin lymphoma cases occur in patients older than 60 years. More than 30% are diffuse large B-cell lymphomas (DLCL).

The CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisone) was considered as the standard treatment in this population. Nevertheless, this treatment is associated with some toxic events in elderly patients and it did does not succeed to increase the 3-year survival rate above 40%.

Two trials in patients above 60 years with DLCL cases were conducted by the GELA in the aim to improve the results of CHOP.

Protocol LNH 93-5 : The primary objective of this study was to compare CHOP to ACVBP in patients aged from 61 to 69 years with aggressive lymphoma and at least one adverse prognostic factor according to the International Prognostic Index.

Unlike the CHOP regimen, the ACVBP regimen includes a more intensive induction followed by a sequential consolidation with drugs different from those used during the induction phase, and includes a prevention of neuromeningeal relapses.

Out of 708 patients included in this study, the results have shown that:

* Complete response rate was the same in the two arms.
* Event free survival was significantly better in the ACVBP arm than the CHOP arm ( 5-year survival rate : 39% versus 29%, p=0.005).
* Overall survival was significantly better in the ACVBP arm than in the CHOP arm (the 5-year survival rate : 46% versus 38%, p=0.036).
* The ACVBP regimen was more toxic than the CHOP regimen, particularly in elderly patients (\> 65 years) and in patients with a low performance status.
* Prevention of neuromeningeal relapses was necessary for these patients.

Protocol LNH 98-5, the objective of this study was to compare the association CHOP + rituximab (R-CHOP) to the CHOP regimen alone in elderly patients with non previously treated diffuse large B-cell lymphoma.

Long-term results based on data from 399 patients, with a median follow-up of 5 years were as follows :

* Complete response rate was better in the R-CHOP arm than in the CHOP arm (76% versus 61%, p\<0.005).
* Significant prolongation of event-free survival (p\<0.0002) and overall survival (p\<0.0073) in the R-CHOP arm.
* No significant difference between the two arms in terms of toxicity. R-CHOP is now considered worldwide as the standard combination for these patients.

These conclusions invited us to propose a randomized trial comparing ACVBP + rituximab to CHOP + rituximab. The study population is limited to patients aged from 60 to 65 years.

Conditions

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Lymphoma, Large-Cell, Diffuse

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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R-ACVBP

Rituximab, Doxorubicin, Cyclophosphamide, Vindesine, Bleomycin, Prednisone

Group Type EXPERIMENTAL

Rituximab

Intervention Type DRUG

375 mg/m², D1, 4 cycles

Doxorubicin

Intervention Type DRUG

75 mg/m², D1, 4 cycles

Cyclophosphamide

Intervention Type DRUG

1200 mg/m², D1, 4 cycles

Vindesine

Intervention Type DRUG

2 mg/m², D1, D5, 4 cycles

Bleomycin

Intervention Type DRUG

10 mg, D1, D5, 4 cycles

Prednisone

Intervention Type DRUG

60 mg, D1-D5, 4 cycles

R-CHOP

Rituximab, Doxorubicin, Cyclophosphamide, Vincristine, Prednisone

Group Type ACTIVE_COMPARATOR

Rituximab

Intervention Type DRUG

375 mg/m², D1, 4 cycles

Prednisone

Intervention Type DRUG

40 mg, D1-D5, 4 cycles

Doxorubicin

Intervention Type DRUG

50 mg/m², D1, 4 cycles

Cyclophosphamide

Intervention Type DRUG

750 mg/m², D1, 4 cycles

Vincristine

Intervention Type DRUG

1.4 mg/m², D1, 4 cycles

Interventions

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Rituximab

375 mg/m², D1, 4 cycles

Intervention Type DRUG

Doxorubicin

75 mg/m², D1, 4 cycles

Intervention Type DRUG

Cyclophosphamide

1200 mg/m², D1, 4 cycles

Intervention Type DRUG

Vindesine

2 mg/m², D1, D5, 4 cycles

Intervention Type DRUG

Bleomycin

10 mg, D1, D5, 4 cycles

Intervention Type DRUG

Prednisone

60 mg, D1-D5, 4 cycles

Intervention Type DRUG

Prednisone

40 mg, D1-D5, 4 cycles

Intervention Type DRUG

Doxorubicin

50 mg/m², D1, 4 cycles

Intervention Type DRUG

Cyclophosphamide

750 mg/m², D1, 4 cycles

Intervention Type DRUG

Vincristine

1.4 mg/m², D1, 4 cycles

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Patient with diffuse large B-cell lymphoma according to the WHO classification (anti CD20 labeling)
* Aged from 60 to 65 years.
* Not previously treated.
* Ann Arbor stage II, III, IV.
* ECOG performance status 0 to 2.
* Minimum life expectancy of 3 months.
* Negative HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV) serologies test 4 weeks (except after vaccination).
* Having previously signed a written informed consent.

Exclusion Criteria

* T-cell 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 (creatinine level\>150micromol/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\<1.5G/l or platelets\<100G/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.
* Adult patient under tutelage.
Minimum Eligible Age

60 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Fondation ARC

OTHER

Sponsor Role collaborator

Lymphoma Study Association

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Herve Tilly, MD

Role: PRINCIPAL_INVESTIGATOR

Lymphoma Study Association

Locations

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Groupe d'Etude des Lymphomes de l'adulte

Yvoir, , Belgium

Site Status

Hôpital Henri Mondor

Créteil, , France

Site Status

Hôpital Saint Louis

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

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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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)

Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, Morel P, Van Den Neste E, Salles G, Gaulard P, Reyes F, Lederlin P, Gisselbrecht C. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002 Jan 24;346(4):235-42. doi: 10.1056/NEJMoa011795.

Reference Type BACKGROUND
PMID: 11807147 (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)

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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LNH01-5B

Identifier Type: -

Identifier Source: org_study_id

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