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