Clinical Study of Mitoxantrone Hydrochloride Liposome Injection vs. Chidamide in Patients With Relapsed/Refractory PTCL
Clinical Study of Mitoxantrone Hydrochloride Liposome Injection vs. Chidamide in Patients With Relapsed/Refractory PTCL
This is a randomized, open-label, active controlled, multi-center, phase 3 clinical study to
 compare the efficacy and safety of Mitoxantrone Hydrochloride Liposome Injection with
 Chidamide in patients with relapsed/refractory Peripheral T Cell Lymphoma (PTCL).
This study is a randomized, open-label, positive control, multicenter, phase Ⅲ study to
 compare the efficacy and safety of Mitoxantrone Hydrochloride Liposome Injection with
 Chidamide in patients with relapsed/refractory Peripheral T Cell Lymphoma (PTCL). The
 eligible patients will be randomly assigned to the experimental and control groups in a 1:1
 ratio. The patients in experimental group will receive Mitoxantrone Hydrochloride Liposome
 Injection (20 mg/m2) once every 28 days for a maximum of 6-8 cycles. Patients in the control
 group will be treated with Chidamide (30 mg) twice per week with 3-day intervals until
 disease progression. Patients in the control group who had confirmed disease progression will
 have the option to switch to the liposomal mitoxantrone hydrochloride treatment. Patients
 will receive treatment until the completion of 6-8 cycles of treatment (this applies only to
 the experiment group), disease progression, intolerable toxicity, death, loss to follow-up,
 withdrawal (patient's decision or investigator's decision), whichever comes first. All
 patients will have post-treatment follow-up for disease status until disease
 progression/recurrence, initiation of new antitumor therapy, or being lost to follow-up.
Inclusion Criteria:

 1. Subjects fully understand and voluntarily participate in this study and sign informed
 consent;

 2. Age ≥18, ≤75 years, no gender limitation;

 3. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2;

 4. Histopathologically confirmed Peripheral T -cell Lymphoma (PTCL) according to World
 Health Organization (WHO) criteria (version 2016), with the subtypes as follows:

 1. Peripheral T-cell lymphoma, unspecified (PTCL, NOS);

 2. Angioimmunoblastic T-cell lymphoma (AITL);

 3. ALK+ systematic anaplastic large T-cell lymphoma (ALCL, ALK+);

 4. ALK-systematic anaplastic large T-cell lymphoma (ALCL，ALK-);

 5. Extranobal NK/T cell lymphoma (nasal type) (NKTCL);

 6. Other subtypes of PTCL which are appropriate to be enrolled in the opinion of the
 investigator.

 5. Patients have relapsed or are refractory to at least one line of prior systemic
 therapy (anthracycline-containing regimen) for PTCL. Relapse is defined as recurrence
 after CR or progress after PR; refractory refers to the efficacy of 2 cycles of
 treatment is PD, or the efficacy of 4 cycles of treatment is SD;

 6. Subjects have at least one measurable lesion in accordance with the Lugano evaluation
 criteria (version 2014): the long axis of the lymph node shall be>1.5 cm, the long
 axis of the extranodal lesions shall be>1.0 cm.

 7. Subjects must provide a written pathology/histological diagnosis report during the
 screening period and must agree to provide a tumor tissue section or tumor/lymph node
 tissue specimen to be sent to the central laboratory.

 8. Life expectancy ≥ 12 weeks;

 9. During the screening period, the patients should meet the following requirements and
 have not received infusion of cell growth factor, platelet and granulocyte within 7
 days of the hematology test; 1) Absolute value of neutrophils ≥ 1.5 × 109/L; absolute
 value of neutrophil ≥ 1.0 × 109/L in patients with involvement of bone marrow; 2)
 Hemoglobin ≥ 90 g/L (no red cell infusion within 14 days), hemoglobin ≥ 75 g/L in
 patients with involvement of bone marrow; 3) Platelet ≥ 75 × 109/L in patients without
 involvement of bone marrow; platelet ≥ 50 × 109/L in patients with involvement of bone
 marrow; 4) Serum total bilirubin ≤ 1.5 × upper limit of normal (ULN) (total bilirubin
 ≤ 3 × ULN if bilirubin level increase is caused by lymphoma invading the liver); 5)
 Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 × ULN; if the
 elevated level of AST or ALT is caused by liver involvement, both AST and ALT shall be
 ≤ 5 × ULN); 6) Creatinine < 1.5 × ULN.

