This clinical trial is a Phase II study investigating the effectiveness and safety of a three-drug combination-Zeprumetostat, Azacitidine, and Mitoxantrone Hydrochloride Liposome-in adults with relapsed or refractory peripheral T-cell lymphoma (PTCL). PTCL is an aggressive type of non-Hodgkin lymphoma that has limited treatment options after the first line of therapy.
The study aims to enroll approximately 26 patients at a single center in China. Eligible participants will receive up to 6 cycles of induction therapy with all three drugs, followed by up to 2 years of maintenance therapy with Zeprumetostat alone if they respond to treatment.
The main goal is to evaluate the overall response rate (how many patients experience tumor shrinkage). Secondary goals include assessing how long patients live without their disease getting worse, how long they survive overall, and the safety profile of this treatment combination. The study will also explore whether specific genetic markers or viral infections are linked to how well patients respond.
This study is important because it tests a novel, potentially less toxic, and more effective combination for a patient population with high unmet medical need. All participants will be closely monitored for treatment response and side effects throughout the trial.
Relapsed or refractory peripheral T-cell lymphoma after first-line or higher treatment.
Age ≥ 18 years.
Eastern Cooperative Oncology Group (ECOG) performance status score ≤ 2.
Presence of measurable target lesions [Note: Target lesions are defined as lesions with at least one longest diameter (LD) measurement > 1.5 cm and longest perpendicular diameter (LPD) measurement ≥ 1.0 cm, as assessed by computed tomography (CT) or magnetic resonance imaging (MRI). A maximum of six target lesions can be selected].
Underwent major surgery or severe trauma within 2 weeks before enrollment, or significant adverse effects have not yet recovered.
Currently suffering from or having had other malignancies within 3 years before enrollment, except for cured basal or squamous cell carcinoma of the skin, superficial bladder cancer, prostatic intraepithelial neoplasia, and cervical carcinoma in situ.
History of stroke or intracranial hemorrhage within the past 3 months.
Presence of complications or medical conditions that may interfere with the conduct of the study or pose a significant risk to the patient, including but not limited to severe cardiovascular diseases (e.g., cardiac disease classified as New York Heart Association class III or IV, myocardial infarction within the past 6 months, unstable arrhythmias, or unstable angina) and/or severe pulmonary diseases (e.g., severe obstructive pulmonary disease and history of symptomatic bronchospasm).
Single group
Zeprumetostat
DrugZeprumetostat is an oral, selective Enhancer of Zeste Homolog 2 (EZH2) inhibitor. EZH2 is a histone methyltransferase often dysregulated in lymphomas. By inhibiting EZH2, zeprumetostat modulates epigenetic programming to reverse aberrant gene silencing, induce cell cycle arrest and apoptosis. In this study, it is administered at 350 mg orally twice daily continuously. It is used both in the 6-cycle induction combination phase and as monotherapy in the up to 2-year maintenance phase for responding patients.
Azacitidine (AZA)
DrugAzacitidine is a DNA methyltransferase inhibitor (hypomethylating agent). As a cytidine analog, it incorporates into DNA and RNA, leading to DNA hypomethylation, reactivation of silenced tumor suppressor genes, and direct cytotoxicity. In this study, azacitidine is administered at 100 mg via subcutaneous injection once daily on Days 1-5 of each 21-day induction cycle. It is part of the initial triple-drug induction regimen and is not used during the subsequent maintenance phase.
Mitoxantrone Hydrochloride Liposome
DrugMitoxantrone Hydrochloride Liposome is a liposomal formulation of the anthracenedione chemotherapy agent mitoxantrone. The liposomal encapsulation aims to improve pharmacokinetics and tissue distribution. Its mechanism involves intercalating into DNA and inhibiting topoisomerase II, causing DNA strand breaks and cell death. In this study, it is administered intravenously at 16 mg/m² on Day 1 of each 21-day induction cycle. It is used only in the initial 6-cycle combination induction phase.
Objective Response Rate (ORR) after 6 treatment cycles
The proportion of participants who achieve a Complete Response (CR) or Partial Response (PR) per the Lugano 2014 classification.
Progression-Free Survival (PFS)
Complete Response (CR) Rate after 6 treatment cycles
Duration of Response (DOR)
Overall Survival (OS)
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