Phase II Study to Evaluate the Combination of Rituximab and DepoCyte® in the C5R Chemotherapy Protocol in Patients Between the Ages of 18 and 60 Years With Primary Cerebral Non-Hodgkin Lymphoma and Systemic Diffuse Large B-cell Lymphoma With Neuromeningeal Invasion at Diagnosis

Prospective Multicentre Phase II Study to Evaluate the Combination of Rituximab and DepoCyte® by Intrathecal Injection in the C5R Chemotherapy Protocol in Patients Between the Ages of 18 and 60 Years With Primary Cerebral Non-Hodgkin Lymphoma and Systemic Diffuse Large B-cell Lymphoma With Neuromeningeal Invasion at Diagnosis

The purpose of this study is to measure the rate of complete response (CR and UCR) at the end of a course of immuno-chemotherapy:

• before cerebral radiotherapy for PCL
• after the course of immuno-chemotherapy for aggressive lymphomas with neuromeningeal involvement Toxicity of the protocol Overall survival Survival without relapse Long-term incidence of neurocognitive toxicity

Inclusion Criteria:

• Primary cerebral or oculocerebral NHL not previously treated with chemotherapy or radiotherapy and diffuse large B-cell lymphomas, with cerebral and / or neuromeningeal involvement at diagnosis.
• Diagnosis proved by histological or cytological examination of cerebral specimens, CSF or vitreous humour.
• Diffuse large cell CD20+ lymphoma.
• Men or women between the ages of 18 and 60 years.
• Presence of a measurable target to evaluate response.
• Negative serological tests for HIV, hepatitis B (except in cases of vaccination), hepatitis C.
• Life-expectancy ≥ 3 months
• Patient having given written consent to participate in this study.

Exclusion Criteria:

• CD20- lymphoma.
• History of indolent lymphoma, treated or untreated.
• Contraindication for one of the products used in polychemotherapy.
• Known hypersensitivity to mouse antibodies.
• Absence of measurable target to evaluate response.
• History of cancer in the 5 years prior to inclusion except for cutaneous basocellular carcinomas and non-invasive carcinomas of the neck of the uterus.
• Cardiac contraindication to treatment with anthracyclines or to hyperhydration:

SEVERE DISTURBANCE OF HEART RHYTHM VENTRICULAR EJECTION FRACTION BELOW 50% HISTORY OF RECENT MYOCARDIAL INFARCTION

• Previously known severe renal insufficiency and/or creatinaemia >150 µM/L (apart from invasion of the kidneys by the lymphoma).
• Total bilirubin >30 µmol/L, ASAT, ALAT >2.5 times the upper normal value (apart from invasion of the liver by the lymphoma).
• Insufficient medullary reserve: PNL < 1 G/L and platelets <100 G/L (apart from invasion of the medulla by the lymphoma).
• History of organ transplantation or other causes of severe immunosuppression.
• Pregnant woman.
• Patient incapable of keeping to regular monitoring.