PHASE III RANDOMIZED STUDY OF ENZASTAURIN/R-CHOP VS PLACEBO/R-CHOP IN FRONTLINE HIGH RISK DIFFUSE LARGE B CELL LYMPHOMA PATIENTS WITH GENOMIC BIOMARKER DGM1 (ENGINE STUDY)

2019 ◽  
Vol 37 ◽  
pp. 70-70
Author(s):  
J. Zhu ◽  
Y. Song ◽  
S.D. Smith ◽  
O.A. O'Connor ◽  
W. Luo ◽  
...  
Keyword(s):  
High Risk ◽  
B Cell ◽  
Cell Lymphoma ◽  
Randomized Study ◽  
B Cell Lymphoma ◽  
Phase Iii ◽  
Large B Cell Lymphoma ◽  
Large B Cell

scholarly journals Adjuvant everolimus in high-risk diffuse large B-cell lymphoma: final results from the PILLAR-2 randomized phase III trial

2018 ◽  
Vol 29 (3) ◽  
pp. 707-714 ◽  
Author(s):  
T.E. Witzig ◽  
K. Tobinai ◽  
L. Rigacci ◽  
T. Ikeda ◽  
A. Vanazzi ◽  
...  
Keyword(s):  
High Risk ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Final results of NCCTG N0489: Epratuzumab and rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy (ER-CHOP) in patients with previously untreated diffuse large B-cell lymphoma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8508-8508
Author(s):  
I. N. Micallef ◽  
M. J. Maurer ◽  
D. A. Nikcevich ◽  
M. W. Cannon ◽  
E. W. Schaefer ◽  
...  
Keyword(s):  
High Risk ◽  
B Cell ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Phase Iii ◽  
Hematological Toxicity ◽  
Free Survival ◽  
Large B Cell Lymphoma ◽  
Large B Cell

8508 Background: A prior pilot study of epratuzumab (Immunomedics) and rituximab in combination with CHOP chemotherapy (ER-CHOP) in untreated patients with diffuse large B-cell lymphoma demonstrated feasibility and safety. This multicenter NCCTG phase II study was carried out to assess efficacy. Methods: Patients received immunochemotherapy on the following schedule: epratuzumab 360 mg/m2, rituximab 375 mg/m2, and standard dose CHOP every 3 weeks for 6 cycles. Weekly blood counts were obtained to monitor hematological toxicity. Primary endpoint was 12 month event free survival (EFS12). Secondary endpoints were response rate, progression free survival, functional CR (PET negative) and toxicity. Results: 107 patients were accrued from Feb 2006 to Aug 2007. 29 patients were ineligible resulting in 78 eligible patients. Baseline patient characteristics for the eligible patients included median age 61 (range 21–82); 59% were male. 81% had advanced stage; IPI was 0–1 in 17 pts (22%), 2 in 22 pts (28%), 3 in 29 pts (37%) and 4–5 in 10 pts (13%). Based on the revised IPI (R-IPI) 50% were poor/high risk (IPI 3–5). 71% had an elevated LDH. Performance score was 0–1 in 69 pts and 2–3 in 9 pts. The ORR was 95% (CR/CRu: 73%). For the low risk IPI (0–2), ORR was 95% (CR/CRu: 74%) and for the high risk IPI (3–5), ORR was 95% (CR/CRu: 72%). The EFS at 12 months was 80%. The 12 month progression free survival (PFS12) and overall survival (OS12) is 82% and 88% respectively. EFS12, PFS12 and OS12 by IPI risk category is shown ( Table ). Conclusions: ER-CHOP every 21 days is feasible and safe. The ORR, EFS and PFS compare favorably to studies using R-CHOP especially in the high-intermediate and high risk IPI subgroups. A randomized phase III trial of R-CHOP vs ER-CHOP is needed to prove that dual antibody targeting in combination with CHOP is better. [Table: see text] No significant financial relationships to disclose.

