Chidamide Combined With Azacitidine and Mitoxantrone Liposome in the Treatment of Relapsed/Refractory (nTFHL)

Inclusion Criteria:

1. R/R nTFHL confirmed by pathological tissue, with diagnostic criteria referring to the 2022 WHO diagnostic criteria.
2. Patients who have undergone at least one previous systemic treatment (including chemotherapy, HSCT, etc.) without remission or relapse after remission.
3. Signed written informed consent and who are able to comply with the visits and related procedures specified in the protocol.
4. whole-body PET/CT performed 28 days prior to study entry, which must have at least 1 evaluable or measurable lesion meeting Lugano 2014 criteria: lymph node lesions, measurable lymph nodes need to be \>1.5 cm in length; non-lymphoid lesions, measurable extra-nodal lesions need to be \>1.0 cm in length.
5. with a PS score of 0 to 2 according to ECOG
6. with adequate organ and bone marrow function, defined as follows: neutrophil count ≥ 1.5×109/L, platelet count ≥ 75×109/L, and hemoglobin ≥ 80 g/L (relaxed to ≥ 1.0×109/L for neutrophil count, ≥ 50×109/L for platelet count, and ≥ 75 g/L for hemoglobin in patients with bone marrow involvement);
7. Liver and kidney function: serum creatinine (Cr) ≤ 1.5 times the upper limit of normal value; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 times the upper limit of normal value (≤ 5 times the upper limit of normal value for patients with liver invasion); total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal value (≤ 3 times the upper limit of normal value for patients with liver invasion);
8. life expectancy of more than 3 months
9. age 18 to 75 years.

Exclusion Criteria:

1. Subjects with a history of prior antitumor therapy that is one of the following.

   1. Previous recipients of mitoxantrone or mitoxantrone liposomes.
   2. Prior treatment with doxorubicin or other anthracyclines with a total cumulative dose of doxorubicin \> 360 mg/m2 (other anthracyclines converted to 1 mg doxorubicin equivalent to 2 mg epirubicin).
   3. Patients who have received autologous hematopoietic stem cell transplantation (ASCT) within 100 days of the first dose, or who have received allogeneic hematopoietic stem cell transplantation.
   4. have received antitumor therapy (including chemotherapy, targeted therapy, hormonal therapy, administration of herbal medicine with antitumor activity, etc.) or participated in other clinical trials and received clinical trial medication within 4 weeks prior to the first administration of this study drug.
2. Hypersensitivity reaction to any investigational drug or its components.
3. Uncontrollable systemic disease (e.g., progressive infection, uncontrollable hypertension, diabetes mellitus, etc.).
4. Cardiac function and disease consistent with one of the following.

   1. Long QTc syndrome or QTc interval \>480 ms.
   2. Complete left bundle branch block, second or third degree atrioventricular block.
   3. Severe, uncontrolled arrhythmias requiring drug therapy.
   4. American New York Heart Association classification ≥ Class III.
   5. Cardiac ejection fraction (LVEF) less than 50%.
   6. History of myocardial infarction, unstable angina, severe unstable ventricular arrhythmia, or any other arrhythmia requiring treatment, history of clinically severe pericardial disease, or electrocardiographic evidence of acute ischemic or active conduction system abnormalities within 6 months prior to recruitment.
5. Active hepatitis B and C infection (positive hepatitis B virus surface antigen and hepatitis B virus DNA greater than 1 x 103 copies/mL; hepatitis C virus RNA greater than 1 x 103 copies/mL).
6. Human immunodeficiency virus (HIV) infection (HIV antibody positive).
7. previous or current concurrent other malignancies (in addition to effectively controlled non-melanoma basal cell carcinoma of the skin, breast/cervical carcinoma in situ and other malignancies that have not been treated and also effectively controlled within the last five years)
8. Primary or secondary central nervous system (CNS) lymphoma or a history of CNS lymphoma at the time of recruitment.
9. Pregnant and lactating women and patients of childbearing age who do not wish to use contraception
10. Persons with mental disorders/unable to obtain informed consent.
11. Those who are judged by the investigator to be unsuitable for participation in this trial.