Phase II Study of Chidamide, a New Subtype-Selective Oral Histone Deacetylase Inhibitor, in Patients with Relapsed or Refractory Cutaneous T-Cell Lymphoma

Background Chidamide (CS055) is a new oral benzamide type of histone deacetylase (HDAC) inhibitor with subtype selective activity against HDAC1, 2, 3 and 10, and it has been approved for relapsed or refractory peripheral T-cell lymphoma (PTCL) in China. This phase II study (ChiCTR-TNC-00000806) was to evaluate the efficacy and safety of chidamide in different dosing regimens in patients with relapsed or refractory cutaneous T-cell Lymphoma (CTCL). Methods Fifty-two patients, all were mycosis fungoides or Sezary syndrome, were enrolled in this study. In the first stage of the study, 26 patients were randomly assigned to receive chidamide 30 mg twice per week for 2 weeks out of a 3-week-cycle (13 patients), or 4 weeks out of a 6-week-cycle (13 patients). Another 26 patients were enrolled in the second stage, and were treated by chidamide of 30 mg twice per week without drug-free holiday. The primary endpoint was objective response rate (ORR). Responses were evaluated based on the overall skin lesions, lymph nodes, blood cells and pruritis. Results The ORRs were 33% (4/12 PRs) for the 3-week-cycle arm, 23% (3/13 PRs) for the 6-week-cycle arm, and 36% (1/25 CR + 8/25 PRs) for the successive dosing arm, respectively. Median duration of response (DOR) was 50, 92, and 169 days for the indicated 3 arms, respectively. Twelve (92%), 11 (85%) and 20 (77%) patients experienced adverse event (AE) in the three arms. Most AEs were in Grade 1 or 2. Thrombocytopenia, leucopenia, fatigue, nausea and diarrhea were most frequently seen. Two serious adverse events (SAE) were reported in the study. One patient in the 3-week-cycle arm was hospitalized for fever and lung infection, and the other in the successive dosing arm was hospitalized for hyperglycemia. Conclusions Chidamide was active and tolerable to relapsed or refractory CTCL. The ORR of chidamide was comparable with the marketed drugs for CTCL. The major toxicities of chidamide were hematologic and gastrointestinal reactions which were controllable. Based on the overall profiles of the three different dosing regimens, 30 mg twice per week successively was clinically recommended. Table 1. Efficacy 3-week-cycle arm(N=12) * 6-week-cycle arm (N=13) Successive dosing arm(N=25) * CR 0 0 1 PR 4 3 8 ORR (%) 4 (33) 3 (23) 9 (36) Median DOR (days) 50 92 169 Median PFS (days) 84 81 88 *patients with ineligible entrance of the study were excluded for the efficacy analysis Table 2. Safety 3-week-cycle arm (N=13) 6-week-cycle arm (N=13) Successive dosing arm (N=26) Patients with AE (%) 12 (92) 11(85) 20 (77) Patients with AE ≥grade 3 (%) 3 (23) 5 (38) 4 (15) Patients with SAE (%) 1 (8) 0 1 (4) AEs in ≥10% of patients (%) Thrombocytopenia 5 (39) 3 (23) 9 (35) Leucopenia 7 (54) 4 (31) 4 (15) Fatigue 3 (23) 3 (23) 3 (12) Nausea 3 (23) 1 (8) 3 (12) Diarrhea 1(8) 1 (8) 3 (12) Fever 0 2 (15) 2 (8) Anemia 1 (8) 2 (15) 1 (4) Disclosures No relevant conflicts of interest to declare.