A Phase IIa Clinical Study of Purinostat Mesylate for Injection in Patients With Peripheral T-Cell Lymphoma and Cutaneous T-Cell Lymphoma

Inclusion Criteria:

1. The patient fully understands this study, voluntarily participates, and signs theinformed consent form (ICF). They are able to communicate well with the investigatorand can adhere to the study's visit schedule, treatment plan, laboratory tests, andother study procedures.

2. Aged ≥18 years, male or female;

3. Histologically confirmed diagnosis based on the 2022 revised World HealthOrganization (WHO) classification criteria, including but not limited to thefollowing subtypes:

4. Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS),

5. NK/T-cell lymphoma (nasal type),

6. Angioimmunoblastic T-cell lymphoma (AITL),

7. Anaplastic large cell lymphoma (ALCL),

8. Enteropathy-associated T-cell lymphoma (EATL),

9. Hepatosplenic T-cell lymphoma (HSTL),

10. Cutaneous T-cell lymphoma at TNMB stage IB-IVA,

11. Other subtypes of PTCL that the investigator considers eligible and areapproved by the sponsor (excluding highly aggressive subtypes).

12. Prior treatment: Relapsed/refractory PTCL refers to patients who have failed or areintolerant to at least one line of systemic standard treatment (≤5 lines). ForNK/T-cell lymphoma, prior treatment must includeasparaginase/pegaspargase/L-asparaginase. For other subtypes, prior treatment mustinclude anthracyclines (unless anthracyclines arecontraindicated).Relapsed/refractory CTCL refers to patients who have relapsed,progressed, or were unresponsive after adequate treatment with at least one systemictherapy (e.g., interferon, retinoids).The detailed definitions ofrelapsed/refractory PTCL are as follows: Relapse: Refers to disease progressionafter achieving remission (including complete remission and partial remission) withprior first-line treatment. This includes: a) Completion of treatment according toclinically recommended standards or conventional regimens (for early-stage patients,combined chemoradiotherapy with at least 2 cycles of recommended chemotherapy; foradvanced-stage patients, systemic treatment with at least 4 cycles for those whoreceived hematopoietic stem cell transplantation consolidation, or at least 6 cyclesfor those who did not). b) Relapse within 1-3 years after remission, and not suitable for or unwilling toundergo autologous hematopoietic stem cell transplantation salvage therapy. Refractory: Refers to patients who did not achieve remission with prior first-linetreatment or experienced disease progression during treatment or within 1 year aftercompleting treatment. This includes:a) Failure to achieve stable disease (SD) after ≥2 cycles of treatment according to clinically recommended standards or conventionalregimens, or failure to achieve partial remission (PR) after ≥3-4 cycles.b) If thebest response or reason for ending treatment was progressive disease (PD), thenumber of treatment cycles is not required. c) Disease progression after receiving ≥2 lines of clinically recommended standardor conventional treatment. d) Relapse after autologous hematopoietic stem celltransplantation.

13. Expected survival > 3 months.

14. ECOG score 0-2.

15. Patients with PTCL have at least one measurable lesion according to the 2014 Luganocriteria (lesions that have received radiotherapy can be used as target lesions ifthere is clear evidence of disease progression after radiotherapy), with ameasurable lesion defined as: an intranodal lesion with a maximum diameter of >1.5cm 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 systemiclymph node invasion;

16. Organ function levels must meet the following requirements: routine blood tests (nogrowth factors or blood transfusions within 14 days prior to screening): absoluteneutrophil 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 beenrolled); 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 kidneyfunction: serum total bilirubin ≤1.5 × upper limit of normal (ULN) (TBiL ≤3.0 × ULNin patients with Gilbert's syndrome may be enrolled); aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ≤2.5 × ULN, orin the judgment of the investigator, when there is hepatic infiltration resulting inhepatic function impairment. ALT, AST, and ALP ≤ 5 × ULN may be enrolled; serumcreatinine ≤ 1.5 × ULN or estimated creatinine clearance ≥ 50 mL/min (according tothe 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;

17. Females and males of childbearing potential should agree that effectivecontraception (hormonal or barrier methods or abstinence) is required during thestudy and for 6 months after study completion; female patients of childbearingpotential must have a negative serum or urine pregnancy test within 7 days prior toadministration of the drug and must be non-lactating.