scholarly journals 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

2020 ◽  
Vol 16 (15) ◽  
pp. 991-999 ◽  
Author(s):  
Grzegorz S Nowakowski ◽  
Jun Zhu ◽  
Qingyuan Zhang ◽  
Joshua Brody ◽  
Xiuhua Sun ◽  
...  
Keyword(s):  
High Risk ◽  
B Cell ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
B Cell Lymphoma ◽  
Phase Iii ◽  
Controlled Study ◽  
Large B Cell Lymphoma ◽  
Frontline Therapy ◽  
Large B Cell

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

scholarly journals Favourable outcomes for high-risk diffuse large B-cell lymphoma (IPI 3–5) treated with front-line R-CODOX-M/R-IVAC chemotherapy: results of a phase 2 UK NCRI trial

2020 ◽  
Vol 31 (9) ◽  
pp. 1251-1259 ◽  
Author(s):  
A.K. McMillan ◽  
E.H. Phillips ◽  
A.A. Kirkwood ◽  
S. Barrans ◽  
C. Burton ◽  
...  
Keyword(s):  
High Risk ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Phase 2 ◽  
Front Line ◽  
Large B Cell Lymphoma ◽  
Large B Cell

scholarly journals Rituximab-CHOP With Early Rituximab Intensification for Diffuse Large B-Cell Lymphoma: A Randomized Phase III Trial of the HOVON and the Nordic Lymphoma Group (HOVON-84)

2020 ◽  
Vol 38 (29) ◽  
pp. 3377-3387
Author(s):  
Pieternella Johanna Lugtenburg ◽  
Peter de Nully Brown ◽  
Bronno van der Holt ◽  
Francesco A. D’Amore ◽  
Harry R. Koene ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Standard Of Care ◽  
Phase Iii ◽  
Free Survival ◽  
Intention To Treat ◽  
Large B Cell Lymphoma ◽  
Large B Cell

PURPOSE Immunochemotherapy with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) has become standard of care for patients with diffuse large B-cell lymphoma (DLBCL). This randomized trial assessed whether rituximab intensification during the first 4 cycles of R-CHOP could improve the outcome of these patients compared with standard R-CHOP. PATIENTS AND METHODS A total of 574 patients with DLBCL age 18 to 80 years were randomly assigned to induction therapy with 6 or 8 cycles of R-CHOP-14 with (RR-CHOP-14) or without (R-CHOP-14) intensification of rituximab in the first 4 cycles. The primary end point was complete remission (CR) on induction. Analyses were performed by intention to treat. RESULTS CR was achieved in 254 (89%) of 286 patients in the R-CHOP-14 arm and 249 (86%) of 288 patients in the RR-CHOP-14 arm (hazard ratio [HR], 0.82; 95% CI, 0.50 to 1.36; P = .44). After a median follow-up of 92 months (range, 1-131 months), 3-year failure-free survival was 74% (95% CI, 68% to 78%) in the R-CHOP-14 arm versus 69% (95% CI, 63% to 74%) in the RR-CHOP-14 arm (HR, 1.26; 95% CI, 0.98 to 1.61; P = .07). Progression-free survival at 3 years was 74% (95% CI, 69% to 79%) in the R-CHOP-14 arm versus 71% (95% CI, 66% to 76%) in the RR-CHOP-14 arm (HR, 1.20; 95% CI, 0.94 to 1.55; P = .15). Overall survival at 3 years was 81% (95% CI, 76% to 85%) in the R-CHOP-14 arm versus 76% (95% CI, 70% to 80%) in the RR-CHOP-14 arm (HR, 1.27; 95% CI, 0.97 to 1.67; P = .09). Patients between ages 66 and 80 years experienced significantly more toxicity during the first 4 cycles in the RR-CHOP-14 arm, especially neutropenia and infections. CONCLUSION Early rituximab intensification during R-CHOP-14 does not improve outcome in patients with untreated DLBCL.

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