Diffuse Large B Cell Lymphoma, DLBCL
Conditions
Interventions
Phase IIa Queue 1:On the 1st, 4th, 8th and 11th days of each dosing cycle, 8.4 mg/m^2 of purinostat mesylate for injection was intravenously infused once. With 21 days as one dosing cycle, the total t
Phase IIa Queue 2:On the 1st, 4th, 8th and 11th days of each dosing cycle, 11.2 mg/m^2 of purinostat mesylate for injection was intravenously dripped once. With 21 days as one dosing cycle, the total
Phase IIb:On the 1st, 4th, 8th and 11th days of each dosing cycle, 11.2 mg/m^2 of purinostat mesylate for injection was intravenously dripped once. With 21 days as one dosing cycle, the total treatmen
Sponsors
West China Hospital of Sichuan University/Ruijin Hospital of Shanghai Jiao Tong University School of Medicine
Eligibility
Sex/Gender
All
Age
18 Years to 100 Years
Inclusion criteria
Inclusion criteria: 1. Age >= 18 years, both males and females are eligible; 2. Histologically confirmed diffuse large B-cell lymphoma (DLBCL) by tissue biopsy (including primary DLBCL and transformed DLBCL from indolent lymphoma; patients with relapse after more than one year require a repeat tissue biopsy to confirm the pathological diagnosis), and must be relapsed/refractory, specifically defined as: DLBCL patients who have received no more than 5 lines of prior systemic therapy. Relapse includes: 1) relapse occurring more than 6 months after the completion of second-line therapy; 2) relapse occurring more than 3 months after sequential hematopoietic stem cell transplantation following second-line therapy. Refractory includes: 1) primary refractory to first-line standard therapy (i.e., no response to treatment or relapse within 6 months after treatment completion); 2) relapse within 6 months after second-line therapy or failure to achieve partial response (PR) after 2 or more cycles of second-line therapy, or progression during second-line therapy (no specific cycle requirement for refractory patients). Prior treatment must include anti-CD20 monoclonal antibody (unless contraindicated) and anthracycline-based chemotherapy (unless anthracycline is contraindicated). Anti-CD20 monoclonal antibody monotherapy for consolidation or induction does not count as a separate line of therapy. Prior stem cell transplantation is allowed; standalone autologous stem cell transplantation does not count as a line of therapy, as induction, consolidation, stem cell collection, conditioning regimen, and transplantation ± maintenance therapy are considered one line of therapy. 3. Presence of measurable lesions, defined as: lymph node lesions with the longest diameter > 15 mm or extranodal lesions with the longest diameter > 10 mm as measured by contrast-enhanced CT, MRI, or PET-CT; willingness to undergo bone marrow aspiration cytology and/or biopsy for efficacy evaluation if required. 4. Prior to the first dose of study treatment, the following intervals must be observed: >= 4 weeks since the last systemic radiotherapy; >= 2 weeks since local radiotherapy or radiotherapy for bone metastases; no radiopharmaceuticals administered within 8 weeks prior to the first dose of study treatment; >= 3 weeks since the last chemotherapy or approved targeted therapy; biological therapy, immunotherapy, and other treatments must be completed at least 4 weeks prior to the first dose of study treatment. 5. ECOG performance status (Appendix 1) 12 weeks; 7. Hematological parameters must meet the following criteria: a) Absolute neutrophil count (ANC) >= 1.0 × 10^9/L; b) Hemoglobin (HGB) >= 80 g/L; c) Platelet count (PLT) >= 75 × 10^9/L, with no platelet or red blood cell transfusions within 2 weeks prior to screening. Note: If the investigator believes that the patient’s laboratory values below the protocol limits are due to bone marrow involvement by lymphoma, the patient’s eligibility may be determined after discussion with the sponsor and CRO medical team. 8. Liver and kidney function test results must meet the following criteria: a) Serum total bilirubin (TBiL) <= 1.5 × upper limit of normal (ULN); b) Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) <= 2.5 × ULN; c) Serum creatinine <= 1.5 × ULN. Note: Patients with Gilbert’s syndrome may be enrolled if TBiL <= 3.0 × ULN; patients with liver involvement by lymphoma
Exclusion criteria
Exclusion criteria: 1. Known severe allergy to the investigational drug or any of its excipients; 2. Primary central nervous system lymphoma or lymphoma involving the central nervous system; 3. Prior chronic lymphoma transformation (e.g., Richter syndrome, prolymphocytic leukemia, etc.); 4. Presence of other active malignancies requiring treatment that may interfere with the study; 5. History of solid organ or allogeneic hematopoietic stem cell transplantation; 6. Coagulation abnormalities, defined as: international normalized ratio (INR) > 1.5 × upper limit of normal (ULN), prothrombin time (PT) > 1.5 × ULN, activated partial thromboplastin time (APTT) > 1.5 × ULN, thrombin time (TT) > 1.5 × ULN, or fibrinogen (FIB) 450 msec (male) or > 470 msec (female) based on three electrocardiogram (ECG) measurements (retesting is required only if the first ECG shows QTcF > 450 msec (male) or > 470 msec (female), and the average of three measurements will be used); c) History of long QT syndrome or confirmed family history of long QT syndrome; history of clinically significant ventricular arrhythmias, or current use of antiarrhythmic drugs or implanted defibrillator for ventricular arrhythmias; d) Clinically significant cardiovascular diseases, including acute myocardial infarction, unstable angina, coronary artery bypass grafting, or cardiomyopathy within 6 months prior to the first dose; congestive heart failure classified as New York Heart Association (NYHA) class 3 or higher, or left ventricular ejection fraction (LVEF) < 50%; 9. Other systemic diseases: a) Poorly controlled diabetes; b) Severe pulmonary disease (CTCAE V5.0 grade III-IV); c) History of psychiatric disorders, family history of psychiatric disorders, or mood disorders as judged by the investigator or psychiatrist, including medical records of depressive episodes, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, suicide attempts or suicidal ideation, or homicidal thoughts (immediate risk of harm to others), or anxiety of grade 3 or higher; 10. Prior treatment conditions: a) Chimeric antigen receptor T-cell immunotherapy (CAR-T therapy) within 3 months prior to the first dose; b) Prior treatment with HDAC inhibitors (except for chidamide) or other small molecule targeted therapies; c) Autologous hematopoietic stem cell transplantation within 3 months prior to the first dose; d) Radiotherapy affecting the efficacy evaluation of this study or local radiotherapy affecting bone marrow function within 3 months prior to the first dose; e) Myelosuppres
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| objective remission rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| Time to response;Duration of remission;Disease control rate;progression free survival;overall survival; | — |
Countries
China
Contacts
Public ContactTing Niu/ Weili Zhao
West China Hospital of Sichuan University/Ruijin Hospital of Shanghai Jiao Tong University School of Medicine
Outcome results
None listed