Study of Purinostat Mesylate for Injection in the Treatment of Relapsed or Refractory Diffuse Large B-cell Lymphoma (R/R DLBCL)

NCT05563844 | Active Not Recruiting Phase 2

• 1 other identifier: ZLPM-001-1.0
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 2

Brief Summary

Purinostat mesylate for injection (PM) was the novel and highly potent Class Ia and IIb HDAC selective inhibitor. The results of regular blood sampling analysis of the mouse B-cell lymphoma model induced by ighmyc transgenic mice showed that the treatment of PM in each group reduced the proportion of peripheral blood tumor cells in mice. Therefore, PM has the potential to treat diffuse large B cell lymphoma. Compared with the blank control group, the body weight of the tumor-bearing animals in each dose of PM group did not decrease significantly during the treatment process, and the animals were in good condition during the whole experiment, indicating that the PM is efficacious and safe. Main purpose: To further explore the safe and effective dose of purinostat mesylate for injection in the treatment of relapsed or refractory diffuse large B-cell lymphoma. To evaluate the objective response rate (ORR) of purinostat mesylate for injection in the treatment of relapsed or refractory diffuse large B-cell lymphoma. Secondary purpose: To evaluate the time to tumor response (TTR), duration of response (DOR), disease control rate (DCR), and progression-free survival (PFS) in the treatment of relapsed or refractory diffuse large B-cell lymphoma with purinostat mesylate for injection ), overall survival (OS). Assessing the safety and tolerability of purinostat mesylate for injection in the treatment of relapsed or refractory diffuse large B-cell lymphoma. Exploratory purpose: To explore the biomarkers related to the efficacy of purinostat mesylate for injection.

Conditions

Diffuse Large B Cell Lymphoma，DLBCL

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR) of PM

  proportion of patients whose tumors have shrunk to the pre-specified value and maintained for required minimum time，including CR and PR.

  each cycle lasts 21 days, and patients are assessed every 2 cycles until maximum of 2 years.

Secondary Outcomes (5)

• TTR

  each cycle lasts 21 days, and patients are assessed every 2 cycles until maximum of 2 years.

• Duration of relief (DOR) of PM

  each cycle lasts 21 days, and patients are assessed every 2 cycles until maximum of 2 years.

• Overall survival (OS) of PM

  each cycle lasts 21 days, and patients are assessed every 2 cycles until maximum of 2 years.

• Progression-free survival (PFS) of PM

  each cycle lasts 21 days, and patients are assessed every 2 cycles until maximum of 2 years.

• Disease control rate (DCR) of PM

  each cycle lasts 21 days, and patients are assessed every 2 cycles until maximum of 2 years.

Study Arms (2)

Purinostat Mesylate for Injection 8.4mg/m^2

EXPERIMENTAL

The medication is administered once via intravenous infusion on days 1, 4, 8, and 11 of each 21-day treatment cycle.

Drug: PM 8.4 mg/m^2

Purinostat Mesylate for Injection 11.2mg/m^2

EXPERIMENTAL

The medication is administered once via intravenous infusion on days 1, 4, 8, and 11 of each 21-day treatment cycle.

Drug: PM 11.2 mg/m^2

Interventions

PM 8.4 mg/m^2 DRUG

The medication is administered once via intravenous infusion on days 1, 4, 8, and 11 of each 21-day treatment cycle. A total of 6 cycles are planned, with tumor response assessments performed every 2 cycles during the treatment period.

Purinostat Mesylate for Injection 8.4mg/m^2

PM 11.2 mg/m^2 DRUG

The medication is administered once via intravenous infusion on days 1, 4, 8, and 11 of each 21-day treatment cycle. A total of 6 cycles are planned, with tumor response assessments performed every 2 cycles during the treatment period.

Purinostat Mesylate for Injection 11.2mg/m^2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years, both males and females are eligible;
• 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.
• 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.
• 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.
• ECOG performance status (Appendix 1) ≤ 2;
• Expected survival \> 12 weeks;
• 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.
• 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 may be enrolled if AST, ALT, and ALP ≤ 5 × ULN.
• Left ventricular ejection fraction (LVEF) ≥ 50% as measured by echocardiography;
• Women of childbearing potential and men must agree to use effective contraception from the time of signing the informed consent form until 6 months after the last dose of pomalidomide mesylate. Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to the first dose. Women of childbearing potential include premenopausal women and women within 1 year of menopause.
• Participants must voluntarily sign the informed consent form, be able to communicate effectively with the investigator, and comply with the study visit schedule, treatment plan, laboratory tests, and other study procedures.

You may not qualify if:

• Subjects who meet any of the following criteria will be excluded from the trial:
• Known severe allergy to the investigational drug or any of its excipients;
• Primary central nervous system lymphoma or lymphoma involving the central nervous system;
• Prior chronic lymphoma transformation (e.g., Richter syndrome, prolymphocytic leukemia, etc.);
• Presence of other active malignancies requiring treatment that may interfere with the study;
• History of solid organ or allogeneic hematopoietic stem cell transplantation;
• 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) \< 1 g/L;
• Active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV), except for the following:
• HBV infection: If hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) is positive, peripheral blood HBV DNA titer must be ≤ 1 × 10\^3 copies/mL for enrollment; antiviral therapy must be continued after enrollment, and HBV DNA titer must be monitored every cycle;
• HCV seropositivity with negative HCV RNA test results is allowed for enrollment; Positive human immunodeficiency virus antibody (HIV-Ab) or positive syphilis antibody (TP-Ab) (patients with positive syphilis antibody in phase IIb may undergo titer testing, and eligibility will be determined by the investigator based on comprehensive assessment);
• Any of the following cardiac function-related criteria:
• Clinically significant arrhythmias or conduction abnormalities requiring clinical intervention;
• Average corrected QT interval (QTcF) \> 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);
• 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;
• 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%;

Sponsors & Collaborators

• Chengdu Zenitar Biomedical Technology Co., Ltd: lead

Study Sites (2)

Ruijin Hospital of Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200025, China

Location

West China Hospital of Sichuan University

Chengdu, Sichuan, 610000, China

Location

MeSH Terms

Conditions

Dendritic Cell Sarcoma, Interdigitating

Condition Hierarchy (Ancestors)

Histiocytic Disorders, Malignant; Neoplasms by Histologic Type; Neoplasms; Histiocytosis; Lymphatic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Ting Niu, Doctor

  West China Hospital

  PRINCIPAL INVESTIGATOR

• Weili Zhao, Doctor

  Ruijin Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 28, 2022
• First Posted: October 3, 2022
• Study Start: November 8, 2022
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: February 4, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)