Exclusion Criteria:

1. Patients with leukemic PTCL (e.g., adult T-cell leukemia/lymphoma, etc.), orlymphomatous leukemia stage (percentage of lymphoma cells ≥20% on bone marrowexamination), or central nervous system (CNS) involvement, or concomitanthemophagocytic syndrome;

2. Have a history of allergy to similar drugs and excipients of the test drug;

3. Have received any other antitumor therapy [including chemotherapy with cytotoxicagents, molecularly targeted therapy, immunotherapy, or other biological therapieswithin 4 weeks prior to the first use of the test drug, mitomycin or nitrosamineswithin 6 weeks, small molecule targeted agents at least 2 weeks or at least 5half-life intervals from the last dose, whichever is longer, and traditional Chinesemedicines with antitumor indications at least 2 weeks from the last dose], and havereceived the test drug within 4 weeks prior to the first use of the test drug, orhave a history of hypersensitivity to similar drugs and excipient components of thetest drug; or have a history of allergy to the test drug. Chinese herbal medicineswith antitumor indications should be administered at least 2 weeks after the lastdose], and local radiotherapy within 4 weeks prior to the first administration ofthe test drug;

4. The presence of persistent Grade 2 or above (CTCAE V5.0 standard) toxicity reactionafter the previous treatment (chemotherapy or biotherapy or targeted therapy, etc.),which has not yet recovered to Grade ≤1 level at the time of enrollment (with theexception of alopecia areata);

5. Vaccination with live attenuated vaccine within 28 days prior to the first dose ofstudy drug or within 60 days of the end of treatment with study drug;

6. Have received a blood transfusion, recombinant human thrombopoietin, erythropoietin,or granulocyte colony-stimulating factor within 2 weeks prior to the first dose ofthe investigational drug;

7. A history of solid organ or allogeneic hematopoietic stem cell transplantation;autologous hematopoietic stem cell transplantation within 3 months prior to thefirst dose of the investigational drug;

8. Patients who have received any of the following treatments within 7 days prior tothe first dose of the investigational drug: drugs known to be potentinhibitors/inducers of CYP 3A4, drugs known to significantly prolong the QT period;

9. Uncontrolled electrolyte disturbances that may interfere with the action of QTcprolonging medications (e.g., hypocalcemia <1.0 mol/L, hypokalemia <lower limit ofnormal, hypomagnesemia <0.5 mmol/L), but retesting after interventional therapy ispermitted;

10. Major surgery (other than tumor biopsy) within 4 weeks prior to the first trial drugadministration, or the patient has not recovered and the side effects of the surgeryhave not stabilized;

11. Presence of uncontrolled Grade 2 or higher (CTCAE V5.0 criteria) active clinicalinfection requiring systemic anti-infective treatment (except if the patient'sinfection has been controlled and anti-infective treatment still needs to bemaintained);

12. Treatment with prednisone >10 mg/day [CTCL >20 mg/d (equivalent prednisone dose)]within 7 days prior to the first dose of the test drug, except for the following:treatment with topical, ophthalmic, intra-articular, intranasal, and inhaledcorticosteroids, short-term prophylactic corticosteroid use for Treatment, e.g.,with contrast media;

