Duvelisib With Rituximab vs R-CHOP in Subjects With Relapsed/Refractory Follicular Lymphoma (FRESCO)

Inclusion Criteria: 1. Diagnosis of FL: Grade 1, 2, or 3a 2. Progressed within 24 months of initiating an alkylator-based chemotherapy regimen given as either first- or second-line therapy; single-agent chlorambucil therapy does not fulfill this requirement Note: subjects must have received at least 2 cycles of alkylator-based chemotherapy to be eligible 3. Previously received rituximab, either as single agent or as part of any combination regimen, and also meet one of the following requirements: 1. Progressed within 24 months of initiating alkylator-based chemotherapy in the first line and received no additional anticancer therapy 2. Progressed within 24 months of initiating alkylator-based chemotherapy in the first line and subsequently progressed within 24 months of receiving any second-line treatment and received no additional anticancer therapy 3. Progressed within 24 months of initiating alkylator-based chemotherapy in the second line and received no additional anticancer therapy 4. Appropriate to receive R-CHOP 5. At least 1 measurable disease lesion \> 1.5 cm in at least one dimension by computed tomography (CT), CT-PET, or magnetic resonance imaging (MRI) 6. Eastern Cooperative Oncology Group (ECOG) performance status ≤2 (corresponds to Karnofsky Performance Status \[(KPS) ≥60%\]) 7. For women of childbearing potential (WCBP): negative serum β human chorionic gonadotropin (βhCG) pregnancy test within 1 week before first treatment (WCBP defined as a sexually mature woman who has not undergone surgical sterilization or who has not been naturally post-menopausal for at least 12 consecutive months for women \>55 years of age) Exclusion Criteria: 1. Clinical evidence of transformation to a more aggressive subtype of lymphoma or grade 3B FL 2. Received ≥ 3 previous anticancer regimens prior to enrollment 3. Received prior R-CHOP therapy 4. Previous receipt of any anthracycline 5. Contraindication to any of the individual components of CHOP (cyclophosphamide, vincristine, doxorubicin and prednisone) Severe allergic or anaphylactic reaction to any monoclonal antibody therapy, murine protein, or known hypersensitivity to any of the study drugs 6. Received prior allogeneic transplant 7. Received prior treatment with a phosphoinositide-3-kinase (PI3K) inhibitor 8. History of tuberculosis treatment within the two years prior to randomization 9. History of chronic liver disease, veno-occlusive disease, alcohol abuse 10. Ongoing treatment with chronic immunosuppressants (e.g., cyclosporine) or systemic steroids \>20 mg of prednisone (or equivalent) QD 11. Ongoing treatment for systemic bacterial, fungal, or viral infection at screening 12. Concurrent administration of medications or foods that are strong inhibitors or inducers of cytochrome P450 3A (CYP3A) 13. Unable to receive prophylactic treatment for pneumocystis, herpes simplex virus (HSV), or herpes zoster (VZV) at screening 14. Concurrent active malignancy other than nonmelanoma skin cancer, carcinoma in situ of the cervix 15. History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or a pacemaker within the last 6 months prior to screening