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

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