A Phase I, Open Label, Multicenter Trial of Oral Azacitidine (CC-486) Plus R-CHOP in Patients with High-Risk, Previously Untreated Diffuse Large B-Cell Lymphoma, Grade 3B Follicular Lymphoma, or Transformed Lymphoma

Introduction : Approximately 40% of patients (pts) with diffuse large B-cell lymphoma (DLBCL) do not achieve complete response (CR) or relapse after receiving R-CHOP. A proposed mechanism of chemoresistance is aberrant DNA methylation. Preclinical data show low doses of DNA methyltransferase inhibitors, such as azacitidine, suppress DLBCL tumor growth, while causing minimal DNA damage and enhancing chemosensitivity. In an earlier phase I clinical trial, subcutaneous (SC) azacitidine + R-CHOP showed 10/11 CRs in DLBCL pts with international prognostic index (IPI) score >2 (Clozel et al. Cancer Discovery 2013), providing a rationale for this study of oral azacytidine (CC-486) which is easier to administer and may achieve more continuous hypomethylation effects.