Treatment of Patients With Diffuse Large B Cell Lymphoma Who Are Not Suitable for Anthracycline Containing Chemotherapy

Inclusion criteria: * Informed written consent for the trial * Histologically proven diffuse large B cell lymphoma (DLBCL) according to the current World Health Organisation (WHO) classification including all morphological variants. The B cell nature of the proliferation must be verified by demonstration of CD20 positivity. A concurrent (synchronous) diagnosis of low grade lymphoma (e.g. on bone marrow trephine or presence of both low grade and DLBCL in a lymph node biopsy) or previous diagnosis of low grade lymphoma which hasn't been treated with a systemic therapy is permitted * Bulky Stage IA (lymph node or lymph node mass ≥ 10cm in maximum diameter), stage IB, stage II, stage III and stage IV disease * ECOG performance status 0-2 * Measurable disease * Age 18 ≥ years * Adequate contraceptive precautions for all patients of childbearing potential * History of malignant disease diagnosed at any time in the past with completed radical treatment and the risk of relapsing within the next 5 years is \<10%. Patients previously treated should be free of sequelae of treatment which would compromise the delivery of study drugs as compared with other eligible patients. * No previous chemotherapy, radiotherapy or other investigational drug for this indication - previous corticosteroids up to a dose equivalent to prednisolone 1mg/kg/day for up to 14 days are permitted prior to randomisation EITHER * Unsuitable for anthracycline-containing chemotherapy due to impaired cardiac function defined by an ejection fraction of ≤ 50% OR Left ventricle ejection fraction \> 50% but in the presence of significant co-morbidities (diabetes mellitus, hypertension or ischaemic heart disease) precluding anthracycline-containing chemotherapy as determined by treating physician. Co-morbidities must be documented on the randomisation form and CIRS score recorded * Adequate bone marrow function (Platelets \> 100x109/l, WBC \> 3.0x109/l, Neutrophils \> 1.5x109/l) at time of study entry unless attributed to bone marrow infiltration by DLBCL * Life expectancy \> 3 months Exclusion criteria: * Symptomatic central nervous system or meningeal involvement by DLBCL * Previous diagnosis of low grade lymphoma which has been treated with a systemic therapy * Non-bulky stage IA disease * ECOG performance status 3-4 * History of chronic liver disease or suspected alcohol abuse * Serum bilirubin greater than upper limit of normal unless attributable to Gilberts syndrome or haemolysis * Alanine and/or aspartate aminotransferase levels (ALT and/or AST) and alkaline phosphatase (ALP) greater than 2.5 times the upper limit of normal * Glomerular filtration rate (GFR) \< 30ml/min. GFR calculated by Cockroft-Gault (not eGFR). * Serological evidence of active hepatitis B or C infection whether acute or chronic (defined as positive anti-HCV serology; positive HBsAg). All positive HBcAb results should also be excluded on safety grounds regardless of HBsAg or HBV DNA status. Antibodies to Hepatitis B surface antigen (anti-HBs) due to a history of past vaccination is acceptable * Known history of HIV seropositive status * Patients with a history of Venoocclusive Disease (VOD) and Sinusoidal Obstructive Syndrome (SOS) * Patients with a screening of QTcF interval \>470msec * Medical or psychiatric conditions compromising the patient's ability to give informed consent * Women who are pregnant or lactating * LVEF \> 50% in the absence of significant co-morbidities that preclude anthracycline use * Patients with a history of severe allergic/anaphylactic reaction to any humanised monoclonal antibody * Patients with serious active infection