SHR2554 Plus Liposomal Mitoxantrone as First-line Treatment for Peripheral T-cell Lymphoma (PTCL)

Official title

An Open-label, Multicenter, Phase Ib/II Exploratory Clinical Study of EZH2 Inhibitor SHR2554 in Combination With Liposomal Mitoxantrone for the First-line Treatment of Peripheral T-cell Lymphoma

Overview

This is a single-arm, multicenter, Phase Ib/IIa study designed to explore the efficacy and safety of SHR2554 in combination with liposomal mitoxantrone for the treatment of patients with treatment-naive peripheral T-cell lymphoma (PTCL). The study is divided into a Phase Ib safety lead-in phase and a Phase IIa dose expansion phase.

Interventions

• Drug SHR2554 combined with Liposomal Mitoxantrone
  Patients will receive 6 cycles of SHR2554 combined with liposomal mitoxantrone as induction therapy. All patients who achieve a complete response (CR) after induction therapy are eligible for transplantation. Patients achieving CR or partial response (PR), as well as those post-transplantation, may receive SHR2554 maintenance therapy in 28-day cycles. Maintenance therapy will continue until disease progression or other reasons for discontinuation. The maximum duration of SHR2554 administration i

Primary outcome measures

• Incidence of Dose-Limiting Toxicities (DLT) [Time frame: Cycle 1 (28 days)]
• Complete response (CR) rate [Time frame: up to 6 months after enrollment]

Secondary outcome measures (6)

• Objective response rate (ORR) [Time frame: up to 6 months after enrollment]
• Duration of Response (DOR) [Time frame: up to 2.5 years post first treatment]
• Duration of complete response (CR) [Time frame: up to 2.5 years post first treatment]
• Progression-free Survival (PFS) [Time frame: Up to 2.5 years]
• Overall survival (OS) [Time frame: Up to 2.5 years]
• Adverse events(AE) [Time frame: From the first day of medication to 28 days after the last dose]

Eligibility criteria

Inclusion criteria

• Age ≥18 years old,regardless of gender;
• Centrally confirmed histopathological/cytologic diagnosis of PTCL with the following subtypes:Peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS);Follicular helper T (TFH) cell lymphoma of lymph nodes, including angioimmunoblastic, follicular, NOS; Enteropathy-associated T-cell lymphoma(EATL); Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL)and any other PTCL subtypes deemed by the investigator to be eligible for inclusion.
• No prior anti-tumor therapy.
• There must be at least one measurable or evaluable lesion that meets the Lugano 2014 criteria for lymphoma: Measurable lesion: Nodal lesions with major diameter greater than 1.5cm and minor diameter greater than 1.0cm as assessed by PET/CT or Computed Tomography (CT) and/or Magnetic Resonance Imaging (MRI); Or the length of extranodal lesions >1.0cm; 2)Evaluable lesions: PET-CT showed increased uptake in lymph nodes or extranodal regions (higher than liver) and imaging features consistent with lymphoma;
• ECOG performance status score: 0-2;
• Expected survival time ≥3 months;
• Have adequate organ and bone marrow functiont;
• No concurrent hemophagocytic lymphohistiocytosis (HLH). If a patient has clinically diagnosed HLH, enrollment eligibility will be determined by the investigator based on an evaluation of the patient's general physical condition following targeted anti-HLH therapy.
• Women of childbearing potential must have a negative serum pregnancy test within 7 days before the first dose of medication; Effective contraception should be used from the time of informed consent until 6 months after the last dose of study drug.
• Capable of understanding the study procedures and voluntarily signing a written informed consent form (ICF).;

Exclusion criteria

• Prior treatment with epigenetic agents before enrollment;
• Patients with a history of severe cardiac disease, history of radiation therapy to the mediastinal/pericardial region, cumulative anthracycline dose > 550 mg (doxorubicin equivalent), prior use of mitoxantrone, baseline left ventricular ejection fraction (LVEF) < 50%, or history of exposure to other cardiotoxic drugs;
• History of other primary aggressive malignancies that are not in remission, or have been in remission for less than 3 years;
• Primary central nervous system (CNS) lymphoma or secondary CNS involvement.
• Known allergy or hypersensitivity to the study drugs or their related metabolites;
• Currently participating in another clinical study, or less than 4 weeks elapsed from the end of treatment in a previous clinical study to the planned start of study treatment;
• Pregnant or lactating women;
• Active infections;
• Medical History and Concurrent Conditions;
• History of Human Immunodeficiency Virus (HIV) infection and/or Acquired Immunodeficiency Syndrome (AIDS);
• Patients with mental disorders or those unable to provide informed consent
• Any other condition deemed by the investigator to be unsuitable for study enrollment;

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07725705 · IIT2026083

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