A Trial Looking at Rituximab and Chemotherapy as a Treatment for Follicular Lymphoma in Elderly Patients

Inclusion Criteria: * Histologically confirmed follicular lymphoma (grade 1,2, and 3a with material available for central review) * Ann Arbor stage II-IV * Aged 60 years or over, or aged less than 60 but anthracycline-based therapy contra-indicated * No prior systemic therapy (one episode of prior local radiotherapy is allowed) * At least one of the following criteria for initiation of treatment: * Rapid generalized disease progression in the preceding 3 months * Life threatening organ involvement * Renal or macroscopic liver infiltration * Bone lesions * Presence of systemic symptoms or pruritus * Haemoglobin \< 10 g/dL or WBC \< 3.0 × 109/L or platelet counts \< 100 × 109/L due to marrow involvement * Adequate haematological function (unless abnormalities are related to lymphoma infiltration of the bone marrow): * Haemoglobin ≥ 8.0 g/dL * Absolute neutrophil count (ANC) ≥ 1.5 x 109/L * Platelet count ≥ 100 x 109/L * Written Informed Consent Exclusion Criteria: * Overt transformation to diffuse large B-cell lymphoma * Grade 3b follicular lymphoma * Presence or history of CNS disease (either CNS lymphoma or lymphomatous meningitis) * WHO performance status 3 or 4 * Impaired renal function defined as estimated Glomerular filtration rate (eGFR) \< 30 mL/min using the Modification of Diet in Renal Disease (MDRD) formula * Impaired hepatic function defined as serum bilirubin more than twice upper limit of normal (unless due to lymphoma or Gilbert's syndrome) * Life expectancy less than 12 months * Pre-existing neuropathy * Active auto-immune haemolytic anaemia * Serological evidence of infection with HIV, hepatitis B (positivity for surface antigen or core antibody) or hepatitis C * Allergy to murine proteins * Corticosteroid treatment during the last 4 weeks, unless administered at a dose equivalent to no more than prednisolone 20mg/day continuously or a single course of prednisolone 1 mg/kg for up to 7 days * Concomitant malignancies except adequately treated localised non-melanoma skin cancer or adequately treated in situ cervical cancer, or cancers that have been in remission for at least 5 years following surgery with curative intent. * Major surgery (excluding lymph node biopsy) within 28 days prior to randomisation * Serious underlying medical conditions, which could impair the ability of the patient to participate in the trial (e.g. ongoing infection, uncontrolled diabetes mellitus, gastric ulcers, active autoimmune disease) * Treatment within a clinical trial within 30 days prior to trial entry * Any other co-existing medical or psychological condition that will preclude participation in the study or compromise ability to give informed consent * Adult patient under tutelage (not competent to sign informed consent) * Pregnant or lactating women * All men or women of reproductive potential, unless using at least two contraceptive precautions, one of which must be a condom