This is a single-arm, multi-cohort, multicenter, phase Ib/IIa clinical study designed to evaluate the safety and efficacy of Zeprumetostat (an EZH2 inhibitor) in combination with different therapeutic agents/regimens - specifically, the JAK1 inhibitor golidocitinib and the GemOx chemotherapy regimen (gemcitabine plus oxaliplatin) - in patients with relapsed or refractory peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) and T-follicular helper cell lymphoma (TFHL). The trial comprises a phase Ib dose-escalation phase and a phase IIa dose-expansion phase. Two combination cohorts are established: Cohort A (zemitostatin + golidocitinib) and Cohort B (zemitostatin + GemOx). Subjects will be randomly assigned to either Cohort A or Cohort B.
Inclusion Criteria:
Age 18 years or older, both males and females are eligible;
Histologically confirmed peripheral T-cell lymphoma (PTCL) including PTCL-NOS and TFHL that has relapsed or is refractory after at least one line of systemic therapy. The definitions are as follows:
Relapse: Patients who achieved a Complete Response (CR) in previous treatments and have new lesions at the original site or elsewhere; Refractory: Patients who did not achieve CR after adequate treatment. For nasal-type NK/T-cell lymphoma, previous treatments must have included a chemotherapy regimen containing asparaginase;
Patients who have undergone prior hematopoietic stem cell transplantation are allowed;
ECOG PS 0-2
Life expectancy greater than 3 months.
Adequate organ function
Contraception during study
Informed consented
Exclusion Criteria:
Prior treatment with EZH2 inhibitors or EZH1/2 inhibitors before enrollment;
Peripheral T-cell lymphoma of subtypes other than PTCL-NOS and TFHL;
History of other primary invasive malignancies that have not been in remission or have been in remission for no more than 3 years;
Central nervous system involvement (meningeal or parenchymal);
Known hypersensitivity to any study drugs;
Participation in another clinical trial of an investigational drug within 4 weeks prior to the start of the study.
Pregnant or lactation
Active infection.
Diseases and medical history:
Uncontrollable autoimmune disease,
Not able to comply to the protocol for mental or other unknown reasons
Any other condition that, in the investigator's judgment, makes the patient unsuitable for study participation.
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