 10. Eligible fertile patients (male and female) must agree to use an effective method of
 contraception (hormonal or barrier or abstinence) with their partners from the study
 initiation until at least 7 months after the last treatment; women of childbearing
 potential must have a negative serum pregnancy test within 14 days prior to
 enrollment.

 Exclusion Criteria (Limit: 15,000 characters)

 1. Patients with leukemia type PTCL (adult T-cell leukemia/lymphoma, etc.), or in
 lymphoma leukemia stage (malignant cell proportion of > 20% in bone marrow
 examination); or with central nervous system (CNS) involvement, or with complicated of
 hemophagocytic syndrome.

 2. History of allergy and contraindications to the same class and excipients of the
 experimental drug.;

 3. Patients have one of the following conditions in the previous anti-tumor treatments:1)
 Patients received mitoxantrone or liposome mitoxantrone within 6 months;2) Patients
 who was treated with Chidamide and the efficacy was evaluated as PD; Patients who was
 treated with Chidamide within 6 months (if the patients have been treated with
 Chidamide for no more than 2 weeks, had no clear evidence of PD and no intolerable
 toxicity during the treatment period, and discontinued therapy for other reasons, may
 be considered with the investigator's consent);3) Those receiving treatment of
 Adriamycin or other anthracyclines previously, with the total cumulative dose of > 360
 mg/m2 (other anthracycline drugs: 1 mg of epirubicin/pyramycin/daunorubicin is
 equivalent to 0.5 mg of doxorubicin, 1 mg of deoxydaunorubicin is equivalent to 2 mg
 of doxorubicin);4) Those received anti-tumor treatment, including cytotoxic
 chemotherapy, radiotherapy and targeted drug therapy within 4 weeks prior to the first
 use of the study drug, or immunomodulators (thalidomide, lenalidomide) within 3 weeks;
 or hormone or herbal therapy with lymphoma as indication within 2 weeks;

 4. Participated in other clinical studies and received therapy within 4 weeks prior to
 the first administration of the study drug;

 5. Those received allogeneic hematopoietic stem cell transplantation previously and
 autologous hematopoietic stem cell transplantation within 6 months;

 6. Adverse reactions from the previous anti-tumor treatment have not yet recovered
 (>Grade 1 in NCI-CTCAE [Version 4.03], with the exception of hair loss and
 pigmentation);

 7. Subjects with the impaired cardiac function or significant heart disease, including
 but not limited to:1) Myocardial infarction, congestive heart failure and viral
 myocarditis occurred 6 months before screening; heart disease with symptoms requiring
 treatment and intervention, such as unstable angina, arrhythmia, etc.;2) Congestive
 heart failure of ≥Grade 2 according to the New York Heart Association
 Classification;3) Cardiac ejection fraction less than 50% or less than the lower limit
 of the reference range of the laboratory examination used in the Research Center;4)
 Persistent myocardial disease;5) QTc > 450 milliseconds, or congenital long QT
 syndrome.

 8. Patients with active infection, including hepatitis B (positive hepatitis B virus
 surface antigen and HBV-DNA titer higher than the upper limit of the reference range)
 and hepatitis C (positive hepatitis C virus RNA and HCV-RNA titer higher than the
 upper limit of the reference range);

 9. History of severe autoimmune disease and immunodeficiency, including positive for
 human immunodeficiency virus (HIV); or other acquired or congenital immune deficiency
 diseases; or a history of organ transplantation;

 10. Patients with other malignant tumors in the past five years (except the cured
 non-melanoma skin basal cell carcinoma and cervical carcinoma in situ);

 11. Major surgery within 6 weeks prior to screening. or have a surgical schedule during
 the study period;

 12. Patients have significant gastrointestinal disorders that may affect the ingestion,
 transportation, or absorption of the drug (e.g., inability to swallow, chronic
 diarrhea, intestinal obstruction, etc.) during the screening period;

 13. Patients have uncontrolled hypertension (systolic pressure of 180 mmHg and/or
 diastolic pressure of 110 mmHg after treatment); or type 2 diabetes that cannot be
 controlled by oral hypoglycemic drugs or insulin therapy;

 14. History of mental illness or history of drug abuse or dependence;

 15. Pregnant or lactating women;

 16. Not suitable for this study as determined by the investigator due to other reasons.