An Open-Label, Multicenter Phase IIa Clinical Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of Purinostat Mesylate for Injection for the Treatment of Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma and Cutaneous T-Cell Lymphoma
Primary Objective To evaluate the preliminary efficacy of Purinostat Mesylate for Injection in patients with relapsed or refractory Peripheral T-Cell Lymphoma (PTCL) and Cutaneous T-Cell Lymphoma (CTCL). Secondary Objectives 1. To evaluate the safety and tolerability of Purinostat Mesylate for Injection in patients with relapsed or refractory PTCL and CTCL. 2. To evaluate the population pharmacokinetic characteristics of Purinostat Mesylate for Injection in patients with relapsed or refractory PTCL and CTCL. Exploratory Objective To investigate the relationship between tumor biomarkers and the therapeutic efficacy/safety profile of Purinostat Mesylate for Injection.
• The patient fully understands this study, voluntarily participates, and signs the informed consent form (ICF). They are able to communicate well with the investigator and can adhere to the study's visit schedule, treatment plan, laboratory tests, and other study procedures.
• Aged ≥18 years, male or female;
• Histologically confirmed diagnosis based on the 2022 revised World Health Organization (WHO) classification criteria, including but not limited to the following subtypes:
‣ Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS),
⁃ NK/T-cell lymphoma (nasal type),
⁃ Angioimmunoblastic T-cell lymphoma (AITL),
⁃ Anaplastic large cell lymphoma (ALCL),
⁃ Enteropathy-associated T-cell lymphoma (EATL),
⁃ Hepatosplenic T-cell lymphoma (HSTL),
⁃ Cutaneous T-cell lymphoma at TNMB stage IB-IVA,
⁃ Other subtypes of PTCL that the investigator considers eligible and are approved by the sponsor (excluding highly aggressive subtypes).
• Prior treatment: Relapsed/refractory PTCL refers to patients who have failed or are intolerant to at least one line of systemic standard treatment (≤5 lines). For NK/T-cell lymphoma, prior treatment must include asparaginase/pegaspargase/L-asparaginase. For other subtypes, prior treatment must include anthracyclines (unless anthracyclines are contraindicated).Relapsed/refractory CTCL refers to patients who have relapsed, progressed, or were unresponsive after adequate treatment with at least one systemic therapy (e.g., interferon, retinoids).The detailed definitions of relapsed/refractory PTCL are as follows: Relapse: Refers to disease progression after achieving remission (including complete remission and partial remission) with prior first-line treatment. This includes: a) Completion of treatment according to clinically recommended standards or conventional regimens (for early-stage patients, combined chemoradiotherapy with at least 2 cycles of recommended chemotherapy; for advanced-stage patients, systemic treatment with at least 4 cycles for those who received hematopoietic stem cell transplantation consolidation, or at least 6 cycles for those who did not).
• b) Relapse within 1-3 years after remission, and not suitable for or unwilling to undergo autologous hematopoietic stem cell transplantation salvage therapy.
• Refractory: Refers to patients who did not achieve remission with prior first-line treatment or experienced disease progression during treatment or within 1 year after completing treatment. This includes:a) Failure to achieve stable disease (SD) after ≥2 cycles of treatment according to clinically recommended standards or conventional regimens, or failure to achieve partial remission (PR) after ≥3-4 cycles.b) If the best response or reason for ending treatment was progressive disease (PD), the number of treatment cycles is not required.
• c) Disease progression after receiving ≥2 lines of clinically recommended standard or conventional treatment. d) Relapse after autologous hematopoietic stem cell transplantation.
• Expected survival \> 3 months.
• ECOG score 0-2.
• Patients with PTCL have at least one measurable lesion according to the 2014 Lugano criteria (lesions that have received radiotherapy can be used as target lesions if there is clear evidence of disease progression after radiotherapy), with a measurable lesion defined as: an intranodal lesion with a maximum diameter of \>1.5 cm on CT cross-sectional images; or an extranodal lesion with a maximum diameter of \>1.0 cm; patients with CTCL must have an mSWAT score ≥10% with or without systemic lymph node invasion;
• Organ function levels must meet the following requirements: routine blood tests (no growth factors or blood transfusions within 14 days prior to screening): absolute neutrophil count (ANC) ≥1.0×10\^9/L; hemoglobin (HGB) ≥80 g/L; platelet count (PLT) ≥75×10\^9/L (patients with bone marrow infiltration of lymphoma ≥50×10\^9/L can be enrolled); liver and kidney function: serum ≥10%, serum ≥10%, serum ≥50×10\^9/L (patients with bone marrow infiltration of lymphoma ≥50×10\^9/L). ); liver and kidney function: serum total bilirubin ≤1.5 × upper limit of normal (ULN) (TBiL ≤3.0 × ULN in patients with Gilbert's syndrome may be enrolled); aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ≤2.5 × ULN, or in the judgment of the investigator, when there is hepatic infiltration resulting in hepatic function impairment. ALT, AST, and ALP ≤ 5 × ULN may be enrolled; serum creatinine ≤ 1.5 × ULN or estimated creatinine clearance ≥ 50 mL/min (according to the Cockcroft and Gault formula); coagulation: activated partial thromboplastin time (APTT), International Normalized Ratio (INR), and prothrombin time (PT) ≤ 1.5 × ULN, and Fibrinogen (FIB) ≥ 1.0 g/L;
• Females and males of childbearing potential should agree that effective contraception (hormonal or barrier methods or abstinence) is required during the study and for 6 months after study completion; female patients of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to administration of the drug and must be non-lactating.