ENGINE: A Phase III Randomized Placebo Controlled Study of Enzastaurin/R-CHOP as Frontline Therapy in High-Risk Diffuse Large B-Cell Lymphoma Patients with the Genomic Biomarker DGM1
Year: 2020
Type: article
Abstract: While combination of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) cures most patients with diffuse large B-cell lymphoma (DLBCL), those with high-risk international prognostic index disease have inferior survival. Enzastaurin as a potent inhibitor of PKC-β and PI3K/AKT pathway suppressor has been tested in many clinical trials including two key studies in DLBCL: Phase III maintenance study (Preventing Relapse in Lymphoma Using Daily Enzastaurin [PRELUDE]) and a first-line Phase II study (S028). DNA extracted from PRELUDE patients' blood samples was retrospectively genotyped identifying a novel genetic biomarker, DGM1 that showed high correlation with response to enzastaurin. A similar finding observed in the S028 study suggested that addition of enzastaurin to R-CHOP may significantly improve outcomes as frontline therapy for high-risk DGM1 positive DLBCL patients. ENGINE is a global, multicenter, placebo-controlled and randomized study to compare the effect of R-CHOP/enzastaurin as frontline treatment in high-risk DLBCL patients. The primary end point for this study is overall survival in patients who are DGM1 positive. Clinical Trial Registration Identifier: NCT03263026.
Source: Future Oncology
Authors: Grzegorz S Nowakowski, Jun Zhu, Qingyuan Zhang, Joshua Brody, Xiuhua Sun, Joseph Maly, Yuqin Song, Syed Rizvi, Yongping Song, Frederick Lansigan, Hongmei Jing, Junning Cao, Jennifer K Lue, Wen Luo, Lei Zhang, Ling Li, Isabel Han, Joan Sun, Manoj Jivani, Young Liu, Thomas Heineman, Stephen D Smith
Institutions: Mayo Clinic, Peking University Cancer Hospital, Third Affiliated Hospital of Harbin Medical University, Icahn School of Medicine at Mount Sinai, Dalian Medical University, Second Affiliated Hospital of Dalian Medical University, Norton Healthcare, Zhengzhou University, The University of Texas Southwestern Medical Center, Dartmouth–Hitchcock Medical Center, Peking University Third Hospital, Fudan University Shanghai Cancer Center, Columbia University Irving Medical Center, Denovo Biopharma LLC (United States), University of Washington, Fred Hutch Cancer Center
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Funder: ScitoVation
OpenAlex ID: W3014367981