Chiauranib in Combination With Chidamide in Patients With Relapsed/Refractory Non-Hodgkin's Lymphoma

Inclusion Criteria:

1. Male or Female, aged ≥ 18 yrs and ≤70 yrs;
2. Patients with NHL refractory to at least 2 different chemotherapies , for which no standard therapy exists;
3. At least 1 lesion can be accurately measured, as defined by Lugano 2014 criteria.
4. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1;
5. Subjects received anti-cancer therapy (including chemotherapy, radiotherapy, immunotherapy and surgical therapy, et al) should beyond 4 weeks prior to study entry; Subjects received mitomycin chemotherapy should beyond 6 weeks prior to study entry; Subjects received autologous stem cell transplantation should beyond 3 months prior to study entry;
6. Laboratory criteria are as follows:

   Complete blood count: hemoglobin (Hb) ≥90g/L ; absolute neutrophil count (ANC) ≥1.5×109/L ; platelets \>=90×109/L Biochemistry test: total bilirubin≦1.5×ULN; alanine aminotransferase(ALT) ,aspartate aminotransferase(AST)≦1.5×ULN; (ALT,AST≦5×ULN if liver involved) ;serum creatinine(cr)≦1.5×ULN; Coagulation test: International Normalized Ratio (INR) \< 1.5
7. Life expectancy of at least 3 months.
8. Willingness to sign a written informed consent document.

Exclusion Criteria:

1. Clinical evidence of central nervous system involvement
2. Patients with prior invasive malignancies with the exception of curatively-treated basal cell or squamous cell carcinoma of the skin or cervical carcinoma in situ, unless received curative treatment and with documented evidence of no recurrence in the past five years;
3. Previous treatment with HDAC inhibitors(include Chidamide) or aurora kinase(include Chiauranib) inhibitors;
4. Have uncontrolled or significant cardiovascular disease, including:

   1. Congestive heart failure, unstable angina pectoris, myocardial infarction within 6 months prior to study entry; arrhythmia, or Left Ventricular Ejection Fraction (LVEF) \< 50% requiring treatment with agents during screening stage.
   2. primary cardiomyopathy(dilated cardiomyopathy, hypertrophic cardiomyocyte, arrhythmogenic right ventricular cardiomyopathy, restrictive cardiomyopathy, et,al)
   3. History of significant QT interval prolongation, or Corrected QT Interval (QTc) \> 450 ms prior to study entry
   4. Symptomatic coronary heart disease requiring treatment with agents
   5. Uncontrolled hypertension (\> 140/90 mmHg) by single agent;
5. Have active bleeding current thrombotic disease, patients with bleeding potential ,or receiving anticoagulation therapy; within 2 months prior to screening;
6. Proteinuria positive(≥1g/24h);
7. History of deep vein thrombosis or pulmonary embolism;
8. Have unsolved toxicities (\> grade 1) from prior anti-cancer therapy;
9. Have clinical significant gastrointestinal abnormality, e.g., unable to swallow, chronic diarrhea, ileus, that would impair the ingestion,transportation or absorption of oral agents, or patients undergone gastrectomy;
10. History of organ transplantation ，Allogeneic bone marrow transplantation or autologous stem cell transplantation;
11. High-risk surgery for vital organs within 6 weeks prior to screening or the investigators determined that other surgical wounds did not heal well;
12. Serologically positive for HIV, hepatitis B or C, or other serious infectious diseases;
13. History of interstitial lung disease(ILD);
14. Any mental or cognitive disorder, that would impair the ability to understand the informed consent document or the operation and compliance of study;
15. Candidate with drug and alcohol abuse;
16. Participants of reproductive potential not willing to use adequate contraceptive measures for the duration of the study (both male and female participants).Pregnant or breastfeeding women. Female participants must have a negative urinary or serum pregnancy test when done or have evidence of post-menopausal status (Defined as absence of menstruation for greater than 12 months, bilateral oophorectomy or hysterectomy);
17. Any other condition which is inappropriate for the study in the opinion of the investigators.