Chidamide Plus Golidocitinib in Relapsed/Refractory Peripheral T-Cell Lymphoma

This is a Phase I/II, open-label, single-arm study investigating the combination of chidamide and golidocitinib in patients with relapsed or refractory peripheral T-cell lymphoma (PTCL). The Phase I portion utilizes a 3+3 dose-escalation design to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of the drug combination. The Phase II portion will then evaluate the efficacy and safety of the RP2D in approximately 28 patients with relapsed or refractory PTCL. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, or meeting other stopping criteria. The primary goal of Phase I is to establish the safety and MTD and the RP2D. The primary goal of Phase II is to evaluate the treatment efficacy and safety of the combination at RP2D.

Phase I Study: The Phase I study will enroll an estimated 6 to 12 subjects. Using a 3+3 dose-escalation design, three dose levels of chidamide and golidocitinib will be explored. Enrolled patients will receive combination therapy with golidocitinib (150 mg QD or 150 mg QOD) and chidamide (20 mg BIW or 25 mg BIW), according to enrollment time. Starting with the lowest dose level, three patients will be treated at each dose level and observed for toxicity during the first cycle. If no dose-limiting toxicity (DLT) is observed, the next higher dose level will be investigated. If one DLT is observed, an additional three patients will be treated at that dose level. Dose escalation will continue if no further DLTs are observed in these additional patients, but will terminate if a DLT occurs. If more than one DLT occurs among the initial three patients, dose escalation will terminate. The dose level immediately below that at which the DLT is determined will be established as the maximum tolerated dose (MTD). If the MTD is determined at Dose Level 1 (chidamide 20 mg BIW / golidocitinib 150 mg QD), Dose Level 0 (chidamide 20 mg BIW / golidocitinib 150 mg QOD) will be further investigated. If the MTD is not established after escalating to Dose Level 2 (chidamide 25 mg BIW / golidocitinib 150 mg QD), the recommended Phase 2 dose (RP2D) will be determined through investigator consensus. Each subject will receive only one dose level and schedule during the study. After completion of the treatment period, subjects will enter the follow-up period. Phase II Study: The Phase II study is expected to enroll approximately 28 patients with relapsed or refractory peripheral T-cell lymphoma (PTCL). Patients will receive treatment with golidocitinib and chidamide. The doses of chidamide and golidocitinib will be the RP2D established in the Phase I study. Each treatment cycle will be 21 days in duration. Subjects will continue to receive treatment per the investigator's assessment, until documented disease progression, intolerable toxicity, withdrawal of consent, or if the subject meets other criteria for treatment discontinuation (whichever occurs first).