Open AccessENGINE: 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
Author(s) -
Grzegorz S. Nowakowski,
Jun Zhu,
Qingyuan Zhang,
Joshua Brody,
Xiuhua Sun,
Joseph Maly,
Yuqin Song,
Syed A. Rizvi,
Yongping Song,
Frederick Lansigan,
Hongmei Jing,
Junning Cao,
Jennifer Kimberly Lue,
Wen Luo,
Lei Zhang,
Li L,
Isabel Han,
Joan Sun,
Manoj A. Jivani,
Young Liu,
Thomas C. Heineman,
Stephen D. Smith
Publication year - 2020
Publication title -
future oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.857
H-Index - 72
eISSN - 1744-8301
pISSN - 1479-6694
DOI - 10.2217/fon-2020-0176
Subject(s) - medicine , oncology , diffuse large b cell lymphoma , clinical endpoint , international prognostic index , rituximab , chop , vincristine , lymphoma , phases of clinical research , cyclophosphamide , clinical trial , chemotherapy
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