Combination of Chidamide with the CHOEP Regimen in Previously Untreated Patients with Peripheral T-Cell Lymphoma (PTCL): A Prospective, Multicenter, Single-Arm, Phase 1b/2 Trial

Background: Chidamide is a novel benzamide class of histone deacetylase (HDAC) inhibitor. In a pivotal phase 2 trial with refractory or relapsed peripheral T-cell lymphoma (PTCL), chidamide produced ORR 28% with CR 14% leading to its approval by the China Food and Drug Administration in 2014 for refractory or relapsed PTCL. We sought to assess the safety, tolerability and efficacy of the novel histone deacetylase inhibitor chidamide in combination with CHOEP (cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone) (Chi-CHOEP) for previously untreated PTCL.

Patients and methods: This was a prospective, multicenter, single-arm Phase 1b - 2 clinical trial conducted exclusively in China. In the phase 1b study, three dose levels of chidamide were explored. In the phase 2 portion, patients were treated at the RP2D. The primary endpoint of the Phase 1b was determination of the maximum tolerated dose (MTD), dose limiting toxicities (DLT) and RP2D. The primary endpoint of the phase 2 study was determination of the overall response rate (ORR).

Results: A total of 82 patients were enrolled between March 2016 and Dec 2017 at 17 sites across China. The cutoff date for the analysis was July 2018. In phase 1b dose-escalation study, 15 patients were treated and the second dose cohort (20 mg biw) was declared the MTD and thus the RP2D. Subsequently, 67 patients were enrolled and treated at the RP2D in the phase 2 part of the study. Overall, among 82 enrolled patients in the entire phase 1b/2 study, the median number of cycles per person was five (range 1-8) and the relative dose intensity was 75.4%. The most common toxicities in the Phase 1b/2 study included leucopenia, anemia, and neutropenia. No reactivation of Epstein-Barr virus or Hepatitis B virus was observed. For entire phase 1b/2 study of 82 patients, the ORR was 68.3% with a CR rate of 43.9%. In the phase 2 part of the study, the ORR was 73.2% with 47.8% CR. with a median follow-up of 12.7 months (range 0.3-30.8 months), the median PFS for entire phase 1b/2 study was 17.4 months and the 1-year PFS was 52.9%. The median OS had not yet been reached, and the 1-year OS was 74.5%. In the phase 2 study, the median PFS was 17.4 months and the 1-year PFS was 53.6%. The median OS had not yet been reached, and the 1-year OS was 76.3%.

Conclusion: Chi-CHOEP is an effective and feasible novel regimen for untreated PTCL. These data warrant further investigation in a randomized phase 3 study. This trial was registered at www.clinicaltrials.gov as #NCT02987244.