Diffuse Large B Cell Lymphoma,DLBCL Clinical Trial
Official title:
An Open-label, Multi-center Phase II Clinical Study on the Efficacy and Safety of Purinostat Mesylate for Injection in the Treatment of Relapsed or Refractory Diffuse Large B-cell Lymphoma (DLBCL)
Purinostat mesylate for injection (PM) was the novel and highly potent Class I a and IIb HDAC-selective inhibitors. 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. The results of in vitro enzymatic activity screening showed that PM has high inhibitory activity on HDAC tumors (including HDAC1, 2, 3, 8 subtypes) and type II HDACs (including HDAC6, 10 isoforms), which are closely related to tumors in the HDAC family. Therefore, the results of in vitro enzyme activity screening showed that the IC50 values of PM for inhibiting HDAC1, HDAC2, HDAC3, HDAC8, HDAC6, and HDAC10 subtypes of HDAC class I and HDAC class IIb were 0.81, 1.4, 1.7, 3.8, 11.5, and 11 nM, respectively. However, the inhibitory activity of HDAC IIa and HDAC IV enzymes was low, and its IC50 values for HDAC4, HDAC5, HDAC7, HDAC9, and HDAC11 subtypes of HDAC IIa and HDAC IV were 1072, 426, 590, 622, and 3349 nM, respectively. These data means PM exist high selectivity for tumor-associated HDAC class I and HDAC IIb. Compared with the blank control group, the body weight of the tumor-bearing animals in each dose of PM group did not decrease seriously during the treatment process, and the animals were in good condition during the whole experiment, indicating that the PM is efficacy and safe. Main purpose: To further explore the safe and effective dose of priinostat mesylate for injection in the treatment of relapsed or refractory diffuse large B-cell lymphoma. To evaluate the objective response rate (ORR) of priinostat mesylate for injection in the treatment of relapsed or refractory diffuse large B-cell lymphoma. Secondary purpose: To explore the biomarkers related to the efficacy of priinostat mesylate for injection. 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 prilinostat mesylate for injection ), overall survival (OS). Assessing the safety and tolerability of priinostat mesylate for injection in the treatment of relapsed or refractory diffuse large B-cell lymphoma.
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