A Phase 1, Open-label Trial of Oral Azacitidine (CC-486) Plus RCHOP in Subjects With Large B-Cell Lymphoma or Follicular Lymphoma or Transformed Lymphoma

Inclusion Criteria: 1. Histologically confirmed previously untreated DLBCL or Grade 3B FL, \[double-positive for BCL2 and c-MYC\] or transformed lymphoma. Transformed lymphoma from FL or marginal zone lymphoma, but not chronic lymphocytic leukemia (CLL) \[Richter Transformation\] are allowed as long as no prior anti-lymphoma therapy of any kind has been administered. 1. A formalin fixed paraffin embedded lymph node or tumor biopsy specimen must be submitted during the Screening Period. The specimen must have been acquired by a surgical or core needle biopsy (≥ 2 cores at baseline); material from a fine needle aspiration is not acceptable. 2. Fresh core biopsy, frozen, must be performed before start of therapy and submitted for storage. This is optional only for the subjects who have a biopsy-accessible site and consent to the procedure. In case no prior fixed formalin paraffin embedded (FFPE) biopsy is available, this specimen can also be used for diagnostic confirmation. 3. No prior anti-lymphoma therapy. However, for subjects with bulky disease,systemic symptoms, compressive disease, or rapidly progressing adenopathies, pre-phase treatment with 1 mg/kg/day prednisone, or equivalent, for a maximum of 7 days is permitted prior to Cycle 1 Day -6 at the discretion of the Investigator. In exceptional cases, if clinically indicated, a higher dose of steroids and/or a slightly longer duration is allowed for the purpose of urgent symptom management, and the subjects is considered eligible. A washout period does not apply. However the fresh core biopsy mentioned above should be performed before starting prednisone. 2. International Prognostic Index score ≥ 2 or DLBCL with double-positive for BCL2 and c-MYC by IHC (immunohistochemistry) or FISH (fluorescent in situ hybridization) based on local pathology lab assessment. 3. Measurable disease on cross section imaging by CT (computed tomography) that is at least 1.5 cm in the longest diameter and measurable in two perpendicular dimensions as defined by IWG (International Working Group) response criteria for NHL (non-Hodgkin Lymphoma). 4. Ann Arbor stage II to IV. 5. Men and women 18 years of age to 80 years of age of any ethnic origin or race at the time of signing the ICD. 6. Understand and voluntarily sign an ICD (Informed Consent Document) prior to any study related assessments/procedures are conducted. 7. Able to adhere to the study visit schedule and other protocol requirements. 8. Performance status ≤ 2 on the Eastern Cooperative Oncology Group (ECOG) scale. 9. Negative serum pregnancy test within 72 hours before starting study treatment on Cycle 1 Day -6 for females of childbearing potential (FCBP). A female of child-bearing potential, defined as a sexually mature woman who: 1) has not undergone a hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of both ovaries) or, 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time during the preceding 24 consecutive months), may participate providing they agree to the following conditions: 1. Either commit to true abstinence\* from heterosexual contact (which must be reviewed on a monthly basis) or agree to the use of a physician-approved contraceptive method (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intrauterine device; barrier contraceptive with spermicide; or vasectomized partner) without interruption, while on CC-486 (including dose interruptions); and for 3 months following the last dose of IP; and 2. Agree to have a medically supervised serum pregnancy test with sensitivity of at least 25 mIU/mL obtained at Screening. A serum pregnancy test is to be performed within 72 hours prior to Day 1 of starting study therapy on Cycle 1 Day -6, and within 72 hours prior to Day 1 of every subsequent cycle, and at the Treatment Discontinuation Visit. The subject may not receive IP until the Investigator has verified that the result of the pregnancy test is negative. 10. Male subjects with a female partner of childbearing potential must either commit to true abstinence\* or agree to the use of a physician-approved contraceptive method throughout the course of the study and avoid fathering a child during the course of the study and for 3 months following the last dose of the IP (Investigational Product). Exclusion Criteria: 1. Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study. 2. Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study. 3. Any condition that confounds the ability to interpret data from the study. 4. Any condition causing an inability to swallow tablets. 5. History of inflammatory bowel disease (e.g., Crohnis disease, ulcerative colitis),celiac disease (i.e., sprue), prior gastrectomy or upper bowel removal, or any other gastrointestinal disorder or defect that would interfere with absorption, distribution, metabolism, or excretion of the IP and/or predispose the subject to an increased risk of gastrointestinal toxicity. 6. Hematologic and Non-hematologic exclusion criteria before start of therapy. 7. Seropositive for or active viral infection with hepatitis B virus (HBV): 1. Hepatitis B surface antigen (HBsAg) positive 2. HBsAg negative, anti-HBs positive and/or anti-HBc positive and detectable viral DNA 3. Subjects who are HBsAg negative, anti-HBs positive, and/or anti-HBc positive, but viral DNA negative are not eligible 4. Subjects who are seropositive because of HBV vaccination are eligible (HBV surface antibody positive, HBV core antibody negative, and HBV surface antigen negative) 8. Prior history of malignancies, other than diffuse large B-cell lymphoma, unless the subject has been free of the disease for ≥ 5 years from the signing of the ICD. Exceptions to the ≥ 5 year time limit include history of the following: 1. Basal cell carcinoma of the skin 2. Squamous cell carcinoma of the skin 3. Carcinoma in situ of the cervix 4. Carcinoma in situ of the breast 5. Incidental histological finding of prostate cancer (TNM stage of T1a or T1b) 9. Known seropositive for or active infection with hepatitis C virus (HCV) 10. Known seropositive for or active viral infection with human immunodeficiency virus (HIV). 11. Known or suspected hypersensitivity to azacitidine or mannitol or any other ingredient used in the manufacture of oral azacitidine (see the current azacitidine IB). 12. Contraindication to any drug in the chemotherapy regimen, and specifically 1. LVEF \< 50% 2. Corrected QT interval \> 480 msec (using the Fridericia formula) 3. Neuropathy uropathy europathy Nemediastinal DLBCL. 13. Primary mediastinal DLBCL. 14. Active uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment) 15. Significant active cardiac disease within the previous 6 months from the signing of the ICD, including: 1. New York Heart Association (NYHA) class III or IV congestive heart failure 2. Unstable angina or angina requiring surgical or medical intervention; and/or 3. Myocardial infarction 16. Pregnant or lactating (breastfeeding) females.