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

Study Overview
=================
Brief 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

Detailed 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.

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)

Conditions
-----------------
Diffuse Large Cell Lymphoma

Intervention / Treatment
-----------------
* Drug: rituximab
* Drug: doxorubicin
* Drug: cyclophosphamide
* Procedure: autologous stem cell transplantation


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 59 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: R-AC<br>rituximab + doxorubicin + cyclophosphamide + autologous stem cell transplantation | Drug: rituximab<br> <br> Drug: doxorubicin<br> <br> Drug: cyclophosphamide<br> <br> Procedure: autologous stem cell transplantation<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete remission rate (CR + CRu) | 4 cycles of ACVBP | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event-free survival and overall survival of patients submitted to autologous transplant and of the entire study population |  | 3 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
rituximab, lymphoma, diffuse large B-cell, chemotherapy, autologous stem cell transplant