Treatment Of Newly-diagnosed Follicular Lymphoma With CELMoD Golcadomide, Rituximab +/​- Nivolumab. (TOP-FLOR)

• Drug: golcadomide
• Drug: Nivolumab 10 MG/ML
• Drug: Rituximab

Inclusion Criteria:

1. Age 18+ years.
2. Histologically proven CD20 positive Follicular non Hodgkin lymphoma (FL) grades 1-3A (i.e. classical follicular lymphoma according to the current World Health Organization classification).3
3. No previous chemotherapya cancer treatment that uses drugs to kill or slow the growth of cancer cells, while minimising damage to healthy cells, or other investigational drug for this indication apart from focal radiotherapy.
4. Stage II-IV disease (Ann Arbor criteria).
5. Eastern Collaborative Oncologythe study, diagnosis and treatment of cancer Group (ECOG) performance status 0 to 1 unless attributable to lymphoma, in which case patients of performance status 2 are also eligible.
6. Measurable FDG avid disease on baseline PET/CT scan.
7. Deemed to need treatment by treating investigator. Reasons for treatment can include, but are not limited to:

a. Any nodal or extranodal tumoura tissue mass that forms from groups of unhealthy cells massa growth of cells that come together to make a lump, may or may not be cancer >7cm AND/OR multiple extranodal disease sites b. Involvement of at least 3 sites each with diameter >3cm c. Symptomatic splenic enlargement d. Organ involvement/compression e. Ascitesa buildup of fluid in the abdomen or pleural effusionabnormal fluid build-up in the pleural space, which can cause chest pain and breathing difficulties f. Lactate Dehydrogenase (LDH) elevated g. Presence of systemic symptoms h. Disease progression in preceding 3 months i. Evidence of marrow infiltration with marrow compromise. (e.g., Hb, WCC or plt count below lower limit of institutional normal range).

h) Adequate bone marrowsoft, spongy tissue found in bones that makes blood cells function including:

1. Haemoglobin >8.0 g/dL
2. White cell count (WCC) ≥2000/μL
3. Neutrophilsa type of white blood cell that act as a first responder to infections in the body >1.5 x 109/L
4. Plateletssmall disc-shaped blood cells that clump together to form clots to stop bleeding >75 x 109/L at the time of study entry, unless attributed to bone marrow infiltration by lymphoma.

i) Adequate renal function with serum creatinine ≤1.5 x ULN or creatinine clearance (CrCl) ≥ 60mL/min (using Cockcroft-Gault formula, 24hr urine collection or eGFR).

Female CrCl = (140 – age in years) x weight (kg) x 0.85 72 x serum creatinine (mg/dL)

Male CrCl = (140 – age in years) x weight (kg) x 1.00 72 x serum creatinine (mg/dL) j) Adequate hepatic function with AST/ALT ≤3x ULN and total bilirubin ≤1.5 x ULN (except subjects with Gilbert syndrome, who can have a total bilirubin ≤3 mg/dL or ≤51.3 μmol/L).

k) Adequate left ventricular ejection fraction of >45% as demonstrated on a Gated Cardiac Bloodthe red bodily fluid that transports oxygen and other nutrients around the body Pool Scan or echocardiograma type of ultrasound that uses sound waves to create detailed images of the heart to assess heart structure, function and blood flow.

l) Life expectancy > 3 months. m) Patients of childbearing potential willing to adhere to the following contraceptive precautions.

1. Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study treatment.
2. Females must not be breastfeeding.
3. FCBP must use appropriate method(s) of contraception to avoid pregnancy for 23 weeks (30 days plus five half-lives of nivolumab) and 28 days for golcadomide post-treatment completion.
4. Men who are sexually active with FCBP must use any contraceptive method with a failure rate of less than 1% per year. They must agree to adhere to contraception for a period of 90 days from the last day golcadomide and refrain from donating sperm.
5. Azoospermic males and FCBP who are continuously not heterosexually active are exempt from contraceptive requirements. However, they must still undergo pregnancy testing as described in this section.

m) Written, informed consenta process in which a patient receives detailed information about a procedure or treatment, including its potential risks, benefits, and alternatives. The patient then has the opportunity to understand the information and voluntarily agree to the procedure or treatment..