Relapsed Follicular Lymphoma Randomised Trial Against Standard ChemoTherapy (REFRACT)

Inclusion Criteria: Biopsy proven relapsed or refractory CD20 positive, grade 1-3a follicular lymphoma (biopsy within 3 months of trial entry) Aged 18 years or over Advanced disease that in the opinion of the treating physician requires treatment Patient suitable for standard available therapy at the Investigator's discretion Prior therapy with at least one line of immunochemotherapy. Previous radiotherapy at any time is permitted and will not count as a line of therapy. Previous rituximab monotherapy is also permitted as long as patients have at any time also received at least one line of immunochemotherapy Assessable disease by PET-CT (at least one involved node with long diameter >1.5cm, or extranodal lesion >1cm ) ECOG performance status of 0, 1 or 2 at trial entry Adequate organ function defined as; i. ANC ≥ 1.0 x 109/L (growth factor use is permitted) ii. Platelet count ≥ 75 x 109/L, or ≥ 50 x 109/L if bone marrow infiltration or splenomegaly iii. ALT and AST level ≤3 x ULN iv. Direct bilirubin level ≤ 2 x ULN, unless due to Gilbert's syndrome v. CrCl ≥ 50mL/min (by Cockcroft-Gault formula) vi. PT, INR and aPTT ≤ 1.5 x ULN, unless receiving anticoagulation vii. LVEF within normal limits by MUGA or echocardiography Able to provide written informed consent Women of childbearing potential (or their partners) must use an effective form of contraception Exclusion Criteria: Current (or within 1 year) transformation to high grade lymphoma, including grade 3b follicular lymphoma (patients with historical high-grade transformation over 1 year ago are eligible) Non-Fluorodeoxyglucose (FDG) avid disease Prior allogenic stem cell transplantation (SCT) or solid organ transplant Prior treatment with lenalidomide Treatment with CAR-T therapy within 100 days of starting trial treatment SCT or maintenance therapy planned within 24 weeks of starting treatment (patients planning SCT/maintenance after at least 24 weeks of treatment are eligible) Immunochemotherapy with a platinum-containing regimen planned Known serological positivity for HIV or uncontrolled HCV Hepatitis B surface antigen (HBsAg) positive and/or detectable viral DNA. Patients positive for Hepatitis B core antibody (anti-HBc) but viral DNA negative are eligible Other malignancy within 2 years of enrolment, excepting cervical carcinoma stage 1B or less, non-invasive basal cell or squamous cell skin carcinoma, non-invasive, superficial bladder cancer, prostate cancer with a current PSA level <0.1ng/mL, any curable cancer with a CR of > 2 years duration Active systemic infection requiring treatment Current or prior CNS involvement with lymphoma History of allergy or anaphylaxis to anti-CD20 monoclonal antibody therapy Known hypersensitivity to any of the experimental arm IMPs. Patients with a known hypersensitivity to a control arm regimen may still be eligible if they have no hypersensitivity to other potential control arm IMPs. Serious medical or psychiatric illness likely to interfere with participation in this clinical study Recent cancer treatment (chemotherapy, immunotherapy, biological therapy) within 4 weeks of starting trial treatment; systemic steroid treatment (prednisolone > 10mg daily (or equivalent)) within 7 days of cycle 1 day 1 dosing Unwilling to use appropriate contraception methods whilst on study treatment and for 12 months following end of treatment (or 18 months for female patients whose ICT regimen contains obinutuzumab) Women who are pregnant or breastfeeding Prior treatment with the experimental therapy under investigation Major surgery within 30 days of starting treatment Severe arrhythmias, heart failure, previous myocardial infarction, acute inflammatory heart disease for ICT regimen containing doxorubicin, or severe heart failure (New York Heart Association Class IV) or severe, uncontrolled cardiac disease for ICT regimen containing rituximab