13. Impaired cardiac function or significant cardiac disease, including but not limitedto:

1. Myocardial infarction, congestive heart failure, viral myocarditis within 6 monthsprior to screening; symptomatic requiring therapeutic intervention for heartdisease, such as unstable angina, arrhythmia, etc; 2) Cardiac function class III toIV (New York Heart Association cardiac function classification NYHA); 3)Leftventricular ejection fraction (LVEF) of less than 50% by cardiac radionuclidescanning (MUGA) or echocardiography (ECHO) or less than the lower limit of thelaboratory test value at the research center; 4) History of persistentcardiomyopathy, primary cardiomyopathy (e.g., dilated cardiomyopathy, hypertrophiccardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, restrictivecardiomyopathy, and undetermined cardiomyopathy); 5) Screening-phase symptomaticcoronary heart disease requiring pharmacologic treatment; 6) A history of clinicallysignificant QTcF interval prolongation or a mean corrected QT interval (QTcF) >450msec (men) or >470 msec (women) on 3 electrocardiograms (ECGs) at rest during thescreening period (retesting is required only if the first ECG suggests a QTcF of >450 msec (men) or >470 msec (women)) and is taken at a later date. 3 averagecorrected values); history of or confirmed family history of long QT syndrome;history of clinically significant ventricular arrhythmia or current use ofantiarrhythmic drugs or implanted defibrillation device for the treatment ofventricular arrhythmias; 14. Cerebrovascular accident (including transient ischemicattack or symptomatic pulmonary embolism) within 6 months prior to screening; 15.patients with uncontrolled hypertension (defined as systolic blood pressure ≥160mmHg and/or diastolic blood pressure ≥95 mmHg after standardized antihypertensivetreatment) or diabetes mellitus with poor glycemic control (random blood glucose ≥13.9 mmol/L after hypoglycemic treatment, or HbA1c ≥8.5%) 16. A history of hepaticfibrosis or cirrhosis, or clinical signs and symptoms suggestive of hepatic fibrosisor cirrhosis. Severe lung disease (CTCAE V5.0 Class III-IV); 17. Presence of thirdinterstitial fluid (e.g., massive pleural fluid and ascites) that cannot becontrolled by drainage or other means.

18. Combination of any other malignancy (adequately treated and effectively controllednon-melanotic cutaneous basal cell or cutaneous squamous epithelial cell carcinomaor cervical carcinoma in situ, carcinoma in situ of the breast/cervix, superficialbladder cancer, limited prostate cancer, other appropriately treated stage 1 orstage 2 cancer in complete remission, or any other cancer in complete remission).

Hepatitis B virus (HBV) (except Stage 1 or Stage 2 cancers in complete remission, or any other cancer that has been in complete remission for more than 5 years); known or existing primary or metastatic central nervous system lymphomas and subjects with symptomatic brain metastases; 19. Active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV), except for the following patients: a) HBV infection: Hepatitis B surface antigen (HbsAg) or Hepatitis B core antibody (HbcAb) positivity, and then peripheral blood Hepatitis B DNA titer test, HBV DNA ≤ 1 x 103 copies/ml (or the lower limit of the assay value) can be enrolled; after enrollment, a holders' license is required. Patients with HBV DNA ≤1×103 copies/ml (or the limit of detection) can be enrolled; after enrollment, they need to continue antiviral treatment and have hepatitis B DNA titer test every cycle; b) Patients with positive HCV serology but negative HCV RNA test can be enrolled. Patients who are seropositive for HCV but negative for HCV RNA may be enrolled.

Antibody (HIV-Ab) or anti-syphilis spirochete antibody (TP-Ab) positive ; 20. History of psychiatric illness, family history of psychiatric illness, or mood disorders as determined by the investigator or psychologist [including medically documented history of depressive episodes, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, suicidal attempts or suicidal ideation, or homicidal ideation (immediate risk of harm to others)].

history of suicide attempts or suicidal ideation, or homicidal ideation (immediate risk of harm to others), anxiety level 3 or higher, etc.]; 21. Participation in another clinical study and treatment with the trial drug within 4 weeks prior to the first dose of trial drug; 22. Any condition that, in the judgment of the investigator, is unstable or may jeopardize the safety of the subject and his/her compliance with the study; 23. Any other factors that, in the opinion of the investigator, make participation in the trial inappropriate.