Study of Purinostat Mesylate for Injection in the Treatment of Diffuse Large B-cell Lymphoma (DLBCL)
Status:
Not yet recruiting
Trial end date:
2025-05-01
Target enrollment:
Participant gender:
Summary
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.