Multi-Cohort Study of Zeprumetostat Combinations for Relapsed/Refractory PTCL

Официальное название

A Multi Cohort Exploratory Clinical Study of the EZH2 Inhibitor Zeprumetostat Combination Regimen in Relapsed/Refractory Peripheral T Cell Lymphoma

Обзор

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.

Вмешательства

• Препарат Zeprumetostat( an EZH2 inhibitor) + X
  Zeprumetostat( an EZH2 inhibitor) + JAK1 inhibitor or GemOx

Первичные конечные точки

• Summary of DLT events (Phase Ib) [Срок оценки: At the end of Cycle 1 (each cycle is 21 days)]
• Overall response rate (Phase Ⅱ) [Срок оценки: Through study completion, an average of 2 years after EZH2+JAK1/GemOx (Day 1)]

Вторичные конечные точки (5)

• Complete response rate [Срок оценки: Through study completion, an average of 2 years after EZH2+JAK1/GemOx (Day 1)]
• Duration of response [Срок оценки: Through study completion, an average of 2 years after EZH2+JAK1/GemOx (Day 1)]
• Progression free survival [Срок оценки: Through study completion, an average of 2 years after EZH2+JAK1/GemOx (Day 1)]
• Overall survival [Срок оценки: Through study completion, an average of 3 years after EZH2+JAK1/GemOx (Day 1)]
• Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE [Срок оценки: Through study completion, an average of 2 years after EZH2+JAK1/GemOx (Day 1)]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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:

• Requires continuous treatment with strong or moderate CYP3A inhibitors or CYP3A inducers
• Has multiple factors affecting oral medication administration (e.g., inability to swallow, chronic diarrhea, intestinal obstruction, etc.);
• Has a history of psychoactive substance abuse that cannot be discontinued
• Has any severe and/or uncontrolled disease.
• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Tianjin Cancer Hospital — Тяньцзинь

Идентификаторы

NCT: NCT07724782 · MA-PTCL-II-003

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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