Zeprumetostat plus azacitidine and liposomal mitoxantrone for relapsed/refractory peripheral T‑cell lymphoma

Clinical Study on the Efficacy and Safety of Zeprumetostat, Azacitidine Combined With Mitoxantrone Hydrochloride Liposome in Relapsed/Refractory Peripheral T-Cell Lymphoma.

This study will test whether combining zeprumetostat, azacitidine, and liposomal mitoxantrone can shrink tumors in adults with relapsed or refractory peripheral T‑cell lymphoma.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 26 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: The First Affiliated Hospital of Soochow University (Academic / other)
• Locations: 1 site (Suzhou, Jiangsu)
• Trial ID: NCT07372352 on ClinicalTrials.gov

What this trial studies

This Phase II, single-center trial in Suzhou, China plans to enroll about 26 adults with relapsed or refractory peripheral T‑cell lymphoma to receive up to six cycles of induction therapy with zeprumetostat, azacitidine, and liposomal mitoxantrone followed by up to two years of zeprumetostat maintenance for responders. The primary goal is to measure overall response rate, with secondary endpoints including progression-free survival, overall survival, and safety. Patients must have measurable disease and adequate organ function and will be monitored for hematologic and non-hematologic toxicities during treatment. The protocol also includes exploratory biomarker and genetic analyses to look for signals associated with response.

Who should consider this trial

Good fit: Adults (≥18 years) with relapsed or refractory peripheral T‑cell lymphoma after prior therapy, ECOG performance status 0–2, measurable lesions, and adequate organ function would be considered eligible.

Not a fit: Patients with poor performance status (ECOG >2), significant uncontrolled comorbidities, severe organ dysfunction, or who cannot tolerate myelosuppressive therapy are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If effective, this combination could increase response rates and prolong disease control for people with relapsed or refractory PTCL.

How similar studies have performed: Azacitidine and other epigenetic agents have shown some activity in T‑cell lymphomas and combinations are an active research area, but this specific triple regimen is novel and has limited prior clinical data.

Eligibility criteria

Inclusion Criteria:

1. Relapsed or refractory peripheral T-cell lymphoma after first-line or higher treatment.
2. Age ≥ 18 years.
3. Eastern Cooperative Oncology Group (ECOG) performance status score ≤ 2.
4. Presence of measurable target lesions \[Note: Target lesions are defined as lesions with at least one longest diameter (LD) measurement \> 1.5 cm and longest perpendicular diameter (LPD) measurement ≥ 1.0 cm, as assessed by computed tomography (CT) or magnetic resonance imaging (MRI). A maximum of six target lesions can be selected\].
5. Adequate function of major organs must meet the following criteria:

   * Hematological parameters: HB ≥ 70 g/L, PLT ≥ 50 × 10\^9/L, NE ≥ 1.0 × 10\^9/L (Note: Patients who have not received transfusions or drugs to support NE, PLT, or HB increase within 1 week before screening are eligible. Patients with bone marrow involvement by lymphoma resulting in cytopenia are not restricted by this criterion).
   * Echocardiographic left ventricular ejection fraction ≥ 50%.
   * Creatinine ≤ 132 umol/L or creatinine clearance ≥ 60 ml/min.
   * ALT and AST ≤ 3 times the upper limit of normal.
6. Women of childbearing potential must have a negative pregnancy test. Both male and female patients must agree to use effective contraception during treatment and for 1 year thereafter.
7. Life expectancy of more than 3 months.
8. Voluntary signed informed consent form.

Exclusion Criteria:

1. Underwent major surgery or severe trauma within 2 weeks before enrollment, or significant adverse effects have not yet recovered.
2. 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.
3. History of stroke or intracranial hemorrhage within the past 3 months.
4. 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).
5. Human immunodeficiency virus infection, or presence of uncontrollable active hepatitis C virus or hepatitis B virus infection.
6. Uncontrollable active infection.
7. Pregnant or breastfeeding women.
8. Any life-threatening disease, medical condition, or organ system dysfunction that may endanger the safety of the patient, as determined by the investigator.
9. Any condition that may interfere with the absorption or metabolism of zemtovistat, azacitidine, or doneda, or place the study results at unnecessary risk.
10. Lymphoma involvement of the central nervous system.
11. Presence of conditions judged by the investigator to interfere with full participation in the study; conditions posing significant risk to the subject; or conditions that may interfere with the interpretation of study data.

Where this trial is running

Suzhou, Jiangsu

• The First Affiliated Hospital of Soochow University — Suzhou, Jiangsu, China (Recruiting)

Study contacts

• Study coordinator: Ting Xu, Doctor

Conditions Peripheral T Cells Lymphoma