Study of RTXM83 Plus CHOP Chemotherapy Versus a Rituximab Plus CHOP Therapy in Patients With Non Hodgkin's Lymphoma

Inclusion Criteria:

1. Patients with measurable disease defined as existence of a unidimensional orbidimensional lesion greater than 2 cm in its longest diameter or malignantlymphocytosis greater than 5x109/L. Any other procedure for measurable disease inparticular cases, may be allowed upon Sponsor approval

2. Newly diagnosed patients with a confirmed pathologic diagnosis of Diffuse large Bcell-non-Hodgkin's lymphoma (DLBCL) with untreated CD20+ receptor (CD20+). Defined bythe local Haematopathologist at the local laboratory according to World HealthOrganization (WHO) criteria

3. Stage II-III or IV or stage I with bulk defined by the referring physician on thebasis of the Cotswolds modification of the Ann Arbor classification 2

4. Age-adjusted International Prognostic Index (IPI) score 0 or 1

5. Age ≥18 to ≤65 years of age

6. Performance status according to Eastern Cooperative Oncology Group (ECOG) of ≤2

7. Written informed consent obtained before starting any study-specific procedure

8. Females of child-bearing potential must test negative on standard serum pregnancy testand must be willing to practice appropriate contraceptive methods for the duration ofthe study (e.g. oral contraceptive, double barrier method, intra-uterine device,intra-muscular contraceptive)

9. All male patients must take adequate contraceptive precautions during the course ofthe study

Exclusion Criteria:

1. Life expectancy of less than three months

2. Any other lymphoma other than CD20+ DLBCL

3. Indolent lymphoma, Primary central nervous system (CNS) Lymphoma or gastro-intestinalMucosa Associated Lymphoid Tissue (MALT) Lymphoma

4. Known hypersensitivity to active ingredients, excipients and murine and foreignproteins

5. Concurrent disease or general status that would exclude giving the treatment asoutlined in the protocol

6. Active uncontrolled infection requiring systemic treatment with antibiotics orantiviral agents at Screening or history of documented recurrent clinicallysignificant infection (e.g. 2 or more viral, bacterial or fungal infections requiringinpatient treatment)

7. Cardiac contra-indication to Doxorubicin therapy: non-compensated heart failure,dilated cardiomyopathy, coronary heart disease with ST segment depression onelectrocardiogram (ECG), myocardial infarction in the last 6 months

8. Neurologic contra-indication to Vincristine as it is indicated in the Summary ofProduct Characteristics (SmPC): (e.g. peripheral neuropathy)

9. Chronic lung disease with hypoxemia measured by pulse oximetry (gasometry is notmandatory)

10. Severe uncontrolled hypertension, despite optimal medical treatment

11. Severe uncontrolled diabetes mellitus, despite optimal medical treatment

12. Renal insufficiency (Serum Creatinine >2 x Upper Normal Limit [UNL])

13. Hepatic insufficiency: aspartate aminotransferase (AST)/ alanine aminotransferase (ALT)>3 x UNL or >5 x UNL with involvement of the liver, total bilirubin >34.2 µmol/L,or both) not related to lymphoma

14. Clinical signs of cerebral dysfunction

15. Severe psychiatric disease

16. Known human immunodeficiency virus (HIV) infection or active chronic hepatitis B or C

17. Abnormal bone marrow function (platelets <100x109/L, neutrophils <1.5x109/L andHaemoglobin <9g/dL)

18. Post-transplantation lymphoproliferative disease

19. Pregnant or lactating women or women that intend to get pregnant during study orwithin 12 months following the last infusion

20. Treatment with any investigational product in the 30 days period before inclusion inthe study

21. Prior radiotherapy to treat the DLBCL Non-Hodgkin's Lymphoma (NHL)

22. Limitation of the patient's ability to comply with the treatment or follow-up protocol