This study is evaluating the study drug CC-486 (oral azacitidine) plus the standard drug therapy that fights cancer cells for patients that are 75 years of age or older who were recently diagnosed with Diffuse Large B Cell Lymphoma (DLBCL).

The study aims to determine if these patients can take the drug for at least 4 cycles of therapy without significantly more side effects than patients taking the standard drug therapy alone, and if disease progressions is longer, shorter, or remains the same compared to the standard therapy alone. It will also compare any side effects that participants may have and their well-being when they take the study drugs and for up to three years.

There is not currently an accepted or usual approach to treat recently diagnosed DLBCL in patients 75 years of age or older. The most common approach for patients who are not in a study is treatment with chemotherapy drugs that have been approved by the Food and Drug Administration (FDA). CC-486 (oral azacitidine) is FDA-approved.
   
Participants in this study will be treated in 1 of 2 ways. Participants will be randomized to receive either the study drug CC-486 (oral azacitidine) plus the most common chemotherapy combination (R-mini-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)) for up to 6 cycles (18 weeks), or the most common combination of drugs R-mini-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) without the CC-486 (oral azacitidine) for up to 6 cycles (18 weeks). Randomization is like flipping a coin and there is an equal chance of being assigned to either group.

All participants will also have tests during the treatment to see if the cancer is getting worse, staying the same, or getting better.