CEOP/IVE/GDP Alternating Regimen Compared with CEOP As the First-Line Therapy for Newly Diagnosed Patients with Peripheral T-Cell Lymphoma: Results from a Phase 2, Multi-Center, Randomized, Controlled Clinical Trial

Background Cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) or CHOP-like chemotherapy is widely used for treatment of peripheral T-cell lymphoma (PTCL). Given the poor response to CHOP-based regimens and the potential anti-lymphoma activity by alternating chemotherapy in PTCL, we conducted a phase 2, multi-center, randomized, controlled trial, comparing the efficacy and safety of CEOP/IVE/GDP alternating regimen with CEOP in a Chinese cohort of newly diagnosed patients with PTCL. Methods The primary endpoint of the study was the complete response rate (CRR). Patients with newly diagnosed PTCL, except for anaplastic large cell lymphoma (ALCL)- anaplastic lymphoma kinase (ALK) positive, were 1:1 randomly assigned. Patients in the CEOP/IVE/GDP group received intravenous cyclophosphamide 750 mg/m², epirubicin 70 mg/m², and vincristine 1.4 mg/m² (up to a maximum of 2 mg) on day 1, and oral prednisone 60 mg/m2 (up to a maximum of 100 mg) on day 1-5 every 21 days, at the 1st and 4th cycle with CEOP. Intravenous ifosfamide 2000 mg/m2 on day 1-3, epirubicin 70 mg/m2 on day 1, and etoposide 100 mg/m2 on day 1-4 every 21 days, at the 2nd and 5th cycle with IVE. Intravenous gemcitabine 1000 mg/m² on day 1, and 8, cisplatin 25 mg/m² on day 1-3, and dexamethasone 40mg on day 1-4 every 21 days, at the 3rd and 6th cycle with GDP, for a total of 6 cycles. Patients in the CEOP group received standard CEOP regimen every 21 days for 6 cycles. Analysis of efficacy and safety was of the intent-to-treat population. The study was registered with ClinicalTrials.gov, number NCT02533700. Findings Between Sep 22, 2015 and Sep 23, 2018, 102 patients were randomly assigned to two treatment groups: 51 each to the CEOP/IVE/GDP and the CEOP group. One patient was excluded because of the change of diagnosis and 3 patients withdrew informed consent before treatment in both study groups. 49 patients in the CEOP/IVE/GDP group and 49 patients in the CEOP group were included into efficacy and safety analysis as intent-to-treatment population. CRR at the end of treatment (EOT) in the CEOP/IVE/GDP group was similar as the CEOP group (36.7% vs. 32.7%, OR 0.84, 95% CI 0.36-1.88; p=0.835), while overall response rate (ORR) at EOT was higher in the CEOP/IVE/GDP group (73.5% vs. 51.0%, OR 0.38, 95% CI 0.17-0.86; p=0.037). There was no difference in median progression-free survival (15.4 months [95% CI 9.8-21.1] vs 10.7 months [4.5-16.8]; HR 0.73, 95% CI 0.45-1.18; p=0.20) or overall