Inclusion Criteria

Inclusion criteria for registration:

- 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

- Bulky Stage IA (lymph node or lymph node mass ≥ 10cm in maximum diameter), stage IB,
stage II, stage III and stage IV disease

- Measurable disease

- Age 18 ≥ years

- Adequate contraceptive precautions for all patients of childbearing potential

- No active malignant disease other than non-melanotic skin cancer or carcinoma in-situ
of the uterine cervix in the last 5 years

- 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 registration 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
registration 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

Inclusion Criteria for randomisation:-

- ECOG performance status 0-2 after steroid pre-phase

- Continue to meet all inclusion criteria detailed in inclusion registration section.

Exclusion criteria for registration:

- Symptomatic central nervous system or meningeal involvement by DLBCL

- Previous diagnosis of low grade lymphoma. A concurrent (synchronous) diagnosis of low
grade lymphoma (e.g. on bone marrow trephine) is permitted

- Non-bulky stage IA disease

- History of chronic liver disease or suspected alcohol abuse

- Serum bilirubin greater than upper limit of normal unless attributable to lymphoma or
Gilberts syndrome

- Glomerular filtration rate (GFR) < 30ml/min. GFR calculated by Cockroft-Gault (not
eGFR).

- Positive test results for chronic hepatitis B or C infection (defined as positive
HBsAg/HCsAg and/or HBcAb/HCcAb). Antibodies to Hepatitis B surface antigen (anti-HBs)
due to a history of past vaccination is acceptable

- Known history of HIV seropositive status

- 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

Exclusion criteria for randomisation:-

- ECOG performance status 3 or 4 after steroid pre-phase

- Meets one or more of the exclusion criteria detailed in exclusion registration
section.