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

Diffuse Large Cell Lymphoma Clinical Trial

Official title:

Study of ACVBP Plus Rituximab in Previously Untreated Patients Aged From 18 to 59 Years With High Risk Diffuse Large B-cell Lymphoma (Age-adjusted IPI = 2-3)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00144807
• Other study ID #: LNH03-3B
• Status: Completed
• Phase: Phase 2
• First received: September 2, 2005
• Last updated: September 1, 2015
• Start date: December 2003
• Est. completion date: April 2012

Study information

• Verified date: September 2015
• 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 trial evaluating the efficacy of R-ACVBP in patients aged 18 to 59 years with high risk diffuse large B-cell lymphoma

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 128
• Est. completion date: April 2012
• Est. primary completion date: September 2008
• 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).

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group 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

Procedure:
• autologous stem cell transplantation

Locations

Country	Name	City	State
Belgium	Groupe d'Etude des Lymphomes de l'adulte	Mont-Godinne
France	Polyclinique Bordeaux Nord	Bordeaux
France	Hôpital Henri Mondor	Créteil
France	Hématologie CHU de Lille	Lille
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
Switzerland	Schweirische Arbeitsgruppe fur klinische Krebsforschung	Lausanne

Sponsors (1)

Lead Sponsor	Collaborator
Lymphoma Study Association

Countries where clinical trial is conducted

Belgium,  France,  Switzerland, 

References & Publications (3)

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

Haioun C, Lepage E, Gisselbrecht C, Salles G, Coiffier B, Brice P, Bosly A, Morel P, Nouvel C, Tilly H, Lederlin P, Sebban C, Brière 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. — 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	Complete remission rate (CR + CRu)	4 cycles of ACVBP	12 weeks	No
Secondary	Event-free survival and overall survival of patients submitted to autologous transplant and of the entire study population		3 years	Yes

External Links

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